@article {pmid42242290, year = {2026}, author = {Al-Burak, SA and Suleiman, A and Voznyy, V and Elganga, M and Zajner, C and Juncal, V and Sheidow, TG and Malvankar-Mehta, MS}, title = {Age-related macular degeneration (AMD) associated with glucagon-like peptide-1 receptor agonist use: a systematic review.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcjo.2026.05.010}, pmid = {42242290}, issn = {1715-3360}, abstract = {BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for diabetes, obesity, and cardiovascular risk reduction. However, their ocular safety profile, particularly regarding age-related macular degeneration (AMD), remains uncertain. This systematic review evaluates the association between GLP-1 RA use and the incidence or progression of AMD including both nonexudative and neovascular subtypes.<br><br>METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD420251183938). MEDLINE, Embase, CENTRAL, Web of Science, and PubMed were searched from inception through 2025 for observational studies and randomized trials evaluating AMD outcomes among adults exposed to GLP-1 RAs. Comparators included nonuse, placebo, or alternative metabolic therapies. Risk of bias was assessed using Risk of Bias in Non-Randomized Studies of Interventions and certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Due to heterogeneity of outcome definitions, results were synthesized qualitatively.<br><br>RESULTS: Eight observational studies encompassing 91 408 to 600 816 participants were included. GLP-1 RA use was associated with a reduced incidence of nonexudative AMD across diabetic and nondiabetic populations, with relative risk reductions varying substantially by population, comparator, and follow-up duration. Findings for neovascular AMD were heterogeneous: most studies reported neutral or protective associations, whereas one population-based cohort of older adults with diabetes observed an increased risk (adjusted hazard ratio 2.21, 95% CI 1.65-2.96), with low absolute event rates. Overall risk of bias was moderate to high, and certainty of evidence for all outcomes was very low.<br><br>CONCLUSIONS: Current evidence does not demonstrate a consistent increase in AMD risk associated with GLP-1 RA therapy and may be associated with a lower incidence of nonexudative AMD, although the certainty of evidence is very low and noncausal explanations cannot be excluded. Prospective studies with standardized endpoints are needed to clarify causal relationships.}, }
@article {pmid42242606, year = {2026}, author = {Boyer, DS and Saad, L and Washington, I and Melamud, A and Graham, KB and O'Malley, AE and DeBartolomeo, GM and Jiang, H and Harris, LD and Kay, CN and Ferrone, PJ and Khan, S and , }, title = {Gildeuretinol Acetate vs Placebo for Geographic Atrophy Secondary to Age-Related Macular Degeneration: The SAGA Randomized Clinical Trial.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.05.018}, pmid = {42242606}, issn = {2468-6530}, abstract = {OBJECTIVE: To assess the effects of gildeuretinol acetate (C20D3-vitamin A) in geographic atrophy (GA).<br><br>DESIGN: 24-month, double-masked, multicenter, randomized, placebo-controlled trial.<br><br>PARTICIPANTS: Participants &#x2265;60 years with GA.<br><br>INTERVENTIONS: Randomized 2:1 to oral gildeuretinol acetate 14 mg daily or placebo.<br><br>MAIN OUTCOME MEASURES: The primary endpoint was GA growth rate from baseline to 24 months. A prespecified sensitivity analysis accounted for a 6-month delay in onset of therapeutic effect. Secondary endpoints included change from baseline in low luminance visual acuity (LLVA), best-corrected visual acuity (BCVA), Visual Function Questionnaire (VFQ)-25, and Functional Reading Independence (FRI) Index.<br><br>RESULTS: Among 198 randomized participants (mean [SD] age 78.4 [7.0] years; 68.7% female), 69.2% completed the 24-month study. In the gildeuretinol and placebo groups, baseline mean (SD) total GA lesion area in mm[2] was 7.72 (6.10) and 7.09 (4.16); BCVA letter scores were 56.2 (21.3) (Snellen equivalent: &#x223c;20/80) and 58.8 (18.0) (&#x223c;20/70); and LLVA letter scores were 31.1 (19.0) (&#x223c;20/200) and 31.6 (17.8) (&#x223c;20/250), respectively. Mean GA growth rates were 1.62 mm[2]/year with gildeuretinol and 1.87 mm[2]/year with placebo (least squares [LS] mean difference: -0.25 mm[2]/year; 95% CI: -0.53, 0.03; P = 0.075), a 13.4% relative reduction for gildeuretinol vs placebo. The LS mean (SE) GA growth rates from 6 to 24 months were 1.90 (0.12) mm[2]/year (placebo) and 1.61 (0.08) mm[2]/year (gildeuretinol), a 15.3% relative reduction (-0.29 mm[2]/year; 95% CI: -0.576, -0.004; nominal P = 0.047). At 24 months, LLVA declined 3.9 and 8.3 ETDRS letters in the gildeuretinol and placebo groups, respectively (difference: 4.4 letters; 95% CI: 0.40, 8.41; nominal P = 0.031). BCVA declined 6.9 letters with gildeuretinol and 10.2 letters with placebo (difference: 3.3 letters; 95% CI: -0.63, 7.23; P = 0.099). VFQ-25 scores declined 4.81 fewer points with gildeuretinol than placebo (95% CI: 0.87, 8.76; nominal P = 0.017) and FRI scores declined 0.35 fewer points (95% CI: 0.11, 0.58; nominal P = 0.004).<br><br>CONCLUSIONS: The prespecified primary endpoint was not met. Prespecified piecewise and secondary functional/patient-reported analyses favored gildeuretinol with nominal P values; these exploratory findings support further evaluation in adequately powered trials.}, }
@article {pmid42243112, year = {2026}, author = {Cui, X and Hui, J and Zhao, Q and Han, Q}, title = {Plant-based diet quality and risk of age-related eye diseases: evidence from multi-cohorts with multi-omics insights.}, journal = {NPJ science of food}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41538-026-00919-z}, pmid = {42243112}, issn = {2396-8370}, support = {NKSGZ202305//Nankai University Eye Institute Key Science and Technology Fund/ ; TJYXZDXK-3-004A-3//Tianjin Key Medical Discipline Construction/ ; }, abstract = {Plant-based diets may influence age-related eye diseases (AREDs), but whether ocular benefits depend on diet quality remains unclear. We examined associations of a healthy plant-based diet index (PDI-H) and an unhealthy plant-based diet index (PDI-U) with age-related macular degeneration (AMD), cataract, glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO) using the UK Biobank prospective cohort and an independent Tianjin hospital-based cross-sectional sample. Cox regression, logistic regression, propensity score matching, restricted cubic splines, subgroup analyses, multi-omics profiling, and machine learning were applied. Higher PDI-H was associated with lower risks of AMD, cataract, glaucoma, and DR, whereas higher PDI-U was associated with increased risks of AMD, cataract, and DR. Associations with RVO were weak or absent. Findings from Tianjin were directionally consistent with UK Biobank results and should be interpreted as supportive cross-sectional evidence. Proteomic and metabolomic analyses linked plant-based diet quality to inflammation, lipid metabolism, glycaemic regulation, and hormonal signalling. Predictive models incorporating dietary indices showed good discrimination for AMD and cataract, with modest but consistent AUC improvements after adding PDI-H and PDI-U to traditional risk factors. These findings suggest that plant-based diet quality, rather than plant-based eating alone, may be a modifiable determinant of major AREDs.}, }
@article {pmid42243270, year = {2026}, author = {Pawloff, M and Linhardt, D and Woletz, M and Hollaus, M and Mylonas, G and Holder, GE and Sacu, S and Windischberger, C and Ritter, M}, title = {Robust and reproducible population receptive field mapping in patients with retinal pathologies.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42243270}, issn = {1476-5454}, support = {KLI 670-B30; P35583//Austrian Science Fund (Fonds zur F&#xf6;rderung der Wissenschaftlichen Forschung)/ ; }, abstract = {PURPOSE: Previous studies have shown high reproducibility of population receptive field (pRF) mapping in young, healthy individuals. The present study examines whether such a level of reproducibility can also be achieved in patients suffering from retinal disease.<br><br>METHODS: Eleven patients with Stargardt disease and eleven patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) were examined in up to four sessions using high-resolution ultra-high field fMRI (Siemens Magnetom 7&#x2009;T) and microperimetry (MP, Nidek MP-3). Reproducibility of the pRF parameters within and between sessions was assessed using Spearman's correlation coefficient.<br><br>RESULTS: Retinotopic maps calculated from ultra-high field MRI had excellent intra- and intersession reproducibility for pRF center position (median correlation between sessions for pRF center eccentricity: r&#x2009;=&#x2009;0.91; polar angle: r&#x2009;=&#x2009;0.90), but only modest reproducibility for pRF size (average correlation r&#x2009;=&#x2009;0.39). Reproducibility was constant across sessions multiple weeks apart, indicating a long-term stability of the method. In addition, the results show that reproducibility is not related to the severity of retinal disease.<br><br>CONCLUSION: The data demonstrate that retinotopic mapping of the primary visual cortex using ultra-high field MRI is a highly reproducible technique for the assessment of macular function in patients with retinal disease. The technique provides an unbiased quantification of retinal function adjunct to conventional clinical assessments and may assist the early diagnosis of retinal disease. In addition, it may be a valuable objective method for monitoring visual deficits during long-term therapeutic interventions or disease progression.}, }
@article {pmid42245065, year = {2026}, author = {Lee, SS and Wang, CA and de Vries, VA and van Hemert, DJ and Schulze, A and Brandl, C and Aman, AM and Alonso-Caneiro, D and Choquet, H and Gorski, M and Hammond, CJ and Heid, IM and Hunter, ML and Hysi, P and Jiang, C and Jonas, J and Klaver, CC and Kneepkens, SC and Konig, S and Lingham, G and Luber, C and Melton, PE and Pennell, CE and Ramdas, WD and Read, SA and Schuster, AK and Wang, YX and Zimmermann, ME and ,  and Khawaja, AP and Gharahkhani, P and MacGregor, S and Guggenheim, JA and Mackey, DA}, title = {Genome-wide discovery reveals 30 loci for choroidal thickness and uncovers potential causal links with angle-closure glaucoma.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.05.26.26354075}, pmid = {42245065}, abstract = {The choroid is critical for maintaining vision and implicated in several ocular diseases, being the sole source of nutrients and waste removal for the outer retina. Genetic discovery can help elucidate the pathways through which choroidal features influence disease risk. Our meta-analysis of genome-wide association studies (n= 78,682 participants) identified 30 genomic regions, including 20 novel loci, associated with choroidal thickness. Findings suggest inflammatory and vascular processes drive choroidal thickness, with overlapping mechanisms shared with refractive error. Genome-wide independently significant SNPs accounted for 18.7% of the genetic variance in choroidal thickness. Mendelian randomisation analyses showed a causal effect of age-related macular degeneration on choroidal thickness, and suggest a bidirectional causal effect between choroidal thickness and primary angle-closure glaucoma. These findings provide insight into the shared genetic architecture and biological pathways linking choroidal thickness and related diseases.}, }
@article {pmid42232161, year = {2026}, author = {Guo, H and Yan, R and Han, X and Yu, W}, title = {Dysregulated Polarized Secretion of Small Extracellular Vesicles in the Retinal Pigment Epithelium: Mechanisms and Pathological Roles in Age-Related Macular Degeneration.}, journal = {Journal of inflammation research}, volume = {19}, number = {}, pages = {612984}, pmid = {42232161}, issn = {1178-7031}, abstract = {The pathogenesis of age-related macular degeneration (AMD) is intrinsically driven by retinal pigment epithelium (RPE) dysfunction. Under physiological conditions, the strictly polarized secretion of small extracellular vesicles (sEVs) by the RPE dictates outer retinal homeostasis. In response to oxidative and hypoxic stress, this secretory architecture is profoundly disrupted, transforming sEVs into mediators of drusen formation, inflammation, and neovascularization. This review systematically delineates the molecular machinery governing RPE-sEV trafficking, unveiling the distinct protein and miRNA cargo profiles segregated between the apical and basolateral domains. We highlight the unique secretory features of RPE and elucidate how AMD stressors disrupt this polarity via cytoskeletal collapse, secretory autophagy, and Rab GTPase dysregulation. Consequently, this altered sEV secretion abolishes apical neurotrophic support while deteriorating the basolateral microenvironment. Crucially, this establishes a vicious pathological loop where microenvironmental deterioration and sEV dysregulation are mutually causative. Recognizing dysregulated sEV polarity as a contributing factor to AMD, we propose that repairing RPE intracellular trafficking offers a fundamental strategy to restore secretory homeostasis and impede disease progression.}, }
@article {pmid42233695, year = {2026}, author = {Battu, P and Sharma, S and Singh, R and Anand, A}, title = {Circulating biomarker profile and its diagnostic predictive utility in age-related macular degeneration.}, journal = {Biomarkers in medicine}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/17520363.2026.2677199}, pmid = {42233695}, issn = {1752-0371}, abstract = {PURPOSE: We evaluated the serum expression profiles of proteins encoded by AMD-related genes in age-related macular degeneration patients and controls.<br><br>METHODS: In our case-control study, we employed Enzyme-linked immunosorbent assay (ELISA) to analyze the expression of Collagen type X alpha 1 chain (COL10A1), Transforming growth factor-beta receptor type 1(TGF&#x3b2;R1) and Tumor Necrosis Factor Receptor Superfamily (TNFRSF10A) in serum. We have also statistically analyzed the correlations among the biomarkers and further assessed their diagnostic potential using the least absolute shrinkage and selection operator (LASSO) regression.<br><br>RESULTS: Out of three evaluated serum protein levels, two were found to be significantly associated with AMD. The expression of COL10A1 was significantly upregulated (p&#x2009;<&#x2009;0.0001), and TNFRSF10A was significantly downregulated (p&#x2009;<&#x2009;0.0001) in AMD patients compared to controls. The LASSO logistic regression revealed that serum expression of COL10A1 and TNFRSF10A proteins can reliably differentiate AMD cases from controls with predictive accuracy of 87.3%.<br><br>CONCLUSION: Our findings indicate that serum levels of COL10A1 and TNFRSF10A are significantly altered in AMD patients compared to controls. LASSO regression analyses further revealed that these proteins together have a strong ability to differentiate between AMD cases and controls, suggesting their potential as reliable biomarkers for risk prediction of AMD.}, }
@article {pmid42234083, year = {2026}, author = {Saraf, A and Garima, K and Dharwadkar, S and Keshav, S and Patwardhan, SD and Giri, NB and Saxena, M and Phadke, Y and Khare, A and Mishra, A and Kumar, V and Singh, S}, title = {Safety of GBL1204-An Ophthalmic Bevacizumab in Prefilled Syringe for Neovascular Age-Related Macular Degeneration: A Phase I Study.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42234083}, issn = {2193-8245}, abstract = {INTRODUCTION: GBL1204 1.25 mg is an ophthalmic-grade bevacizumab formulation, manufactured in accordance with the stringent ophthalmic quality standards, and supplied in a single-use prefilled syringe (PFS). This clinical trial evaluated the short-term safety and biological activity of a single intravitreal injection of ophthalmic bevacizumab in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This phase&#xa0;I, open-label, single-arm, multicentre trial enrolled 16 participants (aged&#x2009;&#x2265;&#x2009;50&#xa0;years) with best-corrected visual acuity (BCVA) score using Early Treatment of Diabetic Retinopathy Study charts of 20/40-20/320 (approximate Snellen equivalent) at five centres across India. Participants were administered a single intravitreal injection of GBL1204 (1.25&#xa0;mg/0.05&#xa0;mL). The main objective was evaluation of ocular and systemic treatment-emergent adverse events (TEAEs), and laboratory parameters over 4&#xa0;weeks.<br><br>RESULTS: GBL1204 complies with the particulate matter standards specified in the United States Pharmacopeia USP&#x2009;<&#x2009;789&#x2009;>&#x2009;for ophthalmic injectable solutions. GBL1204 was safe and well tolerated by the patients over 4&#xa0;weeks. No ocular or systemic serious adverse events occurred. Nine participants (56.25%) reported 14 TEAEs (13 ocular, 1 non-ocular). Of the 14 adverse events, 8 (57.14%) were considered as mild; all adverse events resolved on their own, and without any sequelae. Mean (standard error mean, SEM) BCVA improvement from baseline was +&#x2009;1.80 (0.76) letters at day&#xa0;7 and +&#x2009;3.0 (1.10) letters at day&#xa0;28. The corresponding mean (SEM) central macular thickness reductions were -&#x2009;41.67&#xa0;&#xb5;m (40.35) and -&#x2009;64.67&#xa0;&#xb5;m (42.74) at days&#xa0;7 and 28, respectively. Serum vascular endothelial growth factor levels showed expected suppression consistent with bevacizumab pharmacodynamics.<br><br>CONCLUSION: A single intravitreal injection of GBL1204 demonstrated favourable short-term safety and tolerability, with evidence of visual and anatomical improvements. These findings support further evaluation of GBL1204 1.25&#xa0;mg PFS in a pivotal phase&#xa0;III trial as a standardized alternative to compounded bevacizumab. Trial Registration Clinical Trial Registry-India (CTRI): Identification no. CTRI/2024/02/063012.}, }
@article {pmid42236129, year = {2026}, author = {Zhang, C and Sonik, NR and Ayoubi, M and AbouKasm, G and Zhu, D and Fan, JC and Albini, TA and Yannuzzi, NA}, title = {Clinical efficacy and safety of aflibercept biosimilars in neovascular age-related macular degeneration: a systematic review and meta-analysis of randomised controlled trials.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328196}, pmid = {42236129}, issn = {1468-2079}, abstract = {BACKGROUND: To evaluate the efficacy and safety of aflibercept biosimilars compared with reference aflibercept in the treatment of neovascular age-related macular degeneration (nAMD).<br><br>METHODS: A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on PROSPERO (CRD4201069147). Phase 3 randomised controlled trials (RCTs) comparing aflibercept biosimilars to reference aflibercept in treatment-na&#xef;ve nAMD were included. All included studies employed a standardised on-label aflibercept dosing regimen consisting of three initial monthly loading doses followed by injections every 8&#x2009;weeks. The primary outcome was the mean difference (MD) in best-corrected visual acuity (BCVA) at week 8. Secondary outcomes included BCVA at week 52, proportion of patients gaining &#x2265;15 letters or maintaining vision (<15-letter loss), central subfield thickness (CST) and adverse events (AEs).<br><br>RESULTS: Six RCTs (2022-2024)&#x2009;were included, comprising 2029 eyes (1020 biosimilar; 1009 reference). BCVA at week 8 did not differ significantly between groups (MD -0.34 letters; 95% CI -1.12 to 0.44; I&#xb2;=0%; p=0.39), as was BCVA at week 52 (MD -0.04; 95%&#x2009;CI -1.18 to 1.10; I&#xb2;=1%; p=0.94). No differences were observed in the proportion of patients gaining &#x2265;15 letters, maintaining vision, CST changes or AEs.<br><br>CONCLUSIONS: Aflibercept biosimilars demonstrated no significant difference in efficacy at 8&#x2009;weeks and 52&#x2009;weeks as well as safety relative to reference aflibercept in eyes with treatment-na&#xef;ve nAMD following an on-label aflibercept treatment protocol; however, real-world extended durability remains untested. These findings were supported by a low risk of bias and a high-certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations tool.}, }
@article {pmid42237272, year = {2026}, author = {Kong, M and Jin, R and Cheng, T and Sun, L and Tong, N}, title = {Serum microRNA-34a as a circulating biomarker for age-related macular degeneration and short-term anti-VEGF response in neovascular AMD.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04983-7}, pmid = {42237272}, issn = {1471-2415}, abstract = {OBJECTIVE: To evaluate whether serum microRNA-34a (miR-34a) is associated with age-related macular degeneration (AMD) and whether baseline serum miR-34a has the potential to predict short-term response to anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with neovascular AMD (nAMD).<br><br>METHODS: In a cross-sectional cohort recruited at Qingdao Municipal Hospital between January and December 2024, serum miR-34a was quantified in 160 AMD patients and 122 age- and sex-matched healthy controls. AMD was staged according to Age-related Eye Disease Study (AREDS) criteria. Patients with nAMD received three consecutive monthly intravitreal anti-VEGF injections during the loading phase and were classified as good or poor responders according to prespecified anatomical and functional criteria based on optical coherence tomography (OCT) and best-corrected visual acuity (BCVA) after the loading phase. Peripheral blood samples were collected, and serum miR-34a expression was quantified using standard qPCR protocols.<br><br>RESULTS: Serum miR-34a was significantly higher in patients with AMD than in controls (p&#x2009;<&#x2009;0.001). Receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.740 (95% CI 0.681-0.799; p&#x2009;<&#x2009;0.0001) for discriminating AMD from controls. Across AMD subgroups, serum miR-34a differed significantly overall; patients with geographic atrophy (GA) exhibited higher miR-34a levels than those with nAMD (p&#x2009;<&#x2009;0.05). Among patients with nAMD, baseline serum miR-34a was remarkably higher in good responders than in poor responders after the loading phase (p&#x2009;<&#x2009;0.001). ROC analysis showed an AUC of 0.772 (95% CI 0.687-0.857; p&#x2009;<&#x2009;0.0001) for predicting treatment response, and multivariable logistic regression identified higher serum miR-34a as independently associated with lower odds of poor response (OR 0.143, 95% CI 0.042-0.489; p&#x2009;=&#x2009;0.002).<br><br>CONCLUSION: Elevated serum miR-34a is associated with AMD and may serve as a minimally invasive biomarker for distinguishing AMD from controls. In nAMD, baseline serum miR-34a also showed potential for predicting short-term response to loading-phase anti-VEGF therapy. These findings warrant validation in larger, longitudinal, and preferably multicenter cohorts.}, }
@article {pmid42239431, year = {2026}, author = {Diwedi, B and Neog, A and Baanannou, A and Das, P and Menard, R and Halluin, C and Morse, D and Emmerich, K and Thierer, JH and Patnaude, M and Bonnet, F and Graber, JH and Mumm, JS and Madelaine, R}, title = {Mesenchymal-derived neural progenitors underlie local insulin production and neuronal transdifferentiation during retina regeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.05.20.726251}, pmid = {42239431}, issn = {2692-8205}, abstract = {In humans, retinal-neuron death, optic-nerve injuries, and associated neurodegenerative diseases, such as glaucoma and age-related macular degeneration, often lead to permanent vision loss. While the capacity for regeneration is low in the human nervous system, including the retina, some non-mammalian vertebrate species, including zebrafish, are capable of endogenous neuronal regeneration after injury. Unlike mammals, zebrafish do not form a scar that inhibits axonal and neuronal regeneration after injury. Rather, they harbor neural progenitor and stem-cell populations allowing regeneration of entire parts of the nervous system and restoration of tissue integrity and function. In the zebrafish retina, cycling neural progenitor cells of the ciliary marginal zone and quiescent resident neural stem cells (the latter of which are also called Müller glial cells) participate in neuronal regeneration following different types of injury. In this study, we report the identification of a novel, additional cellular source participating in neuronal regeneration of neurons in the zebrafish retina after genetic ablation of retinal ganglion cells. Before injury, these progenitor cells express molecular markers of neural-crest-cell and/or fibroblast identity, such as sox10 , pdgfrb , and eya2 , while after neuronal ablation they also express proneural factors including the ascl1a and olig2 genes. Combining genetic ablation of neurons with photoconversion or Cre/Lox-dependent genetic lineage tracing of sox10 -expressing cells, we demonstrated that these cells can differentiate into post-mitotic retinal neurons in the ganglion cell layer (GCL) in the absence of cell proliferation. We also showed, surprisingly, that this progenitor population locally produces insulin mRNA, and that insulin signaling is involved in the accumulation of mesenchymal-derived neural progenitors in the GCL and in their subsequent transdifferentiation into RGCs. This work reveals an unexpected and novel cellular mechanism of transdifferentiation, dependent on a neural-crest-derived mesenchymal cell population, participating in neuronal regeneration in the zebrafish retina. The discovery of this plastic cell population could potentially lead to new strategies to promote the formation of new neurons in the mammalian retina.}, }
@article {pmid42239615, year = {2026}, author = {Wang, J and Wang, Q}, title = {IMPG1 Variant Causing Adult-Onset Foveomacular Vitelliform Dystrophy in Chinese: A Case Report.}, journal = {Case reports in ophthalmology}, volume = {17}, number = {1}, pages = {448-454}, pmid = {42239615}, issn = {1663-2699}, abstract = {INTRODUCTION: Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a rare entity and is mostly reported in French individuals. Here, we report a Chinese patient with AOFVD who had IMPG1 mutation and was misdiagnosed with age-related macular degeneration (AMD).<br><br>CASE PRESENTATION: A 59-year-old man complaining of vision loss was misdiagnosed with AMD and treated with intravitreal injections of anti-vascular endothelial growth factor, but with no improvement. Visual acuity was 20/50 in the right eye and 20/40 in the left eye. Fundus examinations revealed a bilateral symmetrical vitelliform "egg yolk" lesion. Spectral-domain optical coherence tomography revealed dome-shaped subretinal hyperreflective materials and cuticular drusen at the retinal pigment epithelium-Bruch's membrane complex in both eyes. No clear neovascularization was observed. Electrooculography revealed a decreased Arden ratio. Based on multimodal imaging analysis and genetic testing, the patient was diagnosed with AOFVD. No therapeutic intervention was administered. One month after the patient's visit, vitelliform "egg yolk" lesion was absorbed in the right eye, and the patient's visual acuity decreased to 20/100 in the right eye.<br><br>CONCLUSION: AOFVD is rare and underdiagnosed. It can disguise as AMD or other similar macular diseases. Clinicians should be alert to this condition, pay attention to its identification, and avoid unnecessary treatments.}, }
@article {pmid42240907, year = {2026}, author = {Güçlü, H and Doğanlar, Z and Şambel Aykutlu, M and Köse, G and Doğanlar, O}, title = {The role of STAT3-targeted therapy created with COLIVELIN in the cross-talk between IL6/JAK2/STAT3 and TGF-β/SMAD2/SMAD3 signaling in a hyperinflammation and ROS-induced in vitro AMD model and its effect on retinal apoptosis.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {42240907}, issn = {1573-2630}, support = {(T&#xdc;BAP-2021/68)//Republic of T&#xfc;rkiye Trakya University Scientific Research Projects Unit/ ; }, abstract = {This study aimed to investigate the therapeutic potential of Colivelin in modulating the cross-talk between the IL-6/JAK2/STAT3 and TGF-β/SMAD2/SMAD3 signaling pathways and its downstream effects on retinal apoptosis in an in vitro AMD model. An in vitro AMD model was established in ARPE-19 human RPE cells using a sublethal combination of lipopolysaccharide and hydrogen peroxide. Apoptosis was quantified via Tali® image cytometry. Gene expression profiling was performed by qRT- PCR. Protein expressions were assessed by Western blot. Formal mediation analysis was employed to quantify pathway-specific mechanistic contributions. The AMD model exhibited significant upregulation of hypoxia-related genes (HIF-1α, VEGF, MMP3, MMP9), pro-inflammatory cytokines (IL-6, TNF-α), and pro-apoptotic markers (BAX, p53, Caspase- 3), accompanied by markedly elevated ROS levels and reduced cell viability. Low-dose Colivelin (1 µM) significantly enhanced STAT3 phosphorylation, restored antioxidant gene expression (GSS, CAT, SOD2), suppressed hypoxia-associated gene expression, and substantially reduced TGF-β receptor, SMAD2, and SMAD3 expression at both transcriptional and protein levels. Formal mediation analysis revealed that 91-98% of Colivelin's anti-apoptotic effect at the therapeutic dose was mediated through STAT3-driven suppression of TGF-β/SMAD2/3 signaling, rather than through direct STAT3 transcriptional activity on apoptotic target genes. Conversely, high-dose Colivelin (10 µM) paradoxically activated SMAD2/3-independent pro-apoptotic cascades, demonstrating a dose- dependent biphasic response. This study provides the first formal mechanistic evidence that Colivelin exerts its cytoprotective effects in AMD primarily through a STAT3 → SMAD2/3 suppression axis. Low-dose (1 µM) Colivelin demonstrated superior and broader therapeutic efficacy compared to Bevacizumab by simultaneously modulating oxidative stress, hypoxia, angiogenesis, and apoptotic signaling pathways. These findings establish Colivelin as a promising multi-target therapeutic candidate for AMD, with its therapeutic window defined by the capacity of STAT3 activation to selectively suppress TGF-β/SMAD-driven apoptotic signaling without engaging compensatory pro-death mechanisms. Rigorous pharmacokinetic optimization and in vivo validation are warranted to advance Colivelin toward clinical translation.}, }
@article {pmid42240995, year = {2026}, author = {Xue, CC and Chee, ML and Li, H and Tham, YC and Cheng, CY}, title = {Reported Metformin Use and Age-Related Macular Degeneration in Patients With Diabetes.}, journal = {JAMA ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1001/jamaophthalmol.2026.1799}, pmid = {42240995}, issn = {2168-6173}, }
@article {pmid42230733, year = {2026}, author = {Jonas, JB and Panda-Jonas, S and Xu, J and Jonas, RA and Wang, YX}, title = {Presence and associations of retinal pigment epithelium and outer retinal atrophy: the Beijing eye study.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-55175-8}, pmid = {42230733}, issn = {2045-2322}, abstract = {The goal of the study was to assess the presence of an incomplete (iRORA) and complete (cRORA) retinal pigment epithelium (RPE) and outer retinal atrophy in a general population and explore their associations with other parameters. Participants of the population-based Beijing Eye Study with age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV) or those without retinal diseases, underwent optical coherence tomography of the macula. Among 5894 eyes, presence of iRORA and cRORA increased from 0/5117 (0%) and 0/5117 (0%) in the normal group and 0/457 (0%) and 0/457 (0%) in early AMD to 5/277 (1.8%;95%CI:0.3,3.3) and 0/277 (0%) in intermediate AMD, 6/6 (100%) and 6/6 (100%) in geographic atrophy, 0/2 (0%) and 2/2 (100%) in exudative AMD, and 10/30 (33.3%;95%CI:17.8,48.8) and 6/30 (25.0%;95%CI:12.0,38.0) in PCV, respectively. Higher iRORA presence was associated (multivariable analysis) with higher AMD stage (OR:54.7;95%CI:6.68,449;P < 0.001), higher PCV presence (OR:1.523 × 10[5];95%CI:834,2.785 × 10[7];P < 0.001), and higher presence of reticular pseudodrusen (OR:19.2;95%CI:1.94,190;P < 0.001). Drusen number (OR:0.97;95%CI:0.91,1.03;P = 0.27) and subfoveal choroidal thickness (OR:1.003;95%CI:0.994,1.013;P = 0.49) were not associated. Higher cRORA presence correlated with higher PCV presence (OR:48.6;95%CI:4.58,517;P = 0.001) and higher presence of reticular pseudodrusen (OR:120;95%CI:13.1,1094;P < 0.001). iRORAs and cRORAs were spatially associated with ellipsoid zone and external limiting membrane defects and intraretinal hyperreflective foci (iHRFs) in the outer and inner retinal layers. The findings suggest that iRORAs and cRORAs presences were relatively low in our population-based study, and were associated with higher presence of reticular pseudodrusen but not with drusen number or subfoveal choroidal thickness. The spatial association with ellipsoid zone defects and external limiting membrane defects and iHRF in the outer retinal layer and beyond fits with the notion of an RPE cell migration playing a role in the development of iRORAs and cRORAs.}, }
@article {pmid42230802, year = {2026}, author = {Swaroop, A and Roska, B}, title = {Revisiting retinal and macular degeneration in the genomics era.}, journal = {Nature reviews. Genetics}, volume = {}, number = {}, pages = {}, pmid = {42230802}, issn = {1471-0064}, abstract = {Retinal and macular degeneration constitute a prominent cause of untreatable vision loss globally. The development of efficacious therapies is impeded by extensive clinical and genetic heterogeneity, poor phenotype-genotype correlation and lack of appropriate disease models. Pioneering advances in next-generation sequencing together with computational methods, human model systems and genetic manipulation technologies have begun to unravel causal genes and variants as well as gene interaction networks. Photoreceptor dysfunction or death represents the end point for both Mendelian and complex traits affecting the retina or its specialized central region, the macula. Here we review the genetic and genomic bases of retinal and macular degeneration and how recent advances are informing therapies to slow the loss of or restore vision.}, }
@article {pmid42230852, year = {2026}, author = {Wu, X and Zhang, X and Jiang, Y and Gu, Z and Li, C and Zhu, X and Huang, Y and Li, B and Ma, M and Zhao, S and Zheng, Z}, title = {Association of high-intensity evening light exposure with risk of incident age-related macular degeneration, cataract, and glaucoma: a prospective cohort study of 82,826 participants.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {42230852}, issn = {2509-2723}, abstract = {Excessive artificial light at night (ALAN) disrupts circadian rhythms and may accelerate ocular aging; however, personal objective dosimetry data linking evening light exposure to specific age-related eye diseases (AREDs) remain sparse. The objective of the study is to determine whether personal high-intensity light exposure during the evening transition window (20:00-23:30) is associated with the risk of incident age-related macular degeneration (AMD), cataracts, and glaucoma. This prospective cohort study utilized data from the UK Biobank. Participants (n = 82,826) were monitored for 7 days via wrist-worn accelerometers equipped with high-resolution light sensors between 2013 and 2015. Individuals with baseline eye diseases were excluded. Average light intensity (lux) during the evening transition period (20:00-23:30) was categorized by percentiles (top 10% threshold ≈1000 lx). Incident AMD, cataract, and glaucoma were identified through linked hospital inpatient records and death registries using ICD-9 and ICD-10 codes. Among 82,826 participants, 6058 incident ARED cases occurred during a median follow-up of 7.85 years. Evening light exposure exceeding 1000 lx (top 10%) was significantly associated with increased hazards of incident AMD (HR, 1.31; 95% CI, 1.06-1.62), cataract (HR, 1.18; 95% CI, 1.08-1.30), and primary open-angle glaucoma (POAG) (HR, 1.47; 95% CI, 1.07-2.03). Significant time-response relationships were observed, with per-hour exposure to > 2250 lx further elevating the risk of overall AREDs (HR, 1.10; 95% CI, 1.04-1.16) and POAG (HR, 1.18; 95% CI, 1.04-1.35). High-intensity artificial light in the evening is an independent, modifiable risk factor for major ocular aging pathologies.}, }
@article {pmid42223803, year = {2026}, author = {Servin, AE and McFadden, I and Esmaeilkhanian, H and Holcomb, D and Lin, J and Awh, CC}, title = {Real-World Utilization and Initial Experience with Aflibercept-ayyh (PAVBLU[®]) for Retinal Disorders in United States Retina Practices: A Descriptive Retrospective Analysis.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42223803}, issn = {2193-8245}, abstract = {INTRODUCTION: Anti-vascular endothelial growth factor (anti-VEGF) therapies are standards of care for vision-threatening retinal diseases. This retrospective observational study describes demographics, utilization, best recorded visual acuity (BRVA), and safety among eyes with neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), diabetic macular edema (DME), or retinal vein occlusion (RVO) treated with the biosimilar aflibercept-ayyh (PAVBLU[®]) in routine clinical practice.<br><br>METHODS: Electronic medical records from the Retina Consultants of America database of patients receiving aflibercept-ayyh (12/1/2024-10/31/2025) were analyzed, focusing on eyes with &#x2265;&#x2009;84&#xa0;days of follow-up. The index date was defined as the first documented aflibercept-ayyh injection. Post-index data were used to evaluate treatment patterns, changes in BRVA, and adverse events of special interest (AESIs). Within-eye changes in BRVA were assessed using the Wilcoxon signed rank test and summarized as mean change in logarithm of the minimum angle of resolution (&#x394;logMAR).<br><br>RESULTS: A total of 1000 consecutive eyes from 989 patients (55% female, 43% male, 2% unknown) received 3730 injections of aflibercept-ayyh; 91% switched from prior anti-VEGF therapy and 9% were anti-VEGF treatment-na&#xef;ve. Disease distribution was 58% nAMD, 19% RVO, 16% DME, and 7% DR. Among switchers, median (IQR) number of prior injections was 21 (8,&#xa0;46). Median (IQR) follow-up was 6.0&#xa0;months (4.6,&#xa0;7.1). Median (IQR) number of aflibercept-ayyh injections per eye was 4 (3,&#xa0;5). Among eyes with &#x2265;&#x2009;84&#xa0;days of follow-up (n&#x2009;=&#x2009;889), mean BRVA logMAR remained stable for switchers (0.4&#xa0;to&#xa0;0.4; P&#x2009;=&#x2009;0.96) and improved from baseline in anti-VEGF-na&#xef;ve eyes (0.5&#xa0;to&#xa0;0.4; P&#x2009;<&#x2009;0.01). Confirmed AESIs included iritis (n&#x2009;=&#x2009;2; 0.05% of injections), with no events of vitreous cells, endophthalmitis, retinal detachment, retinal vasculitis, or vitreous hemorrhage.<br><br>CONCLUSION: In this descriptive real-world analysis, aflibercept-ayyh was associated with stable visual acuity in previously treated eyes and vision improvement in treatment-na&#xef;ve eyes, with no new or unexpected safety findings, consistent with expectations for aflibercept and the established body of evidence supporting biosimilarity between aflibercept-ayyh and reference aflibercept, EYLEA[&#xae;]).}, }
@article {pmid42224684, year = {2026}, author = {Nadar, D and Shende, P}, title = {Unveiling the Potential of Drug Delivery Systems for Tyrosine Kinase Inhibitors in the Treatment of Neovascular Eye Diseases.}, journal = {Critical reviews in therapeutic drug carrier systems}, volume = {43}, number = {2}, pages = {61-123}, doi = {10.1615/CritRevTherDrugCarrierSyst.2026060256}, pmid = {42224684}, issn = {2162-660X}, abstract = {Tyrosine kinase inhibitors (TKIs) represent a promising category of therapeutic agents for managing edema and neovascular eye diseases (NEDs) such as corneal neovascularization, proliferative diabetic retinopathy and neovascular age-related macular degeneration. By impeding the phosphorylation of receptor tyrosine kinases, TKIs prevent the activation of angiogenic signaling pathways that are vital for cell growth and proliferation. However, the TKIs delivery in ophthalmology presents significant challenges such as toxicity and poor bioavailability. This review discusses emerging TKIs for NEDs, their physicochemical properties, and delivery systems, highlighting strategies such as sustained-release ocular implants, hydrogels, particulate and composite systems. Amid each category, we explore groundbreaking research approaches with a focus on preclinical and clinical studies, providing an in-depth look at the latest advancements in TKI-based delivery systems. Numerous TKI formulations currently under investigation (AXPAXLI, DURAVYU, CLS-AX and D-4517.2) hold the potential to improve therapeutic outcomes and enhance patient adherence, transforming the treatment landscape of NEDs. Advanced TKI delivery platforms, integrated with artificial intelligence-driven tools and minimally invasive technologies may enable more effective and personalized treatment options in the field of eye care.}, }
@article {pmid42225822, year = {2026}, author = {Sun, H and Bu, F and Xin, X and Yan, J and Huang, T}, title = {Uncovering drug-associated risk signals for neovascular age-related macular degeneration: an integrative pharmacovigilance and proteogenomic study.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42225822}, issn = {1476-5454}, abstract = {OBJECTIVES: To identify drug-associated risk signals for neovascular age-related macular degeneration (nAMD) and explore their biological basis.<br><br>METHODS: We analysed the US FDA Adverse Event Reporting System (FAERS) to detect drugs with disproportionate nAMD reporting. Drug targets were mapped and causality was assessed by integrating summary-based Mendelian randomisation (SMR) and colocalisation analyses using cis-pQTL data. Single-cell RNA sequencing from nAMD patients evaluated cell type-specific gene expression. Protein-protein interaction and pathway enrichment analyses elucidated underlying mechanisms.<br><br>RESULTS: FAERS analysis identified five drugs (apixaban, carbamazepine, latanoprost, rituximab and semaglutide) significantly associated with higher reporting risks of nAMD. SMR implicated six genes (IGFBP6, MAPKAPK2, NFKB1, RGMA, RNASE1 and WARS1) in nAMD risk, with evidence supporting colocalisation for WARS1. Most candidate genes were predominantly expressed in vascular remodelling endothelial cells, while WARS1 was also highly specific to monocytes. Enrichment analysis highlighted their critical involvement in immune and inflammatory responses, particularly within the Toll-like receptor, TNF and NF-kappa B signalling pathways.<br><br>CONCLUSIONS: This study suggests a potential association between specific drugs and nAMD and reveals six genes as their possible molecular basis, thereby providing prioritised candidate targets and testable biological hypotheses for subsequent experimental validation.}, }
@article {pmid42226100, year = {2026}, author = {He, B and Chen, Y and Cai, P and Xi, R and Shen, X and Guo, S and Chen, J and Li, S and Wu, Y}, title = {Exendin-4 averts all-trans-retinal-driven damage to photoreceptors and the retina via the GLP-1R/PKA/CREB1 signaling axis.}, journal = {Cellular &amp; molecular biology letters}, volume = {}, number = {}, pages = {}, doi = {10.1186/s11658-026-00952-6}, pmid = {42226100}, issn = {1689-1392}, support = {82471093//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Atrophic macular degeneration comprises dry age-related macular degeneration (AMD) and autosomal recessive Stargardt disease (STGD1). These disorders lead to irreversible blindness and still lack effective therapies. The rise of all-trans-retinal (atRAL) brought on by visual cycle disruption closely links to retinal atrophy in both conditions, yet the key downstream targets remain obscure. Exendin-4 (EX-4) is a natural glucagon-like peptide-1 receptor (GLP-1R) agonist. Recent clinical retrospective studies indicate that GLP-1R agonists such as exenatide (synthetic EX-4) can markedly lower the 5-year risk of developing dry AMD. Here, we sought to clarify the protective effect of natural EX-4 against retinal degeneration in atrophic macular degeneration linked to impaired clearance of atRAL.<br><br>METHODS: Cell and animal paradigms of STGD1 and dry AMD were generated by atRAL-loaded 661W cells and light-exposed Abca4[-/-]Rdh8[-/-] mice, respectively. RNA-sequencing, cell viability assays, morphometric analysis, annexin V/propidium-iodide staining using flow cytometry, quantitative polymerase chain reaction (qPCR), western blotting, immunofluorescence, electroretinography (ERG), fundus photography, hematoxylin and eosin (H&amp;E) histology, and TUNEL staining were integrated to delineate the anti-apoptotic actions of EX-4 and to uncover its underlying protective mechanism.<br><br>RESULTS: GLP-1R/cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA)/cAMP response element-binding protein 1 (CREB1) signaling was markedly downregulated in atRAL-challenged 661W cells and in neural retina of light-exposed Abca4[-/-]Rdh8[-/-] mice. EX-4 reinstated this pathway, suppressed caspase-3 activation and DNA damage, and curtailed apoptosis in both cell and tissue contexts. Silencing of Glp1r or the PKA catalytic subunits by small interfering RNA (siRNA) abrogated EX-4-induced activation of the PKA/CREB1 axis in atRAL-loaded 661W cells. Pharmacologic blockade of CREB1 phosphorylation with the PKA inhibitor H-89 or the CREB1 inhibitor 666-15 largely nullified the DNA-protective and anti-apoptotic benefits conferred by EX-4 in 661W cells following atRAL exposure, suggesting that the GLP-1R/PKA/CREB1 signaling axis contributes to its cytoprotection action. More importantly, intraperitoneal injection of EX-4 significantly preserved retinal structure and function in Abca4[-/-]Rdh8[-/-] mice after exposure to light, and mitigated punctate lesions in the fundus.<br><br>CONCLUSIONS: EX-4 exerted anti-apoptotic and DNA-protective effects against atRAL-induced photoreceptor loss and retinal degeneration at least partially through activating the GLP-1R/PKA/CREB1 pathway. These findings suggest that GLP-1R agonists could serve as potential preventive therapeutics for atrophic macular degeneration associated with atRAL toxicity, including dry AMD and STGD1.}, }
@article {pmid42227867, year = {2026}, author = {Palladino, L and Paglia, L and Meschiari, G and Altieri, F and Cesa, S and Iazzetti, A and Cairone, F}, title = {Structural and thermal stability assessment of repackaged bevacizumab using RT-PCR-based differential scanning fluorimetry and intrinsic fluorescence spectroscopy.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {}, number = {}, pages = {10781552261457538}, doi = {10.1177/10781552261457538}, pmid = {42227867}, issn = {1477-092X}, abstract = {IntroductionBevacizumab is a humanized monoclonal anti-VEGF antibody widely used in oncology and ophthalmology for the treatment of age-related macular degeneration and diabetic macular edema. Its intravitreal administration requires galenic repackaging, raising concerns regarding physicochemical stability and sterility assurance during storage. This study evaluated the structural and thermal stability of repackaged bevacizumab stored at 4 °C for up to four weeks.MethodsStability was assessed using intrinsic fluorescence spectroscopy and differential scanning fluorimetry (DSF) performed on a real-time PCR platform. Structural integrity was monitored through fluorescence emission spectra, while thermal stability was determined by melting temperature (Tm) analysis over time.ResultsIntrinsic fluorescence showed a constant emission maximum at 338 nm throughout the storage period, indicating preservation of the tertiary structure. DSF analysis demonstrated stable thermal unfolding profiles, with no significant variation in Tm values between baseline (67.4 ± 0.3 °C) and four weeks (67.2 ± 0.4 °C; p > 0.05).ConclusionsRepackaged bevacizumab maintained structural integrity and thermal stability for up to four weeks under refrigerated storage conditions. These findings support refrigerated batch preparation under the tested conditions and highlight RT-PCR-based DSF as a practical quality-control tool for hospital pharmacy settings.}, }
@article {pmid42227873, year = {2026}, author = {Karl, NAM and Schuhmayer, AC and Pomberger, L and Eidherr, M and Khalil, H and Kallab, M and Rothbächer, J and Strohmaier, C and Huemer, J and Bolz, M and Reisinger, AS}, title = {Difference in Ocular Perfusion Drop After Intravitreal Aflibercept in Patients with Neovascular AMD and Diabetic Macular Edema.}, journal = {Current eye research}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/02713683.2026.2679143}, pmid = {42227873}, issn = {1460-2202}, abstract = {PURPOSE: Vascular endothelial growth factor (VEGF) is a factor in the pathogenesis of Age-Related Macular Degeneration (AMD) and Diabetic Macular Edema (DME), yet they differ in pathogenesis. It has been shown that only patients with diabetic retinopathy have elevated VEGF levels in the aqueous humor. Intravitreal injections of anti-VEGF substances have been the gold standard in treating diseases for several years, but an impact on ocular perfusion has been assumed. This study aimed to investigate the effects of intravitreal aflibercept injection (IVI) on ocular perfusion in patients with AMD and DME.<br><br>METHODS: This prospective study included 36 eyes of 36 patients, with 18 patients having nAMD (n&#x2009;=&#x2009;18) and 18 patients having DME (n&#x2009;=&#x2009;18), all treated with IVI. Ocular perfusion was measured using Laser Speckle Flowgraphy (LSFG). The parameter Mean Blur Rate (MBR) reflects erythrocyte flow velocity and serves as an indirect marker of perfusion. MBR was measured at the optic nerve head (ONH). The device's software can analyze MBR in areas of major retinal vessels (MV) and in microperfusion areas of the tissue (MT). Measurements were conducted at three time points (before scheduled IVI, as well as 1&#x2009;week and 4&#x2009;weeks after).<br><br>RESULTS: In patients with AMD, significant decrease in MV was observed, while no significant change was noted for MV in patients with DME (Analysis of Variance, ANOVA, p&#x2009;=&#x2009;0.04 vs. p&#x2009;=&#x2009;0.2). However, both groups showed a significant decrease in MT (ANOVA, p&#x2009;<&#x2009;0.001 for both groups).<br><br>CONCLUSION: The results indicate that retinal perfusion as measured with LSFG is less impaired in patients with DME following IVI treatment. This could be related to endothelial dysfunction, which appears to be restricted to retinal endothelial cells, as MT as a surrogate marker of choroidal perfusion showed a significant reduction in the DME group. Responses highlight physiological differences between retinal and choroidal capillaries.}, }
@article {pmid42229813, year = {2026}, author = {Cai, CX and Toy, B and Martin, B and Fan, R and Westlund, E and Tran, D and Nishimura, A and Lee, H and Leng, T and Nagy, P and Mathioudakis, N and Zhang, L and Hribar, M and Chen, A and Armbrust, K and Goetz, K and Baxter, S and Boland, MV and Brown, EN and Tsui, E and Barkmeier, AJ and Wang, S and Mehta, N and Stocking, JC and O'Keefe, G and Lee, CS and Payne, PRO and O'Brien, WJ and DuVall, S and Alshammari, T and Falconer, T and Dorr, DA and Humes, I and McCoy, D and Adibuzzaman, M and Mahmood, R and Morgan-Cooper, H and Desai, P and Kothari, SY and Sena, A and Blacketer, C and Ostropolets, A and Shoaibi, A and Rao, G and Hripcsak, G and Ryan, P and Suchard, MA}, title = {Semaglutide and Neovascular Age-Related Macular Degeneration Among Adults with Type 2 Diabetes: An OHDSI Network Study.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.05.034}, pmid = {42229813}, issn = {1549-4713}, abstract = {OBJECTIVE: or Purpose: To investigate the potential association of semaglutide and neovascular age-related macular degeneration (NVAMD) DESIGN: Retrospective study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network during the study period from 12/1/2017-12/31/2024 SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Adults with type 2 diabetes (T2D) on semaglutide, other glucagon-like peptide-1 receptor agonists (GLP-1RAs) (dulaglutide, exenatide), or non-GLP-1RAs (empagliflozin, sitagliptin, glipizide) METHODS, INTERVENTION OR TESTING: The association between semaglutide and NVAMD was assessed using two approaches: an active-comparator cohort design and a self-controlled case-series (SCCS) analysis. The cohort design used propensity score-adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The SCCS used conditional Poisson regression models to estimate incidence rate ratios (IRRs). A random-effects meta-analysis was used to generate network-wide HR and IRR estimates.<br><br>MAIN OUTCOME MEASURES: Two definitions of NVAMD, one based on condition codes alone (NVAMD-C) or condition codes and procedures (NVAMD-CP).<br><br>RESULTS: A total of 227,971 new users of semaglutide were included in the study. The risk of NVAMD among semaglutide users was similar to users of dulaglutide (NVAMD-C HR 0.57, 95% CI 0.21 to 1.57, P=.28; NVAMD-CP HR 0.25, 95% CI 0.05 to 1.27, P=.10), empagliflozin (NVAMD-C HR 0.98, 95% CI 0.54 to 1.79, P=.94; NVAMD-CP HR 0.79, 95% CI 0.38 to 1.64, P=.52), sitagliptin (NVAMD-C HR 2.08, 95% CI 0.90 to 4.83, P=.09; NVAMD-CP HR 1.80, 95% CI 0.55 to 5.86, P=.33), and glipizide (NVAMD-C HR 0.83, 95% CI 0.35 to 2.02, P=0.69; NVAMD-CP HR 0.50, 95% CI 0.21 to 1.19, P=.12). There was no evidence of increased or decreased risk for NVAMD associated with semaglutide exposure (NVAMD-C: incidence rate ratio [IRR] 0.92, 95% CI 0.67 to 1.26, P=.60; NVAMD-CP IRR 1.02, 95% CI 0.76 to 1.36, P=.92) nor any of the other GLP-1RA or non-GLP-1RAs.<br><br>CONCLUSIONS: We detected no differences in the risk of NVAMD associated with semaglutide use among adults with T2D.}, }
@article {pmid42229850, year = {2026}, author = {Hallaj, S and Nishida, T and Kamalipour, A and Longhurst, CA and Freeman, WR and Baxter, SL and Boussina, A}, title = {Glucagon Like Peptide 1 Receptor Agonists and Age-Related Macular Degeneration Incidence.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.05.016}, pmid = {42229850}, issn = {2468-6530}, abstract = {PURPOSE: To evaluate the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and the incidence of age-related macular degeneration (AMD) and neovascular AMD (nAMD) among adults with diabetes.<br><br>DESIGN: Retrospective, propensity score-matched cohort study.<br><br>PARTICIPANTS: Adults with diabetes initiating a GLP-1RA or another non-insulin antidiabetic agent. In Epic Cosmos, 2,797,686 GLP-1RA users were matched 1:1 to 2,797,686 active comparators.<br><br>METHODS: We analyzed de-identified electronic health record data from Epic Cosmos and independently replicated the primary analyses in the University of California Health Data Warehouse. Individuals with prevalent AMD or nAMD and those with prior anti-vascular endothelial growth factor treatment were excluded. One-to-one nearest-neighbor propensity score matching balanced demographics, diabetes duration, comorbidities, smoking, diabetic retinopathy, obesity, and eye-care utilization. Cumulative incidence at 1, 5, and 10 years was estimated using Kaplan-Meier methods, and adjusted associations were evaluated using multivariable Cox proportional hazards models.<br><br>MAIN OUTCOME MEASURES: Incident any AMD and incident nAMD.<br><br>RESULTS: In the matched Epic Cosmos cohort (total N=5,595,372), GLP-1RA use was associated with lower cumulative incidence of any AMD at 1 year (0.187% [95% CI, 0.182%-0.192%] vs 0.294% [95% CI, 0.287%-0.301%]), 5 years (0.924% [95% CI, 0.907%-0.941%] vs 1.278% [95% CI, 1.260%-1.296%]), and 10 years (5.561% [95% CI, 4.719%-6.549%] vs 6.540% [95% CI, 6.017%-7.108%]); all P<.001. Unadjusted cumulative incidence of nAMD was also lower among GLP-1RA users at 1 year (0.047% vs 0.065%), 5 years (0.280% vs 0.340%), and 10 years (1.874% vs 2.393%); all P<.001. In multivariable Cox models, GLP-1RA use was independently associated with lower hazard of any AMD (hazard ratio [HR], 0.84; 95% CI, 0.83-0.86; P<.001) and was not associated with increased hazard of nAMD (HR, 1.00; 95% CI, 0.97-1.04; P=.79). In the independent University of California Health Data Warehouse cohort, GLP-1RA use was likewise associated with lower AMD incidence at 5 and 10 years, whereas nAMD incidence did not differ significantly between groups.<br><br>CONCLUSIONS: Among adults with diabetes, GLP-1RA use was associated with lower incident AMD and was not associated with increased nAMD risk. These findings provide reassurance regarding ocular safety and support a potential protective association for earlier AMD phenotypes.}, }
@article {pmid42218984, year = {2026}, author = {Hyttinen, JMT and Salminen, A and Kauppinen, A and Kaarniranta, K}, title = {The role of Wnt signalling in the pathogenesis and therapy of age-related macular degeneration (AMD).}, journal = {Biochemical pharmacology}, volume = {}, number = {}, pages = {118114}, doi = {10.1016/j.bcp.2026.118114}, pmid = {42218984}, issn = {1873-2968}, abstract = {Age-related macular degeneration (AMD) is an ever-increasing disease which affects the vision of the elderly in the Western world. No preventive therapy exists so far and slowing its progression is only possible for a fraction of the cases, namely neovascular AMD, in which neovascularisation sprouts from the choriocapillaris layer into the retina. Nevertheless, one potential target for modulation as an AMD therapy is the manipulation of Wnt signalling, and especially its canonical type, the Wnt/β-catenin pathway. Wnt signalling is one of the fundamental cellular pathways involved e.g. in morphogenesis, proliferation, cell polarity, tissue maturation, as well as homeostasis, and apoptosis. The rationale of modulating Wnt signalling in AMD therapy, is that weakened autophagy, autophagy, the means of the cell to remove waste material, as well as increased epithelial-mesenchymal cell type transition (EMT), inflammation, and oxidative stress response have been detected in AMD. Corresponding to these, the upregulation of Wnt signalling pathway has been discovered to be related to this disease. Thus, inhibition of Wnt signalling could be used as in therapy, especially in the more common, dry form of AMD in all its stages. On the other hand, the activation of Wnt signalling could be used in the therapy of advanced neovascular AMD, primarily for maintaining the blood-retinal barrier, which preserves the homeostasis of the retinal vasculature. Therefore, several approaches concerning both the inhibition and upregulation of Wnt signaling are discussed in this review, in the context of potentially developing effective therapies against AMD in the future.}, }
@article {pmid42219076, year = {2026}, author = {Mikhail, D and Tao, BK and Yu, P and Calicchia, L and Butt, FR and Dhivagaran, T and Al-Qattan, HM and Feo, A and Quarta, A and Mishra, AV and Seamone, ME and Navajas, EV and Kertes, PJ and Wong, DT and Muni, RH and Kaplan, AJ and Yan, P and Popovic, MM}, title = {Risk of Retinal Detachment After Intravitreal Injection of Anti-VEGF: A Systematic Review and Meta-Analysis.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.05.042}, pmid = {42219076}, issn = {1879-1891}, abstract = {TOPIC: This systematic review and meta-analysis evaluated the literature-pooled risk of retinal detachment (RD) following intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents.<br><br>CLINICAL RELEVANCE: Intravitreal anti-VEGF injections are the most frequently performed intraocular procedure, with RD remaining a poorly quantified complication. Pooled estimates equip clinicians to contextualize RD risk during informed consent.<br><br>METHODS: This systematic review and meta-analysis followed PRISMA guidelines (PROSPERO: CRD420251175527). MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to January 18, 2026. Included studies reported RD risk after anti-VEGF IVI for neovascular age-related macular degeneration (nAMD), diabetic macular edema, macular edema from retinal vein occlusion, proliferative diabetic retinopathy, or myopic choroidal neovascularization. Paired reviewers independently extracted data and assessed risk of bias using ROBINS-I and the Joanna Briggs Institute checklist for case series. A random-effects single-arm meta-analysis of proportions using a generalized linear mixed model generated pooled risk estimates per injection and per eye.<br><br>RESULTS: Twelve studies comprising 834,814 injections and 119 RD events were included. In the meta-analysis of 9 studies (787,849 injections), there were 92 rhegmatogenous RD (RRD) events, with a pooled risk of 0.012% [95% CI (0.009-0.015%), I&#xb2;: 14.4%], equivalent to 1 in 8675 injections. An acute &#x2264;90-day postprocedural sensitivity analysis yielded a consistent RRD risk of 0.013% [95% CI (0.010-0.016%), I&#xb2;: 36.8%] (approximately 1 in 7692 injections). An eye-level sensitivity analysis yielded a per-eye risk of 0.08% [95% CI (0.02-0.31%), I&#xb2;: 66.7%] (approximately 1 in 1250 eyes). Exploratory subgroup analyses showed no differences in RRD risk by injection number (&#x2265;100,000 vs. <100,000; P=0.520), study setting (single-center vs. multicenter; P=0.258), injection indication (nAMD only vs. mixed; P=0.061), injection provider (ophthalmologist vs. mixed; P=0.259), or risk of bias (P=0.356). One study evaluating severe PDR reported tractional RD risk as 3.6% [95% CI (2.3-5.2%)] (approximately 1 in 28 injections), likely reflecting disease-specific fibrovascular contraction.<br><br>CONCLUSION: Low-certainty evidence indicates RRD following anti-VEGF IVI is uncommon, with a per-injection risk of 0.012% (1 in 8675 injections). Per-eye risk was 0.08% (1 in 1250 eyes), which was subject to wider uncertainty but more relevant to patients undergoing long-term treatment; notably, the pooled mean of 13.8 injections per eye in the contributing studies likely underestimates real-world cumulative exposure. Future work should incorporate eye-level denominators and standardized reporting of RD subtypes, ocular characteristics, and injection technique to enable risk stratification and identification of modifiable procedural contributors.}, }
@article {pmid42219104, year = {2026}, author = {Maiti, S and Joseph, J}, title = {From Systemic Disease to the Eye: Why Senescence Deserves Attention in Ocular Infections.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111095}, doi = {10.1016/j.exer.2026.111095}, pmid = {42219104}, issn = {1096-0007}, abstract = {The global increase in life expectancy has led to a growing elderly population, bringing new challenges in managing infectious diseases. Advancing age is accompanied by progressive dysfunction of both innate and adaptive immunity, resulting in impaired responses to pathogens and elevated morbidity and mortality. Cellular senescence, a state of permanent cell-cycle arrest with extensive molecular and phenotypic changes, including chromatin remodeling and the senescence-associated secretory phenotype (SASP), has emerged as a key factor in this process. Though initially protective as a tumor-suppressive mechanism, senescence becomes maladaptive with age, contributing to inflammaging, immune dysregulation, and heightened susceptibility to infection. In ocular diseases, such as age-related macular degeneration and chronic keratitis, senescent cells in retinal pigment epithelium and corneal tissues drive persistent inflammation and fibrosis, exacerbating vulnerability to opportunistic pathogens. Pathogens can exploit senescent cells through virulence factors and persistent inflammatory responses, thereby promoting chronic infection and even age-related diseases. Conversely, senescent cells and their SASP can intensify infection severity, as shown in viral infections such as SARS-CoV-2 and bacterial pathogens including Streptococcus pneumoniae and Mycobacterium tuberculosis. This reciprocal relationship illustrates how infection accelerates cellular aging while aging predisposes individuals to more severe infections. Emerging therapeutic strategies targeting senescence, including senolytics and senomorphics, hold promise for mitigating infection-related pathology. In parallel, vaccines and immunotherapies tailored to the aging immune system will be crucial for reducing infection burden in older populations. This review integrates current evidence on the bidirectional interplay between senescence and infection, emphasizing its clinical relevance and potential for translational intervention.}, }
@article {pmid42221036, year = {2026}, author = {Zhu, Y and Gumustop, SS and Wang, L and Tong, A and Ding, X and Ploumi, I and Romano, F and Chen, C and Nodecker, KN and Shah, SH and Wagner, SL and Vavvas, DG and Husain, D and Miller, JW and Patel, NA and Kim, LA and Wu, DM and Miller, JB}, title = {Influence of Anti-VEGF Injections on Longitudinal Changes in Vascular Metrics Measured by OCTA in Age Related Macular Degeneration: A Retrospective Real-World Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {561121}, pmid = {42221036}, issn = {1177-5467}, abstract = {PURPOSE: To investigate the possible influence of repeated anti-VEGF injections on vascular metrics measured by optical coherence tomography angiography (OCTA) in patients with age-related macular degeneration (AMD).<br><br>METHODS: This retrospective longitudinal study included AMD patients with a follow-up time of at least 18 months from 2019 to 2024. Swept-source OCTA was performed on all eyes. Based on whether an eye received injections or not during follow-up, all eyes were divided into two groups (non-injection group only included non-exudative AMD). Vessel density, Vessel skeleton density in the superficial, deep, and retina slab, as well as foveal avascular zone (FAZ) size, circularity and perimetry of Angio 6mm&#xd7;6mm were calculated. Change in vascular metrics between baseline and last follow-up were compared between the two groups using t-test or Mann-Whitney U-test. Correlation between change in vascular metrics and visual acuity was investigated by Spearman's Rank Correlation test.<br><br>RESULTS: A total of 164 eyes from 107 patients were included. The average follow-up time was 34 months. No statistically significant difference in baseline vascular metrics was detected between the injection group (57 eyes) and non-injection (107 eyes) group. The injection group received 12.56 injections during follow-up. Among all the parameters, only change in FAZ size during follow-up showed a statistically significant difference between the two groups (0.03 vs. 0.02 mm[2], P=0.043). No correlation was found between change in vascular metrics and change in visual acuity (P>0.05).<br><br>CONCLUSION: In this retrospective longitudinal study of 164 eyes, repeated intravitreal anti-VEGF injections were associated with no relevant significant changes in OCTA vascular metrics over time.}, }
@article {pmid42221039, year = {2026}, author = {Swarnkar, PK and Singh Bhangu, J and Stewart, C and Rifat, M and Khalid, S and Winkworth, H and Franklin-Goddard, SL and Awad, MH and Williams, GS}, title = {Challenging the Treatment Threshold: Early Faricimab Prevents Vision Loss in nAMD - A Real-World Welsh Experience.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {604687}, pmid = {42221039}, issn = {1177-5467}, abstract = {PURPOSE: To compare real-world outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients initiated on Faricimab at early (<0.3 logMAR) versus late (0.6-0.7 logMAR) visual thresholds.<br><br>METHODS: Retrospective, single-centre cohort study of 97 patients (53 early, 44 late) treated at a UK centre, with three monthly loading doses followed by treat-and-extend. Outcomes: BCVA change, vision loss (&#x2265;5 letters), stable vision at 6/12/18 months, injection intervals, extension >8&#xa0;weeks, dry macula.<br><br>RESULTS: Baseline VA was 74 &#xb1; 3.5 letters (early) vs 54 &#xb1; 2.0 letters (late), p<0.001. No early patient experienced sustained vision loss at 6, 12, or 18 months compared with 76.7%, 73.3%, and 75.0% of late patients, respectively (p<0.05 for all). At the 7th injection, 67.6% of late patients lost &#x2265;5 letters vs 14.9% of early patients (ARR 52.7%, p<0.001). Cumulatively, 81.8% of late patients experienced &#x2265;5-letter loss vs 41.5% of early patients (ARR 40.3%, NNT 3, p<0.001). Mean injection intervals were similar, but the early cohort sustained extension beyond 8&#xa0;weeks in >50% of eyes from the 4th-5th interval onward. In contrast, the late cohort exhibited a biphasic collapse, with extension rates declining from 62.2% at 6th-7th to only 35.0% by 9th-10th. Despite a significant baseline anatomical disadvantage (18.9% vs 50.0% dry macula, p=0.001), the early cohort achieved 100% dryness by 18 months compared with 96.7% in the late cohort, with crossover occurring by 12 months (95.8% vs 89.7%, p=0.269).<br><br>CONCLUSION: In this retrospective, single-centre study, early faricimab initiation was associated with preservation of high-function vision, a lower risk of clinically significant vision loss, and high rates of anatomical quiescence and durable treatment extension. These findings suggest that proactive early intervention may offer advantages over reactive treatment paradigms, although confirmation in larger, prospective, and multi-centre studies is needed.}, }
@article {pmid42221729, year = {2026}, author = {Zhao, AH and Alam, TA and Das, N and Maatouk, C and Singh, RP and Talcott, KE}, title = {Long-Term Predictive Value of Macular Thickness Fluctuations in Response to Anti-VEGF Treatment for Age-Related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261448432}, pmid = {42221729}, issn = {2474-1272}, abstract = {Purpose: To evaluate whether macular thickness fluctuations are predictive of long-term visual outcomes in patients with neovascular age-related macular degeneration (nAMD) after treatment initiation with antivascular endothelial growth factor (anti-VEGF). Methods: Patients with nAMD treated with anti-VEGF intravitreal injections for 3 and 5 years were evaluated. Anatomic parameters, including central subfield thickness (CST), were evaluated with optical coherence tomography. The cohort was segregated into quartiles based on CST variability over the initial 12 months of treatment. Kruskal-Wallis tests were used to compare 3- and 5-year final best-corrected visual acuity (BCVA), change in BCVA, final CST, and change in CST among quartiles. Multiple linear regression analyses were subsequently performed. Results: Three hundred sixty-six eyes were included in the 3-year analysis and 275 eyes in the 5-year analysis. Patients received an average of 8.4 injections over 12 months and had a final mean BCVA of 60.7 Early Treatment Diabetic Retinopathy Study letters. Those with the greatest CST variability demonstrated significantly lower baseline and final BCVA compared with other quartiles, alongside lower baseline BCVA values. No difference was found between quartiles for final CST and change in BCVA. Multiple linear regression analyses demonstrated that macular thickness variability characterized by the standard deviation of CST, baseline VA, and age was a significant predictor of VA after 3 and 5 years. Conclusions: Macular thickness variability was a statistically significant correlate and limited predictor of long-term response to visual outcomes at 3 and 5 years after anti-VEGF initiation. Macular thickness variability may be a biomarker with limited long-term predictive value in patients with nAMD.}, }
@article {pmid42221733, year = {2026}, author = {Salabati, M and Mallepally, A and Farhani, K and Mahmoudzadeh, R and Brar, V and Randolph, J}, title = {The Effect of Acetylcholinesterase Inhibitors and N-Methyl-D-Aspartate Receptor Antagonists on the Risk of Development and Progression of Age-Related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261450196}, pmid = {42221733}, issn = {2474-1272}, abstract = {Purpose: To investigate whether memantine or acetylcholinesterase inhibitors are associated with reduced risk of developing age-related macular degeneration (AMD) and of progression from nonexudative to exudative AMD. Methods: This retrospective cohort study used data from the TriNetX US Collaborative Network between 2008 and 2023. Adults 50 years and older were included and categorized into AMD-naïve and dry AMD cohorts. Exposure groups were defined by outpatient prescriptions for acetylcholinesterase inhibitors (donepezil, rivastigmine, or galantamine) or memantine. Each exposure group was propensity score-matched 1:1 to unexposed controls based on demographic and clinical characteristics. Outcomes were incident AMD in the AMD-naïve cohort and incident exudative AMD in the dry AMD cohort at least 1 year after the prescription. Risk ratios (RRs) and 95% CIs were estimated, and memantine was compared with acetylcholinesterase inhibitors in a head-to-head analysis. Results: Among AMD-naïve patients, acetylcholinesterase inhibitor use (n = 35 397) and memantine use (n = 13 576) were associated with lower AMD incidence compared with matched controls (RR, 0.490; 95% CI, 0.442-0.543; P < .001; and RR, 0.532; 95% CI, 0.448-0.630; P < .001, respectively). In patients with dry AMD, both acetylcholinesterase inhibitors and memantine were associated with reduced progression to exudative AMD (RR, 0.448; 95% CI, 0.357-0.562; P < .001; and RR, 0.552; 95% CI, 0.362-0.842; P = .005). In head-to-head comparisons, similar risks for incident AMD were seen with memantine and acetylcholinesterase inhibitors (RR, 0.929; 95% CI, 0.762-1.132; P = .46) and progression to exudative AMD (RR, 1.198; 95% CI, 0.720-1.994; P = .49). Conclusions: Memantine and acetylcholinesterase inhibitors were associated with a reduced risk of AMD development and progression. These findings support further investigation into shared neuroprotective pathways and potential drug repurposing.}, }
@article {pmid42222587, year = {2026}, author = {Mercuri, S and Sacu, S and Frank-Publig, S and Schrittwieser, J and Gumpinger, M and Leingang, O and Schmidt-Erfurth, U and Chakravarthy, U and Bogunovic, H and Virgili, G and Reiter, GS}, title = {Fluid Volumes Longitudinal Modeling to Predict Atrophy and Fibrosis in Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {6}, pages = {101190}, pmid = {42222587}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the impact of retinal fluid volumes on the development of atrophy and fibrosis in neovascular age-related macular degeneration (nAMD) during routine care.<br><br>DESIGN: Retrospective longitudinal study.<br><br>PARTICIPANTS: Treatment-na&#xef;ve eyes with nAMD from the Vienna Imaging Biomarker Eye Study (2007-2018), initiating anti-VEGF therapy.<br><br>METHODS: Volumes of intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) were automatically quantified on OCT using an approved artificial intelligence algorithm within the 1-, 3-, and 6-mm ETDRS regions. Macular neovascularization (MNV) type and baseline presence of subretinal hyperreflective material (SHRM) were assessed. Fluid volumes were modeled as time-dependent biomarkers using repeated-measure Cox models to evaluate cumulative effects over time on the development of atrophy and fibrosis, with hazard ratios calculated for quartiles (Qs) at each visit. Associations with change in visual acuity (VA) were performed in a subset of eyes with &#x2265;12 months of follow-up.<br><br>MAIN OUTCOME MEASURES: Retinal fluid volumes, development of atrophy and fibrosis, and change in VA.<br><br>RESULTS: A total of 1060 eyes of 998 patients were included. Higher IRF volumes increased the risk of both atrophy and fibrosis (all P < 0.001). Subretinal fluid reduced the risk of atrophy (Q4, P &#x2264; 0.001) and fibrosis (1-mm, P = 0.028) in the 1- and 3-mm regions, but increased the risk of fibrosis in the 6-mm region (P &#x2264; 0.031). Higher PED volumes increased the risk of atrophy in the 6-mm region (P < 0.001), and fibrosis at all locations (P &#x2264; 0.002). Age and baseline presence of SHRM were associated with atrophy (P < 0.001), whereas type 2 and mixed/undefined MNVs were associated with both atrophy (P < 0.001) and fibrosis (P &#x2264;0.004). In 552 eyes, time-related presence of fibrosis was associated with VA decline at all locations (P < 0.001). In all areas, Q4 of IRF was associated with linear VA decline (P <0.001). Larger SRF volumes (Q4) in the 1-mm region were associated with better vision (P <0.05). Higher PED volumes (Q3, Q4) were linked to VA decline at all locations (P < 0.001).<br><br>CONCLUSIONS: Assessment of the cumulative effects of retinal fluid volumes during anti-VEGF therapy using time-dependent biomarker modeling revealed notable associations with risk of atrophy, fibrosis, and VA decline.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42222588, year = {2026}, author = {de Breuk, A and de Jong, S and Bakker, B and Kersten, E and Luttikhuizen, DT and Fauser, S and Klaver, CCW and den Hollander, AI and Hoyng, CB and Lechanteur, YTE}, title = {Geographic Atrophy in Patients with Age-Related Macular Degeneration Is Associated with Rare Variants in Complement Factor H and Complement Factor I.}, journal = {Ophthalmology science}, volume = {6}, number = {6}, pages = {101171}, pmid = {42222588}, issn = {2666-9145}, abstract = {PURPOSE: To describe the phenotype of patients with age-related macular degeneration (AMD) carrying rare genetic variants in the complement factor H (CFH) and complement factor I (CFI) genes.<br><br>DESIGN: Cross-sectional study.<br><br>PARTICIPANTS: Two hundred thirty-four patients with AMD carrying rare variants in CFH (n = 134) and CFI (n = 100) and 234 AMD noncarriers.<br><br>METHODS: Genetic data of patients with AMD from the European Genetic Database were filtered for rare coding and splice-site variants in CFH and CFI. For each carrier, an age-matched (&#xb1;2 years) patient with AMD without rare variants in CFH and CFI (noncarrier) was selected. Phenotypic characteristics on color fundus photographs were graded according to the Rotterdam Classification and compared between carriers and noncarriers by univariate generalized estimating equations with binary logistic regression analyses, applying a Bonferroni correction for multiple comparisons. We performed subanalyses for pathogenic rare variants only, and we analyzed CFH and CFI carriers separately.<br><br>MAIN OUTCOME MEASURES: Phenotypic characteristics on color fundus photographs.<br><br>RESULTS: Geographic atrophy and intermediate AMD, along with features such as predominant drusen type, largest drusen size, and drusen area, were associated with carriership of rare pathogenic variants in CFH (P < 0.001, P = 0.002, P < 0.001, and P < 0.001, respectively). Geographic atrophy and intermediate AMD, along with features such as drusen size, drusen area, and pigmentation, were associated with carriership of rare pathogenic variants in CFI (P = 0.01, P = 0.006, P < 0.001, and P = 0.006, respectively). Furthermore, carriers of rare pathogenic variants in CFH were younger (P < 0.001) and had a lower genetic risk score for common AMD-associated variants compared with noncarriers (mean [standard deviation] genetic risk score 0.83 [1.01] vs. 1.41 [1.21], P = 0.03).<br><br>CONCLUSIONS: In this study, patients with AMD carrying rare variants in CFH and CFI had a more severe drusen phenotype, and a higher frequency of geographic atrophy at a relatively early age. Identifying this distinct phenotype could aid in pinpointing individuals who are more likely to benefit from complement-inhibiting therapies.<br><br>FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid42215276, year = {2026}, author = {Guo, X and Chen, Y and Yao, J and Huang, J and Xiong, R and Han, X and Huang, W and Congdon, N and Wang, W}, title = {Trends of blindness and visual impairment in individuals aged 70 and older.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328311}, pmid = {42215276}, issn = {1468-2079}, abstract = {BACKGROUND: The global ageing population has heightened the importance of eye health, yet comprehensive assessments of blindness and vision impairment (BVI) burden among older adults remain limited. Using Global Burden of Disease 2021 data, we analysed trends and disparities in BVI and major eye diseases across 204 countries and territories from 1990 to 2021 among adults aged ≥70 years.<br><br>METHODS: Age-standardised prevalence (ASPR), years lived with disability, and average annual percentage change (AAPC) were estimated for BVI and its leading causes, stratified by age, sex, region and Sociodemographic Index (SDI). Temporal trends were assessed using joinpoint regression.<br><br>RESULTS: Globally, between 1990 and 2021, the number of BVI cases increased 156% (94.5 to 242&#x2009;million) with an AAPC of 0.11%. Women experienced a faster rise in ASPR than men (AAPC 0.16% vs 0.11%). Age-specific analysis revealed divergent trends: prevalence rose in the 70-84&#x2009;age group (peak AAPC 1.02% in 70-74 years) but declined in those &#x2265;85 years (AAPC -0.23% in 85-89 years). With increasing SDI, the prevalence rate for BVI and major blinding eye diseases significantly decreased (p<0.001). Regionally, high-income North America showed the largest ASPR reductions (AAPC -0.30%).<br><br>CONCLUSIONS: Demographic expansion and ageing are the primary drivers of the rise in absolute BVI burden among adults aged &#x2265;70 years since 1990, with persistent inequities across sex and SDI levels. Further country-specific analyses, particularly in settings with limited primary data, will help refine estimates and support future research and service planning.}, }
@article {pmid42215633, year = {2026}, author = {Zhu, J and Zeng, C and Tang, R and Lu, W and Wang, S and Huang, L and Xiong, Z and Deng, A and Zhen, Z and Chen, R and Li, X}, title = {Causal relationship between aspirin use and age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42215633}, issn = {1476-5454}, support = {82220108016//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {OBJECTIVE: Although increasing evidence suggests an association between aspirin use and age-related macular degeneration (AMD), the potential causal relationship between them remains controversial. This study aims to explore the causal genetic association and potential mediators between aspirin use and AMD using Mendelian randomisation (MR) analysis.<br><br>METHODS: A bidirectional, two-sample, two-step MR analysis was performed to assess the potential causal relationships among aspirin use, AMD, and possible mediators. Multivariable MR was additionally performed to estimate the direct effect of aspirin use on AMD after adjusting for mediators. Causal estimates were primarily derived using an inverse variance weighted method. Horizontal pleiotropy, heterogeneity, and stability were evaluated using the MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis.<br><br>RESULTS: An MR analysis revealed that aspirin use was associated with an increased risk of both early and dry AMD. A mediation analysis indicated that aspirin use is associated with a lower level of serum low-density lipoprotein cholesterol (LDL-C), an elevated serum apolipoprotein A1 (APOA1) concentration, and an increased risk of early and dry AMD. Multivariable MR analysis further showed that after adjusting for LDL-C and APOA1, the direct effect of aspirin on AMD was attenuated to non-significance.<br><br>CONCLUSION: This study provides robust genetic evidence that aspirin use is associated with an increased risk of early and dry AMD, and demonstrates that this association is fully mediated by decreased serum LDL-C and increased serum APOA1 levels, with no evidence of a direct effect independent of these lipid pathways.}, }
@article {pmid42216114, year = {2026}, author = {Ji, PX and Herman, JE and Sivachandran, N}, title = {Rapid resolution of submacular hemorrhage in neovascular age-related macular degeneration using pneumatic displacement and faricimab.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04978-4}, pmid = {42216114}, issn = {1471-2415}, abstract = {BACKGROUND: Submacular hemorrhage (SMH) is a rare but visually devastating complication of neovascular age-related macular degeneration (nAMD) associated with poor long-term prognosis due to photoreceptor iron toxicity, subretinal fibrosis, and retinal pigment epithelial (RPE) damage. Pneumatic displacement (PD) combined with anti-vascular endothelial growth factor (anti-VEGF) therapy is an established approach for managing acute SMH; however, the role of faricimab, a novel dual inhibitor of VEGF-A and angiopoietin-2 (Ang-2), in this context has not been previously evaluated.<br><br>CASE PRESENTATION: This study reports the outcomes of PD combined with faricimab injection in a case of a 75-year-old female with acute SMH secondary to nAMD. The patient with dense SMH and a large PED secondary to presumed polypoidal choroidal vasculopathy (PCV) underwent PD with 0.40 mL of sulfur hexafluoride and intravitreal faricimab injection (50 &#xb5;L, 6&#xa0;mg) on the same day as presentation, followed by 5 days of face-down positioning with excellent patient compliance confirmed by verbal verification. Two additional faricimab injections were administered at 4 and 8 weeks, followed by treat-and-extend protocol.<br><br>CONCLUSIONS: The use of timely PD with appropriate head positioning can effectively manage patients with acute large SMH and improve visual outcomes. While the combined approach with serial faricimab injections showed longer-term benefits, the immediate improvement was likely due to mechanical techniques. The potential added benefit of faricimab's dual inhibition mechanism over other anti-VEGF therapies in SMH remains to be investigated through larger, comparative trials.}, }
@article {pmid42217617, year = {2026}, author = {Kaushik, S and Bisen, S and Singh, NK}, title = {Retinal pericytes and their role in proliferative retinopathies.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2026.04.021}, pmid = {42217617}, issn = {1525-2191}, abstract = {Vascular dysfunction and abnormal vascularization are primary characteristics of many proliferative retinopathies. Research on proliferative retinopathies has primarily focused on understanding the role of cells and factors that regulate endothelial cell function in ischemic retinopathies. Pericyte coverage of the retina is deemed essential for the survival of endothelial cells, and recently significant efforts have been made to comprehend the role of pericytes under stress conditions such as diabetes and ischemia. Understanding the significance of retinal pericytes in proliferative retinopathies is essential, particularly because of the often-contradictory findings reported regarding their role in these conditions. This review will not only explore the role of retinal pericytes and their interactions with retinal endothelial cells in physiological vascularization but also highlight its importance in the pathogenesis of retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion. A deeper comprehension of pericyte-endothelial interactions in proliferative retinopathies would aid in diagnosis and the formulation of viable therapeutics to avert vision loss associated with these proliferative retinopathies.}, }
@article {pmid42217724, year = {2026}, author = {Harris, C and Nisar, MA and Amamoo, R and Patel, R and Martin, PM and Jadeja, RN and Thounaojam, MC}, title = {Murine Models of Neovascular AMD Revisited: Mechanistic Pathways, Immune-Metabolic Crosstalk, and the Impact of Aging and Sex.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111094}, doi = {10.1016/j.exer.2026.111094}, pmid = {42217724}, issn = {1096-0007}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in older adults. Neovascular AMD (nAMD) is characterized by choroidal neovascularization (CNV), vascular leakage, and fibrotic remodeling. Although anti-vascular endothelial growth factor (VEGF) therapy has improved visual outcomes for some patients, emerging findings highlight growing concerns regarding treatment resistance, persistent disease activity, and progression to subretinal fibrosis, which remain major challenges. Growing evidence indicates that nAMD arises from the interplay among metabolic dysfunction, oxidative stress, chronic inflammation, hypoxia signaling, and extracellular matrix remodeling within the outer retina. Disruption of mitochondrial function, lipid handling in the retinal pigment epithelium, complement activation, inflammasome signaling, macrophage immune-metabolic reprogramming, and hypoxia-driven VEGF expression collectively shape angiogenesis and lesion progression. Murine models, including laser-induced CNV, two-stage laser-induced fibrosis, and spontaneous or genetic systems such as JR5558, VLDLR-deficient, and CYP27A1-deficient mice, have provided essential mechanistic insights into these pathways. Aging and biological sex influence metabolism, mitochondrial efficiency, immune responses, hypoxia responsiveness, and wound-healing capacity. However, many widely used experimental models rely on young adult animals and often use a single sex without accounting for sex- or age-based differences, leaving these critical factors understudied and inadequately integrated into preclinical design. This review integrates current mechanistic understanding with a critical evaluation of murine nAMD models and emphasizes the importance of incorporating biological age and sex into experimental systems to improve mechanistic interpretation and translational relevance.}, }
@article {pmid42217973, year = {2026}, author = {Lankry, P and Loewenstein, A and Trivizki, O}, title = {Insights into age-related macular degeneration.}, journal = {Handbook of clinical neurology}, volume = {218}, number = {}, pages = {165-190}, doi = {10.1016/B978-0-443-22212-2.00020-3}, pmid = {42217973}, issn = {0072-9752}, mesh = {Humans ; *Macular Degeneration/epidemiology/therapy/diagnosis ; Risk Factors ; Angiogenesis Inhibitors/therapeutic use ; }, abstract = {Age-related macular degeneration (AMD) is a complex and prevalent ocular condition with significant implications for vision and quality of life in the aging population. This chapter provides a comprehensive exploration of AMD, encompassing its multifactorial pathophysiology, epidemiologic trends, and associated risk factors. A detailed examination of the distinct features and symptoms characterizing neovascular and dry AMD enhances our understanding of the clinical spectrum. Special emphasis is placed on geographic atrophy (GA), an advanced stage of AMD, highlighting its significant impact on visual outcomes. Apart from examining the present diagnostic methods and criteria for AMD, this chapter assesses current therapeutic approaches, with a specific emphasis on antivascular endothelial growth factor (anti-VEGF) treatments. Additionally, the discussion extends to emerging therapies and potential avenues for future research in AMD. Preventative strategies and lifestyle modifications that may influence disease progressions are also reviewed. By consolidating current knowledge, clinical insights, and future prospects, this chapter aims to serve as a valuable resource for clinicians, researchers, and students engaged in the study and management of age-related macular degeneration.}, }
@article {pmid42217980, year = {2026}, author = {Winebrake, JP and Lim, JI}, title = {Retinal imaging and artificial intelligence analysis.}, journal = {Handbook of clinical neurology}, volume = {218}, number = {}, pages = {3-12}, doi = {10.1016/B978-0-443-22212-2.00011-2}, pmid = {42217980}, issn = {0072-9752}, mesh = {Humans ; *Artificial Intelligence ; *Retina/diagnostic imaging ; Tomography, Optical Coherence/methods ; *Retinal Diseases/diagnostic imaging ; }, abstract = {The retina, uniquely accessible as an extension of the central nervous system, plays a critical role in neurology and ophthalmology. Advances in retinal imaging technologies - including color fundus photography, optical coherence tomography, and OCT angiography - have enabled detailed, noninvasive assessment of ocular and systemic diseases. Artificial intelligence (AI), particularly deep learning, has revolutionized the analysis of these images, facilitating early detection, classification, and prognostication of conditions such as diabetic retinopathy, age-related macular degeneration, optic neuropathies, and inherited retinal diseases. AI applications extend beyond ophthalmology, offering insights into neurologic and cerebrovascular disorders through retinal biomarkers. However, challenges remain regarding dataset bias, generalizability, ethical concerns, and the "black box" nature of AI models. Addressing these limitations, along with integrating multimodal imaging and fostering cross-specialty collaboration, will be pivotal in ensuring that AI technology is adopted effectively and responsibly. The future will be marked by synergistic AI-human workflows to enhance diagnostic accuracy, screening scalability, and personalized patient care. As AI applications evolve, they promise to reshape retinal imaging and its intersection with neurology, expanding opportunities for early intervention and improved outcomes.}, }
@article {pmid42217982, year = {2026}, author = {Jones, BW}, title = {Insights into retinal remodeling in retinal degenerative disease.}, journal = {Handbook of clinical neurology}, volume = {218}, number = {}, pages = {327-339}, doi = {10.1016/B978-0-443-22212-2.00015-X}, pmid = {42217982}, issn = {0072-9752}, mesh = {Humans ; *Retinal Degeneration/pathology/physiopathology ; Animals ; *Neuronal Plasticity/physiology ; *Retina/pathology/physiopathology ; }, abstract = {The retina is a highly organized sensory structure responsible for capturing and processing visual information. Visual computation begins at the first synapse between photoreceptors, bipolar cells, and horizontal cells, before involving amacrine and ganglion cells to generate vision. Retinal degeneration disrupts the precise neural architecture required for vision, initiating a maladaptive process known as retinal remodeling. Photoreceptor degeneration in diseases, like retinitis pigmentosa (RP) and age-related macular degeneration, induces retinal remodeling, but good evidence shows glaucoma and diabetic retinopathy do as well, expanding the clinical significance. Historically, studies relied on histologic measures that assumed photoreceptor degeneration marked disease endpoints. However, retinal remodeling involves extensive structural and functional reorganization across all retinal cell classes, driven by the interdependence between neurons, glia, and the retinal pigment epithelium. Retinal plasticity corrupts normal retinal computations, and recent evidence suggests therapeutic windows close after ∼50% photoreceptor loss. Understanding remodeling mechanisms is critical for effective therapies, as current treatments fail to address the ongoing negative plasticity. Insights from retinal remodeling offer broader implications for neurodegeneration, highlighting the retina as a model for understanding central nervous system diseases like Alzheimer and Parkinson. Advancing knowledge of these processes will be pivotal for developing interventions to preserve vision.}, }
@article {pmid42217985, year = {2026}, author = {Wang, J and Felfeli, T and Ballios, BG}, title = {Stem cell therapy in retinal disease.}, journal = {Handbook of clinical neurology}, volume = {218}, number = {}, pages = {365-385}, doi = {10.1016/B978-0-443-22212-2.00004-5}, pmid = {42217985}, issn = {0072-9752}, mesh = {Humans ; Animals ; *Stem Cell Transplantation/methods ; *Retinal Diseases/therapy/surgery ; Stem Cells/physiology ; }, abstract = {Stem cell therapy presents a new solution to cure degenerative diseases of the retina, which normally have limited ability to regenerate after injury. Stem cells are cells capable of self-renewal and differentiation into more specialized cells, and can be derived from both embryonic and adult sources. This definition encompasses a heterogeneous group of cells possessing varied potency and characteristics. Current attempts in applying stem cell technology to the retina have primarily focused on regenerating the retinal pigment epithelium (RPE) and light-sensing photoreceptor cells. They have not only shown the ability to prevent the death of host photoreceptors, but they can also differentiate into all major retinal cell types to replace lost cells. In vivo experiments, primarily performed in mice, have found that stem cell-derived RPE cells, photoreceptors, and their precursors can survive long-term in animal models without tumorigenicity or immune rejection. Following transplantation, these cells were able to integrate and mature in vivo, forming synapse-like structures with host retinal cells. Furthermore, transplants in mice were able to rescue visual function at a cellular and behavioral level. These promising preclinical results have led to clinical trials testing cell therapy in numerous diseases, including Stargardt macular dystrophy, age-related macular degeneration, retinitis pigmentosa, and central retinal vein occlusion. These trials have demonstrated the safety of cell therapy and have improved visual function in some patients. Scientific advances in the culturing of retinal organoids and the understanding of cell redifferentiation are informing the development of better stem cell therapies, which hold great potential for restoring vision to patients with retinal dystrophies.}, }
@article {pmid42218559, year = {2026}, author = {Zong, Y and Fan, Q and Huang, L}, title = {Biosimilars of anti-VEGF agents in retinal diseases: a narrative review of regulatory, clinical, and pharmacoeconomic aspects.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00872-9}, pmid = {42218559}, issn = {2056-9920}, abstract = {BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) agents are the cornerstone therapy for retinal vascular diseases including neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion. With patent expirations of ranibizumab and aflibercept, biosimilars have emerged as cost-effective alternatives. However, vitreoretinal specialists require consolidated evidence on regulatory standards, clinical equivalence, and practical implementation strategies to guide evidence-based integration of biosimilars into clinical practice.<br><br>METHODS: We conducted a narrative review of regulatory documents from the FDA, EMA, and NMPA, as well as Phase III clinical trials, real-world studies, and pharmacoeconomic analyses of approved ophthalmic anti-VEGF biosimilars. Literature searches were performed across PubMed, Embase, and regulatory databases from 2015 to 2025. Studies were included if they reported regulatory approval pathways, clinical efficacy and safety data, interchangeability studies, or pharmacoeconomic evaluations of anti-VEGF biosimilars in retinal diseases.<br><br>RESULTS: Regulatory frameworks demonstrate rigorous biosimilarity assessment through comprehensive analytical characterization, preclinical evaluation, and clinical trials. Pivotal Phase III studies confirm therapeutic equivalence of approved biosimilars (including ranibizumab-nuna and aflibercept-abzv) with comparable visual acuity outcomes, safety profiles, and immunogenicity to originator products. Real-world evidence for ranibizumab biosimilars supports comparable outcomes to originators, while evidence for aflibercept biosimilars remains preliminary and warrants continued pharmacovigilance. Pharmacoeconomic analyses demonstrate 20-40% cost reduction compared to originators, offering substantial healthcare savings and improved patient access. Key implementation considerations include extrapolation principles, switching protocols, and clinic workflow integration.<br><br>CONCLUSIONS: Although real-world data for aflibercept biosimilars are currently limited, emerging evidence for ranibizumab biosimilars supports comparable outcomes. Approved anti-VEGF biosimilars represent safe, effective, and cost-saving alternatives for retinal diseases. With robust analytical and clinical evidence supporting biosimilarity, vitreoretinal specialists can confidently adopt these agents. Successful integration requires understanding of regulatory science, evidence-based switching protocols, and healthcare system collaborations to maximize patient benefits while maintaining treatment standards. Future research should focus on long-term outcomes, broader implementation studies, and pharmacovigilance monitoring.}, }
@article {pmid42206905, year = {2026}, author = {Kayembe-Mulumba, B and Delcourt, C and Delyfer, MN}, title = {Controversial Links Between Cardiometabolic Factors and Age-Related Macular Degeneration: Methodological Perspectives for Future Research.}, journal = {Current eye research}, volume = {}, number = {}, pages = {1-18}, doi = {10.1080/02713683.2026.2678294}, pmid = {42206905}, issn = {1460-2202}, abstract = {PURPOSE: Epidemiological studies yielded conflicting results regarding the relationship between cardiometabolic factors and age-related macular degeneration (AMD). However, the methodological characteristics of these studies, which may partly explain this controversy, are not currently addressed. This narrative review aimed to examine current evidence between the six most studied cardiometabolic factors and AMD, focusing on identifying key methodological shortcomings and discussing analytical approaches currently available to address them.<br><br>METHODS: We conducted a rigorous, nonsystematic literature search using targeted MeSH terms and keywords in MEDLINE (PubMed), EMBASE, Web of Science and Scopus, with no language restrictions, up to June 2025. We identified and reviewed epidemiological (cross-sectional, case-control, cohort) studies reporting original data on the six targeted cardiometabolic factors: blood pressure, antihypertensive medications, lipid levels, lipid-lowering medications, diabetes mellitus and antidiabetic treatments. A quantitative synthesis of studies was conducted to describe their methodological characteristics and reported associations.<br><br>RESULTS: Across the 116 reviewed associations, prospective cohorts (41%) and cross-sectional designs (37%) predominated. Most originated from America (35%) and Europe (32%). Lipids (21%) and lipid-lowering agents (20%) were the most frequently studied exposures, while advanced AMD was the predominant outcome (56%). Logistic regression was the main analytic approach (70%), and association conclusions were most often null (42%), followed by increased (36%) and decreased (22%) risk. The most common methodological limitations included cross-sectional study designs, static modeling of dynamic exposures, unaddressed interval censoring, not controlling for confounding by indication, and unstandardized selection of confounders, which are likely to bias the reported associations.<br><br>CONCLUSIONS: Future studies should prioritize robust methodological frameworks, including longitudinal designs, survival bias mitigation, standardized and repeated exposure assessments, distinction between AMD subtypes, propensity scores for medications use, and advanced causal inference techniques wherever feasible. Such an effort is foundational to strengthening the validity and reproducibility of findings linking cardiometabolic factors to AMD, thereby improving AMD prevention strategies.}, }
@article {pmid42207296, year = {2026}, author = {Shaikh, A and Pera, MF}, title = {Cell therapy for age-related macular degeneration.}, journal = {Mammalian genome : official journal of the International Mammalian Genome Society}, volume = {37}, number = {1}, pages = {}, pmid = {42207296}, issn = {1432-1777}, mesh = {Humans ; *Macular Degeneration/therapy/pathology/genetics ; Animals ; Retinal Pigment Epithelium/pathology/metabolism ; *Cell- and Tissue-Based Therapy/methods ; }, abstract = {Age-related macular degeneration (AMD) is a major cause of vision loss worldwide. The disease is caused by deterioration of the retinal pigment epithelium (RPE), a tissue that plays critical roles in the support of the photoreceptors. Cell therapies to replace damaged RPE in the non-exudative form of AMD have been under development for several decades. We review the progress of cell therapy to date and highlight some promising future directions for research in this area.}, }
@article {pmid42207540, year = {2026}, author = {Xiong, R and Tan, S and Li, Y and Li, H and Zhu, Z and Chen, Y and He, M and Chen, S and Wang, W}, title = {Pathologic Myopia Globe Shape and Long-Term Prognosis.}, journal = {JAMA ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1001/jamaophthalmol.2026.1561}, pmid = {42207540}, issn = {2168-6173}, abstract = {IMPORTANCE: Three-dimensional (3D) eye shape may play a critical role in predicting long-term structural and functional outcomes in high myopia.<br><br>OBJECTIVE: To determine whether 3D eye shape subtypes defined by high-resolution magnetic resonance imaging (MRI) predict 15-year structural and functional outcomes in high myopia.<br><br>This prospective cohort study involved a subsample of individuals with high myopia (spherical equivalent &#x2264;-6.00 D in both eyes) enrolled in the Zhongshan High Myopia Cohort at a single center in China. Participants underwent biennial ophthalmic examinations over 15 years. Baseline assessments began in August 2011, with biennial follow-ups through September 2025. Data were analyzed from October 2025 through December 2025.<br><br>EXPOSURES: Eye shape was classified into the following 6 categories: spheroidal, ellipsoidal, conical, nasally distorted, temporally distorted, and barrel shaped. Spheroidal and ellipsoidal types were defined as nondeformed and the others as deformed.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcomes were annual axial elongation rate, rapid elongation (&#x2265;0.10 mm/y), macular choroidal thinning (subfoveal choroidal thickness <62 &#xb5;m), progression of myopic macular degeneration (MMD), incidence of posterior staphyloma, visual impairment (best-corrected visual acuity &#x2264;20/40), and visual field defects.<br><br>RESULTS: Of 190 eyes from 95 participants, 152 eyes completed follow-up and were included in the analysis. Of the 152 eyes analyzed, 77 (50.7%) were from female participants, with an overall mean (SD) age of 32.3 (14.1) years. Baseline shapes included spheroidal (83 eyes [54.6%]), nasally distorted (25 [16.4%]), conical (23 [15.1%]), ellipsoidal (11 [7.2%]), temporally distorted (5 [3.3%]), and barrel shaped (5 [3.3%]). Axial elongation followed a morphology-dependent gradient, from slowest in spheroidal eyes (0.045 mm/y) to fastest in nasally distorted eyes (0.095 mm/y). After multivariable adjustment, nasally distorted eyes elongated by 0.050 mm/y (95% CI, 0.020-0.080 mm/y; P&#x2009;=&#x2009;.001) faster and had higher odds of rapid elongation (odds ratio, 5.74; 95% CI, 1.66-19.82; P&#x2009;=&#x2009;.006). Deformed eyes overall had a 7-fold higher risk of macular choroidal thinning (odds ratio, 7.24; 95% CI, 1.77-29.63; P&#x2009;=&#x2009;.006). Nasally distorted and conical eyes showed the greatest risks for both choroidal thinning and MMD progression. For visual field defects, risk was elevated in nasally distorted and conical eyes.<br><br>CONCLUSIONS AND RELEVANCE: Findings from this prospective cohort study suggest that 3D eye shape is an important determinant of long-term outcomes in high myopia. Nasally distorted and conical phenotypes conferred the greatest risks, highlighting the potential value of baseline eye shape stratification for personalized management, risk prediction, or early intervention.<br><br>TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN56368396.}, }
@article {pmid42208846, year = {2026}, author = {Heo, YJ and Bishayee, K and Jhun, JY and Han, SG and Lee, YS and Park, YG and Cho, ML and Park, YS}, title = {Mitochondrial transplantation protects the retinal pigment epithelial cells from the oxidative stress induced by NaIO3.}, journal = {Experimental eye research}, volume = {270}, number = {}, pages = {111090}, doi = {10.1016/j.exer.2026.111090}, pmid = {42208846}, issn = {1096-0007}, abstract = {The retinal pigment epithelium (RPE) is the outermost part of the retina, and it is essential for the photoreceptor survival and function. Oxidative stress, aging, accumulation of lipofuscin, and drusen can lead to retinal degenerative diseases such as age-related macular degeneration (AMD). Those stress conditions increase reactive oxygen species (ROS) levels and oxidative stress, which can induce mitochondrial dysfunction and promote RPE cell death during retinal degeneration. We transplanted mitochondria, isolated from C2C12 cells, into cultured RPE cells, and RPE cell injury was induced by NaIO3 treatment. To evaluate the protective effect of mitochondrial transplantation, Annexin V/PI and cell viability assays were performed to measure the cell survival, and ROS levels were measured by flow cytometry to analyze cellular stress. To understand the underlying protective mechanism of mitochondrial transplantation, we measure expression of the antioxidant genes, mitochondrial fusion/fission markers, and mitophagy makers using qRT-PCR and Western blot methods. Mitochondrial transplantation reduced NaIO3-induced cell death and ROS levels, and antioxidant genes related to the Nrf2 pathway were upregulated, providing a protective effect against retinal damage. In addition, mitochondrial fusion was increased, whereas fission was decreased in the NaIO3 model. Furthermore, mitophagy was increased by mitochondrial transplantation, which could clear damaged mitochondria through a cellular protective pathway. In conclusion, mitochondrial transplantation could protect the RPE cells by maintaining mitochondrial homeostasis and promoting the antioxidant pathway via Nrf2 activation. This study suggests that mitochondrial transplantation could be a potential treatment option for improving AMD progress in the future.}, }
@article {pmid42211220, year = {2026}, author = {Peng, Y and Liang, LY and Wei, HL and Huang, Q and Yuan, LM and Xie, YY and Tang, QY and Wang, AQ and Li, JM and Guo, QS and Huang, BL}, title = {Fructus lycii mitigates oxidative stress in dry age-related macular degeneration models via Nrf2/ARE pathway.}, journal = {International journal of ophthalmology}, volume = {19}, number = {6}, pages = {1048-1056}, pmid = {42211220}, issn = {2222-3959}, abstract = {AIM: To evaluate the effect of Fructus lycii (FL) aqueous extract on dry age-related macular degeneration (AMD) in mice via the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway and investigate the protective effect of FL-containing serum on hydrogen peroxide (H2O2)-treated human retinal pigment epithelial cells (ARPE-19) in vitro.<br><br>METHODS: In vivo dry AMD mouse model was established by intraperitoneal injection of NaIO3 solution and treated with aqueous extract of FL. The pathological changes of mouse retinal tissues were observed by electron microscopy; the activity of superoxide dismutase (SOD) and catalase (CAT) in mouse serum was detected by colorimetric method. In vitro dry AMD model was established by H2O2 induction of ARPE-19 cells and treated with FL-containing serum. Methylthiazolyldiphenyl-tetrazolium bromide assay and scratch assay were performed to detect cell activity and proliferation ability. Expression of Nrf2, heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic subunit (GCLC) in retinal tissues and ARPE-19 cells were detected by Western blot and quantitative real-time polymerase chain reaction (Q-PCR).<br><br>RESULTS: The in vivo study revealed severe deposits under the retinal pigment epithelium and thickened Bruch's membrane in dry AMD mice. However, aqueous extract of FL reduced the formation of deposits and decreased the thickness of Bruch's membrane. SOD and CAT activities were significantly reduced in the serum of dry AMD mice, and aqueous extract of FL upregulated SOD and CAT activities. In addition, gene and protein expression of Nrf2, HO-1, and GCLC were significantly downregulated in dry AMD mice, but significantly upregulated by FL aqueous extract treatment. In vitro studies showed that H2O2 inhibited the activity and proliferative capacity of ARPE-19 cells and downregulated the protein and gene expression of Nrf2, HO-1 and GCLC. However, in H2O2-treated ARPE-19 cells, FL-containing serum not only increased cell activity and proliferative capacity, but also upregulated protein and gene expression of Nrf2, HO-1, and GCLC.<br><br>CONCLUSION: FL reduces oxidative stress in an animal model of dry AMD through the Nrf2/ARE signaling pathway and has a protective effect on dry AMD in vitro and in vivo, providing new insights into the therapeutic use of FL for dry AMD.}, }
@article {pmid42211726, year = {2026}, author = {Berni, A and Shen, M and Liu, J and Kastner, JD and El-Mulki, OS and Beqiri, S and Herrera, G and Trivizki, O and Waheed, NK and Usner, DW and Levy, B and O'Brien, R and Gregori, G and Rosenfeld, PJ}, title = {Novel Clinical Trial Designs for Intermediate Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {6}, pages = {101179}, pmid = {42211726}, issn = {2666-9145}, abstract = {PURPOSE: To develop and model clinical trial designs for intermediate age-related macular degeneration (iAMD) using OCT-based structural biomarkers to define inclusion criteria and estimate sample size requirements for detecting treatment effects over 2 years.<br><br>DESIGN: Retrospective study of a prospectively acquired swept-source OCT cohort.<br><br>SUBJECTS: Patients with iAMD enrolled in a prospective natural history imaging study.<br><br>METHODS: Two clinical trial designs were modeled. The first included eyes with drusen volume (DV) &#x2265;0.20 mm[3] and any hyperreflective foci (HRF). The second included eyes with an area of HRF &#x2265;0.07 mm[2], regardless of DV. Eyes were followed from the time of eligibility and monitored for the onset and growth of large hypertransmission defects (hyperTDs). Power and sample size simulations were performed based on the expected treatment effects.<br><br>MAIN OUTCOME MEASURES: Annual square root growth rates of large hyperTDs and incidence of new large hyperTDs over 2 years.<br><br>RESULTS: In 76 eyes with DV &#x2265;0.20 mm[3] and HRF, the mean annual growth rate of large hyperTDs was 0.153 mm/year (standard deviation [SD] = 0.188), and 35.5% of these iAMD eyes developed hyperTDs by 2 years. In the 79 eyes with HRF area &#x2265;0.07 mm[2], the mean annual growth rate was 0.161 mm/year (SD = 0.172), and 40.5% developed hyperTD by 2 years. With a 2-sided alpha of 0.1, a 50% reduction in the growth rate could be detected with 80% power using &#x2265;89 eyes per arm in the first group and &#x2265;64 eyes per arm in the second group.<br><br>CONCLUSIONS: The growth rate of large hyperTDs is a continuous and reproducible structural endpoint for iAMD trials, influenced by both lesion onset and progression. Drusen volume or the area of HRF serves as high-risk biomarkers for enrolling iAMD eyes. This design allows for a study duration of 1-2 years with no more than 100 subjects per arm.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42212360, year = {2026}, author = {Zhang, W and Chen, J and Zhong, J}, title = {Regulatory mechanisms and therapeutic potential of N6-methyladenosine modification in retinal diseases (Review).}, journal = {Molecular medicine reports}, volume = {34}, number = {1}, pages = {}, doi = {10.3892/mmr.2026.13923}, pmid = {42212360}, issn = {1791-3004}, mesh = {Humans ; *Adenosine/analogs &amp; derivatives/metabolism/genetics ; RNA Methylation ; *Retinal Diseases/metabolism/genetics/drug therapy/therapy/pathology ; Animals ; Epitranscriptome ; Methyltransferases/metabolism/genetics ; RNA, Messenger/metabolism/genetics ; Gene Expression Regulation ; }, abstract = {N6‑Methyladenosine (m6A) modification, the most abundant internal chemical modification in eukaryotic messenger RNA, plays a central role in gene expression by dynamically regulating RNA metabolism. The present review systematically summarizes the regulatory mechanisms and pathological significance of m6A modification in major retinal diseases, including diabetic retinopathy, age‑related macular degeneration, retinoblastoma, uveitis and retinitis pigmentosa. Studies indicate that m6A methyltransferases (METTL3), demethylases (FTO and ALKBH5) and reader proteins (the YTH domain‑containing family of proteins) participate in pathological processes such as angiogenesis, inflammatory responses, pyroptosis and photoreceptor degeneration by modulating the stability, translation efficiency and degradation of key gene mRNAs. Furthermore, this review explores the therapeutic potential of targeting m6A‑modifying enzymes (for example, small‑molecule inhibitors STM2457 and FB23‑2) and highlights challenges in tissue specificity, delivery systems and clinical translation. Future research should integrate multi‑omics technologies and precision intervention strategies to advance the application of m6A modification in the diagnosis and treatment of retinal diseases.}, }
@article {pmid42212881, year = {2026}, author = {Ansari, G and Oertli, J and Mächler, L and Lipsky, T and Jeffrey, BG and Cukras, CA and Feltgen, N and Klaver, CCW and Pfau, K and Pfau, M}, title = {Parafoveal Dark Adaptation in Early and Intermediate Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {5}, pages = {74}, doi = {10.1167/iovs.67.5.74}, pmid = {42212881}, issn = {1552-5783}, mesh = {Humans ; *Dark Adaptation/physiology ; *Macular Degeneration/physiopathology/diagnosis ; Female ; Cross-Sectional Studies ; *Fovea Centralis/physiopathology ; Aged ; Male ; *Retinal Rod Photoreceptor Cells/physiology ; ROC Curve ; Middle Aged ; Aged, 80 and over ; }, abstract = {PURPOSE: Rod-mediated dark adaptation delays are among the earliest functional abnormalities in age-related macular degeneration (AMD), preceding photoreceptor loss. This study evaluated whether parafoveal fundus-tracked dark adaptometry at 2 degrees detects earlier rod dysfunction than mid-macular loci (4 degrees and 6 degrees) and assessed the diagnostic performance of dynamic and steady-state parameters across eccentricities.<br><br>METHODS: In this cross-sectional study, 35 patients with predominantly early/intermediate AMD and 35 healthy volunteers across a broad range of ages underwent fundus-controlled dark adaptometry (S-MAIA-2; iCare/CenterVue) and multimodal imaging. After standardized bleaching, Goldmann III sized (0.43 degrees) cyan stimuli were presented 2 degrees, 4 degrees, and 6 degrees temporal to the fovea. Dark-adaptation curves were modeled to derive rod intercept time (RIT), final (rod) threshold (FT), and cone threshold (CT), each compared with normative data. Diagnostic accuracy was quantified using covariate-adjusted receiver operating characteristic (ROC) analyses, to account for age.<br><br>RESULTS: Among 70 analyzed eyes, RIT was abnormal in 86% of AMD eyes at 2 degrees, 69% at 4 degrees, and 60% at 6 degrees, whereas FT and CT were less frequently abnormal (29% to 51% and 17% to 26%, respectively). Median RIT at 2 degrees reached 60 minutes in the AMD cohort, indicating absence of rod function within the test duration in many eyes. RIT achieved the highest diagnostic accuracy, with covariate-adjusted area under the curve (AUC) values of 0.91 (95% credible intervals [CrI] = 0.80-0.97) at 2 degrees, 0.88 (95% CrI = 0.77-0.96) at 4 degrees, and 0.87 (95% CrI = 0.76-0.95) at 6 degrees.<br><br>CONCLUSIONS: Fundus-tracked dark adaptometry enables spatially precise assessment of parafoveal rod recovery. Parafoveal RIT prolongation represents the earliest and most frequent functional abnormality in AMD and demonstrates excellent diagnostic performance, supporting its potential as a sensitive functional biomarker for early disease and therapeutic trials.}, }
@article {pmid42212887, year = {2026}, author = {Tsai, CY and Weng, CH and Tsai, CY and Sheen, YJ and Chen, JP and Chen, HM and Wang, IJ and Chou, CC}, title = {Association Between PCSK9 Inhibitor Use and Risk of Age-Related Macular Degeneration.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {5}, pages = {29}, doi = {10.1167/tvst.15.5.29}, pmid = {42212887}, issn = {2164-2591}, mesh = {Humans ; Male ; *Macular Degeneration/epidemiology/prevention &amp; control ; Retrospective Studies ; Middle Aged ; *PCSK9 Inhibitors ; Aged ; Female ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Risk Factors ; Hyperlipidemias/drug therapy ; Incidence ; Proprotein Convertase 9 ; *Anticholesteremic Agents/therapeutic use ; Propensity Score ; Proportional Hazards Models ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) has been linked to systemic lipid imbalance, vascular dysfunction, and inflammation. The ocular effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a novel class of lipid-lowering agents, have not been established. We evaluated whether PCSK9 inhibitor use is associated with reduced AMD risk compared with statin therapy.<br><br>METHODS: We conducted a retrospective propensity score-matched cohort study using the TriNetX multinational electronic health record database (2015-2024) with up to 5 years of follow-up. Adults aged &#x2265;50 years with hyperlipidemia but no prior retinal disease were included. Participants were assigned to PCSK9 inhibitor or statin therapy groups and matched 1:1 based on demographic, clinical, and laboratory variables. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs), and Kaplan-Meier analyses illustrated cumulative AMD incidence.<br><br>RESULTS: Among 56,660 matched participants, PCSK9 inhibitor use was associated with a significantly lower risk of AMD compared with statin therapy (HR, 0.82; 95% CI, 0.73-0.90). The association remained robust in sensitivity analyses across different follow-up intervals. Stratified analyses showed consistent findings in both age groups (50-75 and &#x2265;75 years), male participants, those without type 2 diabetes, nonobese individuals, and those with <2 years of hyperlipidemia duration.<br><br>CONCLUSIONS: In this large real-world cohort, PCSK9 inhibitor use was associated with a lower AMD risk compared with statin monotherapy. Prospective studies are needed to confirm causality.<br><br>TRANSLATIONAL RELEVANCE: This study supports further evaluation of PCSK9 inhibition as a potential strategy to modify AMD risk.}, }
@article {pmid42213134, year = {2026}, author = {Cinque, F and Brink, SCAT and Shahabi, M and de Breuk, A and Heesterbeek, TJ and Klaver, CCW and Hoyng, CB and Lechanteur, YTE}, title = {Clinical course of non-exudative macular neovascularisations in sustained unilateral neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42213134}, issn = {1435-702X}, abstract = {PURPOSE: To assess the risk of conversion of non-exudative macular neovascularisations (NEMNV) in relation to disease history in sustained unilateral neovascular age-related macular degeneration (AMD).<br><br>METHODS: This exploratory case-only cohort study included six-monthly visits. Fellow-eye NEMNV were identified using fluorescein and indocyanine green angiography. Patients were stratified by time since first-eye exudation:&#x2009;<&#x2009;5&#xa0;years (G1) or&#x2009;&#x2265;&#x2009;5&#xa0;years (G2). The primary outcome was the cumulative annual conversion rate of NEMNV, expressed as conversion rate ratios (CRR) with 95% confidence intervals (CI). Secondary outcomes were independent grading of foveal involvement, core vessel, central core vessel, round shape, sharp borders, and lesion growth.<br><br>RESULTS: A total of 134 patients (65.7% female) were included. Mean age at baseline was 74.2&#xa0;years (SD 8.0). Median time since first-eye exudation was 2.9&#xa0;years (IQR 1.0-6.3). Patients in G2 had an earlier age at first-eye exudation (66.0 [9.1] years) than G1 (72.7 [7.8]; P&#x2009;<&#x2009;.001). Seven NEMNV lesions were identified (G1:2, G2:5). Cumulative conversion rates were 22.1% overall, 14.3% in G1, and 27.1% in G2. CRR were 2.3 (95% CI 0.6-6.2), 1.3 (95% CI 0.0 - 7.8), and 4.0 (95% CI 0.7 - 16.8). All but one NEMNV showed growth.<br><br>CONCLUSION: In this limited sample, most NEMNV show growth time regardless of conversion to exudative AMD and appear at a higher risk of conversion. The rate of conversion varies with the age of onset of first-eye exudation. Evaluating potential predictive signs of conversion may benefit from incorporating disease history with vascular features.}, }
@article {pmid42213331, year = {2026}, author = {La Torre, G and D'Urso, P}, title = {Evaluating synergistic effects among multiple factors in disease causation: a new approach using a generalized synergy index.}, journal = {European journal of epidemiology}, volume = {}, number = {}, pages = {}, pmid = {42213331}, issn = {1573-7284}, abstract = {The methodological objective of the present study is to extend Rothman's additive interaction framework from two factors to three or more factors considered simultaneously, while preserving its original causal interpretation and operational simplicity. we propose a generalized Synergy Index (Sp) that retains the additive logic of Rothman's original formulation while extending it to an arbitrary number of dichotomous factors. For the analysis we used a database of a previous work in which the synergistic factor was calculated for each couples of two factors (alcohol, tobacco smoke and other risk factors) for age-related macular degeneration. The proposed three-factor Sp is sensitive to the underlying structure of the risk factors considered. When a strong susceptibility component such as family history is included, the combined exposure exhibits clear super-additive behavior (Sp = 1.783). Conversely, when hypercholesterolemia replaces family history, the joint effect remains substantial but does not exceed additivity (Sp = 0.756). The generalized multi-factor Synergy Index represents a valuable conceptual and analytical tool for investigating higher-order interactions. It is particularly well suited for the study of complex diseases, where multiple exposures co-occur and interact. It enables the identification of exposure constellations characterized by true superadditivity, with potential implications for etiological research, risk stratification, and targeted prevention strategies.}, }
@article {pmid42201956, year = {2026}, author = {Ly, K and Bhuckory, MB and Pham-Howard, D and Kochnev Goldstein, A and Jensen, N and Palanker, D}, title = {Residual photoreceptors affect the response of a degenerate retina to electrical stimulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {22}, pages = {e2537064123}, doi = {10.1073/pnas.2537064123}, pmid = {42201956}, issn = {1091-6490}, support = {R01-EY- 035227//HHS | NIH (NIH)/ ; P30-EY-026877//HHS | NIH (NIH)/ ; W81XWH-2210933//U.S. Department of Defense (DOD)/ ; FA9550-19-1-0402//DOD | AF | AMC | AFRL | Air Force Office of Scientific Research (AFOSR)/ ; }, mesh = {Animals ; *Electric Stimulation ; Rats, Long-Evans ; *Retinal Degeneration/physiopathology/therapy ; Rats ; Evoked Potentials, Visual/physiology ; *Photoreceptor Cells, Vertebrate/physiology ; *Retina/physiopathology ; Visual Prosthesis ; Retinal Bipolar Cells ; }, abstract = {Photovoltaic subretinal prosthesis can restore central vision in patients blinded by age-related macular degeneration with letter acuity matching its 100 µm pixel size. Improving resolution requires smaller pixels, but to still reach the target neurons, electric field should be less confined. However, wide-spreading field may engage adjacent photoreceptors and alter the visual perception. We studied the effects of residual photoreceptors on retinal responses to electrical stimulation using monopolar and bipolar photovoltaic arrays implanted subretinally in Long Evans rats with local photoreceptor loss, and compared that to RCS rats lacking all photoreceptors. Patterned retinal activation (880 nm, 0.5 to 10 ms) was assessed using visually evoked potentials under scotopic and photopic conditions, with and without the intravitreal injection of neurotransmitter blockers. Results were analyzed using a computational model of photoreceptor activation by various electric field configurations. We observed two mechanisms of photoreceptors engagement in electrical activation of the degenerate retina: 1) Dark-adapted photoreceptors near the implant can be simulated directly by a negative electric potential of the common return electrode along the edge of the array. 2) Light-adapted photoreceptors can reduce the stimulation threshold of bipolar cells within about 100 mm from the implant's edge. Both effects may lead to reduced perceptual uniformity. Bipolar pixels with local return electrodes generate better confined electric fields than monopolar arrays and thus are less affected by the nearby photoreceptors. However, even such implants should be placed a few hundred micrometers from the edge of scotoma to minimize the unintended percepts.}, }
@article {pmid42202045, year = {2026}, author = {Zhang, J and Chen, L and Zhu, X and Cai, Y and Wei, S and Zhou, X and Shi, Y and Liu, C and Huang, C and Bi, S and Wu, F and Zhou, X and Hong, J and Wang, Y}, title = {Coordinated regulation using small-molecule drugs enables controlled therapeutic genome editing and enhanced genomic precision in situ.}, journal = {Science translational medicine}, volume = {18}, number = {851}, pages = {eadx7857}, doi = {10.1126/scitranslmed.adx7857}, pmid = {42202045}, issn = {1946-6242}, mesh = {Humans ; Animals ; *Gene Editing/methods ; CRISPR-Cas Systems/genetics ; Mice ; *Genomics ; Dependovirus/genetics ; }, abstract = {Achieving precise temporal control over genome editing is essential for safety but remains a challenge, especially when using small-molecule drugs as external regulators over systems like clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated systems). Consequently, controlled therapeutic in situ editing that maintains both precision and efficacy has yet to be demonstrated. Here, we report the PRINCE system, in which nuclease proteins and guide RNAs are both inducible, to deliver programmable nucleases under control more effectively. PRINCE demonstrated temporal precision in human cell cultures over a 2-year period, even after stable genomic integration. The design principles of PRINCE were broadly applicable from CRISPR-Cas9 to a prime editor and also compact programmable nucleases, and the latter platform was named "Little Prince." Upon administration of drug inducers, Little Prince, delivered in a single adeno-associated virus vector in situ to humanized mouse models, ameliorated pathological phenotypes of hypercholesterolemia (average reductions of 45 and 47% in serum total cholesterol and low-density lipoprotein cholesterol, respectively) and neovascular age-related macular degeneration, with significantly reduced lesion size and leakage (P < 0.0001). Last, we demonstrated a consistent and marked reduction in off-target activity across the PRINCE and Little Prince systems in comparison with constitutive editors, with fewer off-target sites and substantially lower editing frequencies, irrespective of nuclease type, delivery method, or genomic target. These results position PRINCE and Little Prince as controlled genome editing platforms with potential for in vivo, particularly in situ, therapeutic applications.}, }
@article {pmid42203079, year = {2026}, author = {Koh, TY and Cho, WR and Jeon, HY and Moon, CH and Yoon, JS and Kim, M and Ha, KS}, title = {Sustained human C-peptide protects against retinal neurodegeneration via PEDF restoration and oxidative stress inhibition in a mouse model of age-related macular degeneration.}, journal = {Free radical biology &amp; medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.freeradbiomed.2026.05.327}, pmid = {42203079}, issn = {1873-4596}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly. The molecular events that initiate retinal degeneration in dry AMD remain incompletely understood, and effective therapeutic options are limited. Here, we investigated the therapeutic potential of K9-C-peptide against sodium iodate (NaIO3)-induced retinal neurodegeneration and explored its underlying molecular mechanisms. K9-C-peptide markedly attenuated NaIO3-induced retinal apoptosis, thinning, and structural disruption. These protective effects were accompanied by significant suppression of ROS generation, decreased expression of pro-inflammatory cytokines, and inhibition of reactive gliosis. Mechanistically, K9-C-peptide restored NaIO3-induced downregulation of pigment epithelium-derived factor (PEDF). Consistently, intravitreal administration of hydrogel-formulated PEDF similarly reduced oxidative stress and retinal degeneration, supporting a central role for PEDF in mediating the protective effects of K9-C-peptide. Both K9-C-peptide and PEDF improved impaired axonal transport, further confirming their neuroprotective efficacy. Notably, sustained intraocular delivery of human C-peptide or PEDF conferred robust protection against NaIO3-induced retinal neurodegeneration for at least three weeks following a single administration. These findings suggest that K9-C-peptide may serve as a long-acting therapeutic candidate that targets early oxidative and inflammatory events, potentially through PEDF restoration, in NaIO3-induced retinal degeneration. This study provides mechanistic insight into the antioxidative and anti-inflammatory actions of C-peptide-based therapy in dry AMD-like pathology.}, }
@article {pmid42205117, year = {2026}, author = {García-Otero, X and Cuartero-Martínez, A and Fernández-Robredo, P and Antas, SG and Gómez-Lado, N and Otero-Espinar, FJ and Hernández, M and Bezunartea, J and García-Layana, A and Recalde, S and Aguiar, P and Fernández-Ferreiro, A}, title = {Intravitreal faricimab pharmacokinetics assessed by PET imaging in a neovascular Age-related Macular Degeneration rat model.}, journal = {International journal of pharmaceutics: X}, volume = {11}, number = {}, pages = {100567}, pmid = {42205117}, issn = {2590-1567}, abstract = {Age-related Macular Degeneration (AMD) is the leading cause of blindness in the elderly, with its neovascular form characterised by abnormal vessel growth. Current anti-VEGF therapies require frequent intravitreal injections and show variable efficacy. Faricimab, a novel bispecific antibody targeting VEGF-A and ANG-2, offers a dual mechanism with the potential for enhanced efficacy and extended dosing intervals. This study aimed to characterise the intravitreal pharmacokinetics, biodistribution, and ocular localization of faricimab in a rat model of laser-induced choroidal neovascularization (CNV) using non-invasive molecular imaging. Faricimab was conjugated with DFO and radiolabelled with zirconium-89 ([[89]Zr]Zr-DFO-faricimab), maintaining functional binding to VEGF-A and ANG-2. Following intravitreal injection, pharmacokinetics was assessed by PET/CT, blood sampling, and autoradiography, alongside structural retinal evaluation by OCT. Both healthy and CNV-induced rats demonstrated biphasic ocular clearance with similar half-lives, obtaining no significant differences (Control AUC0-∞ = 5587.3 ± 1419.3%·hour and AMD AUC0-∞ = 4079.1 ± 1178.6%·hour). Autoradiography confirmed predominant retention in the posterior segment, with AMD eyes showing higher early accumulation, suggesting altered diffusion, and increased retinal binding. Whole-body biodistribution revealed systemic uptake primarily in the liver and spleen, consistent with antibody catabolism. This work represents the first study to report pharmacokinetic data of faricimab as well as its intraocular distribution in an AMD model. Our findings support its therapeutic potential and highlight PET imaging as a powerful non-invasive tool for longitudinal ocular pharmacokinetic studies.}, }
@article {pmid42190944, year = {2026}, author = {Demirel, R and Irgat, SG and Bike, HI}, title = {Subretinal fluid resolution in the fellow eye after unilateral aflibercept injection in bilateral neovascular age-related macular degeneration: coincidence or systemic effect?.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502585}, doi = {10.1016/j.oftale.2026.502585}, pmid = {42190944}, issn = {2173-5794}, abstract = {We report a case of bilateral neovascular age-related macular degeneration (nAMD) in which a unilateral aflibercept injection led to complete resolution of subretinal fluid (SRF) in the untreated fellow eye. A 63-year-old woman undergoing treat-and-extend therapy for the right eye developed new SRF in the left eye, which maintained good vision (best-corrected visual acuity, 0.8; defined as ≥0.5 Snellen or ≤0.3 logMAR). To avoid injection-related risks in a high-vision eye, only the right eye was treated. Three weeks later, optical coherence tomography demonstrated complete SRF resolution in the left eye, which persisted for 8 weeks before recurrence. This case raises the possibility that systemic absorption of anti-vascular endothelial growth factor (anti-VEGF) may temporarily suppress choroidal neovascularisation activity in the fellow eye. However, this single observation cannot guide clinical practice and requires prospective validation.}, }
@article {pmid42190948, year = {2026}, author = {Kavyasree, PKV and Jayadevan, K and Abdullah, M and Therayil, A}, title = {Redox-inflammation pathways in ocular disease: targets for nutritional modulation.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502581}, doi = {10.1016/j.oftale.2026.502581}, pmid = {42190948}, issn = {2173-5794}, abstract = {Visual impairment remains a major global health burden caused by diverse ocular diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, uveitis, and ocular surface disorders. Despite differing etiologies, growing evidence identifies oxidative stress and chronic inflammation as a shared pathogenic axis affecting both anterior and posterior ocular segments. High metabolic demand, sustained light exposure, dense mitochondrial content, and limited antioxidant defences render ocular tissues particularly susceptible to redox imbalance. Excess reactive oxygen species induce cellular injury and activate redox-sensitive inflammatory signalling, promoting neurodegeneration, microvascular dysfunction, immune-mediated damage, and progressive vision loss. This review summarises key mechanisms underlying redox-inflammatory crosstalk in ocular tissues, highlighting mitochondrial dysfunction, Nrf2-Keap1 antioxidant responses, NF-κB-driven inflammation, and MAPK and PI3K-Akt signalling as central molecular integrators. Tissue-specific responses in the retina, retinal pigment epithelium, trabecular meshwork, uveal tract, and ocular surface demonstrate how shared mechanisms generate distinct disease phenotypes. The modulatory potential of bioactive nutrients, including omega-3 fatty acids, carotenoids, and polyphenols, is critically discussed. Although preclinical evidence is strong, clinical outcomes remain variable, underscoring the need for precision nutrition strategies and mechanism-based clinical trial design.}, }
@article {pmid42191674, year = {2026}, author = {Sampson, J and Segrè, AV and Bujakowska, KM and Clark, SJ and Bishop, PN and Haynes, S and Baralle, D and Al-Deek, J and Holden, S and Anderson, B and Hayes, A and Kemal, RA and Thomas, HB and O'Keefe, RT and Banka, S and Black, GC and Sergouniotis, PI and Ellingford, JM}, title = {Paired DNA and RNA sequencing uncovers common and rare variation regulating human retinal gene expression.}, journal = {Nature communications}, volume = {17}, number = {1}, pages = {}, pmid = {42191674}, issn = {2041-1723}, mesh = {Humans ; *Retina/metabolism ; Quantitative Trait Loci/genetics ; *Gene Expression Regulation ; Retinal Pigment Epithelium/metabolism ; *Genetic Variation ; Sequence Analysis, RNA ; Polymorphism, Single Nucleotide ; DNA Copy Number Variations ; Whole Genome Sequencing ; }, abstract = {Genetic disorders impacting vision affect millions of individuals worldwide, including age-related macular degeneration (common) and inherited retinal disorders (rare). There is an incomplete understanding of the impact of genetic variation on gene expression in the human retina and its role in genetic disorders. Through the generation of whole genome sequencing and bulk RNA-sequencing of neurosensory retina and retinal pigment epithelium from 201 post-mortem eyes, we uncover common and rare genomic variants shaping retinal expression profiles. This includes 1,483,595 significant cis-expression quantitative trait loci impacting 9,959 and 3,699 genes in neurosensory retina and retinal pigment epithelium, respectively, with associated genomic variants enriched to cis-candidate regulatory elements and notable shared eGenes between both tissues. We also detect 1051 expression outliers and prioritise 299 rare non-coding single-nucleotide, structural variants or copy number variants as plausible drivers for 28% of outlier events. This study increases understanding of gene expression regulation in the human retina.}, }
@article {pmid42193268, year = {2026}, author = {Gopi, S and Prodanoff, GT and Passaglia, CL and Kindy, MS and Sutariya, V and Halade, GV and Lewin, AS and Biswal, MR}, title = {Non-Erythropoietic EPO (EPO-R76E) Protects RPE Cells from Ferroptosis by Modulating the Labile Iron Pool and NRF2-GPX4 Axis.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {5}, pages = {}, doi = {10.3390/antiox15050647}, pmid = {42193268}, issn = {2076-3921}, support = {1R00EY027013-04/NH/NIH HHS/United States ; 1R01EY033415-03/NH/NIH HHS/United States ; }, abstract = {Retinal pigment epithelium (RPE) degeneration remains a formidable challenge in dry age-related macular degeneration (AMD) research, primarily due to the toxic interplay between iron overload and ferroptosis. We investigated whether EPO-R76E, a non-erythropoietic modified variant of erythropoietin, could effectively interrupt this destructive cycle. Using ARPE-19 cells challenged with ferric ammonium citrate (FAC) to model iron-induced toxicity, we show that EPO-R76E confers protection against ferroptosis. Our results demonstrate that this variant significantly reduces the intracellular labile iron pool, directly quenching the lipid peroxidation that drives ferroptotic cell death. This resilience is fueled by a robust upregulation of Glutathione Peroxidase 4 (GPX4) and the broad transcriptional activation of the NRF2 (Nuclear factor erythroid 2-related factor 2) NRF2 antioxidant axis. Furthermore, we found that EPO-R76E enhances autophagic flux, ensuring that cells maintain essential proteostasis and "housekeeping" functions even under metabolic crisis. By integrating iron sequestration with reinforced antioxidant signaling and cellular clearing mechanisms, EPO-R76E stands out as a potent candidate for preserving RPE health. These findings uncover a novel molecular framework for protecting the retina against iron-mediated injury, positioning EPO-R76E as a versatile and targeted gene-based therapeutic for addressing the fundamental causes of retinal degeneration.}, }
@article {pmid42193449, year = {2026}, author = {Xiong, C and Zhou, S and Hu, Y and Xu, X}, title = {Exploring Biomarkers and Mechanisms of Action of Adaptive Immune Response in Age-Related Macular Degeneration Based on Transcriptomics.}, journal = {Biomedicines}, volume = {14}, number = {5}, pages = {}, doi = {10.3390/biomedicines14051123}, pmid = {42193449}, issn = {2227-9059}, support = {82374214//National Natural Science Foundation of China/ ; }, abstract = {Background: Age-related macular degeneration (AMD) is a common retinal degenerative disease linked to adaptive immune response dysregulation. This study aimed to identify shared immune-related biomarkers and explore their underlying mechanisms. Methods: GSE29801 and GSE135092 served as training and validation sets. Adaptive immune response-related genes (AIR-RGs) from MSigDB were intersected with AMD-related differentially expressed genes (DEGs) to identify candidate genes. Machine learning algorithms were applied to screen biomarkers, validated in datasets and a mouse model of choroidal neovascularization by qPCR. A nomogram was constructed and assessed. GSEA and immune infiltration analyses explored mechanisms and immune microenvironment associations. Results: A total of 148 DEGs were identified, yielding 15 candidate genes after intersection with AIR-RGs. Machine learning identified C3 and HLA-DOA as potential biomarkers, with their differential expression validated across datasets. A nomogram based on these biomarkers demonstrated good predictive performance for AMD pathology (AUC = 0.795). Biomarkers were associated with some immune-inflammatory pathways. Significant differences in immune cell infiltration were observed between AMD and control groups, with biomarkers positively correlated with differentially infiltrated immune cells, such as natural killer cells. Conclusions: The identification of the established biomarker C3 serves as a proof-of-principle for the analytical approach, rather than a novel discovery, thereby validating the model's capacity to uncover other critical immune targets. Consequently, C3 and HLA-DOA serve as potential biomarkers for AMD, significantly correlated with disease progression via immune pathways and offering insights for immune-based therapeutic strategies.}, }
@article {pmid42193986, year = {2026}, author = {Bhattacharya, S and Ang, C and Soucy, M and Tsang, SH and Chaum, E}, title = {Prominin-1 and Retinal Degenerative Disorders: Expanding the Biology from Photoreceptors to the Retinal Pigment Epithelium.}, journal = {Biomolecules}, volume = {16}, number = {5}, pages = {}, doi = {10.3390/biom16050635}, pmid = {42193986}, issn = {2218-273X}, support = {GF02527//International Retinal Research Foundation/ ; GR020592//Carl Marshall and Mildred Almen Reeves Foundation/ ; Unrestricted Research Grant to the Vanderbilt Eye Institute//Research to Prevent Blindness/ ; Margy Ann and J Donald M. Gass Chair Endowment//Vanderbilt University Medical Center/ ; R24EY028758//Research to Prevent Blindness/ ; R24EY027285//Research to Prevent Blindness/ ; }, mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; Animals ; *AC133 Antigen/metabolism/genetics ; *Retinal Degeneration/metabolism/pathology/genetics ; Autophagy ; }, abstract = {Prominin-1 (Prom1/CD133) has long been recognized as a structural determinant of photoreceptor outer segment (OS) morphogenesis, yet rapidly accumulating evidence extends its role to retinal pigment epithelium (RPE) homeostasis, encompassing autophagy-lysosomal flux, outer segment phagocytosis, mitochondrial function, and regulation of inflammatory stress. This review synthesizes mechanistic and transcriptomic insights that position PROM1 as a central regulator of photoreceptor and RPE integrity, reframing Prom1 disease as a multi-compartment retinal disorder relevant to both inherited retinal dystrophies (IRDs) and atrophic age-related macular degeneration (aAMD). We develop a dual-axis conceptual model in which Prom1 dysfunction can initiate pathology in either the photoreceptors (OS morphogenesis failure) or the RPE, including impaired autophagic flux, lysosomal activity, defective phagocytosis, and Epithelial-Mesenchymal Transition (EMT)-like de-differentiation, with secondary cross-compartmental degeneration. Clinically, autosomal-dominant missense variants associate with macular or cone-rod dystrophy, whereas biallelic truncating/splice-site mutations drive early-onset rod-cone disease and panretinal/RPE atrophy, illustrating genotype-phenotype diversity. By integrating recent high-resolution transcriptomic data from Prom1-deficient RPE cells with long-standing insights into photoreceptor biology, we highlight converging pathways of degeneration that challenge a photoreceptor-centric view and unify disparate phenotypes within a single molecular framework. These insights broaden the therapeutic landscape, advancing gene augmentation and pathway-targeted strategies to preserve RPE integrity, sustain photoreceptor function, and modify disease course in PROM1-associated IRDs and atrophic AMD.}, }
@article {pmid42194525, year = {2026}, author = {Szymańska, K and Sałasińska, K and Młynarczyk, A and Miszczak, J and Dmoch, W and Maciejewicz, P}, title = {The Gut-Eye Axis and Microbiome in Ophthalmic Diseases: A Narrative Review.}, journal = {Journal of clinical medicine}, volume = {15}, number = {10}, pages = {}, doi = {10.3390/jcm15103563}, pmid = {42194525}, issn = {2077-0383}, abstract = {The gut microbiome regulates host metabolism, barrier integrity, and immune homeostasis through microbe-host signaling and bioactive metabolites. Growing evidence suggests that dysbiosis may also influence ocular immune privilege and blood-retinal barrier stability, supporting the emerging concept of the gut-eye axis. This narrative review aimed to integrate retinal, uveal, and ocular surface disorders within a shared functional framework, with emphasis on recurring mechanistic pathways and their translational relevance rather than on single diseases or isolated taxonomic findings. The review was based on a literature search of PubMed and Scopus and primarily included English-language studies published between 2015 and 2025, with earlier seminal papers included when needed. The search was last updated in March 2026, and 101 sources were included in the final narrative synthesis. Across age-related macular degeneration, diabetic retinopathy, glaucoma, uveitis, dry eye disease, and Sjögren's syndrome, the most consistent microbiome-related signals were functional rather than taxonomic. Recurrent mechanistic themes included Th17/Treg immune programming, barrier dysfunction with microbial product translocation, and systemic metabolite signaling, particularly involving short-chain fatty acids, bile acid receptor pathways, and tryptophan-derived metabolites. Age-related macular degeneration and diabetic retinopathy showed the strongest multi-layered support, whereas uveitis provided a compelling immune-centered biological model that remains limited by treatment-related confounding in human studies. In glaucoma and ocular surface disease, evidence supports biological plausibility, especially in relation to neuroinflammation, mucosal immune dysregulation, and metabolite-dependent anti-inflammatory pathways, although much of the available human literature remains associative. Overall, current evidence supports dysbiosis as a disease modifier that may influence ocular inflammation, angiogenesis, neurodegeneration, and barrier stability. However, clinical translation remains limited by cohort heterogeneity, methodological variability, and incomplete control of confounding factors. Further progress will depend on longitudinal multi-omics cohorts and controlled intervention trials focused on actionable microbial functions.}, }
@article {pmid42194903, year = {2026}, author = {Benites-Narcizo, G and Juvier-Riesgo, T and Pérez-Negrón, AP and García-Dussán, L and Wang, J and Hong, J and Mendoza-Santiesteban, CE and Lam, BL}, title = {Quantitative Flavoprotein Fluorescence Parameters in Retinal and Optic Nerve Diseases: A Scoping Review.}, journal = {Journal of clinical medicine}, volume = {15}, number = {10}, pages = {}, doi = {10.3390/jcm15103942}, pmid = {42194903}, issn = {2077-0383}, abstract = {Background: Retinal and optic nerve disorders remain major causes of visual morbidity worldwide. Ocular fundus flavoprotein fluorescence (FPF) imaging has emerged as a potential noninvasive biomarker of mitochondrial dysfunction for earlier detection and evaluation of disease severity. Methods: We conducted a Systematic Scoping Review of the diagnostic and correlational utility of quantitative FPF parameters in retinal and optic nerve diseases compared with healthy controls. Following PRISMA-ScR guidelines, we searched MEDLINE, Web of Science, Scopus, and CENTRAL for peer-reviewed human studies available online before 31 December 2025. Results: Seventeen studies were included, encompassing 1914 eyes and 1339 participants, and were predominantly cross-sectional. In healthy eyes, mean macular and optic nerve head FPF intensity were reported as 24.1 ± 12.2 gsu and 30.6 ± 14.6 gsu, respectively. Higher signals were reported in several disorders, including diabetes mellitus (76.0 [67.0-92.0] gsu), neovascular age-related macular degeneration (67.47 ± 17.77 gsu), and retinitis pigmentosa (50.5 ± 12.2 gsu). However, lower, unchanged, or stage-dependent signals were also observed within the same disease categories. Interpretation across studies was limited by substantial heterogeneity in patient selection, disease definitions, imaging protocols, control groups, and FPF outcome metrics. The precise cellular and sublayer origin of the detected signal also remains challenging to determine. Conclusions: Ocular fundus FPF imaging provides promising metabolic insight into retinal and optic nerve diseases. However, current evidence remains heterogeneous and largely cross-sectional, limiting clinical interpretability and generalizability. Longitudinal studies, technical standardization, and multimodal integration are needed to define reproducible disease-specific FPF profiles and improve translational applicability.}, }
@article {pmid42195076, year = {2026}, author = {Çatak, O and Keleş, JK and Çatak, Z}, title = {Circulating Claudin-5 and Systemic Inflammatory Indices in Wet and Dry Age-Related Macular Degeneration.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {62}, number = {5}, pages = {}, doi = {10.3390/medicina62050823}, pmid = {42195076}, issn = {1648-9144}, mesh = {Humans ; Female ; *Claudin-5/blood/analysis ; Male ; Case-Control Studies ; Prospective Studies ; Aged ; *Macular Degeneration/blood/physiopathology ; *Inflammation/blood ; Middle Aged ; Biomarkers/blood/analysis ; Aged, 80 and over ; }, abstract = {Background and Objectives: Age-related macular degeneration (AMD) is a multifactorial retinal disease in which inflammation and blood-retinal barrier dysfunction may contribute to disease pathogenesis. Claudin-5 is a key tight-junction protein involved in endothelial barrier integrity. Hemogram-derived indices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) reflect systemic inflammatory status. This study aimed to evaluate circulating claudin-5 levels and systemic inflammatory indices in patients with wet and dry AMD and to investigate their associations with visual function. Materials and Methods: This prospective case-control study included 90 participants: 30 patients with wet AMD, 30 patients with dry AMD, and 30 healthy controls. All participants underwent detailed ophthalmologic examination, including best-corrected visual acuity (BCVA) assessment and optical coherence tomography. Serum claudin-5 levels were analyzed by enzyme-linked immunosorbent assay, and NLR, PLR, MLR, and PIV were calculated from complete blood count parameters. Group comparisons, correlation analyses, and age-adjusted analyses were performed using appropriate statistical methods. Results: Age differed significantly among the groups (p = 0.032), with the highest median age in the dry AMD group. BCVA (logMAR) also differed significantly (p < 0.001), and both AMD groups had worse visual acuity than controls. Median serum claudin-5 levels were 2.42 in controls, 3.28 in the wet AMD group, and 3.10 in the dry AMD group, with no significant between-group difference (p = 0.280). NLR, MLR, and PIV were also comparable among the groups (p = 0.310, p = 0.410, and p = 0.752, respectively). PLR differed among the groups (p = 0.019), and post hoc analysis showed higher PLR values in the dry AMD group than in the wet AMD group (p = 0.013). However, this difference was no longer statistically significant after adjustment for age (adjusted p = 0.098). Serum claudin-5 was not significantly correlated with age, BCVA, NLR, PLR, MLR, or PIV. Conclusions: Circulating claudin-5 did not differ significantly across AMD phenotypes and was not associated with age, visual function, or systemic inflammatory indices. Although PLR differed between wet and dry AMD before adjustment for age, the overall findings suggest that single-point peripheral serum measurements of claudin-5 may have limited utility in reflecting local retinal barrier-related changes in AMD. Larger longitudinal studies are needed to clarify its potential biomarker role.}, }
@article {pmid42195115, year = {2026}, author = {Chang, HL and Wang, LU and Huang, TL and Chang, PY and Ho, WT and Hsu, YR and Chen, FT and Chen, YJ and Lin, CD and Wang, JK}, title = {The Short-Term Outcomes of Intravitreal Faricimab for Treatment-Naïve and -Refractory Neovascular Age-Related Macular Degeneration: A Real-World Study.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {62}, number = {5}, pages = {}, doi = {10.3390/medicina62050863}, pmid = {42195115}, issn = {1648-9144}, support = {NSTC 114-2221-E-003-037//National Science and Technology Council/ ; }, mesh = {Humans ; Retrospective Studies ; Intravitreal Injections/methods ; Female ; Male ; Treatment Outcome ; Aged ; Visual Acuity/drug effects ; Aged, 80 and over ; *Macular Degeneration/drug therapy ; Polypoidal Choroidal Vasculopathy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Angiogenesis Inhibitors/therapeutic use ; Antibodies, Bispecific ; }, abstract = {Background and Objectives: Neovascular age-related macular degeneration (nAMD), including typical nAMD (tAMD) and polypoidal choroidal vasculopathy (PCV), is a leading cause of visual impairment. This study investigated the real-world short-term outcomes of faricimab, a bispecific antibody targeting Ang-2 and VEGF-A, in patients with treatment-naïve or -refractory nAMD. Materials and Methods: This retrospective study analyzed treatment-naïve or -refractory nAMD eyes receiving one, two, or three monthly intravitreal faricimab injections. Primary outcomes were changes in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) one month after the last injection. Secondary outcomes included the dry macula rate (absence of subretinal and intraretinal fluid) and subgroup comparisons between tAMD and PCV. Results: After a single injection, both treatment-naïve (n = 76) and -refractory (n = 44) eyes showed significant CFT reduction (p < 0.0001) but no significant BCVA improvement (p > 0.05). Dry macula was achieved in 63.2% of treatment-naïve and 71.4% of treatment-refractory eyes. In 38 treatment-naïve eyes receiving three injections, both CFT and BCVA significantly improved from baseline (p < 0.001 and p = 0.02, respectively), with a 94.7% dry macula rate. Subgroup analysis of those receiving three injections revealed that PCV eyes exhibited significant visual improvement, whereas tAMD eyes did not. No serious systemic or ocular adverse events were observed over the short-term follow-up period. Conclusions: Intravitreal faricimab is effective for both treatment-naïve and -refractory nAMD in the short term. While anatomical improvements were comparable between subtypes, the PCV subgroup showed a trend toward greater visual improvement in this small cohort; however, this may be influenced by the significantly younger age of PCV patients. These findings are exploratory and require validation in larger, age-matched prospective studies.}, }
@article {pmid42195150, year = {2026}, author = {Jovanović, M and Milošević, J and Carrasco Guijarro, M and Jovanović, S and Todorović, D and Petrović, N and Paunović, S and Janićijević, K and Živković, MLJ}, title = {Outer Retinal Hyperreflective Foci as a Predictor of Hyperreflective Material Boundary Remodeling and Visual Outcomes in Neovascular Age-Related Macular Degeneration.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {62}, number = {5}, pages = {}, doi = {10.3390/medicina62050895}, pmid = {42195150}, issn = {1648-9144}, mesh = {Humans ; Retrospective Studies ; Bevacizumab/therapeutic use ; Visual Acuity/physiology ; Tomography, Optical Coherence/methods ; Female ; *Macular Degeneration/drug therapy/physiopathology ; Male ; Aged ; Angiogenesis Inhibitors/therapeutic use ; Aged, 80 and over ; Intravitreal Injections ; Treatment Outcome ; *Retina/physiopathology ; }, abstract = {Purpose: The purpose of this study was to characterize the distribution and longitudinal evolution of intraretinal and subretinal hyperreflective foci (HF) in treatment-naive neovascular age-related macular degeneration (nAMD), and to examine associations between HF burden, hyperreflective material boundary remodeling (HRM-BR), and best-corrected visual acuity (BCVA) outcomes following bevacizumab treat-and-extend therapy. Methods: This was a retrospective observational study of 84 treatment-naive nAMD eyes receiving intravitreal bevacizumab via a treat-and-extend protocol. Spectral-domain OCT (Revo FC, Optopol) was performed at baseline (M0), month 3 (M3), and month 6 (M6). HF were quantified in the intraretinal and subretinal compartments using ImageJ software (version 1.54, National Institutes of Health, Bethesda, MD, USA) by two masked graders, with inter-rater agreement assessed by intraclass correlation coefficient (ICC). Eyes were classified into four HRM evolution patterns following the framework of Yu et al. Primary outcome was BCVA change from M0 to M6. Multivariable linear regression was performed to assess independent predictors of BCVA change. Results: Baseline intraretinal HF counts increased significantly across HRM Patterns 1 through 4 (median 0, 6, 4, and 8, respectively; Kruskal-Wallis p < 0.001; 95% CI for Spearman r = 0.471: [0.286, 0.623]). A higher baseline intraretinal HF count correlated with worse BCVA change at M6 (r = -0.300, 95% CI [-0.483, -0.092], p_adj = 0.010). In the primary multivariable model (n = 67), both intraretinal HF burden (β = -0.449, 95% CI [-0.879, -0.020], p = 0.041) and HRM width (β = -0.003, 95% CI [-0.005, -0.001], p = 0.014) were independent predictors of BCVA change. The transient M3 intraretinal HF peak in Pattern 3 eyes (median 4 → 12 → 4) was statistically confirmed by Wilcoxon signed-rank testing (M0 → M3: p = 0.004; M3 → M6: p = 0.001). Conclusions: Intraretinal HF burden is a graded marker of HRM pattern severity and an independent predictor of visual outcomes in nAMD, alongside HRM width. The statistically validated transient M3 HF peak in Pattern 3 may represent an early OCT signal of active boundary remodeling.}, }
@article {pmid42195311, year = {2026}, author = {Hajdari, A and Uka, V}, title = {Real-World Experience with Brolucizumab in Treatment-Naïve nAMD with Low Baseline Visual Acuity: Short-Term Outcomes from a Prospective Single-Institution Study.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {5}, pages = {}, doi = {10.3390/life16050754}, pmid = {42195311}, issn = {2075-1729}, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a progressive chronic disease that represents a major cause of irreversible vision loss worldwide. In this study we aim to assess the short-term functional and anatomical outcomes of brolucizumab therapy in treatment-naïve patients with nAMD presenting with low baseline visual acuity in a single institution setting.<br><br>METHODS: This is a prospective non-randomized study that included 154 treatment-na&#xef;ve eyes with low baseline visual acuity. We measured visual outcomes (BCVA, logMAR) and structural outcomes (CST, &#x3bc;m). We also stratified the study population into respective age subgroups to evaluate any possible trend between outcome changes and age differences. BCVA and CST were measured at baseline, at each consecutive month (month 1, 2 and 3) of the loading phase, as well as at the final timepoint (6 months). Intraocular pressure (IOP) before and after injection, as well as the incidence of serious adverse events, were monitored throughout the study.<br><br>RESULTS: Mean BCVA improved by 0.41 logMAR (+20 ETDRS letters) after the first injection, 0.65 logMAR (+32 letters) after the second, and reached a maximum improvement of 0.80 logMAR after the third injection. The most important BCVA improvement was seen in younger patients (<50 years), with mean BCVA decreasing from approximately 1.0 logMAR at baseline to around 0.3-0.4 logMAR at the final measurement. Mean CST declined by 45.5 &#x3bc;m after the first injection, 78.5 &#x3bc;m after the second, 117.8 &#x3bc;m after the third, and 143.6 &#x3bc;m at the final timepoint, indicating a pronounced anatomical response to intravitreal brolucizumab therapy.<br><br>CONCLUSIONS: In conclusion, this study demonstrates that brolucizumab therapy provides significant short-term anatomical and functional improvements in treatment-na&#xef;ve patients with nAMD and poor baseline visual acuity. Baseline visual acuity, treatment-na&#xef;ve status, and patient age appear to be key determinants of visual gain.}, }
@article {pmid42195365, year = {2026}, author = {Skarbek, D and Sochocka, A and Sidło, O and Sapiaszko, A and Drab, A and Baj, J and Rejdak, R and Dolar-Szczasny, J}, title = {Nanocarrier-Based Ocular Drug Delivery Systems for Retinal Diseases: Therapeutic Potential.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {5}, pages = {}, doi = {10.3390/life16050810}, pmid = {42195365}, issn = {2075-1729}, abstract = {BACKGROUND: Posterior segment eye diseases, including age-related macular degeneration and diabetic retinopathy, are preeminent causes of vision loss worldwide. Effective drug delivery to the retina poses an ongoing therapeutic difficulty due to the presence of the anatomical and physiological barriers. Nanotechnology-based drug delivery systems represent a promising strategy to overcome those limitations.<br><br>METHODS: A narrative literature review was conducted using the PubMed, Scopus, and Google Scholar databases, covering publications published between 2019 and 2026. Publications evaluating nanoparticles for the treatment of the vitreoretinal disorders, including pre-clinical in vitro and in vivo studies, were analyzed.<br><br>RESULTS: Nanocarriers, including liposomes, polymeric nanoparticles, and lipid-based systems, established improved drug bioavailability, stability, and targeted delivery. The analyzed systems facilitate sustained drug release and potentially reduce the prevalence of invasive intravitreal injections. The nanocarriers' effectiveness is primarily influenced by their physicochemical properties, such as particle size, surface charge, and encapsulation efficiency. Nonetheless, the production costs and safety aspects, including cytotoxicity, oxidative stress, and inflammatory responses, remain as significant limitations.<br><br>CONCLUSIONS: Nanotechnology-based drug delivery systems serve as an auspicious therapeutic approach for posterior segment eye diseases. However, further standardized preclinical and clinical research is required to assure long-term safety and enable successful clinical transition.}, }
@article {pmid42196569, year = {2026}, author = {De Silva, S and Xu, B}, title = {Beneficial Effects of Natural Bioactive Compounds on Eye Health: A Narrative Review.}, journal = {International journal of molecular sciences}, volume = {27}, number = {10}, pages = {}, doi = {10.3390/ijms27104592}, pmid = {42196569}, issn = {1422-0067}, support = {UICR0400015-24B &amp; UICR0400016-24B//Beijing Normal-Hong Kong Baptist University/ ; }, mesh = {Humans ; Animals ; *Eye Diseases/drug therapy/metabolism ; Antioxidants/pharmacology/therapeutic use ; *Biological Products/pharmacology/therapeutic use ; Oxidative Stress/drug effects ; Flavonoids/pharmacology/therapeutic use ; *Eye/drug effects/metabolism ; Polyphenols/pharmacology/therapeutic use ; Macular Degeneration/drug therapy ; Fatty Acids, Omega-3/pharmacology/therapeutic use ; Carotenoids/pharmacology/therapeutic use ; }, abstract = {Ocular diseases like age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and cataracts are major causes of visual impairment all over the world and are closely linked to oxidative stress, inflammation and mitochondrial dysfunction. This narrative review critically summarizes the available evidence on how various natural bioactive compounds, such as carotenoids, polyphenols, flavonoids, omega-3 fatty acids and botanical extracts, can affect important molecular pathways associated with ocular degeneration. Their antioxidant, anti-inflammatory, anti-angiogenic and neuroprotective properties are given particular emphasis, especially regarding the Nrf2, NF-κB and VEGF signaling pathways. This review is different from past reviews that simply discuss the potential of bioactives in the general nutritional context; rather, it unfolds the disease-specific mechanisms and compound-specific molecular actions and gives special attention to recent advances in nano-delivery systems and precision nutrition strategies to increase the bioavailability and therapeutic targeting of these nutrients in the eyes. Moreover, it offers a framework for a comparison of evidence between preclinical and clinical studies, as well as identifying current translational gaps, including limited bioavailability and a lack of long-term clinical trials, and suggesting future directions such as genotype-guided nutrition and microbiome-informed interventions. In general, this review provides a mechanistic and translational overview of how dietary bioactive compounds relate to eye health and offers the perspective of their possible use in prevention and complementary treatment for vision-related diseases.}, }
@article {pmid42196841, year = {2026}, author = {Vilkeviciute-Petraite, A and Bruzaite, A and Cebatoriene, D and Zaliuniene, D and Lukosevicius, R and Skieceviciene, J and Kupcinskas, J and Liutkeviciene, R}, title = {The Role of Kynurenine and 5-Hydroxytryptophan in Modulating Microbiota and Their Implications in Exudative Age-Related Macular Degeneration.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {10}, pages = {}, doi = {10.3390/diagnostics16101475}, pmid = {42196841}, issn = {2075-4418}, support = {No. S-MIP-23-96//Lietuvos Mokslo Taryba/ ; }, abstract = {Background/Objectives: This study explores the roles of kynurenine and 5-hydroxytryptophan (5-HTP) in modulating gut microbiota and their potential implications for exudative age-related macular degeneration (AMD). By examining the interplay between these metabolites and the microbiome, we aim to uncover novel pathways that may influence the pathogenesis of AMD. Understanding these associations could lead to innovative therapeutic approaches for managing this leading cause of vision loss in the elderly. To investigate the roles of kynurenine and 5-HTP, alongside the composition of the nasopharyngeal microbiota, in patients with exudative AMD. Methods: Blood metabolite profiling was performed using LC-MS-based metabolomics. Metabolites were extracted with cold methanol/water containing internal standards, filtered through a 10 kDa cutoff filter, separated on a ZIC-HILIC HPLC column, and detected using an Orbitrap mass spectrometer. Metabolites were identified using MZmine 2 software. Results: Patients with exudative AMD exhibited a profound systemic shift in tryptophan metabolism, characterized by significantly lower plasma levels of 5-HTP and higher levels of kynurenine compared to control subjects (p < 0.001 for both). Logistic regression analysis confirmed that both metabolites were independent predictors of AMD status; higher kynurenine levels were associated with increased disease probability, while higher 5-HTP levels demonstrated a protective effect. The kynurenine/5-HTP ratio emerged as a robust biomarker, achieving an area under the curve (AUC) of 0.85 with an optimal threshold of 3.43 (74.1% sensitivity, 84.4% specificity). When integrated with age and gender, the diagnostic performance of the model reached an excellent AUC of 0.92. After adjusting for demographic factors, the kynurenine/5-HTP ratio remained a potent independent risk factor, with each unit increase associated with a 6.30-fold increase in the odds of exudative AMD. Conclusions: Exudative AMD is characterized by a shift in tryptophan metabolism toward the kynurenine pathway, with decreased 5-HTP, increased kynurenine, and an elevated kynurenine/5-HTP ratio. This ratio showed a strong independent association with AMD and excellent diagnostic performance, highlighting its potential as a biomarker and its role in disease pathogenesis.}, }
@article {pmid42196921, year = {2026}, author = {Prus-Ludwig, A and Wylęgała, A and Wylęgała, E and Kijonka, M and Wowra, B}, title = {Optical Coherence Tomography Biomarkers Predicting Progression to Atrophy in Non-Exudative Age-Related Macular Degeneration.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {10}, pages = {}, doi = {10.3390/diagnostics16101555}, pmid = {42196921}, issn = {2075-4418}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide. Geographic atrophy (GA) is an advanced, currently incurable stage of non-exudative AMD and is characterized by progressive atrophy of the retinal pigment epithelium and outer retina, resulting in substantial visual impairment. Optical coherence tomography (OCT) has revolutionized the diagnosis and monitoring of AMD by enabling in vivo visualization of retinal microstructure and identification of imaging biomarkers associated with progression to late-stage disease. Improved understanding of these lesions may clarify disease pathogenesis and inform the development of new therapeutic strategies and clinical trial endpoints. This review summarizes OCT-based biomarkers reported as predictors of progression to late atrophic forms of AMD, with emphasis on early atrophic changes that precede GA.}, }
@article {pmid42197042, year = {2026}, author = {Azalati, MM and Jiang, H and Zhang, K and Kong, L and Wang, L and Li, Z and Fan, Y and Chen, F and Ma, L and Zhang, W}, title = {Dietary Patterns and Age-Related Macular Degeneration: A Matched Case-Control Study.}, journal = {Nutrients}, volume = {18}, number = {10}, pages = {}, doi = {10.3390/nu18101582}, pmid = {42197042}, issn = {2072-6643}, support = {82373570//The National Natural Science Foundation of China/ ; xtr052023010//The Fundamental Research Funds of Xi'an Jiaotong University/ ; }, mesh = {Humans ; *Macular Degeneration/prevention &amp; control/epidemiology/etiology ; Case-Control Studies ; Female ; Male ; Aged ; *Feeding Behavior ; *Diet ; Odds Ratio ; Logistic Models ; Risk Factors ; Fruit ; Vegetables ; Middle Aged ; Principal Component Analysis ; Multivariate Analysis ; Aged, 80 and over ; Diet, Healthy ; }, abstract = {Background: Previous research on diet and age-related macular degeneration (AMD) has emphasized primarily particular nutrients or foods, and the influence of comprehensive dietary patterns that represent actual eating behaviors is largely unknown. Objective: The aim of this study was to assess the association between dietary patterns and the odds of AMD. Methods: A case-control study involving 246 participants with AMD and 246 controls are individually matched by age and gender. Dietary patterns were identified through principal component analysis using a validated food frequency questionnaire. Multivariable conditional logistic regression models were applied to examine the association between the extracted dietary patterns and the likelihood of AMD. Results: Three major dietary patterns were found, accounting for 50.59% of the total variance explained. The prudent dietary pattern represented a high intake of vegetables, fruits, soybeans and its products, edible fungi and algae, and nuts were associated with reduced odds ratios (ORs) of the highest tertile compared to the lowest tertile (OR, 0.29, 95% confidence interval [CI], 0.14-0.59, p for trend = 0.001). The estimated likelihood for AMD in the highest tertile of egg and milk dietary pattern intake, which is characterized by a high intake of eggs, milk and dairy products, and refined grains, was 0.40 (95% CI, 0.23-0.67, p for trend < 0.001) compared with those in the lowest tertile. No association with AMD was identified for the animal dietary pattern (p > 0.05). Conclusions: Adherence to dietary patterns rich in fruits, vegetables, nuts, refined grains, eggs, milk and dairy products is associated with reduced odds of AMD, emphasizing the potential relevance of dietary habits to visual health among middle-aged and elderly adults.}, }
@article {pmid42198422, year = {2026}, author = {Chakraborty, D and Sinha, TK and Sinha, S and Biswas, RK and Das, A and Maiti, A and Bhattacharya, R and Dan, S and Rungta, D and Das, S}, title = {Real-World Comparison of Biosimilar Ranibizumab (Ranieyes) and Innovator Ranibizumab (Lucentis/Accentrix) Across Multiple Retinal Vascular Diseases (The BRIO Study).}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {5}, pages = {}, doi = {10.3390/ph19050747}, pmid = {42198422}, issn = {1424-8247}, abstract = {Background: Retinal vascular diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and myopic choroidal neovascularization (mCNV), often require repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Although ranibizumab is well established, long-term affordability remains challenging. Objective: To compare the functional, anatomical, treatment-burden, and safety outcomes of biosimilar ranibizumab (Ranieyes) and innovator ranibizumab (Lucentis/Accentrix) in routine clinical practice. Methods: This multicenter retrospective comparative study included 4997 eyes from 3577 patients treated across five tertiary eye-care centers in India. The biosimilar group comprised 2543 eyes from 1812 patients (10,893 injections), and the innovator group comprised 2454 eyes from 1765 patients (10,136 injections). Eligible indications were nAMD, DME, BRVO, CRVO, mCNV, and an exploratory miscellaneous preoperative adjunct subgroup. BCVA (logMAR), central subfield thickness (CST; µm), injection burden, and ocular/systemic adverse events were assessed over 24 months. Results: Both groups showed early improvement in BCVA and CST across the major disease categories, followed by long-term stabilization. Between-group differences were generally small, not sustained over follow-up, and of limited clinical magnitude. Serious ocular and systemic adverse events were rare in both groups, and no new safety signal emerged. Conclusions: In this large real-world cohort, the biosimilar ranibizumab Ranieyes showed outcomes broadly comparable to innovator ranibizumab across the major retinal disease subgroups, although these findings should be interpreted as observational comparative evidence rather than formal proof of equivalence.}, }
@article {pmid42198424, year = {2026}, author = {Tsai, HR and Hsu, JZ and Loh, CH and Huang, HK}, title = {PCSK9 Inhibitor Use and the Risk of Age-Related Macular Degeneration in Patients with Atherosclerotic Cardiovascular Disease.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {5}, pages = {}, doi = {10.3390/ph19050750}, pmid = {42198424}, issn = {1424-8247}, support = {TCRD115-012//Hualien Tzu Chi Medical Center/ ; }, abstract = {Background/Objectives: Emerging evidence suggests that alterations in lipid metabolism may play a contributing role in the pathogenesis of age-related macular degeneration (AMD). Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a novel class of lipid-lowering agents, offer anti-inflammatory and antioxidant benefits, which may provide protective effects against AMD. We aimed to evaluate the risk of developing AMD among patients with atherosclerotic cardiovascular disease (ASCVD) who were newly treated with PCSK9 inhibitors compared with those receiving statins. Methods: This retrospective cohort study utilized data from the Global Collaborative Network within the TriNetX Research Network. Patients with ASCVD who were newly initiated on PCSK9 inhibitors or statins were identified and matched for age, sex, race, laboratory data, comorbidities, and concomitant medications. The primary outcomes were the hazard ratios (HRs) for developing AMD, dry AMD, and wet AMD. Propensity score matching (PSM) was used to adjust for baseline demographics and comorbidities. Results: After PSM, 50,102 patients were included in each group (PCSK9 inhibitor users vs. statin users). Compared to statin users, PCSK9 inhibitor users had significantly lower risks of AMD (HR, 0.81; 95% confidence interval [CI], 0.72-0.92) and dry AMD (HR, 0.78; 95% CI, 0.65-0.94), but not wet AMD (HR, 0.90; 95% CI, 0.70-1.16). Stratified and subgroup analyses showed reduced AMD risk among patients aged ≥65 years, White patients, female patients, and evolocumab users. Conclusions: In patients with ASCVD, compared with use of statins, use of PCSK9 inhibitors is associated with reduced risks of AMD and dry AMD, suggesting a potential novel strategy for managing a condition with limited therapeutic options.}, }
@article {pmid42199036, year = {2026}, author = {Karunainathan, MG and Lee, C and Zohalinejad, KD and Mæng, MO and Fabrin, NW and Jónsdóttir, S and Hassing, AK and Yde, SK and Wykoff, CC and Vorum, H and Subhi, Y and Ørskov, M and Cehofski, LJ}, title = {Real-world insights on switching aflibercept dosage for enhanced outcomes in age-related macular degeneration (RISE-AMD): Safety data.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70160}, pmid = {42199036}, issn = {1755-3768}, abstract = {PURPOSE: To evaluate real-world safety experience with aflibercept 8 mg in a large case series of patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Due to a high proportion of patients on short treatment intervals, patients with nAMD at a Danish tertiary retina clinic were systematically switched to aflibercept 8&#x2009;mg. Safety data from May 2024 to October 2025 were obtained through a retrospective review of medical records by an experienced retina specialist and an additional reviewer. Symptomatic intraocular pressure (IOP) increase was defined as any symptom (e.g. pain) in conjunction with IOP&#x2009;>&#x2009;21&#x2009;mmHg.<br><br>RESULTS: In total, 8675 intravitreal injections of aflibercept 8&#x2009;mg were administered in 1429 eyes with nAMD, including 139 glaucomatous eyes. A total of 25 AEs were reported (2.88 per 1000 injections). Intraocular inflammation (IOI) was reported in 11 eyes (1.27 per 1000 injections), with 10 eyes being managed with topical dexamethasone, while one case required vitrectomy. Symptomatic IOP increase was observed in 10 cases (1.15 per 1000 injections). The occurrence of symptomatic IOP increase did not differ between glaucomatous and non-glaucomatous eyes (p&#x2009;=&#x2009;0.24). Two cases of bacterial endophthalmitis were registered. No case of retinal vasculitis or retinal vascular occlusion was observed.<br><br>CONCLUSION: Incidence rates of symptomatic IOP increase and IOI were generally low. Despite a large glaucoma cohort, the higher incidence rate of symptomatic IOP increase in glaucomatous eyes did not reach statistical significance.}, }
@article {pmid42199109, year = {2026}, author = {Ni, Y and Li, J and So, KF}, title = {Beyond antioxidation: Retinal neuroprotection by Lycium barbarum polysaccharides via multiple signaling pathways.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-01602}, pmid = {42199109}, issn = {1673-5374}, abstract = {Age-related macular degeneration, glaucoma, retinitis pigmentosa, and diabetic retinopathy are the major retinal degenerative disorders, and each ultimately leads to irreversible vision loss. In this context, single-target therapies aimed at isolated pathways have delivered only modest benefits. Lycium barbarum polysaccharides, the predominant bioactive components of goji berries, emerge as far more than simple antioxidants, functioning instead as orchestrators of interconnected signaling networks. Growing evidence shows that Lycium barbarum polysaccharides engages pathways well beyond redox control to interrupt disease-driving cascades: it limits cellular senescence through the SIRT1/p53 axis, preserves blood-retinal barrier integrity by maintaining aquaporin-4 at astrocytic endfeet, and biases microglia from proinflammatory M1 toward reparative M2 states. Beyond immunomodulation, Lycium barbarum polysaccharides promotes clearance of pathogenic protein aggregates and suppresses pathological neovascularization via the miR-15a-5p/ VEGFR2 axis. While antioxidant effects may predominate in early disease, the actions of LBP become more targeted as pathology advances, a stage-dependent selectivity that helps explain its cross-disease efficacy. In age-related macular degeneration, Lycium barbarum polysaccharides sustains metabolic homeostasis in retinal pigment epithelium by tuning autophagic flux through the miR-181/BCL-2 axis. In glaucoma, it safeguards mitochondrial membrane potential in retinal ganglion cells, supporting energy metabolism and survival. Collectively, these properties position Lycium barbarum polysaccharides as a pleiotropic regulator capable of reshaping multiple disease trajectories. Realizing its clinical potential will require precise identification of active metabolites, rigorous in vivo pharmacokinetic profiling, and rational combination with current standard-of-care therapies.}, }
@article {pmid42199324, year = {2026}, author = {Cukurova, F and Ramsey, DJ}, title = {Rapid Macular Thinning as a Biomarker for Geographical Atrophy.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {602755}, pmid = {42199324}, issn = {1177-5467}, abstract = {PURPOSE: To assess the rate of retinal thinning as a biomarker for incident late-stage age-related macular degeneration (AMD).<br><br>METHODS: This retrospective cohort study included patients (aged &#x2265;50 years) with &#x2265;3 optical coherence tomography (OCT) macular scans &#x2265;6 months apart. Eyes that developed &#x2265;250&#xa0;&#x3bc;m of complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) with associated hypertransmission through Bruch's membrane on OCT were considered to have developed geographic atrophy (GA). The spatial pattern of macular thinning was assessed using the ETDRS rings centered on the foveola, calculated as a percentage change relative to its baseline value by eye.<br><br>RESULTS: A total of 201 eyes met inclusion criteria. At last follow-up, 17 eyes developed GA (8.5%) at a median observation of 5.2 (2.4) years. The central subfield (1-mm) and inner ring (3-mm ETDRS subfield) thinned faster in eyes that developed incipient GA (central subfield thickness [CST]: -1.59% vs. -0.47% per year, p=0.007; inner ring: -1.48% vs. -0.65% per year, p<0.001), while the outer ring (6-mm ETDRS subfield) thinned less rapidly (-0.75% vs. -0.30% per year, p=0.003). Linear regression identified the rate of inner ring thinning as the most significant predictor of GA, with a receiver operating characteristic curve demonstrating a high predictive accuracy (area under the curve [AUC], 0.821; 95% CI, 0.746-0.896; p<0.001).<br><br>CONCLUSION: Rapid thinning of the inner ETDRS ring is associated with incipient GA. Identifying eyes at risk of late AMD using serial OCT scans would permit personalized monitoring and treatment strategies critical for safeguarding vision.}, }
@article {pmid42200766, year = {2026}, author = {Invernizzi, A and Romano, F and Corvi, F and Cozzi, M and Sadda, SR and Freund, KB and Staurenghi, G}, title = {Real-Time High-Resolution OCT for Imaging Retinal and Choroidal Blood Flow.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {5}, pages = {69}, doi = {10.1167/iovs.67.5.69}, pmid = {42200766}, issn = {1552-5783}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/diagnostic imaging ; *Regional Blood Flow/physiology ; Cross-Sectional Studies ; *Retinal Vessels/physiology/diagnostic imaging ; Female ; Male ; Blood Flow Velocity/physiology ; Middle Aged ; Feasibility Studies ; Aged ; *Retinal Diseases/physiopathology ; }, abstract = {PURPOSE: To evaluate the feasibility of visualizing intravascular moving particles within retinal and choroidal vessels using real-time high-resolution optical coherence tomography (High-Res OCT), a prototype device offering 3-µm axial resolution.<br><br>METHODS: In this cross-sectional study, 20 healthy eyes were imaged using both High-Res OCT and the standard SPECTRALIS HRA+OCT. A dedicated in-built research tool enabled ART-1 B-scan movie acquisition with real-time eye-tracking. Two masked graders qualitatively assessed visibility and direction of intravascular moving particles, and intergrader agreement was evaluated using Gwet's agreement coefficient 1 (AC1). Four additional patients with retinal vascular disorders (retinal artery occlusion, diabetic retinopathy, hypertensive retinopathy, and neovascular age-related macular degeneration) were imaged with High-Res OCT to explore illustrative clinical applications.<br><br>RESULTS: High-Res OCT demonstrated superior visualization of intravascular moving particles compared with standard OCT in both arteries (80% vs. 50%; P = 0.01) and veins (90% vs. 60%; P = 0.03). Intergrader agreement was high for High-Res OCT (AC1, 0.82-0.89) and moderate-to-substantial for standard OCT (AC1, 0.53-0.71). Flow direction assessment did not differ significantly between devices, although correct identification was numerically higher with High-Res OCT. In pathological eyes, real-time High-Res OCT enabled dynamic visualization of pulsatile and disturbed flow patterns and distinct intravascular motion across multiple vascular conditions.<br><br>CONCLUSIONS: Real-time High-Res OCT enables direct, non-invasive visualization of intravascular moving particles within retinal and choroidal vessels and improves flow detectability compared with conventional OCT. This technique offers novel qualitative insights into ocular vascular dynamics and may guide future quantitative and translational applications.}, }
@article {pmid42201156, year = {2026}, author = {Fathee, HN and Babayev, R and Sahmoud, S and Ağaoğlu, N}, title = {Advancing AMD Detection: Dataset Design and Deep Learning Optimization for Unconstrained Retinal Images.}, journal = {Vision (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, doi = {10.3390/vision10020028}, pmid = {42201156}, issn = {2411-5150}, abstract = {Age-related macular degeneration (AMD) is one of the leading causes of vision impairment worldwide, making early and accurate detection essential for effective clinical intervention. Recent advances in deep learning have demonstrated promising results in automated retinal image analysis; however, most existing approaches rely on datasets acquired under controlled conditions, limiting their generalizability to real-world clinical environments. In this paper, we propose a novel AMD dataset designed to simulate unconstrained imaging conditions, by incorporating noise, luminance variations, and device-related artifacts commonly encountered during retinal scan acquisition. Using this dataset, we conduct a comprehensive comparative evaluation of six widely adopted deep learning architectures: VGG16, VGG19, InceptionV3, MobileNetV2, ResNet50, and DenseNet. Experimental results indicate notable performance variations across models, highlighting the impact of architectural design on robustness to image degradation. Among the evaluated approaches, VGG16 achieved the best overall performance. By further optimizing this architecture through targeted training and fine-tuning strategies, the proposed system reached an accuracy of 88% in AMD detection. These findings demonstrate the effectiveness of the optimized VGG16 model and underline the importance of realistic datasets for developing reliable deep learning-based diagnostic tools for practical clinical settings.}, }
@article {pmid42201157, year = {2026}, author = {Lixi, F and Troisi, M and Calabresi, V and Giagoni, A and Rossi, C and Timofte-Zorila, MM and Tarași, TC and Vitiello, L and Tomi, MI and Gheorghe, AG and Coco, G and Lanzolla, G and Giannaccare, G}, title = {Beyond Glycemic Control: Ocular Effects of Glucagon-like Peptide-1 Receptor Agonists.}, journal = {Vision (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, doi = {10.3390/vision10020029}, pmid = {42201157}, issn = {2411-5150}, abstract = {Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and newer dual-incretin therapies have become central to the treatment of diabetes mellitus and obesity, with benefits extending beyond glycemic control. Their expanding use has prompted growing interest in their potential ocular effects. Experimental data support plausible protective mechanisms, including reduction in oxidative stress and neuroprotective effects on retinal and optic nerve tissues. Clinical evidence, however, remains heterogeneous. In diabetic retinopathy, the main concern appears to be transient early worsening associated with rapid glycemic improvement rather than direct retinal toxicity. A potential semaglutide-associated signal for non-arteritic anterior ischemic optic neuropathy has raised concern, although the absolute risk appears low and causality remains unproven. Emerging studies also suggest possible beneficial associations with glaucoma, ocular surface diseases, and certain retinal vascular outcomes, whereas the evidence regarding age-related macular degeneration and cataract remains conflicting or preliminary. Overall, ocular outcomes associated with incretin-based therapies seem to reflect a complex interplay among drug-specific pharmacology, systemic metabolic changes, and individual patient susceptibility rather than a class effect. Baseline ophthalmic assessment and individualized follow-up may be advisable in selected high-risk patients. Further prospective ophthalmology-focused studies are needed to clarify long-term safety and identify the patients most likely to benefit or develop adverse events.}, }
@article {pmid42201532, year = {2026}, author = {Mimura, T and Nishijima, Y and Hasegawa, D and Yoshida, Y and Noma, H}, title = {Global association between ambient air pollution and age-related macular degeneration: an ecological analysis across 203 countries.}, journal = {Environmental science and pollution research international}, volume = {}, number = {}, pages = {}, pmid = {42201532}, issn = {1614-7499}, abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide, and both environmental and lifestyle factors have been implicated in its development; however, international-scale evidence regarding the impact of air pollution remains limited. We conducted a cross-sectional ecological study to evaluate national-level associations between AMD burden and environmental as well as lifestyle factors using data from the Global Burden of Disease study. Disability-adjusted life years (DALYs), age-standardized DALYs, and age-standardized prevalence of AMD from 1990 to 2020 were analyzed in relation to ambient air pollutants, including particulate matter ≤ 2.5 μm (PM2.5), PM ≤ 10 μm (PM10), nitrogen dioxide, sulfur dioxide, ozone, household air pollution from solid fuel use, and national smoking prevalence obtained from global databases. Between 1990 and 2020, global DALYs attributable to AMD increased by 26.7%, whereas age-standardized DALYs and age-standardized prevalence decreased by 19.2% and 3.4%, respectively. In 2020, age-standardized AMD prevalence showed significant positive correlations with PM2.5 (r = 0.65, p < 0.001), ozone (r = 0.55, p < 0.001), and household air pollution (r = 0.30, p < 0.001), and a significant negative correlation with smoking prevalence (r = -0.25, p < 0.001). Multivariable regression analyses identified PM2.5 (odds ratio [OR] 8.09, p < 0.001) and ozone (OR 5.42, p < 0.001) as independent predictors of AMD prevalence. These findings suggest that exposure to ambient air pollution, particularly fine particulate matter and ozone, may contribute to the global burden of AMD and represent potentially modifiable risk factors, underscoring the need for further research to clarify causal relationships and to inform public health and environmental policy interventions.}, }
@article {pmid42182542, year = {2026}, author = {Al-Tamimi, NY and Amer, M and Graini, FNE}, title = {Clinical Low Vision Rehabilitation Interventions in Age-Related Macular Degeneration: A Case Report.}, journal = {Cureus}, volume = {18}, number = {5}, pages = {e109419}, pmid = {42182542}, issn = {2168-8184}, abstract = {A 70-year-old female with bilateral age-related macular degeneration (AMD) - wet AMD in the right eye and dry AMD in the left eye - presented with reduced unaided distance visual acuity of 20/200 (6/60) and near visual acuity of 3.2M (20/160, 6/48) OU. Retinoscopy and subjective refraction showed a prescription of -2.25 -2.50 × 175 in the right eye and +0.50 -1.50 × 120 in the left eye, achieving corrected visual acuities of 20/125 (6/37.5) OU. With an additional +3.00 diopters sphere for near tasks, the patient was able to read up to 2.5M (20/125, 6/37.5), indicating a coexisting refractive error. Amsler grid testing revealed central metamorphopsia and scotomas OU. Optical coherence tomography (OCT) confirmed bilateral drusen, retinal pigment epithelium (RPE) atrophy, and vitreomacular adhesion (VMA), with findings consistent with AMD. Functional contrast sensitivity was reduced (20/100, 6/30) OU, and visual field testing showed central scotomas and metamorphopsia. Low vision rehabilitation included the prescription of a 2.5× binocular Galilean telescope (Eschenbach 1639; Eschenbach Optik GmbH, Nuremberg, Germany) for distance, achieving 20/40 (6/12) vision OU, and a 5× illuminated hand magnifier (Eschenbach Mobilux 15105; Eschenbach Optik GmbH) for near tasks, enabling reading of 1.0M print (approximately 20/50, equivalent to 6/18+). Environmental modifications and contrast-enhancing filters were recommended. Nutritional counseling and ongoing monitoring were initiated, and the patient was educated on self-assessment with the Amsler grid. At three-month follow-up, visual function remained stable, and low vision strategies continued to support functional independence. This case underscores the importance of early low vision intervention, multidisciplinary care, and personalized rehabilitation strategies in maintaining quality of life in patients with AMD.}, }
@article {pmid42184268, year = {2026}, author = {Xu, X and Liu, W and Li, H and Wang, Y and Li, Y and Wang, B and Liu, M and Li, Y}, title = {The Trajectory of Retinal Microcirculation Imaging: From Angiography to Artificial Intelligence.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {231}, pages = {}, doi = {10.3791/70115}, pmid = {42184268}, issn = {1940-087X}, mesh = {Humans ; *Artificial Intelligence ; *Retinal Vessels/diagnostic imaging/physiology ; Microcirculation/physiology ; Tomography, Optical Coherence/methods ; Animals ; *Angiography/methods ; }, abstract = {Retinal and choroidal microcirculation are highly specialized vascular networks essential for vision and are increasingly recognized as indicators of systemic diseases. For decades, its assessment relied on invasive dye-based angiography, which infers pathology from secondary effects such as vascular leakage. A paradigm shift is now underway, driven by non-invasive imaging modalities that directly visualize and quantify the microvasculature with unprecedented resolution. Chief among these is optical coherence tomography angiography, which provides depth-resolved, three-dimensional maps of perfused vessels, enabling the generation of objective biomarkers for vascular integrity and ischemia. Complementary techniques further probe absolute blood flow, high-frequency hemodynamics, and cellular-level perfusion, creating a rich, multi-scale dataset. This technological evolution is transforming clinical practice, facilitating preclinical detection of diabetic retinopathy, refining therapeutic strategies for neovascular age-related macular degeneration, and providing new insights into the vascular contributions to glaucoma. Looking ahead, integrating these multimodal data streams with artificial intelligence promises to convert the wealth of information into predictive models of disease risk and progression. This heralds a new era in precision ophthalmology and oculomics (the large-scale, data-driven analysis of ocular imaging biomarkers to assess systemic health and predict disease risk), with transformative gains in processing, quantification, and access.}, }
@article {pmid42184794, year = {2026}, author = {Stitou, B and Hung, J and Tran, THC}, title = {[Comparison between in-person physical examination and telemedicine with portable equipment in elderly fall-risk patients].}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {6}, pages = {104901}, doi = {10.1016/j.jfo.2026.104901}, pmid = {42184794}, issn = {1773-0597}, abstract = {PURPOSE: To assess diagnostic and clinical decision concordance between a face-to-face ophthalmological examination using handheld equipment and an asynchronous teleophthalmology assessment in disabled elderly fall-risk patients as well as the feasibility of this approach.<br><br>PATIENTS AND METHODS: This prospective single-center study evaluated a diagnostic method. Disabled elderly fall-risk patients underwent an in-person ophthalmological examination using a handheld slit-lamp followed by an asynchronous teleophthalmology assessment based on videos acquired by handheld anterior segment and fundus cameras. Diagnostic and management concordance were assessed using Cohen's kappa coefficient. Feasibility was evaluated by the rate of readable examinations.<br><br>RESULTS: A total of 142 patients (281 eyes) were included. Concordance was very good for phakic/pseudophakic status assessment (kappa=0.87-0.96), moderate for lens assessment (kappa=0.51-0.58) and macular evaluation (kappa=0.48-0.57), and low for other anterior (cornea, iris) and posterior segment (optic nerve head, retinal vessels) assessment as well as for overall clinical decision-making (kappa=0.15-0.35). Feasibility was excellent for anterior segment examination (90-98%) and acceptable for posterior segment assessment (61-81%). A clinical decision could be proposed via teleophthalmology in 50-72% of cases. The main causes of visual impairment were cataract, age-related macular degeneration, and optic neuropathy.<br><br>CONCLUSION: Asynchronous teleophthalmology using handheld equipment appears feasible in disabled elderly patients, with variable reliability depending on the parameters assessed. Technological, organizational, and methodological improvements are required before broader implementation.}, }
@article {pmid42186202, year = {2026}, author = {Chang, TW and Kuo, CY and Lee, CY and Hung, CH}, title = {GLP-1 Receptor Agonists and Risk of Age-Related Macular Degeneration in Older Adults With Obesity: A Target Trial Emulation.}, journal = {Diabetes, obesity &amp; metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1111/dom.70910}, pmid = {42186202}, issn = {1463-1326}, abstract = {AIMS: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults. Whilst glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for obesity management, their potential impact on AMD risk in individuals without diabetes remains unclear. This study aimed to evaluate the association between GLP-1RA initiation and the risk of incident AMD in obese adults without diabetes.<br><br>MATERIALS AND METHODS: We conducted a target trial emulation using the TriNetX global health research network (January 2014-June 2025). Eligible participants were adults aged &#x2265;&#x2009;60&#x2009;years with obesity but without diabetes mellitus. New users of GLP-1RAs were compared with new users of other weight-loss medications. Following 1:1 propensity score matching, Cox proportional hazards models estimated hazard ratios (HRs) for incident AMD over a maximum 7-year observation window (median follow-up: 1.11&#x2009;years [IQR: 1.48] in the GLP-1RA group versus 2.56&#x2009;years [IQR: 3.89] in the comparator group).<br><br>RESULTS: In 157&#x2009;880 matched patients (78&#x2009;940 per group), GLP-1RA use was associated with a significantly lower risk of incident AMD (HR 0.82; 95% CI 0.68-0.98) compared with other weight-loss medications. Subtype analyses revealed reduced risk for unspecified AMD (HR 0.70; 95% CI 0.52-0.93) and a potential trend towards a lower risk of nonexudative AMD (HR 0.78; 95% CI 0.60-1.00; p&#x2009;=&#x2009;0.050). Subgroup analyses suggested stronger effects in women and adults aged 60-69&#x2009;years; all subgroup findings should be interpreted as exploratory.<br><br>CONCLUSIONS: GLP-1RA use is associated with a reduced risk of incident AMD-statistically significant for unspecified AMD, with a potential trend towards a lower risk of nonexudative AMD-in obese adults without diabetes. Whether this reflects direct GLP-1RA neuroprotective mechanisms, greater weight-loss magnitude or both remains to be determined. Further mechanistic research and prospective clinical trials are warranted.}, }
@article {pmid42186654, year = {2026}, author = {Kar, SK and Nemivant, K and Sharma, UK and Priya, P and Abbasi, S and Yadav, NK}, title = {Transforming Eye-Care Diagnostics Through Artificial Intelligence, Biometric Evaluation, and Tele-Optometry.}, journal = {Cureus}, volume = {18}, number = {4}, pages = {e107620}, pmid = {42186654}, issn = {2168-8184}, abstract = {Visual impairment remains a major global health concern associated with disorders such as diabetic retinopathy, glaucoma, cataract, and age-related macular degeneration. Early detection of ocular abnormalities remains essential for preventing irreversible visual loss. Conventional diagnostic methods rely on clinical examination and specialised imaging, yet limitations in accessibility, diagnostic variability, and delayed detection continue to affect effective eye-care delivery in many settings. Advances in digital technologies have introduced innovative diagnostic approaches integrating artificial intelligence (AI), ocular biometric evaluation, and tele-optometry to improve efficiency and reach of ophthalmic care. The objective of this review involves a comprehensive examination of recent developments in digital ophthalmic diagnostics, focusing on AI-based image analysis, biometric measurement technologies, and tele-optometry platforms. Relevant literature addressing AI applications, ocular biometric assessment, and remote ophthalmic screening systems was evaluated to synthesise current knowledge on diagnostic capability and clinical relevance. Current evidence indicates that AI algorithms enable automated interpretation of retinal images and facilitate early identification of ocular diseases. Biometric evaluation provides precise anatomical measurements that support refractive assessment and surgical planning. Tele-optometry systems expand diagnostic access through remote imaging and consultation services, improving screening coverage in underserved populations. Integration of AI, biometric technologies, and tele-optometry demonstrates strong potential to enhance disease detection, strengthen clinical decision support, and expand accessibility of ophthalmic diagnostic services.}, }
@article {pmid42187268, year = {2026}, author = {Rynjah, H and Sarma, B and Parasar, K}, title = {Comment on "Conjunctival Microbiota in retinal diseases requiring anti-VEGF therapy: Age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion".}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261445283}, doi = {10.1177/11206721261445283}, pmid = {42187268}, issn = {1724-6016}, }
@article {pmid42188557, year = {2026}, author = {Judge, LW and Garcia-Carrillo, E}, title = {Combining Multisensory Cueing and Velocity-Based Training to Enhance Shot Put Performance in an F12 Para-Athlete: A Case Report.}, journal = {Sports (Basel, Switzerland)}, volume = {14}, number = {5}, pages = {}, doi = {10.3390/sports14050181}, pmid = {42188557}, issn = {2075-4663}, abstract = {This case report documents the multi-season development of a 38-year-old elite F12 shot putter with macular degeneration (<10% functional vision) who improved from 13.00 m to a personal best of 14.41 m between 2021 and 2023. Athletes classified as F11-F13 compete with significant visual impairment that limits spatial feedback during rotational tasks, yet longitudinal evidence describing integrated training frameworks remains scarce. A 12-month macrocycle integrated phase-dependent velocity-based resistance training using mean concentric velocity targets (0.70-1.00 m·s[-1]) monitored via linear position transducers with a 10% velocity loss threshold, combined with structured auditory and tactile cueing, including metronome pacing and environmental anchors. High-volume warm-ups and prehabilitation addressed a prior L4-L5 disk herniation. The athlete achieved 14.41 m at the 2023 U.S. Para Athletics Trials, with TrackMan[®]-verified release velocity of 11.3 m·s[-1]. Bench throw velocity improved by 35.4% (0.65 to 0.88 m·s[-1]) and squat jump velocity improved by 22.9% (1.18 to 1.45 m·s[-1]), while post-session RPE remained manageable, indicating improved neuromuscular readiness and training tolerance. No lumbar symptom recurrence occurred. This case illustrates that integrating velocity autoregulation, multisensory stabilization, and injury-informed preparation can support meaningful performance gains in visually impaired throwers and offers an applied framework for coaches working with F11-F13 athletes.}, }
@article {pmid42190107, year = {2026}, author = {Kim, HM and Bae, Y and Kim, M and Lee, H and Chung, H}, title = {Systemic cancer risk profile in neovascular age-related macular degeneration: insights into shared aging-related mechanisms from a nationwide population-based study.}, journal = {Aging}, volume = {18}, number = {1}, pages = {593-604}, doi = {10.18632/aging.206383}, pmid = {42190107}, issn = {1945-4589}, abstract = {Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in older adults and is increasingly recognized as a manifestation of systemic aging involving vascular and inflammatory pathways. Emerging evidence suggests that nAMD may also be linked to systemic diseases, including malignancies. Using data from the Korean National Health Insurance Service, we conducted a nationwide, population-based cohort study of 334,091 individuals (83,742 with nAMD and 250,349 matched controls) followed for up to 10 years. Patients with nAMD showed a modest but significant increase in overall cancer risk (adjusted hazard ratio [aHR], 1.084; P < 0.001), with selectively elevated risks for pancreatic (aHR, 1.155; P < 0.001), lung (aHR, 1.128; P < 0.001), thyroid (aHR, 1.241; P < 0.001), renal (aHR, 1.177; P = 0.002), bladder (aHR, 1.121; P = 0.002), and prostate (aHR, 1.085; P < 0.001) cancers. No significant associations were observed for other malignancies. These findings indicate that nAMD may serve as a clinical marker of systemic vulnerability to selected cancers, possibly through shared angiogenic, inflammatory, and polygenic mechanisms underlying aging-related disease susceptibility.}, }
@article {pmid42190237, year = {2026}, author = {Lee, C and Karunainathan, MG and Zohalinejad, KD and Mæng, MO and Fabrin, NW and Yde, SK and Wykoff, CC and Abildgaard, SK and Vorum, H and Subhi, Y and Ørskov, M and Cehofski, LJ}, title = {Real-World Outcomes after Switch to Aflibercept 8 mg in Neovascular AMD: Twelve Months Follow-up on 654 Eyes.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004888}, pmid = {42190237}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate 12-month outcomes following systematic switch to aflibercept 8 mg in previously treated eyes with age-related neovascular macular degeneration (nAMD).<br><br>METHODS: Eyes in a plateau phase (&#x2265;10 prior anti-VEGF injections) that were switched to aflibercept 8 mg were retrospectively evaluated. Treatment intervals, best corrected visual acuity (BCVA), central retinal thickness (CRT), and data on intraretinal fluid (IRF) or subretinal fluid (IRF) were assessed at switch and after 3, 6, and 12 months.<br><br>RESULTS: In total, 654 eyes from 567 patients were included (mean [SD] age 82.4 [7.4], 34.5 [21.5] injections per eye before switch). The proportion of eyes with dry maculae increased from 55% at switch to 76% at 3 months (P<0.001), 73% at 6 months (P<0.001), and 69% at 12 months (P<0.05). Eyes treated at 3-5-week intervals declined from 46% to 18% at 12 months (P<0.001). Eyes on 9-12-week intervals increased from 11% to 34% (P<0.001). The mean treatment interval increased from 6.0 (2.1) to 7.8 (2.4) weeks (P<0.001). Eyes with dry maculae at switch were extended by 2.6 (1.8) weeks (P<0.001). The mean CRT decreased from 234.7 (49.7) to 223.5 (46.7) &#xb5;m (P<0.001). BCVA declined from 68.5 (12.2) to 67.3 (13.9) ETDRS letters in the overall cohort, and from 68.5 (12.3) to 66.6 (14.3) ETDRS letters in eyes with a dry macula at switch (P < 0.001).<br><br>CONCLUSION: Switching to aflibercept 8 mg improved anatomical outcomes and reduced the proportion of eyes on short intervals. A slight decline in BCVA was observed, warranting long-term follow-up.}, }
@article {pmid42177487, year = {2026}, author = {Simaku, E and Eddien, AN and Popa, M and Shafei, AE}, title = {Non-infectious occlusive retinal vasculitis following switching from aflibercept 2 mg to aflibercept 8 mg in neovascular age-related macular degeneration: a case report.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04953-z}, pmid = {42177487}, issn = {1471-2415}, abstract = {BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy represents the standard of care for neovascular age-related macular degeneration (nAMD). Aflibercept 8 mg was recently introduced with extended dosing intervals and favorable safety outcomes in phase III trials. Although no confirmed cases of occlusive retinal vasculitis were reported in pivotal studies, rare inflammatory vascular events may emerge during broader real-world exposure.<br><br>CASE PRESENTATION: A 74-year-old pseudophakic male with active nAMD in the left eye demonstrated significant anatomical and functional improvement following intravitreal aflibercept 2&#xa0;mg. After switching to aflibercept 8&#xa0;mg, the patient presented 26 days later with painful visual deterioration. Fundus examination revealed mild vitritis, segmental arterial sheathing, venous narrowing, and peripheral intraretinal hemorrhages. Fluorescein angiography demonstrated capillary non-perfusion and late vascular leakage. Optical coherence tomography confirmed cystoid macular edema. Extensive infectious and autoimmune investigations were negative. Systemic and local corticosteroid therapy resulted in regression of inflammation with partial visual recovery.<br><br>CONCLUSIONS: Non-infectious occlusive retinal vasculitis may rarely occur following switching to aflibercept 8&#xa0;mg. Early recognition and prompt anti-inflammatory treatment are critical to minimize irreversible ischemic damage. Continued post-marketing pharmacovigilance is warranted.}, }
@article {pmid42177686, year = {2026}, author = {Lains, I and Bhat, R and Mendez, K and Gil, J and Providencia, J and Barreto, P and Sourirajan, K and Kang, H and Nigalye, A and Miller, JB and Kim, I and Vavvas, D and Liang, L and Silva, R and Lasky-Su, J and Miller, JW and Husain, D}, title = {Association of age-related macular degeneration with exposome related metabolomics.}, journal = {Metabolomics : Official journal of the Metabolomic Society}, volume = {22}, number = {3}, pages = {}, pmid = {42177686}, issn = {1573-3890}, support = {K12EY016335/GF/NIH HHS/United States ; R01EY030088/GF/NIH HHS/United States ; R01EY030088/GF/NIH HHS/United States ; R01EY030088/GF/NIH HHS/United States ; }, mesh = {Humans ; *Macular Degeneration/metabolism/urine/blood ; *Metabolomics/methods ; Male ; Female ; Cross-Sectional Studies ; Aged ; Middle Aged ; *Exposome ; *Metabolome ; Aged, 80 and over ; Biomarkers/blood/urine ; }, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a multifactorial disease, but it remains unclear how external exposures - the exposome - promote its development. Metabolomics can provide insights to better understand AMD pathophysiology. Previous work to date has focused primarily on associations between endogenous metabolites and AMD.<br><br>OBJECTIVES: This study aimed for the first time to investigate associations of exogenous metabolites in plasma and urine and AMD.<br><br>METHODS: Cross-sectional study including patients with AMD and a control group (>&#x2009;50 years) from Boston, US and Coimbra, Portugal (PT). Color fundus photographs (CFP) of all participants were used for AMD staging. Fasting plasma and urine samples were used for metabolomic profiling using Ultrahigh Performance Liquid Chromatography - Mass Spectrometry (Metabolon, Inc). Multivariate and ordinal logistic mixed-effect regression models were computed for each cohort and then combined by meta-analysis. Primary outcome was association of metabolites with AMD (vs. no AMD). False discovery rate (FDR) was used to account for multiple comparisons and significant q-values are reported.<br><br>RESULTS: We included 1023 eyes (823 from the US and 580 from PT). Meta-analysis revealed significant associations of tartronate, thioproline and 2-methoxyhydroquinone sulfate levels with both presence and staging of AMD (q&#x2009;<&#x2009;0.005 for all). Similar trends were seen in urine.<br><br>CONCLUSION: To the best of our knowledge, this is the first study to identify associations between exogenous metabolites and AMD. These findings are crucial for identifying possible targets for preventive strategies for this blinding disease.}, }
@article {pmid42177934, year = {2026}, author = {Gilead, N and Chong, YJ and Cheng, MFS and Kikushima, W and Sherif, M and George, L and Ong, C and Sun, C and Hong, CH and Ibrahim, FNI and Teo, KYC and Cheung, CMG}, title = {Predictors of 1-Year Visual Outcome in Central-Involving Submacular Hemorrhage Secondary to Neovascular AMD.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.05.035}, pmid = {42177934}, issn = {1879-1891}, abstract = {PURPOSE: To identify clinical and imaging predictors of 12-month visual outcome in patients with fovea-involving submacular hemorrhage (SMH) due to neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV).<br><br>DESIGN: Prospective observational clinical cohort study.<br><br>SUBJECTS: Asian patients with nAMD or PCV presenting with fovea-involving SMH.<br><br>METHODS: Between January 2016 and July 2024, eyes presenting with fovea-involving SMH &#x2265;1 disc diameter with no evidence of blood organization were included. All patients received standard-of-care treatment. Clinical and multimodal imaging parameters were analyzed to identify predictors of visual outcome at 12 months.<br><br>MAIN OUTCOME MEASURES: Good (&#x2264;0.3 logMAR) and poor (&#x2265;1.0 logMAR) visual outcomes at 12 months.<br><br>RESULTS: Among 487 treatment-na&#xef;ve eyes, 75 met inclusion criteria for fovea-involving SMH. Mean (SD) age was 71.40 (9.59) years, 74.4% were male, and 76.0% had PCV. Mean hemorrhage size was 18.92 (22.56) mm&#xb2;. All eyes received anti-VEGF therapy, 2.6% underwent additional pneumatic displacement, and 5.3% received photodynamic therapy. Best-corrected visual acuity (BCVA) improved from 1.04 (0.67) logMAR to 0.69 (0.62) at 12 months. 25 eyes (33.3%) achieved good visual outcome, while 22 eyes (29.3%) had poor visual outcome. On multivariable analysis, younger age (OR=0.47 per decade, 95% CI 0.26-0.86; P=0.02), better baseline BCVA (OR=0.87 per 0.1 logMAR, 95% CI 0.79-0.97; P<0.01), and thicker subfoveal choroid (OR=1.50 per 50 &#xb5;m, 95% CI 1.07-2.10; P=0.02) independently predicted good visual outcome. Conversely, larger hemorrhage size predicted poor visual outcome (OR=1.04 per mm[2], 95% CI 1.01-1.07; P=0.02).<br><br>CONCLUSION: One-third of eyes with SMH achieved 0.3 logMAR (Snellen equivalent 20/40) or better vision. In addition to age, baseline BCVA, and hemorrhage size, we identified choroidal thickness as a biomarker associated with visual outcome.}, }
@article {pmid42179647, year = {2026}, author = {Patel, MJ and Datta, M and Baredes, V and Fuentes-Gonzalez, T and Bass, S and Alba, D and Soloff, AC and Hackam, AS}, title = {Chronic exposure to aerosolized Arizona test dust reduces visual acuity in mice.}, journal = {Toxicology reports}, volume = {16}, number = {}, pages = {102263}, pmid = {42179647}, issn = {2214-7500}, abstract = {Air pollution is associated with increased incidence of age-related macular degeneration (AMD), glaucoma and other retinal diseases. The time course of molecular and cellular changes induced by chronic air pollution exposure that lead to retinal pathology are unknown. In this study, we investigated the effects of moderate levels of air pollution on visual acuity and retinal phenotypes in mice using Arizona test dust (ATD) as a surrogate for ambient air pollution. Mice were exposed to aerosolized standardized test dust for three hours a day, four days a week, for up to four months in a custom-built chamber. Controls were exposed to room air. Visual function was assessed using an optomotor assay and demonstrated reduced visual acuity after one month of exposure that persisted throughout the study. Rod and cone photoreceptors also showed temporarily decreased light-evoked responses that returned to normal levels by four months. Furthermore, reduced cone photoreceptors and retinal ganglion cells were observed whereas markers of retinal stress, including Iba1-positive microglia/macrophage and GFAP expression in macroglia, were not significantly elevated. Molecular analyses indicated elevated expression of genes in the Nrf2-ARE oxidative stress response pathway. Therefore, moderate levels of aerosolized ATD caused a persistent decline in visual acuity, mild retinal degeneration and transient functional changes. This study provides new information into the pathogenesis of pollution-induced retinal damage and establishes a new mouse model for investigating detrimental effects of moderate levels of air pollution in the retina.}, }
@article {pmid42179661, year = {2026}, author = {Uzundede, T and Karatas, G and Yildiz, D and Cakir, A}, title = {The Comparison of Intracystic Hyperreflectivity in Different Macular Edema Etiologies. Is It a New Optical Coherence Tomography Biomarker?.}, journal = {Beyoglu eye journal}, volume = {11}, number = {1}, pages = {50-57}, pmid = {42179661}, issn = {2587-0394}, abstract = {OBJECTIVES: To detect the difference in internal hyperreflectivity of macular cystoid spaces in diabetic retinopathy (DR), exudative (wet) age-related macular degeneration (wet AMD), branch retinal vein occlusion (BRVO).<br><br>METHODS: The medical records of the consecutive patients who were followed up from Prof. Dr. Cemil Ta&#x15f;c&#x131;o&#x11f;lu City Hospital, from 01 April 2023 to 01 June 2023, in the retina department, have been included in this study. The mean gray value (GV) and max-min GV parameters of the cystoid spaces which were detected in the spectral domain optical coherence tomography (OCT) scans, were measured by using the ImageJ program (National Institutes of Health, Bethesda, Maryland, USA). The established diagnosis, baseline best corrected visual acuities (BCVA), OCT biomarkers such as serous macular detachment, hard exudate, hyperreflective foci and central macular thicknesses were also noted. The parameters were compared to each other regarding the different pathologies.<br><br>RESULTS: The mean-max GV of cystoid spaces and the mean-max GV of cystoid/vitreous ratio were found to be highest in the DR, followed by BRVO, and lowest in wet AMD (p<0.001 and p<0.001; respectively). Correlation analyses revealed a positive correlation between OCT biomarkers and intracystic hyperreflectivity (ICH) (p<0.001, respectively). Besides, the max GV cystoid/vitreous ratio is positively correlated with the BCVA (p<0.046; p=0.04, respectively).<br><br>CONCLUSION: This pilot study investigates ICH in macular edema of various etiologies. The ICH was highest in the DR group, followed by the BRVO group, and lowest in the AMD group. It has been observed that there is a high correlation between ICH and OCT biomarkers. Findings support the hypothesis that ICH may reflect underlying inflammatory processes and contribute to individualized treatment approaches in retinal vascular pathologies.}, }
@article {pmid42179664, year = {2026}, author = {Demir, U and Gunturkun, PN and Bozgul, P}, title = {Evaluation of the Association of Senile Macular Degeneration in Patients with Glaucoma.}, journal = {Beyoglu eye journal}, volume = {11}, number = {1}, pages = {42-49}, pmid = {42179664}, issn = {2587-0394}, abstract = {OBJECTIVES: The aim of the study was to evaluate the incidence of senile macular degeneration (SMD) in patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEG).<br><br>METHODS: The medical files of 2600 patients with glaucoma were analyzed. In this study, 168 patients (90 females and 78 males) with POAG and PEG were included. Patients diagnosed with POAG and PEG with SMD were also recorded. SMD was classified in two categories: Wet type and dry type. Lens status was classified as pseudophakic and phakic. Glaucoma severity was classified according to the Hodapp-Parrish-Anderson criteria. All patients underwent complete ophthalmologic examinations.<br><br>RESULTS: Ninety (53.57%) patients were female, and 78 (46.43%) were male. The mean age was 63&#xb1;8.4 years for women and 66.5&#xb1;7.8 years for men. Sixty-six (73.3%) of women and 60 (76.9%) of men had POAG, 24 (26.7%) of women and 18 (23.1%) of men had PEG. 18 (20.0%) right and 25 (27.8%) left eyes of women and 30 (38.5%) right and 24 (30.8%) left eyes of men were pseudophakic, 72 (80.0%) right and 65 (72.2%) left eyes of women and 48 (61.5%) right and 54 (69.2%) left eyes of men were phakic. SMD was observed in 10 patients (5.95%); four women and five men had dry-type SMD, while one man had wet-type SMD.<br><br>CONCLUSION: In our study, when gender, age, severity of glaucoma, pseudophakic and phakic status of the lens were evaluated in patients with the association of glaucoma and SMD, these variables had no statistically significant effect on the association of glaucoma and SMD.}, }
@article {pmid42179847, year = {2026}, author = {Weiss, ER and Han, Z}, title = {Editorial: Retinitis pigmentosa, macular degeneration and related diseases.}, journal = {Frontiers in cellular neuroscience}, volume = {20}, number = {}, pages = {1856506}, pmid = {42179847}, issn = {1662-5102}, }
@article {pmid42180516, year = {2026}, author = {Sannan, NS}, title = {Genetic determinants of age-related macular degeneration in Middle Eastern populations: a systematic review.}, journal = {Frontiers in genetics}, volume = {17}, number = {}, pages = {1776779}, pmid = {42180516}, issn = {1664-8021}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss, with genetic factors playing a key role in disease susceptibility and progression. While extensive genetic research is being conducted, the genetic architecture of AMD in Middle Eastern populations remains understudied. This systematic review summarizes current evidence on genetic variants associated with AMD in Middle Eastern populations.<br><br>METHODS: A comprehensive literature search was conducted in PubMed, Web of Science Core Collection, and Medline databases. Studies were included if they: (1) examined cohorts from Middle Eastern participants; (2) with clinically diagnosed AMD; (3) explored genetic variants or other genomic markers; (4) no restrictions on year of publication; and (5) were published in English.<br><br>RESULTS: The search yielded 449 articles (PubMed: 164, Web of Science: 99, Medline: 186). After removal of 221 duplicates, 228 unique articles were screened. Of these, 28 studies met the inclusion criteria, covering a total of 4,247 AMD cases and 3,447 controls from five countries: Turkey (n = 11), Iran (n = 11), Israel (n = 4), Jordan (n = 1), and Egypt (n = 1). Most analyses were targeted, with 25 studies targeting one to four genetic loci, two studies examining 12 variants, and one genome-wide association study. The most frequently studied genes were CFH, ARMS2, and HTRA1. The CFH Y402H variant (rs1061170) showed overall positive but heterogeneous associations with AMD risk across studied Middle Eastern populations, with reported odds ratios ranging from 0.36 to 17.34 and statistically significant p values ranging from <0.001 to 0.02 (total AMD cases and controls = 2,079). The ARMS2 A69&#xa0;S variant (rs10490924) and HTRA1 promoter variant (rs11200638) demonstrated strong associations with neovascular AMD.<br><br>CONCLUSION: Few studies have examined genotype-phenotype correlations across this region, and many Middle Eastern countries lack published AMD genetic data. Consequently, the genetic landscape of AMD in the Middle East remains incompletely characterized. Available evidence suggests that variants in CFH, ARMS2, and HTRA1 are important AMD-associated loci in studied Middle Eastern populations, consistent with findings in other population groups.}, }
@article {pmid42181643, year = {2026}, author = {Hu, Y and Liu, S and Liu, Q and Liu, B and Zhang, J and Su, H and Yang, L and Gan, L and Guo, Y and He, Y}, title = {Case Report: A typical triad of Danon disease caused by a LAMP2 splice-donor variant with multilevel functional validation.}, journal = {Frontiers in cardiovascular medicine}, volume = {13}, number = {}, pages = {1695991}, pmid = {42181643}, issn = {2297-055X}, abstract = {Danon disease is a rare X-linked dominant disorder caused by pathogenic variants in LAMP2, typically presenting with cardiomyopathy, skeletal myopathy, and intellectual disability, and showing a severe course in males. In this study, we report the case of a 29-year-old Han Chinese male with the classic triad, plus macular degeneration and a complex neuromuscular phenotype including axonal-demyelinating sensorimotor polyneuropathy. Whole-exome sequencing identified a hemizygous splice-donor variant in LAMP2 (NM_002294.2:c.928 + 1G > A). A functional analysis in peripheral blood with matched controls experimentally confirmed markedly reduced LAMP2 mRNA levels and decreased LAMP2 protein expression, supporting the variant as a loss-of-function allele. The patient rapidly progressed to end-stage heart failure and died 18 months after diagnosis, highlighting the severe multisystem impact of this variant. This case expands the functional evidence for pathogenic LAMP2 splice-site variants and suggests peripheral nervous system involvement in severe multisystem Danon disease.}, }
@article {pmid42181881, year = {2026}, author = {Melecchi, A and Amato, R and Lapi, D and Dal Monte, M and Rusciano, D and Bagnoli, P and Cammalleri, M}, title = {Correction: Increased efficacy of dietary supplement containing wax ester-rich marine oil and xanthophylls in a mouse model of dry macular degeneration.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1850473}, doi = {10.3389/fphar.2026.1850473}, pmid = {42181881}, issn = {1663-9812}, abstract = {[This corrects the article DOI: 10.3389/fphar.2022.1038730.].}, }
@article {pmid42173432, year = {2026}, author = {Namakin, K and Mostafaei, M and Behboodi, S and Dolikhani, M and Boroujerdi, T and Araghi, AS and Masoumi, A and Zolbin, MM}, title = {Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosome on the Retinopathy of Prematurity.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111067}, doi = {10.1016/j.exer.2026.111067}, pmid = {42173432}, issn = {1096-0007}, abstract = {Retinopathy of prematurity is a leading cause of childhood blindness caused by insufficient vascularization of the peripheral retina, which eventually leads to retinal ischemia. In the ischemic state, pro-angiogenic factors such as vascular endothelial growth factor (VEGF), Transforming Growth Factor Beta (TGF-b), and Insulin-like Growth Factor 1 (IGF1) are excessively produced leading to pathological neovascularization. One of the current approaches in regenerative medicine is exosomes, derived from mesenchymal stem cell have shown promise as potential anti-angiogenic agents in various ocular diseases, including macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, autoimmune uveitis (AU), optic nerve crush (ONC), and retinopathy of prematurity (ROP). In this narrative review, we aimed to consolidate the current literature on exosomes as a therapeutic strategy for ROP with a brief overview of the applied exosome and available sources and mechanism of action.}, }
@article {pmid42173886, year = {2026}, author = {Kai, JY and Gong, SY and Li, DL and Lanca, C and Grzybowski, A and Ke, C and Pan, CW}, title = {A multimodal ocular aging index reveals proteomic pathways and predicts incident age-related eye diseases.}, journal = {npj aging}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41514-026-00418-1}, pmid = {42173886}, issn = {2731-6068}, support = {2024YFC2510800//National Key R&amp;D Program of China/ ; }, abstract = {Chronological age incompletely captures heterogeneity in biological aging. In this prospective study of 45,819 UK Biobank participants, we developed a multimodal ocular aging index (MOAI) by integrating ophthalmic phenotypes with plasma proteomic and metabolomic profiles using machine learning. The MOAI quantifies divergence between ocular biological and chronological age. Over 13.80 years of follow-up, accelerated ocular aging was significantly associated with higher risks of incident age-related macular degeneration and cataract, even after adjustment for chronological age and established risk factors. Incorporation of the MOAI significantly improved risk reclassification beyond traditional predictors. Explainable modeling and pathway enrichment analyses identified inflammation-related proteins and pathways, including cytokine-cytokine receptor interactions and PI3K-Akt signaling, as key drivers of accelerated ocular aging. These findings establish a multimodal framework for quantifying organ-specific biological aging, link ocular aging to systemic inflammatory processes, and highlight the eye as a sensitive readout of aging biology with implications for healthspan.}, }
@article {pmid42174147, year = {2026}, author = {Fukuda, Y and Shiose, S and Notomi, S and Maehara, Y and Yuge, K and Kiyohara, K and Yasaka, Y and Mori, K and Fujiwara, K and Kano, K and Ishikawa, K and Murakami, Y and Sonoda, KH}, title = {Two-year treatment outcomes in neovascular age-related macular degeneration with type 3 macular neovascularisation.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42174147}, issn = {1476-5454}, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) with type 3 macular neovascularisation (MNV) carries a high risk of macular atrophy (MA) during anti-vascular endothelial growth factor (anti-VEGF) treatment. Previous studies have suggested that a greater injection burden is associated with a higher MA risk. We evaluated 2-year outcomes of patients with nAMD with type 3 MNV following the treat and extend (TAE) and pro re nata (PRN) regimens and identified the risk factors for MA.<br><br>SUBJECTS: This retrospective study included 97 eyes of 68 treatment-na&#xef;ve nAMD patients with type 3 MNV. All eyes received monthly anti-VEGF injections for 3 months as a loading phase and were followed for >2 years. Analyses were performed at the eye level for clinical outcomes; for risk-factor analyses of incident MA, one eye per patient was included. Outcomes included best-corrected visual acuity (BCVA) and central macular thickness (CMT).<br><br>RESULTS: Compared with PRN, TAE achieved better BCVA at 24 months (mean difference, -0.26 logMAR; 95% CI, -0.50 to -0.02). CMT was lower with TAE at 12 months (mean difference, -47.0&#x2009;&#xb5;m; 95% CI, -86.1 to -8.0). Retinal haemorrhage recurrence was less frequent with TAE (16.4% vs. 52.4%; risk difference, -36.0%; 95% CI, -57.8% to -9.5%). In multivariable models, greater injection number and thinner baseline central choroidal thickness were associated with incident MA (P&#x2009;<&#x2009;0.05), whereas regimen type itself was not.<br><br>CONCLUSIONS: Despite a higher injection burden, TAE maintained superior functional outcomes over two years relative to PRN.}, }
@article {pmid42177462, year = {2026}, author = {Nakamura, M and Koido, S and Bito, T and Horiguchi, H and Shimizu, Y and Shimabuku, M and Taguchi, J and Gunji, H and Sugiyama, H and Nakano, T}, title = {WT1-pulsed dendritic cell vaccination for neovascular age-related macular degeneration: a phase I pilot feasibility study.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04946-y}, pmid = {42177462}, issn = {1471-2415}, support = {2022-016SR//The Jikei University Research Fund/ ; }, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss. Although anti-VEGF therapy is effective, frequent injections carry risks and may not fully address the underlying disease process. Wilms' tumor gene 1 (WT1), an upstream regulator of VEGF, is expressed in choroidal neovascular membranes and may represent a biologically relevant adjunctive target in nAMD. This pilot study evaluated the safety, tolerability, and immunogenicity of WT1-targeted dendritic cell (WT1-DC) vaccines and their effects on retinal morphology and visual function in nAMD patients, with secondary endpoints including clinical outcomes and in vitro WT1-specific T-cell responses.<br><br>METHODS: Two patients initially received three monthly intravitreal injections of aflibercept (2&#xa0;mg each), followed by 15 subcutaneous vaccinations with WT1-DCs. The vaccine contained both WT1-specific helper and killer peptides restricted to HLA-A*24:02. In addition, a helper peptide restricted to MHC class II and class I (HLA-A*02:01/02:06) was used.<br><br>RESULTS: WT1-DC vaccination was well tolerated, and adverse events were limited. One patient maintained a stable retinal morphology and visual acuity without additional anti-VEGF therapy, whereas the other experienced recurrent subretinal fluid accumulation requiring intermittent rescue injections and a gradual decline in best-corrected visual acuity. Peripheral blood mononuclear cells from both patients exhibited functional CD4&#x2009;+&#x2009;and CD8&#x2009;+&#x2009;T-cell responses during vaccination and produced IFN-&#x3b3; and TNF-&#x3b1; upon WT1 peptide stimulation in vitro.<br><br>CONCLUSIONS: WT1-DC vaccination was feasible and well tolerated in these two patients who were clinically managed within the nAMD spectrum. Exploratory laboratory findings suggested WT1 peptide-responsive T-cell activity in vitro, but clinically meaningful in vivo immunogenicity was not established. Given the extremely small sample size, the confounding effect of prior anti-VEGF loading therapy, and diagnostic uncertainty regarding CNV etiology in one patient, no conclusions regarding therapeutic efficacy can be drawn. These observations support further investigations of WT1-DC vaccination in larger controlled studies.<br><br>TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTc030210068), registered May 7, 2021.}, }
@article {pmid42171393, year = {2026}, author = {Shen, T and Li, J and Yang, X and Xia, J and Zhou, H and Ma, Q and Wang, Y and Wang, J and Wang, Z and Liu, K and Yan, B}, title = {Genetic and epidemiological analyses of alcohol consumption patterns and age-related macular degeneration risk among current drinkers: a role for TNFRSF10A.}, journal = {Journal of global health}, volume = {16}, number = {}, pages = {04124}, doi = {10.7189/jogh.16.04124}, pmid = {42171393}, issn = {2047-2986}, mesh = {Humans ; *Alcohol Drinking/epidemiology/genetics/adverse effects ; *Macular Degeneration/genetics/epidemiology ; Female ; Male ; Middle Aged ; Risk Factors ; Aged ; Mendelian Randomization Analysis ; Proportional Hazards Models ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Alcohol intake, a major modifiable lifestyle factor, has been variably associated with age-related macular degeneration (AMD). We aim to investigate the association and potential causal relevance of alcohol consumption with AMD risk using complementary epidemiological and genetic approaches.<br><br>METHODS: We used nonlinear Cox proportional hazards models to evaluate incident AMD associations among 440&#x2009;052 participants of European ancestry with a mean age of 56.7 years and of whom 53.7% were female. We employed two-sample Mendelian randomisation (MR), integrating summary-level genetic associations with cis-expression quantitative trait locus colocalisation between alcohol consumption (UK Biobank n&#x2009;=&#x2009;433&#x2009;353) and AMD (GWAS Catalog n&#x2009;=&#x2009;105&#x2009;248; FinnGen study n&#x2009;=&#x2009;474&#x2009;181), to refine genetic instruments for biologically relevant measures of alcohol consumption. We also used inverse-variance weighting (IVW) and conducted sensitivity analyses. In addition, we integrated publicly available single-cell RNA sequencing (scRNA-seq) data from human retina and retinal pigment epithelium/choroid tissues to assess cell-type-specific expression patterns of genes implicated in AMD.<br><br>RESULTS: Over the follow-up period, 1553 participants were diagnosed with AMD. Alcohol consumption was inversely associated with AMD risk (hazard ratio (HR)&#x2009;=&#x2009;0.83; 95% confidence interval (CI)&#x2009;=&#x2009;0.73&#x2009;-&#x2009;0.95), with the association being most pronounced for wine (HR&#x2009;=&#x2009;0.86; 95% CI&#x2009;=&#x2009;0.76&#x2009;-&#x2009;0.97). Beer consumption showed a positive association with AMD risk. These results were supported by MR analyses (IVW &#x3b2;&#x2009;=&#x2009;-0.13; P&#x2009;=&#x2009;0.02) and remained consistent in sensitivity analyses. Colocalisation analysis highlighted TNFRSF10A (PP.H4&#x2009;=&#x2009;0.98) as a shared locus associated with both alcohol intake and AMD risk. Integration with scRNA-seq data from human samples suggested endothelial cell-enriched expression of TNFRSF10A in AMD tissues, providing functional context for the genetic prioritisation of this locus.<br><br>CONCLUSIONS: Epidemiological and genetic data suggest that TNFRSF10A and its variants may be involved in AMD, with alcohol consumption patterns potentially contributing to this association. This provides new hypotheses for how lifestyle factors may influence disease risk. These findings should not be interpreted as evidence supporting alcohol consumption for AMD prevention, given the potential for residual confounding and the well-established health risks of alcohol.}, }
@article {pmid42171426, year = {2026}, author = {Muqit, MMK and Villani, GM and Dami, M and Druchkiv, V and Spampinato, G and Cadoni, S and Hornig, R and Holz, FG and Bittner, AK}, title = {Patient Preferences for the PRIMA Retinal Prosthesis for Vision Restoration for Dry Age-Related Macular Degeneration: An International Survey Study.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {5}, pages = {18}, doi = {10.1167/tvst.15.5.18}, pmid = {42171426}, issn = {2164-2591}, mesh = {Humans ; Male ; Female ; *Visual Prosthesis ; Aged ; Activities of Daily Living ; *Patient Preference ; Middle Aged ; Aged, 80 and over ; *Macular Degeneration ; Surveys and Questionnaires ; Visual Acuity ; *Geographic Atrophy/rehabilitation/physiopathology ; *Electric Stimulation Therapy ; }, abstract = {PURPOSE: To gauge age-related macular degeneration (AMD) patient opinions on the potential acceptability of the PRIMA neurostimulation device for partial vision restoration during activities of daily living (ADLs).<br><br>METHODS: An international multisite survey study was completed by 196 visually impaired AMD individuals online through a foundation or society (United States, United Kingdom) or via telephone or in-person interviews (Italy, France, Germany) to inquire about ADLs for which retinal implant systems could potentially offer assistance.<br><br>RESULTS: A high level of interest ("very likely") to use a vision restoration device was reported by approximately half of the respondents for completing documents, recognizing people, hobbies, identifying money, reading street signs and store names, and seeing signs in public. The odds of being very likely to use a vision restoration device for these tasks were not statistically significantly related to whether the participant had partial or severe sight loss. Odds of being very likely to use it for completing documents or reading mail (odds ratio = 2.33; 95% confidence interval, 1.2-4.5; P = 0.013) were significantly greater among those who had stopped doing these tasks or relied on others. The majority (66.5%) indicated that they would be comfortable wearing the vision restoration glasses around others. Participation in vision rehabilitation was acceptable if the training duration was not excessive.<br><br>CONCLUSIONS: AMD respondents with varying vision loss indicated interest and acceptability of a vision restoration device for ADLs.<br><br>TRANSLATIONAL RELEVANCE: In support of future research and development efforts, AMD respondents endorsed high levels of willingness to use a vision restoration system involving a surgically implanted device and electronic glasses.}, }
@article {pmid42172633, year = {2026}, author = {Mei, L and Weh, E and Yu, M and Walsh, L and Fahim, AT and Liu, Y and Besirli, CG and Schwendeman, A}, title = {High-Density Lipoprotein Nanoparticles Delivering Liver X Receptor Agonist for the Treatment of Age-Related Macular Degeneration.}, journal = {Molecular pharmaceutics}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.molpharmaceut.5c01852}, pmid = {42172633}, issn = {1543-8392}, abstract = {Liver X nuclear receptor (LXR) agonists are promising therapeutic agents whose efficacy has been demonstrated in vitro and in vivo for the treatment of atherosclerosis. The accumulation of lipids is a common pathogenic mechanism between both atherosclerosis and age-related macular degeneration (AMD). As such, a growing number of studies have implicated LXR agonists as a potential therapeutic option for the treatment of AMD. Unfortunately, the clinical application of LXR agonists has been hindered by their undesirable side effects when administered systemically, as well as their limited aqueous solubility, necessitating a drug delivery system (DDS) for targeted local delivery. Synthetic high-density lipoprotein (sHDL) nanoparticles have intrinsic cholesterol transport and anti-inflammatory functions, making them ideal for the treatment of diseases where cholesterol accumulation and inflammation contribute to the pathology. These nanoparticles also excel as an effective DDS for hydrophobic drugs due to their ability to encapsulate drugs in their hydrophobic core. Thus, we developed a new strategy for AMD treatment by encapsulating an LXR agonist, T0, in sHDL nanoparticles (sHDL-T0). Our in vitro studies showed that sHDL-T0 can effectively upregulate cholesterol transport from mature iPSC-RPE (retinal pigment epithelium) due to increased transcription of cholesterol transporters and by serving as an acceptor for effluxed cholesterol. Encapsulating T0 in sHDL nanoparticles increased the aqueous solubility of T0 significantly, allowing for direct delivery to the eye without organic solvents. In vivo delivery of sHDL-T0 caused upregulation of the Abca1/g1 transporters in the retina and retinal pigment epithelium, suggesting that T0 can escape sHDL nanoparticles and stimulate the LXR pathway. Most importantly, in a murine model of nonexudative (dry) age-related macular degeneration (dAMD), sHDL-T0 administration resulted in the down-regulation of Tnfα, Il-6, and Nlrp3 mRNA expression, and reduced the number of CD45-positive inflammatory cells in comparison to vehicle-treated eyes. Our results provide proof-of-concept for using sHDL nanoparticles to deliver the LXR agonist T0 to restore cholesterol homeostasis and reduce local inflammation in the outer retina, offering a novel therapeutic strategy for dAMD.}, }
@article {pmid42164977, year = {2026}, author = {Dhoot, DS and Garg, SJ and Brown, DM and Suñer, IJ and Rahimy, E and Boyer, DS and Naidu, K and Li, C and Baumal, CR and Guymer, RH}, title = {Efficacy of Continuous Pegcetacoplan Treatment for Subfoveal Geographic Atrophy in Age-Related Macular Degeneration: 36-Month Results from OAKS, DERBY, and GALE Open-Label Extension.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {579237}, pmid = {42164977}, issn = {1177-5467}, abstract = {PURPOSE: To report efficacy of intravitreal pegcetacoplan treatment over 36 months in eyes with subfoveal geographic atrophy (GA).<br><br>PATIENTS AND METHODS: The GALE (NCT04770545) open-label extension trial adds 12 months of results to the 24-month Phase 3 OAKS (NCT03525613) and DERBY (NCT03525600) trials, representing up to 36 months of continuous pegcetacoplan treatment. They included a heterogeneous population of eyes with subfoveal GA (63%). Pegcetacoplan-treated eyes enrolling in GALE continued at the same interval of pegcetacoplan monthly (PM) or every other month (PEOM). Patients' eyes in sham monthly or every-other-month arms crossed over to receive pegcetacoplan in GALE at the same interval (sham crossover). Consequently, projected sham, calculated from prior 24-month GA growth rate of sham-observed eyes in OAKS and DERBY averaged across four 6-month segments, was the comparator for the first 12 months of GALE (months 24-36). This analysis reports results of eyes with subfoveal GA at baseline.<br><br>RESULTS: In eyes with subfoveal GA, 84% had best corrected visual acuity (BCVA) &#x2265;20/200 and 38% had BCVA &#x2265;20/63 at OAKS and DERBY baseline. Pegcetacoplan reduced subfoveal GA growth rate by 21% (p<0.0001) with PM and 19% (p=0.0001) with PEOM over 36 months. Increasing efficacy over time was noted between months 24 and 36; 31% reduction in subfoveal GA growth rate with PM and 25% reduction with PEOM (both p<0.0001) compared with projected sham. Microperimetry demonstrated significant reduction in formation of absolute scotomas with PM at 24 months (-2.5 number of scotomas formed; 95% confidence interval [CI]: -4.5, -0.4; p=0.0205) and 36 months (-4.0 number of scotomas formed; 95% CI: -6.8, -1.2; p=0.0050), compared to sham crossover in subfoveal GA. Safety profile in GALE was consistent with OAKS and DERBY.<br><br>CONCLUSION: Long-term efficacy of pegcetacoplan in slowing GA progression was demonstrated over 36 months in eyes with subfoveal GA.}, }
@article {pmid42165512, year = {2026}, author = {Yeh, TC and Lin, JB and Mruthyunjaya, P and Leng, T and DeBoer, C and Sepah, YJ and Almeida, DRP and Smith, S and Mahajan, VB}, title = {A Simplified Classification for Age-Related Macular Degeneration Based on Optical Coherence Tomography.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {}, number = {}, pages = {1-7}, doi = {10.3928/23258160-20260409-02}, pmid = {42165512}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: As optical coherence tomography (OCT) has enabled the identification of an expanding set of age-related macular degeneration (AMD) risk biomarkers and become central to routine clinical practice, there remains a need for a simplified grading scheme that allows physicians to communicate and synchronize AMD grading directly from standard OCT imaging rather than relying on traditional color fundus imaging. This study aims to establish a standardized OCT-based AMD classification that balances diagnostic accuracy with practicality for use across clinical and research settings.<br><br>PATIENTS AND METHODS: Spectral-domain OCT scans were independently graded by two retinal specialists following the newly proposed Stanford OCT-Based AMD Classification (SOAC). Discrepancies were adjudicated by a third independent retinal specialist. Inter-grader agreement was assessed using weighted kappa coefficients.<br><br>RESULTS: Among the 109 eyes from 108 patients (mean age 79.61 &#xb1; 7.57 years; 41.7% men, 58.3% women), AMD staging based on SOAC was distributed as follows: normal aging in nine patients (8.3%), early AMD in 16 (14.7%), intermediate AMD in 32 (29.4%), neovascular AMD (nAMD) in 18 (16.5%), geographic atrophy (GA) in 20 (18.3%), and combined nAMD and GA in 14 (12.8%). The overall intergrader agreement demonstrated robust consistency, with a weighted kappa value of 0.95 (95% CI: 0.92-0.98), signifying excellent intergrader reliability and reinforcing the validity of SOAC.<br><br>CONCLUSION: SOAC provides a standardized, OCT-based framework for AMD grading that demonstrates high intergrader agreement. By enabling consistent classification from commonly acquired OCT scans, SOAC supports reliable disease staging and facilitates integration across clinical studies and translational research. As imaging and molecular data continue to expand, SOAC can serve as a common OCT-based reference for phenotype refinement and longitudinal AMD studies.}, }
@article {pmid42166380, year = {2026}, author = {Prieto-Nevárez, HM and Tarango-García, A and Ollivier-Valenzuela, LI and Álvarez-Cardona, A and Lugo-Reyes, SO}, title = {Immune Privilege of the Eye: A Delicate Balance Between Clarity and Chaos.}, journal = {Ocular immunology and inflammation}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/09273948.2026.2677099}, pmid = {42166380}, issn = {1744-5078}, abstract = {PURPOSE: This review aims to describe the key mechanisms behind ocular immune privilege and how disruption of this immunological balance contributes to ocular disease.<br><br>METHODS: A narrative review of the literature was performed focusing on ocular immune privilege and diseases in which these mechanisms are altered. The review considered evidence related to corneal transplantation, peripheral ulcerative keratitis, age-related macular degeneration, autoimmune uveitis, diabetic retinopathy, ocular tumors, and allergic conjunctivitis.<br><br>RESULTS: The reviewed literature demonstrates how ocular immune privilege is maintained mainly by a combination of anatomical barriers, local immunomodulatory mediators, regulatory immune-cell interactions, and ACAID-mediated systemic tolerance. Across the ocular conditions reviewed, disease was generally associated with partial disruption, remodeling, or exploitation of these mechanisms rather than complete loss of immuneprivilege. These alterations varied according to the affected ocular compartment and clinical context, but recurrently involved disruption of immune homeostasis, increased inflammatory signaling, altered leukocyte activity, impaired barrier integrity, and reduced local immune restraint. Overall, the evidence supports ocular immune privilege as a dynamic system that is not absolute, preserving ocular homeostasis under normal conditions but contributing to disease when its protective mechanisms are disrupted.<br><br>CONCLUSIONS: Ocular immune privilege is best understood as a protective but conditional state. Its disruption does not entirely explain most ocular diseases by itself, but it helps illustrate why inflammation, transplantation, tumors, allergy, and other pathologies can behave differently in ocular tissues. Recognizing which elements are preserved or lost in each setting may improve understanding of ocular pathology and support more precise immune-directed approaches.}, }
@article {pmid42168916, year = {2026}, author = {Wang, YX and Holz, FG and Coenen, M and Sun, X and Xie, W and Panda-Jonas, S and Dong, L and Jonas, JB}, title = {Safety and pharmacokinetics of intravitreally repeatedly injected panitumumab in non-human primates - a study performed under good laboratory practice.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04909-3}, pmid = {42168916}, issn = {1471-2415}, support = {2019-4//Research Development Fund of Beijing Municipal Health Commission/ ; }, abstract = {BACKGROUND: Epidermal growth factor (EGF) has been suggested to play a role in myopic axial elongation, and EGF receptor blockade may be of potential therapeutic benefit. Here we examined the ocular and systemic toxicity of panitumumab, a clinically used EGF receptor blocker in oncology, when repeatedly administered intravitreally in non-human primates.<br><br>METHODS: The experimental study included six non-human cynomolgus primates (3 males) which underwent five (n&#x2009;=&#x2009;1 animal) or three (n&#x2009;=&#x2009;5 animals) 4-weekly intravitreal injections of panitumumab (dose: 0.78&#xa0;mg (78&#xb5;L)) or of phosphate buffered solution (PBS) (78&#xb5;L).<br><br>RESULTS: The study group with panitumumab injections consisted of 7 eyes and the control group with PBS injections of 5 eyes. Two animals of the study group developed on Day 59 (two days after the third injection) signs of a slight intraocular inflammation (cells in anterior chamber and vitreous) and reduction of intraocular pressure, with most of the signs having resolved at study end (Day 86). Panitumumab reached the serum peak concentration at 24&#xa0;h after the first dose (Cmax 18.3 to 946ng/mL; serum exposure 2120 to 37300&#xa0;h*ng/mL). Four weeks after the third injection (Day 86), panitumumab concentrations in aqueous humor ranged from 12.8 ng/mL to 65.0 ng/mL, and in the vitreous from 1.74 ng/mL to 531 ng/mL, with a panitumumab accumulation factor between 0.891 and 0.012. TUNEL staining did not reveal pathological results.<br><br>CONCLUSIONS: Except for mild and reversible intraocular inflammation in some eyes, repeated intravitreal application of 0.78&#xa0;mg panitumumab did not result in ophthalmological or systemic adverse effects in non-human primates.}, }
@article {pmid42156641, year = {2026}, author = {Kuznik, A and Coughlan, A and Pinsent, A and Toro-Diaz, H and Sherman, S and Patel, NA}, title = {Summary of Research: Economic Benefit of Aflibercept 8 mg Versus Faricimab for Neovascular Age-Related Macular Degeneration or Diabetic Macular Edema in the US.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42156641}, issn = {2193-8245}, abstract = {This is a summary of the original article "Economic Benefit of Aflibercept 8 mg Versus Faricimab for Neovascular Age-Related Macular Degeneration or Diabetic Macular Edema in the US". Aflibercept 8 mg and faricimab are medications given by injections into the eye for treating the eye diseases neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Comparing costs of these medications is important for patients, healthcare practitioners, and the people who pay for medications (payers). This research used an economic model to compare the estimated costs of aflibercept 8 mg and faricimab over 5 years in the United States, based on numbers of injections given in clinical trials. The analysis indicated that the lower number of injections needed for aflibercept 8 mg would lead to lower costs compared with faricimab for patients with nAMD or DME, which could benefit patients, healthcare providers, and payers.}, }
@article {pmid42156919, year = {2026}, author = {Singappuli, R and Abeysiri, P and Rahman, W}, title = {Infographic: Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, Phase 3 trial.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42156919}, issn = {1476-5454}, }
@article {pmid42159203, year = {2026}, author = {Yu, HN and Ying, GS}, title = {Associations Between Age-Related Eye Diseases and Mental Health Conditions.}, journal = {Ophthalmic epidemiology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/09286586.2026.2675294}, pmid = {42159203}, issn = {1744-5086}, abstract = {PURPOSE: Age-related eye conditions, including cataract, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and dry eye disease (DED), are prevalent and have been linked to mental health disorders, though findings are mixed. This study systematically examines associations between these ocular diseases and mental health conditions using a large real-world dataset.<br><br>METHODS: A retrospective cohort study was conducted using the Global TriNetX database. Five cohorts (aged&#x2009;&#x2265;&#x2009;40&#x2009;years) with diagnoses of cataract, glaucoma, AMD, DR, and DED were propensity score matched 1:1 with controls without these eye diseases based on demographic and clinical covariates. Outcome measures were the incidence of mood, anxiety, and psychotic disorders, identified using ICD-10 codes. Hazard ratios (HRs) and 95% confidence intervals (95% CI) from the Cox proportional hazards models were used to assess associations.<br><br>RESULTS: Study included patients with cataract (N&#x2009;=&#x2009;121,060), glaucoma (N&#x2009;=&#x2009;122,663), AMD (N&#x2009;=&#x2009;39,915), DR (n&#x2009;=&#x2009;43,495), DED (n&#x2009;=&#x2009;148,221), and their median follow-up ranging 1263-2191&#x2009;days. Cataracts, glaucoma, DR, and DED were each associated with mildly increased risks of mood (HR range: 1.05-1.10), anxiety (HR range: 1.04-1.12), and psychotic disorders (HR range: 1.18-1.36). When accompanied by visual impairment, risks were higher: mood (HR range: 1.22-1.57), anxiety (HR range: 1.16-1.32), and psychotic disorders (HR range: 1.54-2.15).<br><br>CONCLUSION: Age-related ocular diseases, particularly when presented with vision impairment, are independently associated with elevated risks of mental health disorders. These findings underscore the need for integrated ophthalmic-psychiatric care and early intervention before vision loss to address the complex needs of affected patients.}, }
@article {pmid42162248, year = {2026}, author = {Korobelnik, JF and Leal, S and Lanzetta, P and , }, title = {Infographic: Efficacy and Safety of HighDdose Intravitreal Aflibercept 8 mg in Patients with Treatment-Naïve Neovascular Age-Related Macular Degeneration: Week 96 Results from the Phase 3 PULSAR Trial.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41433-026-04486-1}, pmid = {42162248}, issn = {1476-5454}, }
@article {pmid42162254, year = {2026}, author = {Ezzine, S and Gale, R and Bailey, C and Patel, PJ and Sivaprasad, S and Keshk, Z and Eissing, T and Höchel, J and Gilbert, R and Morgan-Warren, P}, title = {Pharmacological principles of intravitreal drug therapy and their implications for clinical practice: a primer for the ophthalmologist.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42162254}, issn = {1476-5454}, abstract = {Intravitreal (IVT) anti-vascular endothelial growth factor (anti-VEGF) therapies are the standard of care for retinal diseases such as neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO). Despite the favourable efficacy and safety profiles of these therapies, decreasing the treatment burden is still an unmet need because frequent injections may be required over many years. The pharmacokinetic and pharmacodynamic properties of IVT therapies, such as ocular half-life and clearance, can affect the duration of VEGF suppression and thus influence clinical outcomes. Although some properties are inherent to the drug molecule (such as molecular weight, binding affinity and potency) and cannot be altered without changing the structure of the molecule, other factors (such as the dose of the drug) can be increased, which may prolong VEGF suppression time in the eye and, in turn, may lead to a more durable effect of the drug. In addition to pharmacokinetic and pharmacodynamic properties, individual patient factors such as age, surgical history and disease status can also affect the pharmacokinetics, pharmacodynamics and observed effectiveness of a drug. This article reviews the key pharmacological properties of IVT anti-VEGF treatments for nAMD and DMO often referred to in the literature, and aims to elucidate their meaning and clinical relevance for managing retinal diseases.}, }
@article {pmid42162902, year = {2026}, author = {Lin, R and Cai, Z and Zheng, T and Wu, Y and Xu, Z and Luo, Y and Liang, F and Zhu, M and Yu, J and Cai, W}, title = {Macrophage-derived SPP1 promotes subretinal fibrosis by YAP1 phase separation in retinal pigment epithelium.}, journal = {Metabolism: clinical and experimental}, volume = {}, number = {}, pages = {156648}, doi = {10.1016/j.metabol.2026.156648}, pmid = {42162902}, issn = {1532-8600}, abstract = {BACKGROUND: Subretinal fibrosis (SRF) is a critical end-stage feature of neovascular age-related macular degeneration (nAMD) with limited treatment options. However, the pathological mechanism during the transformation of choroidal neovascularization (CNV) into SRF remains unclear.<br><br>METHODS: Bulk RNA-seq of mouse macrophages treated with succinate or lactate in acidic hypoxia identified Spp1 as a key fibrosis-associated gene. Dynamic Spp1 expression was tracked by single-cell RNA-seq in a CNV model, while laser-induced CNV and SRF models assessed the pro-fibrotic role of Spp1 in vivo. In vitro, the binding of SPP1 to RPE CD44 was identified through bioinformatics and Co-IP, and Western blotting examined downstream CD44/RhoA/YAP1 pathway proteins. qPCR quantified nine YAP1 isoforms to identify the predominant one after SPP1 intervention. The specific YAP1 isoform undergoing liquid-liquid phase separation (LLPS) was determined by visualizing intracellular localization and biomolecular condensates via EGFP-tagged plasmid transfection, with LLPS characteristics confirmed by live-cell imaging and fluorescence recovery after photobleaching (FRAP). ATAC-seq identified the transcription factors co-activated with YAP1 driving fibrosis, while EMT phenotypes were evaluated using pro-fibrotic gene expression, migration, and collagen contraction assays.<br><br>RESULTS: Succinate and lactate upregulated Spp1 and activated correlated Ca[2+] influx pathways. An expanding Spp1[+] M&#x3c6; population was found in early-to-mid CNV. SRF mice showed elevated Spp1in M&#x3c6;s, and intravitreal Spp1 worsened CNV fibrosis, which blocked by small interfering extracellular matrix receptor III (siCD44). In vitro, SPP1 bound to CD44 activated the RhoA/YAP1 pathway, characterized by a predominant isoform shift from YAP1-1&#x3b1; to YAP1-2&#x3b1;. The nuclear translocation and LLPS of YAP1-2&#x3b1; facilitated pro-fibrotic gene transcription by binding to TEAD4, thereby promoting EMT-like changes in RPE.<br><br>CONCLUSIONS: Under accumulation of acidic metabolites, SPP1-overexpressing M&#x3c6;s promote EMT in the RPE via CD44/RhoA-mediated YAP1-2&#x3b1; LLPS. This process involves binding to TEAD4 to co-activate pro-fibrotic gene transcription, revealing novel pathomechanisms involved in SRF progression.}, }
@article {pmid42163181, year = {2026}, author = {Akkan Aydogmus, FS and Gursoy, T and Ozdemir, O and Elalmis, OU and Kalayci, D}, title = {Outcome and factors affecting prognosis in treat and extend treatment for neovascular age-related macular degeneration-a real world study.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04905-7}, pmid = {42163181}, issn = {1471-2415}, abstract = {BACKGROUND: To evaluate the outcome of treat and extend (T&amp;E) for neovascular age related macular degeneration (nAMD) at 12, 18 and 24 months and the impact of clinical characteristics on treatment success defined as extension of treatment interval to ≥12 weeks and functional improvement or stability.<br><br>METHODS: Visual and anatomical outcomes evaluated by optical coherence tomography (OCT) and extension of treatment interval to &#x2265;12&#x2009;weeks were analyzed retrospectively. Clinical factors effective on extension of the treatment interval and visual outcome were evaluated.<br><br>RESULTS: There were 138 eyes with at least 18&#x2009;months of follow-up. Patients exhibited a significant improvement in visual acuity and reduction in central subfield thickness (CST), subretinal fluid (SRF), intraretinal fluid (IRF) and pigment epithelial detachment (PED) at both the 12[th] and 18[th] months. There was recurrence of IRF and a reduction in gain of visual acuity at 24&#x2009;months. In 15.2%, 36.2% and 40.6% of eyes, the treatment interval could be extended to &#x2265;12-weeks at 12, 18 and 24&#x2009;months. Presence of a large PED was found as the only independent variable effecting extension of treatment interval to 12&#x2009;weeks at 18&#x2009;months. Baseline BCVA of >20/100 and no IRF at baseline were identified as independent predictive factors for better visual acuity at 18&#x2009;months.<br><br>CONCLUSION: Presence of IRF and a visual acuity of &#x2264;20/100 at baseline were found to be negative predictors for visual prognosis, while large PED was a negative predictive factor for less frequent treatment, but it did not affect visual outcome. Treatment interval should be extended cautiously in patients with baseline intraretinal fluid and visual acuity of &#x2264;20/100 in order to balance decreasing the burden of treatment by longer treatment intervals with improvement of visual gain.}, }
@article {pmid42163661, year = {2026}, author = {Liu, S and Zhang, M and Xie, H and Ding, X and Chen, Y and Wang, X and Cui, H and Wang, X}, title = {Neuroprotective Effects of Glucagon-like Peptide-1/glucagon-like Peptide-1 Receptor Agonists on Neurodegenerative Eye Diseases and their Molecular Mechanisms: A Recent Update.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/011570159X446766260311123827}, pmid = {42163661}, issn = {1875-6190}, abstract = {Glucagon-like peptide-1 receptor agonists (GLP-1RAs), a novel class of glucose-lowering drugs, specifically bind to the glucagon-like peptide-1 receptor and substantially improve glycemic control by mimicking the physiological effects of endogenous glucagon-like peptide-1 (GLP-1). Recent studies have shown multiple beneficial effects of GLP-1 and GLP-1RAs, including anti-inflammatory, antioxidant, and neuroprotective effects, indicating their potential therapeutic applications in treating neurodegenerative diseases. Notably, several ocular disorders, including diabetic retinopathy, glaucoma, age-related macular degeneration, and dry eye disease, also exhibit neurodegeneration-related pathophysiological changes. Hence, it is critical to explore new therapeutic strategies to address the clinical challenges posed by these neurodegenerative ocular diseases. Given this background, we conducted a review of recent preclinical and clinical studies to update and summarize (1) the therapeutic potential of GLP-1/GLP-1RAs for neurodegenerative ocular diseases, (2) clinical evidence supporting the neuroprotective effects of GLP-1/GLP-1RAs in these ocular diseases, and (3) the molecular mechanisms underlying the neuroprotective effects of GLP-1/GLP-1RAs on ocular neural cells, including inflammatory and oxidative stress response inhibition and Ca2+ homeostasis regulation. This review aims to provide a theoretical foundation and research outlook for extending the application of GLP-1RAs to treat neurodegenerative ocular diseases.}, }
@article {pmid42164429, year = {2026}, author = {Raghavendra, AJ and Saeedi, OJ and Hammer, DX and Liu, Z}, title = {Single-scan adaptive optics-enabled quantitative optical coherence tomography angiography for absolute three-dimensional retinal blood flow mapping.}, journal = {Optica}, volume = {13}, number = {1}, pages = {125-134}, pmid = {42164429}, issn = {2334-2536}, abstract = {Accurate measurement of blood flow is critical for understanding metabolic function and disease progression, particularly in the retina, where conditions such as diabetic retinopathy, macular degeneration, and glaucoma are closely linked to impairment in microvascular circulation. However, current imaging techniques, including optical coherence tomography angiography (OCTA) and Doppler OCT, do not generally provide direct and absolute blood flow measurements, particularly at the capillary level. Adoption of adaptive optics (AO) and high-speed swept-source lasers in OCT systems has enabled video-rate volumetric acquisition with the ability to resolve individual red blood cells (RBC). Here, we present a quantitative AO-OCTA approach that enables 3D blood flow mapping by integrating OCTA-based vessel morphology with a 3D Radon transform of RBC streaks to measure cell velocity from the raw spatio-temporal OCT data. We describe a complete post-processing pipeline to determine single-cell velocity, vessel diameter, and flow rate using a single scan. We demonstrate depth-resolved flow rates across retinal vessels with diameters from 5 to 120 μm and velocities ranging from 0.5 to 54 mm/s, capturing the wide range of flow dynamics in the human retina. Our methodology is a powerful tool for quantitative blood flow imaging, establishing a robust method for noninvasive, high-resolution microvascular flow quantification with multiple potential applications in biomedical research and clinical diagnostics.}, }
@article {pmid42164909, year = {2026}, author = {Dihan, QA and Brown, AD and Alshammari, N and Shakarchi, AF and Chauhan, MZ and Sallam, AB}, title = {Eye on the Eclipse: Demographic Trends in Solar Retinopathy From 2012 to 2024.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261447500}, pmid = {42164909}, issn = {2474-1272}, abstract = {Purpose: To characterize demographic, psychiatric, and retinal comorbidities associated with solar retinopathy in the United States from 2012 to 2024 and to evaluate incidence trends in relation to solar eclipse years. Methods: This retrospective, population-based cohort study was conducted using the TriNetX US Collaborative Research Network. Patients with newly diagnosed solar retinopathy (International Classification of Diseases, 10th edition, code H31.02) were identified and included if they had a documented ophthalmology visit and retinal imaging. Annual incidence rates were compared between eclipse and non-eclipse years. Demographic characteristics and the prevalence of psychiatric disorders, substance use disorders, and concurrent retinal conditions were analyzed. Results: Among 1 042 995 patients, 555 were diagnosed with solar retinopathy. The mean annual incidence was 44.5 cases, with a peak observed in 2017 (71 cases). There was no statistically significant difference between eclipse years (51.5 cases/year) and non-eclipse years (37.3 cases/year; P = .062). The median age at diagnosis was 54.1 ± 21.3 years, and 59% of patients were men. Sixty-eight percent of individuals were White, 27% were Black, and 5% were Asian. Psychiatric comorbidities were common, with 32% diagnosed with anxiety disorders, 24% with major depressive episodes, and 10% with psychotic disorders. Substance use disorders were also observed, including nicotine dependence (18%) and cannabis-related disorders (6%). Concurrent retinal conditions included age-related macular degeneration (8%), hereditary retinal dystrophies (7%), and central serous chorioretinopathy (3%). There was no correlation between solar retinopathy incidence and geographic exposure to eclipse totality. Conclusions: The incidence of solar retinopathy remained low over the study period, with no significant increase during eclipse years. However, psychiatric and retinal comorbidities were prevalent among affected individuals. These findings highlight demographic and psychosocial disparities and support the need for targeted, culturally informed preventive education and eye safety initiatives before future eclipses.}, }
@article {pmid42156546, year = {2026}, author = {Ghareeb, AE and Chang, B and Mitchener, L and Yiu, A and Szostkiewicz, CJ and Shved, D and Gyimesi, GJ and Laurent, JM and Wright, SM and Razzak, MT and White, AD and Finnemann, SC and Hinks, MM and Rodriques, SG}, title = {A multi-agent system for automating scientific discovery.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41586-026-10652-y}, pmid = {42156546}, issn = {1476-4687}, abstract = {Scientific discovery is driven by the iterative process of observation, hypothesis generation, experimentation, and data analysis. Despite recent advancements in applying artificial intelligence to biology, no system has yet automated all these stages [1, 2, 3]. Here, we introduce Robin, the first multi-agent system capable of fully automating both hypothesis generation and data analysis for experimental biology. By integrating literature search agents with data analysis agents, Robin can generate hypotheses, propose experiments, interpret experimental results, and generate updated hypotheses, achieving a semi-autonomous approach to scientific discovery. By applying this system, we were able to identify promising therapeutic candidates for dry age-related macular degeneration (dAMD), the major cause of blindness in the developed world [4, 5]. Robin proposed enhancing retinal pigment epithelium phagocytosis as a therapeutic strategy, and identified and confirmed in vitro efficacy for ripasudil and KL001. Ripasudil is a clinically-used Rho kinase (ROCK) inhibitor that has never previously been proposed for treating dAMD. To elucidate the mechanism of ripasudil-induced upregulation of phagocytosis, Robin then proposed and analyzed a follow-up RNA-seq experiment, which revealed upregulation of ABCA1, a lipid efflux pump and possible novel target. All hypotheses, experimental directions, data analyses, and data figures in the main text of this report were produced by Robin. As the first AI system to autonomously discover and validate novel therapeutic candidates within an iterative lab-in-the-loop framework, Robin establishes a new paradigm for AI-driven scientific discovery.}, }
@article {pmid41952137, year = {2026}, author = {Park, HY and Joo, K and Woo, SJ}, title = {Therapeutic effect of faricimab in macular telangiectasia type 1 and Coats' disease: case series.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {}, pmid = {41952137}, issn = {1471-2415}, support = {RS-2025-02263279//Ministry of Health &amp; Welfare, Republic of Korea/ ; }, abstract = {BACKGROUND: To report the anatomical and functional outcomes of intravitreal faricimab injection in cases of macular telangiectasia type 1 and Coats’ disease that were refractory to previous treatments.<br><br>METHODS: We describe four cases of macular telangiectasia type 1 and Coats&#x2019; disease with macular edema, which were treated with intravitreal faricimab injection.<br><br>RESULTS: Four patients with persistent cystoid macular edema despite prior treatment received intravitreal faricimab injections, and two of them showed anatomical and visual improvement. In case 1, a patient with Coats&#x2019; disease achieved improved telangiectatic vessel at macula and visual recovery following eight monthly injections of faricimab, with central macular thickness (CMT) reduced from 645&#xa0;&#x3bc;m to 217&#xa0;&#x3bc;m and BCVA improved from 20/30 to 20/25. In case 2, a patient with diabetic retinopathy and suspected macular telangiectasia type 1 showed improvement in CMT (670&#xa0;&#x3bc;m to 219&#xa0;&#x3bc;m) and visual acuity (20/63 to 20/40) with resolution of telangiectatic vessel with leakage after four faricimab injections. Case 3 and 4 were chronic and long-standing cases; in case 3, a patient with Coats&#x2019; disease demonstrated partial response with reduced macular edema, while in case 4, with a Coats&#x2019; disease, showed no response after two faricimab injections.<br><br>CONCLUSIONS: Faricimab may provide therapeutic benefits in cases of macular telangiectasia type 1 and Coats&#x2019; diseases unresponsive to previous anti-VEGF agents, potentially due to its dual inhibition of vascular endothelial growth factor-A and angiopoietin-2. However, its efficacy may be limited in patients with chronic phase. Further studies are warranted to assess its role in vascular retinal diseases beyond currently approved indications.}, }
@article {pmid42078357, year = {2026}, author = {Hönes, GS and Liao, XH and Mahler, EA and Herrmann, P and Eckstein, A and Führer, D and Castillo, JM and Chiang, J and Vincent, AL and Weiss, RE and Dumitrescu, AM and Refetoff, S and Moeller, LC}, title = {THRB splice site variants lead to exon 4 skipping and TRβ1 gain-of-function syndrome.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {42078357}, abstract = {BACKGROUND: Heterozygous c.283+1G>A and c.283G>A variants in the THRB gene, encoding for thyroid hormone receptor (TR)β1 and β2, lead to autosomal dominant macular dystrophy (ADMD). We report the detailed clinical characterization of two first-degree relatives with ADMD, heterozygous for THRB c.283+1G>A, and an unrelated ADMD patient with a novel variant, c.283G>C. The genomic and molecular consequences of both variants were studied.<br><br>METHODS: gDNA and mRNA were obtained from leukocytes. Clinical characterization included biochemistry, bone density and body composition, ECG, echocardiography, ultrasound, audiometry and color-vision. In vitro assays investigated TR function and DNA binding.<br><br>RESULTS: The patients manifested no resistance to thyroid hormone beta (RTH&#x3b2;) and had normal FT4 and TSH. Detailed studies in two patients showed no goiter, tachycardia, hypercholesterinemia or hepatic steatosis. Hearing was not impaired. Both had impaired color vision and reduced bone density. RT-PCR from all three patients revealed skipping of exon 4 exclusive to TR&#x3b2;1, producing a deletion of 87 amino acids in the N-terminal domain (TR&#x3b2;1[&#x394;NTD]). In vitro, DNA-binding affinity of TR&#x3b2;1[&#x394;NTD] to DR4-TRE with or without RXR&#x3b1; was comparable to TR&#x3b2;1[WT]. Surprisingly, TR&#x3b2;1[&#x394;NTD] was transcriptionally twice more active than TR&#x3b2;1[WT] with a similar EC50 for T3, demonstrating gain-of-function of TR&#x3b2;1[&#x394;NTD]. THRA expression in leukocytes was increased by 3-fold compared to unrelated controls and different from RTH&#x3b2; patients.<br><br>CONCLUSION: These THRB splice site variants produce TR&#x3b2;1 exon 4 skipping, resulting in a gain-of-function mutant, TR&#x3b2;1[&#x394;NTD]. This explains the dominant ADMD phenotype devoid of RTH&#x3b2; and suggests a TR&#x3b2;1 gain-of-function syndrome.}, }
@article {pmid42150558, year = {2026}, author = {Zalke, J and Rotake, DR and Barve, VP and Rout, C and Singh, SG and Singh, R}, title = {Ultra-sensitive GO-MoS2/AuNPs hybrid biosensor for early-stage age-related macular degeneration via complement component C3 detection.}, journal = {Nanotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1088/1361-6528/ae6f20}, pmid = {42150558}, issn = {1361-6528}, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss, where early diagnosis remains critical for effective intervention. Complement Component 3 (C3) plays a central role in AMD pathogenesis, making it a promising biomarker for early-stage detection. In this study, we report an electrochemical immunosensor based on a graphene oxide-molybdenum disulfide/gold nanoparticle (GO-MoS2/AuNPs) hybrid nanocomposite for the ultrasensitive detection of C3 in tear samples via a non-invasive approach. The GO-MoS2 platform provides a high surface area with abundant functional groups for efficient antibody immobilization, while AuNPs enhance electron transfer and signal amplification. The sensor response was evaluated using electrochemical impedance spectroscopy, where antigen-antibody interactions modulate charge transfer resistance (Rct). The developed biosensor exhibits a wide linear detection range from 10 fg mL[-1] (1 x10-8 ppm) to 500 pg mL[-1] (5 x 10-4 ppm) and an ultralow theoretical limit of detection of 1.17 fg mL[-1], calculated using the 3.3σ/slope method. Additionally, a high sensitivity of 518.05 % (ΔRct/Rct) (g mL[-1])[-1] cm[-2] was achieved, indicating efficient signal transduction. These results demonstrate the strong potential of the proposed platform for rapid, sensitive, and non-invasive detection of C3, offering a promising strategy for early AMD diagnosis.}, }
@article {pmid42150954, year = {2026}, author = {Chen, H and Tan, Q and Hu, Y and Liu, L and Liang, X and Hou, L}, title = {DAPL1 deficiency impairs autophagy in retinal pigment epithelium to drive age-dependent retinal pathologies.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jfma.2026.05.038}, pmid = {42150954}, issn = {0929-6646}, abstract = {BACKGROUND/PURPOSE: Age-related retinopathy, mainly age-related macular degeneration (AMD), is a major cause of irreversible blindness in the elderly worldwide. Its precise mechanisms remain incompletely understood. Although autophagy deficiency in retinal pigment epithelial (RPE) cells is associated with AMD in patients, the regulatory pathways involved are still unclear. The research purpose is to investigate the functional role and underlying mechanism of DAPL1 in autophagy deficiency in the age-dependent retinal pathologies.<br><br>METHODS: In this study, 18-month-old wild-type (WT) and Dapl1[-/-] mice were used. Fundus photography and optical coherence tomography (OCT) were employed to detect morphological abnormalities. Immunofluorescence was performed to examine GFAP, Rhodopsin/Opsin, IBA1, and LC3, and on RPE flat mounts for ZO-1. Lipid deposition was analyzed by Oil Red O staining. To investigate downstream mediators of DAPL1, western and RT-qPCR were used to identify and validate candidate genes, followed by functional validation using lentiviral overexpression and RNA interference.<br><br>RESULTS: At 18 months of age, Dapl1-deficient mice exhibit age-related retinal dysfunction and structural abnormalities. These include increased retinal stress, damage to photoreceptors and RPE cells, lipid accumulation, and microglial activation. Autophagy is impaired in the RPE cells of Dapl1-deficient mice. DAPL1 overexpression in RPE cells enhances autophagy activity. Furthermore, DAPL1 suppresses the expression of E2F1 and c-MYC. This downregulates mTOR and upregulates the expression of ATG16 and Beclin1 through DAPK1 in RPE cells, promoting autophagy.<br><br>CONCLUSION: These findings suggest DAPL1 is a novel regulator of autophagy in RPE cells, and its deficiency increases susceptibility to age-dependent retinal pathologies in mice.}, }
@article {pmid42151388, year = {2026}, author = {Miura, M and Trinh, M and Juan, EG and Shu, X}, title = {Macular degeneration collection.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {42151388}, issn = {2045-2322}, mesh = {Humans ; *Macular Degeneration/therapy/diagnosis/pathology ; }, abstract = {Age-related macular degeneration (AMD) remains a leading cause of severe vision loss among the older adults in developed countries. Improving patient outcomes is dependent on elucidating the complex pathogenesis of the disease and refining clinical and therapeutic strategies. This Collection showcases a diverse range of papers exploring the frontiers of imaging-based prediction, treatment optimization, mechanistic biology, and the assessment of visual function. Together, these studies provide critical insights to inform the next generation of AMD management.}, }
@article {pmid42152120, year = {2026}, author = {Gong, J and Ghotbaldini, S and Viniak, R and Rajesh, A and Lavine, JA}, title = {Tissue-resident macrophages maintain choroidal homeostasis by complement dependent and independent mechanisms.}, journal = {Journal of neuroinflammation}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12974-026-03872-6}, pmid = {42152120}, issn = {1742-2094}, support = {Unrestricted Departmental Grant//Research to Prevent Blindness/ ; Research and Education Award//The Retina Society/ ; EY034486/EY/NEI NIH HHS/United States ; CA060553/CA/NCI NIH HHS/United States ; 1S10OD032270-01A1/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is characterized by disruption of the choriocapillaris (CC) and retinal pigment epithelium (RPE) dysfunction, leading to drusen accumulation. The CC and RPE form a tightly interdependent unit that maintains homeostasis where the CC supplies oxygen and nutrients to the RPE, while the RPE produces vascular endothelial growth factor (VEGF) to maintain the CC. Genetic studies link alternative complement pathway variants to AMD, and complement deposition on the CC increases during both aging and AMD. Macrophages express complement protein, receptors, and inhibitors, suggesting that they may be a missing link in understanding the role of complement in AMD. In support, previous groups have shown that macrophage depletion disrupts RPE-CC homeostasis, leading to AMD-like pathology, but the mechanism remains unclear.<br><br>METHODS AND RESULTS: To investigate the role of macrophages in CC-RPE homeostasis, we generated Cx3cr1[CreER]Csf1r[i-DTR] and Ms4a3[Cre]Rosa26[DTR] mice. In Cx3cr1[CreER]Csf1r[i-DTR] mice, tamoxifen administration induced diphtheria toxin receptor (DTR) expression, allowing ablation of all macrophages (many tamoxifen injections) or long-lived, tissue-resident macrophages (tamoxifen followed by a 3-4 week wash out period). Ms4a3[Cre]Rosa26[DTR] mice were used to deplete monocyte-derived macrophages. Ablation of all macrophages caused decreased CC density, increased CC apoptosis, RPE disorganization, and membrane attack complex (MAC) accumulation. Tissue-resident macrophage ablation phenocopied this result while monocyte-derived macrophage ablation had no phenotype. Additionally, long-term depletion of tissue-resident macrophages led to formation of drusen-like sub-RPE deposits and retinal thinning, mimicking AMD pathology. Finally, pharmacologic depletion of all macrophages similarly reduced CC density to genetic ablation, but C3[-/-] mice showed an attenuated phenotype.<br><br>CONCLUSIONS: These data demonstrate that long-lived, tissue-resident macrophages are essential for maintaining CC-RPE homeostasis while monocyte-derived macrophages are dispensable in this context. Further, ocular macrophage ablation led to MAC accumulation, while C3[-/-] mice were resistant to CC regression. Together, these findings suggest that tissue-resident choroidal macrophages maintain CC-RPE homeostasis partially by complement dependent mechanisms. Further, the loss of tissue-resident choroidal macrophages over time is a potential mechanism of AMD pathogenesis.}, }
@article {pmid42152481, year = {2026}, author = {Cai, J and Jiang, Y and Liu, X and Yang, T and Yang, P and Chen, L}, title = {FASN mediates crosstalk between autophagy and lipid metabolism via the AMPK-MTOR pathway in early age-related macular degeneration.}, journal = {Autophagy}, volume = {}, number = {}, pages = {1-20}, doi = {10.1080/15548627.2026.2673559}, pmid = {42152481}, issn = {1554-8635}, abstract = {Age-related macular degeneration (AMD) involves sub-retinal pigment epithelium (sub-RPE) lipid deposition in the early stage, with dysregulated lipid metabolism and impaired macroautophagy/autophagy implicated, yet the molecular mechanisms underlying their interaction remain unclear. In this study, transcriptomic analysis of human macular tissues identified FASN (fatty acid synthase), a regulator of lipid metabolism and lysosomal function, as a significantly upregulated key hub gene in early AMD. In apoe[-/-] mice fed a high-fat diet (HFD), retina-RPE-choroid complexes revealed elevated FASN alongside autophagy suppression, lysosomal dysfunction, and lipid accumulation. In vitro, FASN protein levels increased in RPE cells treated with the autophagy inhibitor 3-methyladenine (3-MA), but decreased with the autophagy activator rapamycin (RAPA), without transcriptional changes; lysosomal blockade with chloroquine (CQ) induced FASN accumulation, which was significantly delayed following autophagy inhibition. These findings indicate that FASN accumulation results from insufficient autophagic degradation. Conversely, FASN knockdown or pharmacological inhibition enhanced autophagic flux and promoted lysosomal lipid clearance in RPE cells. Mechanistically, FASN inhibition increased AMPK phosphorylation and decreased MTOR activity, thereby facilitating autophagy and lipophagy. Collectively, our findings reveal a self-amplifying pathological circuit in early AMD: autophagy impairment drives FASN accumulation, which in turn exacerbates lysosomal dysfunction and lipid accumulation. Targeting the FASN-AMPK-MTOR axis may offer a promising therapeutic strategy for early AMD.}, }
@article {pmid42153784, year = {2026}, author = {Estay-Ahumada, CE and Roux, M and Ciocca, D and El-Kholti, N and Birling, MC and Rossolillo, P and Felder-Schmittbuhl, MP and Hicks, D}, title = {Abca4 Knockdown in the Cone-Rich Rodent Psammomys Obesus Leads to Stargardt's Disease-Like Progressive Retinal Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {5}, pages = {47}, doi = {10.1167/iovs.67.5.47}, pmid = {42153784}, issn = {1552-5783}, mesh = {Animals ; Gerbillinae ; *ATP-Binding Cassette Transporters/genetics ; Electroretinography ; Stargardt Disease/genetics ; Disease Models, Animal ; *Retinal Cone Photoreceptor Cells/metabolism/pathology ; Tomography, Optical Coherence ; *Macular Degeneration/genetics/congenital/metabolism ; *Retinal Degeneration/genetics/metabolism ; CRISPR-Cas Systems ; Gene Knockdown Techniques ; Genetic Vectors ; Dependovirus/genetics ; }, abstract = {PURPOSE: Mutations in the gene ABCA4 coding for photoreceptor-specific ATP-binding cassette subfamily A member 4, are responsible for Stargardts disease type 1 (STGD1), the most common form of inherited macular degeneration. We recently showed that injection of viral vectors expressing CRISPR/Cas9 tools directed against Abca4 into young Sand Rat (Psammomys obesus) eyes led to extensive structural and functional retinal degeneration resembling STGD1. Here we provide further evidence that this is highly likely due to specific knockdown of Abca4 and not off-target errors.<br><br>METHODS: We performed subretinal injections of Adeno-Associated Virus-CRISPR/Cas9-Abca4 constructs into postnatal (&#x223c;P15) Psammomys obesus. Eyes were examined by noninvasive exploration (ocular coherence tomography, fundus and electroretinography) at 15-60 days after injection. Additionally, subgroups were euthanized over the same time period, and ocular tissue was used for immunochemical analyses.<br><br>RESULTS: RNAscope analysis of injected eyes showed knockdown of Abca4, rhodopsin and cone transducin mRNA in transduced regions; neighbouring tissue that was not transduced showed robust expression of all three. Injection of control AAV, expressing CAS9 alone, induced only mild glial activation. Statistically significant decreases in visual responses to light flashes were only seen in eyes injected with the fully active CRISPR/Cas9-Abca4 probes.<br><br>CONCLUSIONS: Taken together, these data rule out off-target effects as responsible for the observed degeneration, and indicate that Psammomys obesus faithfully recapitulates many of the features seen in human STGD1, thus positioning it as an important research opportunity to further explore genotype-phenotype relationships and test putative therapeutic approaches.}, }
@article {pmid42154370, year = {2026}, author = {Benekos, K and Katsanos, A and Laspas, P and Panos, GD and Vagiakis, I and Fousekis, FS and Luca, R and Zhou, B and Kostoulas, C and Georgiou, I and Katsanos, KH and Skondra, D and Konstas, AG}, title = {An Update and Overview of the Ocular and Extraocular Microbiome and Its Impact on Ophthalmic Care.}, journal = {Advances in therapy}, volume = {}, number = {}, pages = {}, pmid = {42154370}, issn = {1865-8652}, abstract = {The microbiome has been described as the last human "organ" and is currently the topic of great research interest worldwide. The application of culture-independent methods, like 16S ribosomal next-generation sequencing, has offered researchers the opportunity to identify bacterial populations that were impossible to detect previously using conventional culture methods. Further standardization of these new approaches to characterizing the microbiome is desirable. The present review discusses the mounting evidence suggesting that alterations in the microbiome and microbial metabolites, such as short-chain fatty acids in the gut, mouth, and ocular surface, may play a key role in the pathogenesis of ocular pathologies such as ocular surface disease, glaucoma, uveitis, age-related macular degeneration, and diabetic retinopathy. Clarifying the probable role of the microbiome in ocular diseases would not only offer valuable insights into pathogenesis but could also enable the development of novel therapeutic approaches. As yet, microbial-based therapeutic applications in ophthalmology are limited. Nevertheless, recently emerging strategies utilizing probiotics and prebiotics, or even fecal transplantation to regulate microbiome composition, offer promising research avenues for developing future innovative therapies for ocular diseases. Further studies employing standardized methodological protocols are needed to ensure the reproducibility of results and to eventually unlock the precise links between the microbiome and the eye.}, }
@article {pmid42154378, year = {2026}, author = {Matsumoto, H and Hoshino, J and Numaga, S and Asatori, Y and Akiyama, H}, title = {One-year outcomes of treat-and-extend regimen with intravitreal aflibercept 8 mg for treatment-naïve neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {42154378}, issn = {1613-2246}, abstract = {PURPOSE: To evaluate 1-year outcomes of loading phase treatment followed by a treat-and-extend (TAE) regimen with intravitreal aflibercept 8 mg for neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Retrospective, interventional case series.<br><br>METHODS: We retrospectively studied 83 eyes of 80 consecutive patients with treatment-na&#xef;ve nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), central choroidal thickness (CCT), total number of injections over 1 year, and intended injection interval at the last visit.<br><br>RESULTS: Sixty eyes (72.3%) completed the 1-year aflibercept 8mg treatment. Their BCVA improved significantly, with significant reductions in FT and CCT, for up to 1 year. The total number of injections was 6.5&#xb1;0.7, and the intended injection interval at the last visit was 13.4&#xb1;3.3 weeks. Of the 23 eyes (27.7%) failing to complete the 1-year treatment, 9 (10.8%) developed non-infectious intraocular inflammation (IOI) associated with retinal vasculitis during the loading phase, leading to treatment discontinuation. Moreover, 7 eyes (8.4%) were switched to intravitreal brolucizumab due to persistent exudation with an 8-week interval of aflibercept 8mg injections in the maintenance phase. The remaining 7 eyes (8.4%) dropped out.<br><br>CONCLUSIONS: Loading phase treatment followed by a TAE regimen with intravitreal aflibercept 8 mg appears to be effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, there might be cases in which exudative changes cannot be adequately controlled with injections of aflibercept 8 mg. Moreover, careful monitoring is required due to the potential development of IOI associated with retinal vasculitis during the loading phase.}, }
@article {pmid42154379, year = {2026}, author = {Yoneyama, S and Sakurada, Y and Fukuda, Y and Shijo, T and Kotoda, Y and Kikushima, W and Mabuchi, F and Kashiwagi, K}, title = {Genetic factors associated with response to as-needed brolucizumab treatment for exudative age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {42154379}, issn = {1613-2246}, abstract = {PURPOSE: To investigate the association between genetic variants susceptible to exudative age-related macular degeneration (AMD) and the treatment response to as-needed intravitreal brolucizumab (IVBr) therapy.<br><br>STUDY DESIGN: Interventional study METHODS: This retrospective study included 103 treatment-na&#xef;ve eyes with exudative AMD. All eyes received three monthly IVBr injections (6.0 mg/0.05 mL) followed by a pro re nata regimen for 12 months. Seven major AMD-associated single nucleotide polymorphisms-ARMS2 A69S (rs10490924), CFH I62V (rs800292), CFH rs1329428, C2-CFB-SKIV2L rs429608, C3 rs2241394, CETP rs3764261, and ADAMTS9 rs6795735-were genotyped using TaqMan assays. The requirement for retreatment, the number of additional injections, and visual outcomes were compared across genotypes.<br><br>RESULTS: Of the 103 patients, 68 (66.0%) required additional injections. The T allele of ARMS2 A69S was significantly more frequent in the retreatment group than in the retreatment-free group (65.0% vs. 42.9%, p = 1.9 &#xd7; 10&#x207b;[3]) and remained independently associated with retreatment after adjustment for age, sex, and baseline visual acuity (p = 3.0 &#xd7; 10&#x207b;[3]). Eyes with the TT genotype required significantly more additional injections than those with the TG or GG genotypes (2.4 &#xb1; 1.7 vs. 1.3 &#xb1; 1.6 and 1.3 &#xb1; 1.5, respectively; p = 5.0 &#xd7; 10&#x207b;[3]). Kaplan-Meier analysis demonstrated a significant difference in retreatment-free survival among ARMS2 genotypes (p = 4.1 &#xd7; 10&#x207b;[4]). Visual outcomes did not differ across any genotypes.<br><br>CONCLUSIONS: ARMS2 A69S may serve as a predictor of recurrence and number of additional injections in as-needed brolucizumab therapy for exudative AMD.}, }
@article {pmid42154394, year = {2026}, author = {Spartalis, C and Ullrich, M and Winkler, S and Leisser, C and Ruiss, M and Pilwachs, C and Findl, O}, title = {Prospective Real-World Outcomes After Switching to Aflibercept 8 mg in Neovascular Age-Related Macular Degeneration with High Treatment Burden.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42154394}, issn = {2193-8245}, abstract = {INTRODUCTION: This study aimed to evaluate functional, anatomical, and safety outcomes after switching from aflibercept 2 mg to aflibercept 8 mg in patients with neovascular age-related macular degeneration (nAMD) requiring short re-treatment intervals in a real-world setting.<br><br>METHODS: This single-center prospective observational study included patients with nAMD insufficiently responsive to prior anti-vascular endothelial growth factor (anti-VEGF) therapy requiring re-treatment every 4-6&#xa0;weeks. All eyes had received four consecutive intravitreal injections of aflibercept 2&#xa0;mg prior to switching to aflibercept 8&#xa0;mg as part of routine clinical management. Functional outcome was assessed by distance-corrected visual acuity (DCVA). Anatomical outcomes included central retinal thickness (CRT), central subfield thickness (CST), and optical coherence tomography (OCT) features. Injection burden, responder status, discontinuation, and safety outcomes were evaluated. Follow-up occurred at 3, 6, 9, and 12&#xa0;months.<br><br>RESULTS: Fifty patients (50 eyes) were included (mean age 78.4&#x2009;&#xb1;&#x2009;6.9&#xa0;years; 60% female). Median baseline DCVA was 0.19&#xa0;logMAR (IQR 0.12-0.32; 75.5 ETDRS letters), median CST 272&#xa0;&#xb5;m, and median CRT 338&#xa0;&#xb5;m. DCVA improved significantly at months&#xa0;3, 6, and 9 (p&#x2009;&#x2264;&#x2009;0.046) and remained stable at month&#xa0;12. CRT and CST decreased early and remained improved. Over 12&#xa0;months, 24 patients (48%) completed follow-up, while 26 (52%) discontinued early. Intraocular inflammation (IOI) occurred in 10 eyes (20%), corresponding to 3.0% per injection, and was temporally associated with off-label aliquoted preparation; all cases resolved without permanent visual loss. No further IOI events were observed after transition to on-label preparation. During safety evaluation, seven patients discontinued aflibercept 8&#xa0;mg as a result of precautionary safety measures. Seventeen (34%) required&#x2009;&#x2264;&#x2009;8 injections per year.<br><br>CONCLUSIONS: In chronically treated patients with nAMD requiring short re-treatment intervals, switching to aflibercept 8&#xa0;mg was associated with modest anatomical improvement and stable visual function. A reduction in treatment burden was observed in a subset of patients, although overall durability remained heterogeneous and discontinuation rates were high. A cluster of sterile inflammatory events occurred during off-label aliquoted preparation, highlighting the importance of appropriate drug handling. Careful patient selection and strict adherence to on-label preparation procedures are essential to optimize safety. These findings should be interpreted cautiously given the exploratory design, lack of a comparator group, and high discontinuation rate.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT07390253.}, }
@article {pmid42155048, year = {2026}, author = {Sbrana, F and Dal Pino, B and Schettler, VJJ and Muso, E and Harada-Shiba, M and Di Mola, M and Kagitani, M and Pineda, E and Selke, N and Jenke, S and Zimmermann, T and Bernhardt, W and Bigazzi, F and Heigl, F and Grützmacher, P and Löhlein, I and Klingel, R and Corciulo, C and Hohenstein, B and Ramlow, W and Vogt, A and Ramunni, A and Emdin, M and Sampietro, T and Julius, U and Schlieper, G and Stefanutti, C and Moriarty, PM}, title = {Lipoprotein apheresis in the era of new lipid-lowering therapies.}, journal = {European heart journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/eurheartj/ehag328}, pmid = {42155048}, issn = {1522-9645}, abstract = {During the 1960s, in a pioneering way, plasmapheresis was used to treat children with homozygous familial hypercholesterolaemia (HoFH). Over the years, apheresis has evolved to increasingly selective methods, which have been used in paediatric HoFH since the 1990s. Today, lipoprotein apheresis (LA) is able to selectively remove atherogenic apoB100-containing lipoproteins from the blood: the main component of LDL-cholesterol, VLDL-cholesterol, and lipoprotein(a). Lipoprotein apheresis has demonstrated protective effects in the endothelium and microcirculation, prevention of the development of new aortic and coronary lesions in HoFH, reducing the incidence of major cardiovascular events, and proving helpful in subjects who fail to reach the LDL-cholesterol target or who have elevated lipoprotein(a) levels in secondary prevention. Although advances in pharmacological therapies (proprotein convertase subtilisin/kexin Type 9 inhibitors, antisense oligonucleotides, and siRNA-based treatments) have expanded the options for lipid management, LA remains a safe therapeutic approach for patients with severe lipid disorders, including HoFH, to reduce their cardiovascular risks. Currently, to put LA into perspective, some obstacles need to be overcome, including (i) the underdiagnosis of HoFH and high lipoprotein(a) level; (ii) therapeutic inertia resulting from the use of new lipid-lowering drugs with partial achievement of lipid targets; and (iii) availability of qualified LA centres and practitioners. Further prospective studies may prove useful to identify other therapeutic scenarios for LA, such as renal disease, diabetic foot ulcer, peripheral arterial disease, pre-eclampsia, macular degeneration, or sudden sensorineural hearing loss. In these clinical settings, prospective, randomized clinical trials are therefore warranted.}, }
@article {pmid42156503, year = {2026}, author = {Diaz-Marin, R and Hata, M and Guber, V and De Guire, V and Wilson, AM and Crespo-Garcia, S and Sapieha, P}, title = {Adipocytes influence choroidal neovascularization via PRDM16.}, journal = {EMBO molecular medicine}, volume = {}, number = {}, pages = {}, pmid = {42156503}, issn = {1757-4684}, support = {183779//Canadian Institutes of Health Research (CIHR)/ ; 529136//Canadian Institutes of Health Research (CIHR)/ ; M2022015I//BrightFocus Foundation (BFF)/ ; }, abstract = {Neovascular age-related macular degeneration (nAMD) is a prominent cause of blindness in the elderly, characterized by pathological subretinal choroidal neovascularization (CNV). While age and genetics predispose to AMD, modifiable factors such as body adiposity are also thought to contribute. In a mouse model of nAMD, we identified a role for adipose tissue (AT) in exacerbating CNV, specifically pathways in adipocytes expressing Prdm16. Laser-induced CNV in the retina led to heightened expression of genes associated with browning and inflammation in distal inguinal white AT (iWAT). Selective deletion of the browning-associated transcription factor Prdm16 in adipocytes inhibited AT browning and reduced CNV. Reintroduction of Prdm16-expressing adipose tissue was sufficient to aggravate CNV in Prdm16-deficient mice. Ex vivo experimentation suggested that Prdm16-expressing adipocytes secrete angiogenic factors such as IGFBP5 and contribute to pathological angiogenesis. Thus, Prdm16-expressing adipocytes contribute to CNV, highlighting communication between the retina and distal tissues in the pathogenesis of AMD.}, }
@article {pmid42139589, year = {2026}, author = {Xiao, J and Yavari, N and Nimmagadda, H and Mruthyunjaya, P and Rahimy, E and Smith, SJ and Ludwig, CA and Koo, E and Wai, KM}, title = {Association Between Mental Health Disorders in Age-Related Macular Degeneration: A Cohort Study Using a Global Health Records Network.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {57}, number = {5}, pages = {301-308}, doi = {10.3928/23258160-20260311-02}, pmid = {42139589}, issn = {2325-8179}, mesh = {Humans ; Female ; Aged ; Male ; *Mental Disorders/epidemiology/etiology ; *Wet Macular Degeneration/complications/epidemiology ; Aged, 80 and over ; Retrospective Studies ; Risk Factors ; *Macular Degeneration/complications ; Electronic Health Records ; Global Health ; Middle Aged ; Propensity Score ; Angiogenesis Inhibitors ; }, abstract = {BACKGROUND AND OBJECTIVE: This study assessed risk of mental health disorders in patients with age-related macular degeneration (AMD).<br><br>PATIENTS AND METHODS: Data were obtained from an aggregated electronic health records database. Patients who were diagnosed with AMD with cataract were propensity score-matched with cataract controls. Diagnoses were identified using International Classification of Diseases, 10th Revision (ICD-10) codes. Subgroup analyses evaluated relative risk (RR) of new diagnoses of mental health disorders among patients with dry AMD, neovascular AMD (nAMD), vision impairment, and receipt of intravitreal therapy.<br><br>RESULTS: After matching, 126,799 cases comprising 53.1% female patients with a mean age of 74.6 &#xb1; 8.9 years were included. Patients with AMD and cataract had elevated risk of receiving diagnoses of depression (RR = 1.27; 95% CI 1.24-1.29) and anxiety (RR = 1.19; 1.17-1.22). These patients were also at increased risk for self-harm (RR = 1.16), substance use (RR = 1.10), dysthymia (RR = 1.41), and psychosis (RR = 1.22) (all P < .05). The presence of visual impairment amplified these risks, particularly for depression (RR = 1.97) and anxiety (RR = 1.62). Patients with dry AMD had an increased risk of depression and anxiety compared to those with nAMD. Treatment with intravitreal injections in nAMD patients was associated with decreased risk of depression (RR = 0.88) and anxiety (RR = 0.82).<br><br>CONCLUSIONS: AMD is associated with increased risk of mental health disorders, including anxiety, depression, and self-harm, particularly in the first year following diagnosis. Risk varies by disease subtype, visual function, and treatment status.}, }
@article {pmid42142069, year = {2026}, author = {Kim, H and Joe, BH and Nam, D and Yoo, TK}, title = {Oculomics of lipid metabolism: A scoping review across anterior and posterior segment diseases.}, journal = {Science progress}, volume = {109}, number = {2}, pages = {368504261453276}, pmid = {42142069}, issn = {2047-7163}, mesh = {Humans ; *Lipid Metabolism ; *Dyslipidemias/metabolism ; *Eye Diseases/metabolism ; Biomarkers/metabolism ; Macular Degeneration/metabolism ; }, abstract = {Dyslipidemia comprises interacting disturbances in lipids and lipoproteins that track with metabolic status, vascular biology, and inflammation. Ocular imaging offers scalable, quantifiable phenotypes to interrogate lipid-related pathways and to develop oculomics. We conducted a scoping review to map evidence linking dyslipidemia and lipid-related biomarkers with ocular phenotypes across the ocular surface, lens, macula, retinal microvasculature, and vascular occlusive disease, and to consider implications for AI-based risk modeling. We searched PubMed, Embase, Scopus, and Web of Science, supplemented by reference screening, and charted lipid exposures such as LDL-C, non-HDL-C, apoB/apoA-I, and the triglyceride-glucose index. The biologically grounded patterns were observed in macular disease, where cholesterol- and apolipoprotein-related material within the RPE-Bruch's membrane complex and drusen-related phenotypes support lipid-handling and innate immune pathways in age-related macular degeneration. Retinal vascular phenotypes showed generally consistent signals compatible with endothelial stress and microvascular remodeling. Epidemiologic associations were apparent in metabolically co-traveling conditions such as meibomian gland dysfunction and diabetic retinopathy, in which triglyceride-rich dyslipidemia and insulin resistance markers were often more informative than LDL-C alone and associations were often non-linear or interaction-dependent. By contrast, findings for glaucoma and cataract were modest and inconsistent, while vascular occlusive phenotypes clustered with broader atherosclerotic risk. Statin associations varied by outcome and were vulnerable to confounding. Predicting individual lipid analytes from retinal images appears limited, whereas integrated ocular signatures may support cardiovascular risk stratification. Future studies should refine phenotype definitions, model non-linearity, account for lipid-lowering therapy, and prospectively validate multimodal oculomics and AI across devices and populations.}, }
@article {pmid42144178, year = {2026}, author = {Nguyen, VP and Zheng, M and Lee, Y and Park, S and Dang, C and Tran, K and Wei, Z and Yang, D and Paulus, YM}, title = {A Low-Cost, Tunable Suprachoroidal Injection Platform with Real-Time OCT Guidance for Gene Therapy Delivery.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111060}, doi = {10.1016/j.exer.2026.111060}, pmid = {42144178}, issn = {1096-0007}, abstract = {Gene therapy shows considerable promise for treating vision impairments, including retinitis pigmentosa (RP), age-related macular degeneration (AMD), and diabetic retinopathy (DR). Current delivery methods, such as subretinal, intravitreal, and conventional suprachoroidal injections, are effective but pose significant challenges, including inflammation and complications that hinder their clinical translation. In this study, we present an integrated suprachoroidal injection (SCI) platform that combines a low-cost, tunable needle design with real-time optical coherence tomography (OCT) guidance for precise and safe suprachoroidal delivery. The injection device is constructed from a standard insulin syringe fitted with an adjustable silicone sheath that enables rapid and continuous control of needle penetration depth, eliminating the need for complex nested-needle assembly used in prior approaches. Real-time spectral-domain OCT imaging was incorporated to dynamically monitor needle positioning and confirm suprachoroidal delivery. In vivo studies in rabbits demonstrated accurate delivery of indocyanine green (ICG) and adeno-associated virus (AAV) vectors without ocular or systemic toxicity. Furthermore, AAV delivery exhibited dose-dependent transgene expression over 28 days, validating the platform for gene therapy applications. Compared with existing microneedle and catheter-based systems, this approach offers a simplified, scalable, and cost-effective alternative while maintaining precision through imaging guidance. This combined platform provides a practical solution for suprachoroidal drug delivery and facilitates broader adoption in both preclinical and translational research.}, }
@article {pmid42147074, year = {2026}, author = {Nowosielska, AJ and Rotuski, G}, title = {Impact of treatment gap on visual acuity in patients with submacular hemorrhage secondary to neovascular age-related macular degeneration treated with quadruple intervention strategy.}, journal = {Therapeutic advances in ophthalmology}, volume = {18}, number = {}, pages = {25158414261447184}, pmid = {42147074}, issn = {2515-8414}, abstract = {BACKGROUND: Submacular hemorrhage (SMH) is an uncommon complication of neovascular age-related macular degeneration (AMD).<br><br>OBJECTIVES: The study aim was to evaluate the efficacy of combination therapy vitrectomy with subretinal recombinant tissue plasminogen activator (rtPA) given under the retina and anti-VEGF given into the vitreous cavity in patients with SMH based on duration of symptoms and to identify biomarkers to help predict potential visual acuity gain after the procedure.<br><br>DESIGN: Retrospective case series.<br><br>METHODS: Patients with SMH secondary to AMD were treated with quadruple therapy: (1) vitrectomy; (2) rtPA administration; (3) bevacizumab injection into the vitreous cavity; followed by (4) monthly intravitreal double-dose bevacizumab 2.5&#x2009;mg.<br><br>RESULTS: Forty-eight patients were treated (68.8% women; mean age, 80&#x2009;years). A median of 14&#x2009;days elapsed between SMH onset and surgical intervention (range, 2-120&#x2009;days), with vitrectomy performed after &#x2a7e;30&#x2009;days in 39.6% of patients. A significant improvement from baseline in mean best-corrected visual acuity (BCVA) was observed 6&#x2009;months after SMH treatment (1.6 (baseline) vs 0.9 (Month 6) logMAR; p&#x2009;<&#x2009;0.001). Overall, 46 (95.8%) patients had improved BCVA and two (4.2%) had stable (unchanged) BCVA in the treated eye. Improvement in BCVA at Month 6 was similar between the cohort with only SMH and patients with coexisting subretinal pigment epithelium hemorrhage (p&#x2009;=&#x2009;0.11). The main biomarkers predicting surgical outcome were the state of the retina in the foveal center point and hemorrhage thickness. Treatment &#x2a7e;30&#x2009;days after SMH onset resulted in poorer BCVA at Month 6 compared with treatment occurring <30&#x2009;days after onset (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: A combination of vitrectomy, subretinal rtPA, and bevacizumab, performed in patients with submacular hemorrhage due to neovascular AMD, followed by monthly intravitreal double-dose bevacizumab for SMH, was an effective intervention to achieve visual acuity improvement.}, }
@article {pmid42147450, year = {2026}, author = {Gurnani, B and Kaur, K}, title = {Artificial intelligence in ophthalmology: from innovation to clinical integration.}, journal = {Frontiers in ophthalmology}, volume = {6}, number = {}, pages = {1839194}, pmid = {42147450}, issn = {2674-0826}, abstract = {Artificial intelligence (AI) has emerged as a transformative force in modern ophthalmology, enabling rapid advances in disease detection, clinical decision support, workflow optimization, and tele-ophthalmology. Ophthalmology is particularly suited for AI integration because of its reliance on imaging modalities such as fundus photography, optical coherence tomography (OCT), and visual field testing. Over the past decade, deep learning algorithms have demonstrated high diagnostic accuracy in identifying retinal diseases including diabetic retinopathy, age-related macular degeneration, and glaucoma. The approval of autonomous AI diagnostic systems for diabetic retinopathy screening marked a significant milestone in clinical adoption. Beyond diagnostics, AI is increasingly influencing surgical planning, predictive analytics, education, and patient engagement. Despite these promising advances, significant challenges remain regarding algorithm generalizability, ethical considerations, regulatory approval, data privacy, and integration into routine clinical practice. This perspective article reviews current innovations in AI applications within ophthalmology and discusses their clinical impact while outlining future directions for research and implementation. We argue that the next phase of AI in ophthalmology will involve multimodal learning systems, integration with large language models, and deployment in global eye-care networks to address disparities in access to care. A collaborative approach involving clinicians, data scientists, regulators, and industry will be essential to ensure safe, ethical, and effective adoption of AI technologies in ophthalmic practice.}, }
@article {pmid42147501, year = {2026}, author = {Karagiannis, D and Bouratzis, N and Kontomichos, L and Batsos, G and Paroikakis, E}, title = {Prognosis and Treatment Approach for Stage 1 Retinal Angiomatous Proliferation Lesions: A Case Series With Long-Term Follow-Up.}, journal = {Cureus}, volume = {18}, number = {4}, pages = {e107009}, pmid = {42147501}, issn = {2168-8184}, abstract = {Retinal angiomatous proliferation (RAP) accounts for approximately 10%-20% of all neovascular (wet) age-related macular degeneration and is classically classified into three stages, with stage 1 representing the earliest form of disease. Despite its clinical relevance, limited evidence exists on the long-term prognosis of treatment-naïve stage 1 RAP, particularly regarding recurrence patterns and the development of macular atrophy or fibrosis over extended follow-up. This retrospective case series evaluates outcomes in four patients diagnosed with stage 1 RAP using optical coherence tomography (OCT) and fluorescein angiography. All patients were planned to receive a loading regimen of three monthly intravitreal aflibercept injections, followed by monthly review for at least 24 months. The loading phase was modified according to findings at each visit. At every appointment, best-corrected visual acuity (BCVA), slit-lamp examination, and OCT assessment of macular anatomy were performed, with recurrence defined as clinical and/or OCT evidence of exudative activity warranting re-treatment. Over the follow-up period, all four patients demonstrated stable or improved BCVA after anti-vascular endothelial growth factor (VEGF) therapy. Two patients had no recurrences across 24 months, while two patients each experienced a single recurrence, occurring at seven months and 24 months, respectively. Importantly, no eyes developed macular atrophy or fibrotic scarring during the observation period, and visual acuity remained stable or improved in all cases. These findings support the concept that early identification and prompt treatment of stage 1 RAP may be associated with a low recurrence burden and a favourable anatomic course, potentially limiting progression to atrophy or fibrosis and preserving long-term vision. They also suggest that a personalised management strategy, combining an initial loading phase with close surveillance and re-treatment only upon recurrence, may be effective in carefully selected early-stage RAP patients and could reduce overall injection burden. Larger studies with longer follow-up are required to confirm these preliminary observations and to better define stage-specific treatment strategies for RAP.}, }
@article {pmid42148323, year = {2026}, author = {Jiang, L and Cuomu, G and Jijia, S and Yang, Y and Liu, J and Tao, Y}, title = {Crosstalk between endoplasmic reticulum stress and mitochondrial homeostasis: A new perspective on ophthalmic disease treatment.}, journal = {Journal of cell communication and signaling}, volume = {20}, number = {}, pages = {e70080}, pmid = {42148323}, issn = {1873-9601}, abstract = {Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are hallmarks of many ophthalmic diseases; however, they have traditionally been examined as isolated pathological processes. Recent evidence indicates that these organelles are inextricably coupled through mitochondria-endoplasmic reticulum contact sites, also known as mitochondria-associated membranes (MAMs), which coordinate Ca[2+] signaling, lipid transfer, mitochondrial dynamics, redox balance, and cell death decisions. Consequently, dysregulated ER-mitochondria communication has emerged as a key vulnerability that links the cellular stress responses among diverse ocular tissues, including lens epithelial cells, retinal ganglion cells, the retinal pigment epithelium, and corneal endothelial cells. In this review, we summarize the recent advances involving the molecular architecture and regulatory function of ER-mitochondria crosstalk. We focus on how the unfolded protein response signaling, pathological MAM remodeling, Ca[2+] dysregulation, and disrupted mitochondrial quality control collectively drive disease progression. By integrating evidence from cataract, glaucoma, diabetic retinopathy, age-related macular degeneration, and Fuchs endothelial corneal dystrophy, we reveal that these disorders are not driven by a uniform mechanism of organelle failure, but rather by the dominance of pathological nodes along the ER-mitochondria axis. We propose that ophthalmic diseases should be stratified based on these distinct failure nodes, which provides a mechanistic framework for developing therapeutics. Within this context, interventions targeting maladaptive ER stress, MAM destabilization, bioenergetic failure, or defective mitophagy should be considered complementary and context-dependent strategies. By reframing ophthalmic disorders as diseases of inter-organelle stress integration, this review positions the ER-mitochondria axis as a modifiable upstream determinant of ocular cell fate, which provides a foundation for stage-specific precision therapies.}, }
@article {pmid42149082, year = {2026}, author = {Chen, PJ and Wan, L and Yip, HT and Tien, PT and Wang, IM and Tsai, FJ and Huang, YT and Lin, HJ}, title = {Bidirectional Association Between Age-Related Macular Degeneration and Cardiovascular Disease: A Population-Based Cohort Study in Taiwan with 15-Year Follow-up.}, journal = {Ophthalmic epidemiology}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/09286586.2026.2675291}, pmid = {42149082}, issn = {1744-5086}, abstract = {PURPOSE: To investigate the bidirectional association between age-related macular degeneration (AMD) and cardiovascular disease (CVD), including acute myocardial infarction (AMI) and ischemic stroke (IS), in a large Taiwanese cohort.<br><br>METHODS: We conducted a retrospective cohort study using electronic health records from China Medical University Hospital (CMUH), Taiwan. From 2003 to 2014, we identified 9,333 AMD patients with 37,332 matched controls, and 26,897 CVD patients with 107,588 matched controls. All patients were followed through December 31, 2019. Multivariable Cox regression was used to estimate the risk of CVD in AMD patients and the risk of AMD in CVD patients. The effects of common cardiovascular medications were also analyzed.<br><br>RESULTS: AMD patients had an increased risk of AMI (adjusted HR&#x2009;=&#x2009;1.45, 95% CI&#x2009;=&#x2009;1.25-1.69) and IS (adjusted HR&#x2009;=&#x2009;1.78, 95% CI&#x2009;=&#x2009;1.52-2.09) compared to controls. CVD patients had a higher risk of AMD (adjusted HR&#x2009;=&#x2009;2.57, 95% CI&#x2009;=&#x2009;1.30-5.09). Aspirin use among CVD patients was associated with a lower risk of AMD (HR&#x2009;=&#x2009;0.69, 95% CI&#x2009;=&#x2009;0.50-0.94). Several comorbidities, including diabetes, hypertension, and chronic kidney disease, further increased risks in both directions.<br><br>CONCLUSION: This population-based study demonstrates a significant bidirectional association between AMD and CVD in Taiwan. Integrated screening and management should be considered for patients with either condition.}, }
@article {pmid42149141, year = {2026}, author = {Purola, P and Hujanen, P and Uusitalo, H and Uusitalo-Järvinen, H}, title = {Impact of delayed appointments on treatment outcomes in neovascular macular degeneration.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70169}, pmid = {42149141}, issn = {1755-3768}, support = {//Tampere University Hospital Support Foundation/ ; //The Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital/ ; //The Finnish Eye Foundation/ ; //State Funding for University-Level Health Research, Tampere University Hospital, Wellbeing Services County of Pirkanmaa/ ; //Suomen Kulttuurirahasto/ ; //Sokeain Yst&#xe4;v&#xe4;t/ ; //Finnish Federation of the Visually Impaired/ ; }, abstract = {PURPOSE: To evaluate the real-world visual outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy, the frequency of delayed appointments and the relationship between delays and visual outcomes in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This single-centre retrospective study included a cohort of 3831 treatment-na&#xef;ve nAMD patients who were treated with bevacizumab monotherapy using a pro re nata protocol between 2008 and 2023, comprising a total of 79&#x2009;545 visits. Visual acuity (VA) was measured at the time of diagnosis and during follow-up visits and was converted into Early Treatment Diabetic Retinopathy Study letters. One eye per patient was included in the analysis. Delayed visits were categorised as >6&#x2009;weeks and &#x2264;8&#x2009;weeks, >8&#x2009;weeks and &#x2264;&#x2009;10&#x2009;weeks and >10&#x2009;weeks.<br><br>RESULTS: After an initial stabilisation in VA during the first treatment year, VA started to decline. The proportion of visits delayed >6&#x2009;weeks varied between 24% and 36% per treatment year, with delays being more common during the early years of the study when the new therapies were introduced. In general, the decline in VA was more severe with a higher number and longer duration of delayed visits.<br><br>CONCLUSIONS: Delays in anti-VEGF injections are common and strongly associated with vision loss. Therefore, it is important to improve patient awareness and compliance. Use of new longer-acting therapies may support this process.}, }
@article {pmid42138654, year = {2026}, author = {Pierre-Henry, G and Creuzot-Garcher, C}, title = {Re: Shaheen et al: Efficacy and Safety of Anti-VEGF Injections and Surgery for Age-Related Macular Degeneration-Related Submacular Hemorrhage: A Systematic Review and Meta-analysis (Ophthalmol Retina. 2025;9:4-12).}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.04.015}, pmid = {42138654}, issn = {2468-6530}, }
@article {pmid42139166, year = {2026}, author = {Lim, JI and Leng, T and Siedlecki, J and Lupidi, M and Wells, JA and Keane, PA and Nudleman, E and Mar, F and Gibson, K and Margaron, P and Tabano, D and Bührer, C and Holekamp, N}, title = {A Matching-Adjusted Comparison of Faricimab and Aflibercept 8 mg in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema.}, journal = {Ophthalmic research}, volume = {}, number = {}, pages = {1-14}, doi = {10.1159/000552388}, pmid = {42139166}, issn = {1423-0259}, abstract = {INTRODUCTION: Matching adjusted network meta-analyses (NMA) provide an established method to indirectly compare treatments across trials that share a common comparator. In this exploratory analysis, we conducted a matching-adjusted NMA to compare the efficacy of faricimab with aflibercept 8 mg for treatment of diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) via the common comparator of aflibercept 2 mg during the first 12 weeks of treatment when all agents are dosed equally.<br><br>METHODS: Weighting was applied to match patient populations from YOSEMITE/RHINE (NCT03622580/NCT03622593) and TENAYA/LUCERNE (NCT03823287/NCT03823300) based on their baseline characteristics to published aggregated baseline characteristics for PHOTON (NCT04429503) and PULSAR (NCT04423718), respectively. The matched populations were used to recalculate outcomes from faricimab trials and an NMA anchored to aflibercept 2 mg was conducted. The analysis focused on change in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters and central subfield thickness (CST) in &#xb5;m during the first 12 weeks of treatment when dosing was every 4 weeks for all three agents. Results are expressed as mean difference in change in BCVA or CST for each aflibercept dose.<br><br>RESULTS: For nAMD, BCVA change was similar between faricimab and aflibercept 2 mg and 8 mg, whereas CST reduction was greater for faricimab versus aflibercept 8 mg (-17.0 &#xb5;m; 95% credible interval [CrI], -25.0, -8.4) and 2 mg (-19.0 &#xb5;m; 95% CrI, -24.0, -13.0). For DME, BCVA change from baseline at 12 weeks was similar between faricimab and aflibercept 2 mg and 8 mg, while CST reduction was greater for faricimab versus aflibercept 8 mg (-19.0 &#xb5;m; 95% CrI, -35.0, -3.2) and 2 mg (-19.0 &#xb5;m; 95% CrI, -27.0, -12.0).<br><br>CONCLUSION: This matching-adjusted NMA indicated that dual angiopoietin-2/vascular endothelial growth factor (VEGF)-A inhibition with faricimab was associated with greater retinal drying during the matched-dosing phase in patients with nAMD and DME. Early dual pathway inhibition may therefore improve outcomes beyond anti-VEGF monotherapy.}, }
@article {pmid42135020, year = {2026}, author = {Ferro Desideri, L and Scandella, D and Anguita, R and Schmitz-Valckenberg, S and Chakravarthy, U and Holz, FG and Querques, G and Wolf, S and Sznitman, R and Zinkernagel, M}, title = {Assessing intergrader variability in incomplete outer retinal atrophy (iRORA) grading.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328470}, pmid = {42135020}, issn = {1468-2079}, abstract = {BACKGROUND/AIMS: To assess the intergrader variability in detecting incomplete outer retinal atrophy (iRORA), an optical coherence tomography (OCT) biomarker for early atrophic changes in age-related macular degeneration (AMD) and a potential clinical trial endpoint.<br><br>METHODS: We performed a cross-sectional intergrader agreement study using 60 OCT B-scans enriched for iRORA features from non-exudative AMD eyes. Five international retinal experts independently graded images for iRORA presence according to the current Classification of Atrophy Meeting (CAM) criteria, using a standardised online annotation platform. Pairwise agreement was assessed with Cohen's Kappa; agreement with the majority vote, sensitivity and specificity were calculated using a leave-one-out approach. Annotation lead times were recorded to explore links between decision speed and grading consistency.<br><br>RESULTS: Mean pairwise Cohen's Kappa was 0.425 (range 0.19-0.73), indicating mild agreement. Agreement with the majority vote ranged from &#x3ba;=0.48&#x2009;to 0.67, with classification accuracy between 0.73 and 0.83. Sensitivity varied from 0.59 to 0.83, while specificity remained high (0.85-0.96). Annotation lead times were generally shorter when grader decisions aligned with the majority consensus.<br><br>CONCLUSION: Despite standardised CAM definitions, intergrader reproducibility for iRORA detection remains limited, reflecting challenges in consistent early atrophy identification. Refinement of grading guidelines and integration of automated detection systems could improve reliability for AMD clinical trials and clinical practice.}, }
@article {pmid42135021, year = {2026}, author = {Romano, F and Stettler, I and Finn, M and Vingopoulos, F and Ding, X and Overbey, K and Cort, T and Chen, C and Ploumi, I and Baldwin, G and Zhu, Y and Nodecker, KN and Gumustop, SS and Shah, SH and Laíns, I and Kim, L and Vavvas, D and Husain, D and Miller, JW and Miller, JB}, title = {Multimodal imaging determinants of contrast sensitivity loss in geographic atrophy.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-329036}, pmid = {42135021}, issn = {1468-2079}, abstract = {AIMS: To investigate associations between imaging biomarkers and quantitative contrast sensitivity (CS) function (qCSF) metrics in geographic atrophy (GA).<br><br>METHODS: Cross-sectional study including 97 eyes from 70 patients (>55 years) with GA within 1500&#x2009;&#xb5;m of the fovea and visual acuity (VA)>20/320. Participants underwent VA and qCSF testing (area under the log CS function (AULCSF), contrast acuity (CA), and CS at 1-18 cycles per degree (cpd)) and multimodal imaging with blue autofluorescence (BAF), optical coherence tomography (OCT), and, in 55 eyes, swept-source OCT angiography (SS-OCTA). Imaging biomarkers included GA size, prior growth rate, configuration, BAF pattern, circularity, percentage of foveal involvement (%FI), foveal distance and macular inner choroid flow deficit percentage (mICFD%). Generalised linear mixed-effects and random forest (GRF) models evaluated structure-function relationships.<br><br>RESULTS: Participants (age 78.8&#xb1;5.6 years; 70% female) had a median GA size of 4.0&#x2009;mm&#xb2;, with 64% showing subfoveal involvement. Larger GA size and higher %FI were significantly associated with worse VA, AULCSF, CA and CS at 1-12&#x2009;cpd (all p<0.01). Unifocal lesions correlated with lower VA and CS at 6 cpd, while diffuse/banded BAF patterns and greater mICFD% were linked to reduced CS at 1-1.5&#x2009;cpd. GRF analysis identified GA size and %FI as primary predictors of CS loss, with best performance for AULCSF and CS at 3 cpd (R&#xb2;=0.319, 0.314).<br><br>CONCLUSIONS: GA size and %FI are key determinants of CS loss in GA. qCSF outperformed VA in predictive accuracy, supporting its use as a sensitive functional endpoint in GA trials.}, }
@article {pmid42135289, year = {2026}, author = {Zhang, C and Wu, J and Shen, X and Liu, Y and He, J and Zheng, X and Ding, W and Li, Z and Zhu, Y and Xu, Z and Su, W and Liu, X and Zhuo, Y}, title = {Metal ions in aging and ocular diseases: biology, pathophysiology, and therapeutic strategies.}, journal = {npj aging}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41514-026-00396-4}, pmid = {42135289}, issn = {2731-6068}, support = {2021HXFH026//Clinical Research Incubation Project, West China Hospital, Sichuan University/ ; 23JZH039//Aier Ophthalmology-Sichuan University Scientific Research Fund Project/ ; 82501266//National Natural Science Foundation of China/ ; 82471074//National Natural Science Foundation of China/ ; BX20240440//China National Postdoctoral Program for Innovative Talents/ ; 2025M772142//China Postdoctoral Science Foundation/ ; 2025QNJS18//Research Funds of the State Key Laboratory of Ophthalmology/ ; 2024A1515013058//Guangdong Basic and Applied Basic Research Foundation/ ; 202206080005//Science and Technology Program of Guangzhou, China/ ; }, abstract = {Metal ions are indispensable for sustaining normal cellular functions and preserving tissue integrity, as they participate in enzymatic catalysis, signal transduction, and antioxidant defense. However, dysregulation of metal ion homeostasis, particularly during aging, disrupts cellular balance and significantly drives the development and progression of age-related ocular diseases, including age-related macular degeneration, glaucoma, diabetic retinopathy, and cataracts. Specifically, metal ions modulate key stress responses that are central to aging and ocular pathogenesis. Excessive accumulation of redox-active metals triggers the generation of reactive oxygen species that induce oxidative damage to lipids, proteins, and DNA. Meanwhile, deficiencies in essential metals, such as iron, zinc, copper, and calcium, impair antioxidant enzyme activity and disrupt DNA repair, exacerbating cellular dysfunction and senescence. The therapeutic potential of these metal chelators and antioxidants in restoring their balance, alleviating oxidative stress, and slowing the progression of age-related ocular diseases has been well documented. A deeper understanding of how metal ions influence these processes is crucial for developing more targeted and effective treatments. This article systematically reviews the roles of metal ions in age-related ocular diseases, with a focus on their effects on stress responses and potential therapeutic strategies.}, }
@article {pmid42137658, year = {2026}, author = {Istanaksai, A and Jama, K and Hammadieh, T and Ali, A and Siddiqui, E and Azizi, S}, title = {The Effect of Nutrition on Dry Age-Related Macular Degeneration: A Systematic Narrative Review of Evidence and Clinical Implications.}, journal = {Cureus}, volume = {18}, number = {4}, pages = {e106966}, pmid = {42137658}, issn = {2168-8184}, abstract = {Age-related macular degeneration (AMD) is a progressive retinal condition characterised by degeneration of the macula, leading to central vision loss. Whilst the underlying mechanism of AMD is not fully understood, oxidative stress is believed to be the main driving force behind retinal damage. Although the prevalence of AMD increases with factors such as age, smoking, and sun exposure, these alone do not fully explain individual risk. Nutritional factors, in particular dietary antioxidant intake, have been shown to influence the progression of dry AMD by mitigating oxidative stress and supporting retinal cellular function. By considering the effects of nutrition on retinal health and disease outcomes, we can further our understanding of AMD pathogenesis.}, }
@article {pmid42138517, year = {2026}, author = {Chen, R and Lu, W and Zhu, J and Huang, L and Chen, W and Huang, G and Ren, X and Sun, Q and Hu, J and Li, J and Wang, S and Kuang, H and Lee, C and Lu, W and Xiong, Z and Liu, Y and Wang, X and Prodeus, A and Zhu, X and Zhang, Q and Li, K and Deng, A and Cao, Y and Yao, Y and Gariepy, J and Liu, X and Yang, Z and Jiang, Q and Li, X}, title = {An Inhibitory Aptamer Against PDGF-C Overcomes Anti-VEGF Refractoriness and Reduces Choroidal Neovascularization and Fibrosis.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {5}, pages = {36}, doi = {10.1167/iovs.67.5.36}, pmid = {42138517}, issn = {1552-5783}, mesh = {*Choroidal Neovascularization/metabolism/drug therapy/pathology/prevention &amp; control ; Animals ; *Aptamers, Nucleotide/pharmacology/therapeutic use ; Humans ; Mice ; *Platelet-Derived Growth Factor/antagonists &amp; inhibitors ; Fibrosis/prevention &amp; control ; Disease Models, Animal ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Lymphokines/antagonists &amp; inhibitors/metabolism ; Cell Proliferation/drug effects ; Mice, Inbred C57BL ; Cell Movement/drug effects ; Cells, Cultured ; Angiogenesis Inhibitors/pharmacology ; Surface Plasmon Resonance ; Fibroblasts/drug effects/metabolism ; Signal Transduction ; *Choroid/pathology ; }, abstract = {PURPOSE: Wet age-related macular degeneration is a leading cause of irreversible vision loss, primarily due to choroidal neovascularization (CNV) and subsequent fibrosis. Although current anti-vascular endothelial growth factor A (anti-VEGF) therapies offer significant benefits, many patients exhibit limited or no response and develop drug resistance over time, necessitating the exploration of complementary or alternative therapeutics. This study aimed to identify and characterize a platelet-derived growth factor-C (PDGF-C)-targeting DNA aptamer and to evaluate its therapeutic potential for suppressing CNV and fibrosis, including in an anti-VEGF-refractory setting.<br><br>METHODS: A DNA aptamer against PDGF-C (&#x3b1;-PC aptamer) was identified using systematic evolution of ligands by exponential enrichment. Its binding to PDGF-C and inhibition of PDGF-C/platelet-derived growth factor receptor alpha (PDGFR&#x3b1;) interaction were assessed using surface plasmon resonance. The effects of the &#x3b1;-PC aptamer on PDGF-C-induced proliferation, migration, and PDGFR&#x3b1;, Akt, and extracellular-regulated kinase (ERK) signaling were examined in fibroblasts and human umbilical vein smooth muscle cells (HUVSMCs). In vivo efficacy was evaluated in a laser-induced CNV mouse model, including anti-VEGF refractory aged mice.<br><br>RESULTS: The &#x3b1;-PC aptamer specifically bound to PDGF-C and effectively blocked its binding to PDGFR&#x3b1;. The &#x3b1;-PC aptamer significantly inhibited PDGFR&#x3b1;, Akt, and ERK activation and suppressed PDGF-C-induced proliferation and migration of both fibroblasts and HUVSMCs. Importantly, in a laser-induced CNV mouse model, the &#x3b1;-PC aptamer markedly reduced neovascularization and fibrosis; it particularly retained efficacy in suppressing CNV in anti-VEGF refractory aged mice, where anti-VEGF treatment failed to do so.<br><br>CONCLUSIONS: These findings suggest that the &#x3b1;-PC aptamer represents a promising therapeutic agent for treating neovascular diseases, especially in patients refractory to anti-VEGF treatment.}, }
@article {pmid42128044, year = {2026}, author = {Hu, Z and Qi, H and Dong, X and Tian, Y and Sun, M and Jia, X and Yu, H}, title = {Metabolic Reprogramming and Mitochondrial Dynamics: Novel Therapeutic Perspectives for Age-Related Macular Degeneration.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111064}, doi = {10.1016/j.exer.2026.111064}, pmid = {42128044}, issn = {1096-0007}, abstract = {Age-related macular degeneration (AMD) represents the leading cause of irreversible vision loss in the elderly, affecting over 200 million individuals worldwide. Despite recent advances, therapeutic options remain severely limited, particularly for dry AMD characterized by progressive geographic atrophy. Emerging evidence implicates mitochondrial dysfunction and metabolic reprogramming of retinal pigment epithelium (RPE) cells as central pathogenic drivers. Under pathological conditions, RPE cells exhibit profound bioenergetic collapse marked by declining oxidative phosphorylation, compensatory glycolytic activation, and aberrant tricarboxylic acid cycle intermediate accumulation. This metabolic catastrophe is structurally underpinned by dysregulated mitochondrial dynamics. The resultant accumulation of fragmented, dysfunctional mitochondria perpetuates reactive oxygen species overproduction and mitochondrial DNA damage, establishing a self-amplifying vicious cycle driving RPE degeneration. Mechanistically, this involves dysregulation of the AMPK/mTOR energy-sensing axis, SIRT1/PGC-1α transcriptional control, and Nrf2/ARE antioxidant defenses. Multi-omics profiling reveals distinct metabolic signatures. These discoveries have catalyzed mechanism-based interventions. However, translational applications still face many challenges, and the combination of single-cell multi omics and multimodal therapies is expected to play a role.in restoring mitochondrial homeostasis and preserving vision in aging population in the future.}, }
@article {pmid42129346, year = {2026}, author = {Enzendorfer, ML and Reiter, GS and Bogunović, H and Riedl, S and Mai, J and Schrittwieser, J and Stapf, C and Mares, V and Mihelčič, M and Little, JA and Jaki-Mekjavić, P and Barthelmes, D and Hatz, K and Zarranz-Ventura, J and Creuzot-Garcher, C and Hogg, R and Sadeghipour, A and Schmidt-Erfurth, U and , }, title = {I-SCREEN: Development of an AI-based infrastructure for community-wide screening and prediction of progression in age-related macular degeneration providing accessible shared care.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42129346}, issn = {1476-5454}, abstract = {OBJECTIVES: This work describes the design and methodological framework of the I-SCREEN project, which aims to develop an artificial intelligence (AI)-based infrastructure utilising optical coherence tomography (OCT) for early detection of AMD and assessment of progression risk.<br><br>METHODS: The pan-European project is conducted across clinics and optometry/optician practices in six European countries. I-SCREEN encompasses seven work packages covering community-based AMD identification, clinical follow-up, AI development and project dissemination. Three interconnected clinical studies are carried out by optometry/optician practices (PYRENEES) and ophthalmology clinics (SUDETES and APENNINES).<br><br>RESULTS: The PYRENEES study is a prospective, cross-sectional study evaluating the feasibility of detecting subclinical AMD in optometry/optician practices under ophthalmologist supervision via telemedicine. A robust screening network comprising 28 community-based optometry/optician practices and 7 ophthalmology clinics has been established. Patients with suspected non-neovascular AMD are referred to partnered&#xa0;clinics. In the hospital setting, patients with early or intermediate AMD are followed in the longitudinal SUDETES study, while patients with non-foveal geographic atrophy are invited to take part in the APENNINES study. Data obtained inform AI development for community-based AMD detection and monitoring. Predictive modelling will further enable personalised risk assessments.<br><br>CONCLUSIONS: I-SCREEN brings together multidisciplinary experts across Europe to establish an AI-driven shared care model for AMD detection and monitoring. By combining high-quality OCT imaging from community practices with longitudinal clinical studies, the initiative provides novel insights into early AMD progression and &#xa0;establishes a foundation for innovative AI-based detection and prediction throughout the real-world population.}, }
@article {pmid42129509, year = {2026}, author = {Yamamoto, A and Nakanishi, Y and Ideyama, M and Akada, M and Tamiya, R and Miyata, M and Kido, A and Tamura, H and Ooto, S and Tsujikawa, A and Hata, M}, title = {Experimental and clinical evidence of multilayer retinal damage caused by subretinal hemorrhage in neovascular age-related macular degeneration.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-52680-8}, pmid = {42129509}, issn = {2045-2322}, support = {No. 24K02293//Japan Society for the Promotion of Science/ ; grant JP25gm6510029h0003//Japan Agency for Medical Research and Development/ ; grant M2025006N//BrightFocus Foundation/ ; }, abstract = {Neovascular age-related macular degeneration (AMD) with subretinal hemorrhage (SRH) is associated with a poor visual prognosis. This study investigated the effects of SRH in neovascular AMD on visual function and retinal integrity. An SRH mouse model, established by subretinal injection of autologous blood, exhibited early apoptotic cell death across both outer and inner retinal layers, ultimately resulting in retinal ganglion cell loss and inner retinal thinning. Clinically, we retrospectively reviewed consecutive treatment-naïve neovascular AMD patients who visited Kyoto University Hospital between December 2012 and December 2013. Among 43 eyes from 43 patients, the presence of baseline SRH was independently associated with poorer best-corrected visual acuity at 1 year (β = 0.16, P = 0.03). Eyes with SRH exhibited significant thinning of the ganglion cell complex (GCC) and outer nuclear layer (ONL). Reductions in GCC and ONL thickness were significantly correlated with worse 1-year BCVA (ρ = 0.51, P = 0.02; and ρ = 0.62, P = 0.003, respectively). These findings indicate that SRH induces neuronal damage not only in the outer retina adjacent to the hemorrhage but also in the inner retinal layers, both of which contribute to sustained visual impairment in neovascular AMD.}, }
@article {pmid42130720, year = {2026}, author = {Ding, L and Xie, B and Lv, J and Zhou, Z and Zhou, X and Wu, K and Zhang, Q and Lu, F and Wang, C and Qu, J and Xiang, L and Chen, Q}, title = {Bemarituzumab Suppresses Choroidal Neovascularization in Mice by Downregulating Melanoma Cell Adhesion Molecule and Yes-Associated Protein 1.}, journal = {ACS pharmacology &amp; translational science}, volume = {9}, number = {5}, pages = {1099-1108}, pmid = {42130720}, issn = {2575-9108}, abstract = {In recent years, some fibroblast growth factors (FGFs) have been reported to be promising therapeutic targets for neovascular age-related macular degeneration (nAMD). Interestingly, we found that the FGFR2b inhibitor bemarituzumab (FPA144) exerts a beneficial effect in a mouse choroidal neovascularization (CNV) model. Our current study aims to uncover the potential molecular mechanism by which FPA144 alleviates CNV. The effect of FPA144 was evaluated in a laser-induced CNV mouse model. Fundus fluorescein angiography (FFA), optical coherence tomography (OCT), and choroidal flat mounts were carried out for the quantitative assessment of CNV. Label-free quantitative proteomics analysis was performed to assess changes in molecular pathways. Primary cultured human umbilical vein endothelial cells (HUVECs) were used for further confirmation of the target pathway in vitro. FFA, OCT, and choroidal flat mounts demonstrate the protective effect of FPA144 in a mouse CNV model. Compared to the control group, the treated group has smaller vascular leakage areas or smaller CNV lesions. Proteomic analyses indicate that the melanoma cell adhesion molecule (MCAM, CD146)-Yes-associated protein 1 (Yap1) pathway may be involved in the effect of FPA144. Immunostaining of choroidal flat mounts and cryosections reveals decreased expression of CD146 and Yap1 in the vascular endothelial cells of the treated animals. Experiments on HUVECs further verify the inhibitory effect of FPA144 on vascular endothelial cells. Our findings demonstrate that FPA144 can efficiently inhibit the development of choroidal neovascularization in mice by downregulating CD146 and Yap1.}, }
@article {pmid42131406, year = {2026}, author = {Lin, TY and Wang, CY and Chen, L and Huang, SP}, title = {Adaptive immune crosstalk and complement dysregulation in the aging retina.}, journal = {Tzu chi medical journal}, volume = {38}, number = {2}, pages = {145-151}, pmid = {42131406}, issn = {2223-8956}, abstract = {The eye, long viewed as immune-privileged, is now recognized as a dynamic immunological environment where innate and adaptive mechanisms intersect to maintain retinal homeostasis. In aging and age-related retinal diseases such as age-related macular degeneration (AMD), this balance deteriorates as chronic, low-grade inflammation replaces immune quiescence. Adaptive immune involvement in AMD is reflected by increased antiretinal autoantibodies and systemic immune changes, including accelerated aging of CD8[+] T-cells. Complement activation further amplifies adaptive responses; C5a stimulates T-cell secretion of proinflammatory cytokines, such as interleukin-17 (IL-17) and IL-22, which contribute to retinal injury. Retinal cells exhibit context-dependent immune plasticity. Retinal pigment epithelial (RPE) cells upregulate major histocompatibility complex molecules in response to stress and can express the regulatory transcription factor forkhead box p3 (FOXP3), indicating an intrinsic immunomodulatory capacity. Myeloid populations are likewise heterogeneous: Resident microglia maintain immune surveillance, whereas infiltrating monocyte-derived macrophages often drive maladaptive inflammation and lesion progression. The complement system also contributes to age-related synaptic remodeling, with C1q and C3 tagging synapses for elimination. This pathway is normally limited by Complement Factor H (CFH), whose regulatory function is strengthened by binding to apolipoprotein E (APOE). However, the neurodegeneration-associated APOE ε4 isoform shows reduced CFH affinity, promoting excessive complement activity. Sex-specific immune aging further modifies complement signaling, microglial behavior, and APOE-dependent susceptibility. Together, these insights illustrate how adaptive immunity shifts from protective surveillance to chronic, pathological inflammation, driving the initiation and progression of age-related retinal degeneration.}, }
@article {pmid42131590, year = {2026}, author = {Bao, L and Ying, H and Wang, X and Wu, M and Liu, H}, title = {Subtle outer retinal and choroidal alterations in patients at high risk of progression to age-related macular degeneration.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1807534}, pmid = {42131590}, issn = {2296-858X}, abstract = {AIM: To explore the changes in the microstructure and blood supply of the outer retina in eyes at high risk of progression to age-related macular degeneration (AMD).<br><br>METHODS: Forty-seven patients with unilateral neovascular AMD (nAMD) were enrolled. Twenty-two of the contralateral eyes were considered at high risk of progression to nAMD (Group 1), while the remaining 25 eyes had dry AMD (Group 2) Fifty healthy subjects (50 eyes) were enrolled as control. Swept-source optical coherence tomography (SS-OCT) equipped with angiovue (OCTA) was used to obtain three-dimensional retinal thickness maps and microvascular images of the superficial and deep retinal capillary plexuses (SCP and DCP) around the macula and choroid vessel index (CVI). Quantitative analysis was automatically calculated by an inbuilt algorithm in the SS-OCTA (VG200; SVision Imaging, Ltd., Luoyang, China). One-way analysis of variance (ANOVA) was used to compare the differences among the groups, and post hoc procedures were used to compare differences between the two groups. Associations between OCTA-derived parameters and retinal/choroidal thickness were evaluated using Pearson correlation coefficients.<br><br>RESULTS: Compared to the controls, the densities of the SCP and DCP were significantly decreased in Group 2 in some regions (p <&#x202f;0.05). However, the CVI of patients in superior (S) and temporal (T) regions was significantly decreased compared to the controls (P: 0.009, 0.020). The outer retinal thickness of Group 2 in the central (C), S, and temporal (T) regions were significantly decreased compared to the controls and Group 1 (P: 0.004-0.048). Meanwhile, compared to the controls, the thickness of total retina and choroid of Group 2 were significantly decreased in most regions (P: 0.001-0.034). The outer retinal thickness was significantly correlated to choroidal thickness in AMD patients (r =&#x202f;0.346, p =&#x202f;0.034).<br><br>CONCLUSION: Significant thinning of outer retina and choroid were observed in patients with dry AMD. In eyes at high risk of progression to AMD, choroidal thickness and CVI tend to be decreased. SS-OCTA might be useful in evaluating microstructural and blood supply disorders of the outer retinal layers in healthy eyes of unilateral nAMD patients, which might be helpful to identify the earliest progression of AMD.}, }
@article {pmid42131985, year = {2026}, author = {Lin, Q and Oh, XY and Owh, C and Sim, B and Ow, V and Wong, JHM and Boo, YJ and Ong, NWX and Truong, VX and Loh, XJ and Lim, JYC}, title = {Visible Light Photo-Cross-Linked Thermogel─A Single-Component Hybrid Supramolecular-Covalent Hydrogel for Sustained Drug Release.}, journal = {ACS applied materials &amp; interfaces}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsami.6c01197}, pmid = {42131985}, issn = {1944-8252}, abstract = {Temperature-responsive supramolecular thermogels, advanced biomaterials that exhibit sol-to-gel phase transitions when warmed, show great promise as next-generation in vivo drug delivery depots for their excellent biocompatibility and ease of formulation and administration. However, the lack of permanent covalent cross-links within the gel framework often results in short in vivo persistence and rapid gel swelling, in turn limiting duration of sustained drug release attainable. Herein, we developed a general strategy that retains the thermogels' intrinsic ease of injectability, yet allowing significantly enhanced sustained drug release durations. By incorporating a visible light-cross-linkable chromophore into the thermogel polymer structure, in situ cross-linking can be achieved after depot administration with facile external control. As compared to conventional photo-cross-linking strategies utilizing ionizing and hazardous UV light, our thermogels can be covalently cured using blue light or even under ambient indoor lighting conditions, making them potentially suitable for sensitive applications such as ophthalmic drug release. We show that these thermogels can be applied as an in situ cross-linked depot that allows the release of the antivascular endothelial growth factor biologic, Aflibercept, to be prolonged for more than 3 months, achieving a marked improvement over existing treatment regimens for diseases such as neovascular age-related macular degeneration that necessitate monthly injections. Additionally, these photo-cross-linked thermogels can also prolong the release of small proteins (e.g., bovine serum albumin) from membrane-based delivery systems by more than 3 times compared to nonirradiated controls. These visible light-photo-cross-linkable gels offer new versatile platforms for achieving long-duration drug release suitable for different biological applications and delivery modalities.}, }
@article {pmid42132121, year = {2026}, author = {Munk, M and Holz, FG and Chow, D and Sala-Puigdollers, A and Arias, L and Heier, J and Sakamoto, T and Souied, E and Godfrey, J and Douglas, K and Johnson, Z and Treece, T and Yiu, G}, title = {Real-world durability challenges with nAMD treatments and the potential promise of gene therapy.}, journal = {Current medical research and opinion}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/03007995.2026.2670008}, pmid = {42132121}, issn = {1473-4877}, abstract = {The introduction of anti-vascular endothelial growth factor (VEGF) therapies changed the treatment landscape for neovascular age-related macular degeneration (nAMD), slowing the progression of central vision loss. However, current anti-VEGF therapies are limited by the need for frequent intravitreal injections to maintain disease control, which places a substantial burden on patients, caregivers, and healthcare systems, and contributes to poorer treatment adherence and persistence in the real-world setting. To extend the dosing interval, flexible dosing strategies were implemented; however, they carry the risk of both undertreatment and overtreatment. Emerging longer-acting strategies include continuous-release delivery systems (e.g. ranibizumab port delivery system) and gene therapy. Investigational gene therapies have been designed to preferentially target non-dividing retinal cells, enabling sustained expression of a therapeutic protein for the lifespan of these cells. While the therapeutic effect is designed to persist for years following the one-time administration of gene therapy, early clinical trials show that a subset of patients do receive supplemental anti-VEGF injections. Emerging patterns of retreatment support the concept that supplemental treatment does not necessarily indicate waning efficacy, but rather the adjuvant treatment may be used transiently to fine tune for increased disease activity levels at the patient level. In summary, multiple factors need to be considered to understand the durability of future therapies, not only reduced procedural frequency but also continuous disease control and improved quality of life - key metrics that will guide the evolution of care in nAMD.}, }
@article {pmid42132461, year = {2026}, author = {Vujosevic, S and Zanzottera, E and Brotto, L and Piccoli, G and Alovisi, C and Bucceri, V and Rui, C and Poletti, E and Brambilla, M and Coppola, M and Nucci, P and Chakravarthy, U}, title = {Spectrally Resolved Fundus Autofluorescence as a Biomarker of Retinal Metabolic Integrity in Intermediate and Atrophic AMD.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {5}, pages = {31}, doi = {10.1167/iovs.67.5.31}, pmid = {42132461}, issn = {1552-5783}, mesh = {Humans ; Cross-Sectional Studies ; Male ; Female ; Tomography, Optical Coherence/methods ; Aged ; *Fluorescein Angiography/methods ; *Retinal Pigment Epithelium/pathology/metabolism ; *Geographic Atrophy/metabolism/diagnosis ; Aged, 80 and over ; Fundus Oculi ; Middle Aged ; Biomarkers/metabolism ; Retinal Drusen/metabolism/diagnosis ; *Macular Degeneration/metabolism/diagnosis ; Optical Imaging ; *Retina/metabolism/pathology ; }, abstract = {PURPOSE: To evaluate the association between spectrally resolved fundus autofluorescence (Sr-FAF) signals and four macular lesion types identified on spectral-domain optical coherence tomography (SD-OCT): (1) drusen, (2) incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) and complete retinal pigment epithelium and outer retinal atrophy (cRORA), (3) retinal pigment epithelium (RPE) and outer retinal atrophy, and (4) nascent geographic atrophy (nGA) in eyes with intermediate and atrophic age-related macular degeneration (AMD).<br><br>METHODS: This cross-sectional observational study analyzed 775 SD-OCT B-scans from 62 eyes (62 patients) with AMD. Lesions were classified according to established OCT criteria (290 drusen, 49 iRORA, 390 cRORA, 46 nGA). All eyes underwent SD-OCT imaging (97 B-scans) and Sr-FAF using a 450-nm wavelength. Quantitative Sr-FAF metrics (average red emission fluorescence component [REFC] and average green emission fluorescence component [GEFC]) were determined using custom software, and lesion groups were compared via one-way analysis of variance with Scheff&#xe9; post hoc testing.<br><br>RESULTS: Significant differences among lesion types were observed for REFC (F = 59.3, P < 0.001) and GEFC (F = 13.5, P < 0.001). Drusen exhibited higher REFC intensities than iRORA, cRORA, and nGA (all P < 0.001), and higher GEFC intensities than cRORA (P < 0.001) and nGA (P = 0.002). Wavelength (nm) progressively decreased from drusen to iRORA, nGA, and cRORA. Lesion size (in pixels) differed significantly (iRORA < nGA < drusen < cRORA; P < 0.001) and was the strongest predictor (&#x3b2; = -0.31, P < 0.001) in the regression analysis.<br><br>CONCLUSIONS: Sr-FAF reveals distinct metabolic signatures across AMD lesion types. Higher fluorophore signals in drusen suggest preserved photoreceptor-RPE activity, whereas reduced signals in cRORA and nGA reflect advanced atrophy. Combined SD-OCT and Sr-FAF may enhance the detection of early atrophic changes and improve AMD risk stratification.}, }
@article {pmid42132463, year = {2026}, author = {Vallino, V and Porreca, A and Bandello, F and Batlle-Ferrando, S and Bernal-Morales, C and Boscia, F and Breazzano, MP and Bucceri, V and Chaundhary, V and Chhablani, J and Cicinelli, MV and Couturier, A and Dolz-Marco, R and Sadeghi, E and Elkobi, T and Eller, AW and Gallego-Pinazo, R and Cheung, CMG and Kapoor, S and Melgar, S and Montero, J and Peronetti, M and Pignataro, MG and Puligheddu, S and Termite, AC and Viggiano, P and Vujosevic, S and Zarranz-Ventura, J and Zur, D and Reibaldi, M and Borrelli, E}, title = {Peripapillary Choroidal Neovascularization in Adults: Spectrum of Etiologies and Clinical Features.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {5}, pages = {29}, doi = {10.1167/iovs.67.5.29}, pmid = {42132463}, issn = {1552-5783}, mesh = {Humans ; Retrospective Studies ; *Choroidal Neovascularization/etiology/diagnosis/drug therapy ; Male ; Female ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Visual Acuity/physiology ; Aged ; Middle Aged ; Aged, 80 and over ; Adult ; *Optic Disk/pathology ; Fundus Oculi ; Multimodal Imaging ; Angiogenesis Inhibitors/therapeutic use ; Macular Degeneration/complications/diagnosis ; Indocyanine Green/administration &amp; dosage ; }, abstract = {PURPOSE: To characterize etiologies and clinical-imaging features of peripapillary choroidal neovascularization (CNV) and identify predictors of underlying disease (i.e., including age-related macular degeneration [AMD] vs. non-AMD etiologies) and visual outcomes.<br><br>METHODS: This multicenter retrospective case series included 156 eyes of 138 treatment-na&#xef;ve patients with peripapillary CNV from 12 tertiary centers. Peripapillary CNV was defined as sub-RPE or subretinal neovascularization within one disc diameter of the optic disc. Multimodal imaging (optical coherence tomography [OCT], fluorescein and indocyanine green angiography, and/or OCT angiography) was used to confirm CNV and etiology. Baseline OCT features included CNV type, exudation pattern, foveal involvement, peripapillary location, and distance to the disc. Longitudinal OCT and best-corrected visual acuity (BCVA, logMAR) were analyzed when available. Management followed routine clinical practice with variable administration of anti-VEGF therapy. Regression models and a conditional inference tree assessed predictors of diagnosis and visual outcome.<br><br>RESULTS: The most common etiologies were AMD (51.9%), pachychoroid disease (27.6%), and angioid streaks (6.4%). CNV most frequently involved the temporal peripapillary quadrant (84.6%). Aneurysmal type 1 CNV predominated in pachychoroid disease, whereas type 2 CNV was more common in other etiologies. Baseline BCVA was worse in AMD and angioid streaks and was independently associated with underlying disease and foveal involvement. The Conditional Inference Tree associated age >71 years and nonaneurysmal type 1 or type 2 CNV with AMD.<br><br>CONCLUSIONS: Peripapillary CNV most commonly arises from AMD and pachychoroid disease. Simple clinical and imaging features can assist etiological classification and visual prognostication in clinical practice.}, }
@article {pmid42133019, year = {2026}, author = {Ferrucci, M and Lazzeri, G and Pinelli, R and Biagioni, F and Bumah, VV and Giambelluca, MA and Busceti, CL and Lenzi, P and Fornai, F}, title = {Neuronal death and accumulation of lipid droplets and glycogen granules within retinal pigment epithelium under the influence of mTOR and autophagy.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {42133019}, issn = {1435-1463}, support = {Ricerca Corrente 2026, IRCCS Neuromed//Ministero della Salute/ ; }, abstract = {In the course of age-related macular degeneration (AMD) the retinal pigment epithelium undergoes a number of cytopathological alterations that are generated by a dysfunction of specific metabolic pathways. In detail, these include lipid and glycogen accumulation along with dismantling of specific proteins from the plasma membrane. In the present study we analyzed whether 3-methyladenine (3-MA), a classic autophagy inhibitor, may reproduce the pathobiochemical and structural alterations occurring in AMD. Different doses of 3-MA produce a loss of cell viability with lipids and glycogen accumulation, which were quantified by ultrastructural morphometry. This was concomitant with displacement and suppression of autophagy-related proteins along with increased activity of mTOR. A dismantling of phenotype-specific proteins composing tight junctions was observed as well. All these alterations were reverted by the phytochemical autophagy stimulator curcumin which was shown to act as a powerful mTOR inhibitor with an efficacy that was like the classic mTOR inhibitor rapamycin. When these compounds activating autophagy/inhibiting mTOR were administered alone, a beneficial effect was observed even in control cells. The occurrence of 3-MA-induced retinal degeneration was found to be associated with a remarkable aggregation of p62 which is reminiscent of central neurodegenerative disorders, and it was fully prevented by curcumin similarly to rapamycin. These protective effects concern cell viability, altered glycogen and lipid accumulation, and ultrastructural alterations. The present work contributes to understanding degeneration in AMD while extending key biochemical steps to neurodegenerative disorders. The use of natural phytochemicals and light-induced by-products may be used for therapeutic purposes.}, }
@article {pmid42133343, year = {2026}, author = {Jacobs, A and Anselmo, D and McHugh, R and Fernandez-Garcia, I and Fang, C and Lasko, R and Mukherjee, S and Holekamp, N}, title = {Generative Artificial Intelligence-Driven Voice Assistance for Patient Education in Ophthalmology.}, journal = {JAMA ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1001/jamaophthalmol.2026.1307}, pmid = {42133343}, issn = {2168-6173}, }
@article {pmid42134448, year = {2026}, author = {Rajapakse, D and Fan, J and Daily, D and Dong, L and Peterson, K and Fariss, R and Wistow, G}, title = {A Human Amelotin Transgenic Mouse Model with Calcified Deposits Similar to Those in Dry Age-related Macular Degeneration.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111068}, doi = {10.1016/j.exer.2026.111068}, pmid = {42134448}, issn = {1096-0007}, abstract = {Amelotin (AMTN), a protein involved in enamel formation, is induced in retinal pigment epithelial (RPE) in patients with dry age-related macular degeneration (AMD) and is associated with calcification in drusen. To examine the effects of constitutive expression of human AMTN in RPE we created a transgenic (TG) mouse model that expresses human AMTN specifically in the RPE using the regulatory components of the mouse Rpe65 gene. This led to several AMD-like abnormalities in RPE but did not produce calcified depositions. Reasoning that other aspects of cell stress or damage may be needed for calcification we tested moderate laser injury of the retina in young TG and WT mice. TG mice, but not WT, developed AMTN-dependent deposits containing AMTN, cholesterol, and calcium phosphate/HAP in the laser lesions, reminiscent of deposits seen in dry AMD drusen. While laser lesions in WT mice healed normally, those in TG mice progressed, obliterating adjacent photoreceptors and recruiting microglia. This shows that chronic expression of AMTN can induce pathologies in RPE and that when coupled with injury can form structures similar to calcified drusen. These deposits are associated with increased retinal damage and inflammation. The model presents a system to test possible therapeutic effects of inhibition or suppression of AMTN in RPE in vivo.}, }
@article {pmid42134616, year = {2026}, author = {Smith, RT and Rosenfeld, PJ}, title = {Cardiovascular Disease and Age-Related Macular Degeneration.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.05.003}, pmid = {42134616}, issn = {1879-1891}, abstract = {PURPOSE: To provide an update on the published associations between cardiovascular disease (CVD) and age-related macular degeneration (AMD).<br><br>DESIGN: Evidence-based perspective.<br><br>METHODS: Review of literature and experience of authors.<br><br>RESULTS: CVD is the leading cause of death worldwide, and AMD is the leading cause of irreversible blindness among the elderly. Both these conditions are associated with hypertension and smoking. Thus, it was expected that patients with CVD might be at higher risk for AMD, and AMD would be closely associated with CVD. However, such a general association has never been shown in dozens of studies. Instead, current evidence suggests that there are associations only between certain subsets of CVD and AMD. A strong association was shown to exist between specific high-risk cardiovascular diseases (HRCVDs) that confer compromised choroidal perfusion and the presence of subretinal drusenoid deposit (SDD), not ordinary soft drusen, which are considered the hallmark of intermediate AMD. We propose that this compromised choroidal perfusion is the underlying mechanism driving the formation of SDDs. We also propose, more generally, that the formation of SDDs result from the disruption of the normal metabolic support between the choriocapillaris and photoreceptors (PRs). We recommend that HRCVDs need to be studied in association with genetic risk-alleles to better understand the association between decreased choroidal perfusion and AMD progression.<br><br>CONCLUSION: The strong association between SDDs to HRCVDs merits further investigation, especially in cardiovascular patients with SDDs carrying the high-risk alleles for AMD. Further prospective studies in both HRCVD and AMD patients are needed to elucidate the totality of clinical and genetic factors that drive AMD. These disease models can then be deployed to identify vasculopathic patients who need a retinal referral for AMD as well as AMD patients who need a cardiovascular workup to address undetected HRCVDs in patients with SDDs.}, }
@article {pmid42134650, year = {2026}, author = {Jonas, JB and Jonas, RA and Bikbov, MM and Kazakbaeva, GM and Dong, L and Wang, YX and Panda-Jonas, S}, title = {Mechanism of myopic axial Elongation related to Bruch´s membrane.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {100329}, doi = {10.1016/j.apjo.2026.100329}, pmid = {42134650}, issn = {2162-0989}, abstract = {PURPOSE: The process of myopic axial elongation has not been fully uncovered yet. Here we propose a Bruch´s membrane (BM)-related hypothesis und present anatomical and clinical findings supporting it.<br><br>METHODS: The hypothesis is that ocular axial elongation beyond the age of 3 years occurs by a retina-triggered annular segmental growth of BM in the posterior fundus midperiphery between approximately 10&#xb0; to 80&#xb0; anterior to the posterior pole, with a maximum growth at approximately 25&#xb0; anterior to the posterior pole.<br><br>RESULTS: The location of the posterior midperiphery is supported by anatomical findings of an axial length-related thinning of retinal layers, sclera, and retinal pigment epithelium in the posterior midperiphery, the location of pathologic changes at the anterior and posterior border of the BM growth zone (patchy atrophies, parapapillary myopia beta zone and gamma zone, optic nerve head canal widening, cobble stones), and results of clinical trials on myopia prevention in adolescents by circular progressive contact lenses or glasses. The notion of BM as compared to sclera as the primary structure elongating the eye is supported by the axial length-related choroidal thinning most marked at the posterior pole, the axial length-related increase in BM volume, the axial length-related shift of BM-opening of the ONHC into the macular direction, the biomechanical properties of BM, and by primarily not involving the retina, RPE and choriocapillaris in the foveal region.<br><br>CONCLUSIONS: If BM is the primary effector structure for axial elongation, future research may address the retinal messenger molecule directing the RPE to locally produce BM.}, }
@article {pmid42134759, year = {2026}, author = {Kashihara, T and Akiyama, Y and Morita, A and Deguchi, S and Odaka, R and Nakahara, T}, title = {Characterization of mitochondrial dysfunction induced by BAX trigger site activator 1 in the ARPE-19 retinal pigment epithelial cell model.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {178975}, doi = {10.1016/j.ejphar.2026.178975}, pmid = {42134759}, issn = {1879-0712}, abstract = {Mitochondrial dysfunction in the retinal pigment epithelium (RPE) is a key pathological feature of age-related macular degeneration (AMD). However, mechanistically defined experimental models that recapitulate stress-mediated mitochondrial injury remain limited. Bcl-2-associated X (BAX), a key pro-apoptotic effector, serves as a critical upstream regulator of mitochondrial outer membrane permeabilization. In this study, we systematically characterized mitochondrial dysfunction induced by BAX trigger site activator 1 (BTSA1), a selective small-molecule BAX activator, in ARPE-19 cells. Treatment with BTSA1 (3-60 μM) for 24 and 48 h induced a concentration- and time-dependent reduction in cell viability, accompanied by caspase-3 activation. Mitochondrial membrane potential, assessed via tetramethylrhodamine ethyl ester staining, was markedly reduced in a BAX-dependent manner and associated with increased reactive oxygen species production following prolonged exposure or at high concentrations. BTSA1 profoundly altered mitochondrial dynamics by promoting DRP1-mediated fission while suppressing fusion through MFN2 downregulation and stress-associated OPA1 processing, resulting in pronounced mitochondrial fragmentation. Furthermore, BAX activation elicited a biphasic response in mitochondrial quality control pathways: mild stress induced impaired autophagic flux and compensatory mitochondrial biogenesis, whereas severe stress triggered mitophagy accompanied by failure of biogenic compensation. These coordinated alterations closely mirror mitochondrial pathologies observed in the degenerating RPE in AMD. Collectively, our findings demonstrate that BAX activation by BTSA1 is sufficient to induce a comprehensive cascade of mitochondrial dysfunction. This system represents a mechanistically defined experimental model for dissecting BAX-mediated mitochondrial pathology and evaluating therapeutic strategies to preserve mitochondrial integrity in AMD.}, }
@article {pmid42115584, year = {2026}, author = {Alshahrouri, B and Blass, BE and Dürig, T and Fassihi, R}, title = {Applications of Thermoresponsive Hydrogels for Sustained Drug Release in Ocular and Intravitreal Formulations Treating Visual Impairments.}, journal = {The AAPS journal}, volume = {28}, number = {3}, pages = {}, pmid = {42115584}, issn = {1550-7416}, mesh = {*Hydrogels/chemistry/administration &amp; dosage ; Humans ; Delayed-Action Preparations/administration &amp; dosage ; Temperature ; *Drug Delivery Systems/methods ; Intravitreal Injections ; Drug Liberation ; Animals ; *Vision Disorders/drug therapy ; Ophthalmic Solutions/administration &amp; dosage ; *Eye Diseases/drug therapy ; Administration, Ophthalmic ; }, abstract = {Vision loss is one of the most debilitating eye impairments, with the leading causes such as cataracts, glaucoma, injuries to the surface of the eye and age-related macular degeneration, significantly affecting a person's quality of life and placing a substantial burden on healthcare systems. Effective treatment of these conditions remains challenging due to the complex anatomical and physiological barriers of the eye, which limit the penetration and retention of topically and intravitreally administered drugs. As a result, conventional ocular therapies often exhibit poor therapeutic efficacy, low bioavailability, necessitating frequent administration, reducing patient compliance, and increasing the risk of treatment-related complications. Thermoresponsive hydrogels have emerged as a promising class of in situ-forming drug delivery systems that utilize physiological temperature as a trigger to transition from a sol to a gel state upon administration. This sol-gel transition enhances precorneal or intraocular residence time, improves mucoadhesion, and facilitates sustained drug release. These characteristics make thermoresponsive hydrogels particularly suitable for ocular and intravitreal formulations targeting both anterior and posterior-segment diseases. Thermoresponsive polymers may exhibit lower critical solution temperature (LCST), upper critical solution temperature (UCST), or combined LCST-UCST phase behavior depending on polymer composition, enabling tunable gelation properties to control rate of drug release profiles. This review provides an overview of recent developments in thermoresponsive hydrogels for ophthalmic drug delivery, including emerging dual-responsive systems, with emphasis on gelation mechanisms, drug-release kinetics, and therapeutic applications in anterior and posterior-segment diseases. Key translational considerations, including formulation stability, sterilization, scalability, and regulatory challenges, are also discussed. In addition, the article highlights future research directions to support the continued application and clinical translation of thermoresponsive hydrogel-based ocular drug delivery systems.}, }
@article {pmid42116404, year = {2026}, author = {Han, Y and Feng, J and Gong, X and Tang, G and Yin, Y and Li, J and Liu, Y and Zhang, J and Song, J and Bi, H}, title = {Mitophagy in ophthalmic pathologies: Molecular mechanisms and therapeutic implications.}, journal = {Medicine}, volume = {105}, number = {19}, pages = {e47600}, pmid = {42116404}, issn = {1536-5964}, support = {2021LCZX09//the Focus on Research and Development Plan in Shandong Province/ ; ZR2021LZY045//the Natural Science Foundation of Shandong Province/ ; 202307021729//the Shandong Province Medical and Health Science and Technology Project/ ; No. Q-2023015//Traditional Chinese Medicine Science and Technology Project of Shandong Province/ ; }, mesh = {Humans ; *Mitophagy/physiology ; Macular Degeneration/physiopathology ; *Eye Diseases/physiopathology ; Diabetic Retinopathy/physiopathology ; Mitochondria/metabolism ; Glaucoma/physiopathology ; }, abstract = {Mitophagy, a selective autophagic process responsible for the degradation of dysfunctional mitochondria, serves as a critical regulator of cellular homeostasis. Despite its emerging significance in ocular pathophysiology, comprehensive analyses bridging molecular mechanisms to clinical translation remain scarce. The retina, with its high metabolic demands and reliance on mitochondrial bioenergetics, is particularly vulnerable to mitophagic dysregulation, which has been mechanistically linked to the pathogenesis of major ophthalmic disorders. This review systematically elucidates the molecular architecture of mitophagy, focusing on its dual roles in disease progression and cytoprotection across glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). By integrating mechanistic insights with therapeutic implications, we not only delineate conserved regulatory pathways (e.g., PINK1 [PTEN-induced kinase 1]/Parkin, BNIP3 [BCL2/adenovirus E1B 19 kDa interacting protein 3], FUNDC1 [FUN14 domain containing 1]) but also propose a roadmap for targeting mitophagic checkpoints through precision pharmacology and combinatorial regimens. Our synthesis underscores the urgency of translating mitophagy modulation into clinical strategies to address unmet needs in retinal degenerative diseases.}, }
@article {pmid42122923, year = {2026}, author = {Rinaldi, M and Cennamo, G and Passaro, ML and Chiosi, F and Falco, F and D'Alessandro, A and Strianese, D and Costagliola, C}, title = {Targeting Macular Pigment in Intermediate Age-Related Macular Degeneration: Oral Supplementation Versus Transscleral Iontophoresis in a Prospective Pilot Study.}, journal = {Journal of clinical medicine}, volume = {15}, number = {9}, pages = {}, doi = {10.3390/jcm15093188}, pmid = {42122923}, issn = {2077-0383}, abstract = {Background/Objectives: Macular pigment optical density (MPOD) represents a biomarker of retinal antioxidant status in intermediate age-related macular degeneration (iAMD). Strategies aimed at increasing macular carotenoid availability may contribute to disease stabilization. This study evaluated the effects of oral supplementation and transscleral iontophoresis on MPOD and retinal parameters in iAMD. Methods: This prospective, non-randomized pilot study included 60 eyes of 60 patients with intermediate AMD enrolled at the Eye Clinic of the University of Naples Federico II between July 2024 and May 2025 (ClinicalTrials.gov NCT06465342). Patients received either oral carotenoid supplementation (n = 30) or transscleral iontophoresis (n = 30). Best-corrected visual acuity (BCVA), central macular thickness (CMT), and MPOD measured by one-wavelength reflectometry (Visucam 200; Carl Zeiss Meditec, Jena, Germany) were assessed at baseline and 6 months. Results: BCVA remained stable in both groups without significant changes (p > 0.05). MPOD significantly increased in the iontophoresis group (0.40 ± 0.11 to 0.49 ± 0.12, p < 0.001) with no statistically significant difference between them (p = 0.09). CMT showed a mild, non-significant increase in both groups (p > 0.05). No adverse events were observed. Conclusions: Both oral supplementation and transscleral iontophoresis were associated with a significant increase in MPOD while preserving visual acuity in intermediate AMD. Within the limitations of this non-randomized pilot study, transscleral iontophoresis produced MPOD changes comparable to those observed with oral supplementation. These findings are exploratory and support further investigation of localized delivery strategies in larger, randomized trials.}, }
@article {pmid42122986, year = {2026}, author = {Shakaki, N and Yu, M}, title = {Targeting Neuroinflammation and Oxidative Stress to Slow Neurodegeneration in the Visual System.}, journal = {Journal of clinical medicine}, volume = {15}, number = {9}, pages = {}, doi = {10.3390/jcm15093254}, pmid = {42122986}, issn = {2077-0383}, support = {P30-EY025585/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE: Neuroinflammation and oxidative stress are increasingly recognized as central, interconnected drivers of neurodegeneration in the visual system. This review examines the pathogenic mechanisms shared across glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and Alzheimer's disease (AD), and evaluates the therapeutic rationale for targeting both pathways simultaneously.<br><br>METHODS: A narrative review of peer-reviewed literature was conducted using PubMed. Searches combined the following MeSH terms: neuroinflammation, oxidative stress, retinal neurodegeneration, microglia, M&#xfc;ller glia, mitochondrial dysfunction, glaucoma, age-related macular degeneration, diabetic retinopathy, and Alzheimer's disease. Priority was given to original research, systematic reviews, and high-impact publications from 2000 through 2025. However, seminal foundational works were included regardless of publication date. Studies were selected based on relevance to glial activation, mitochondrial dysfunction, reactive oxygen and nitrogen species, and disease-specific neuronal outcomes.<br><br>RESULTS: Across all four diseases, persistent microglial and M&#xfc;ller glial activation, mitochondrial electron transport chain dysfunction, and excess reactive oxygen species (ROS) and reactive nitrogen species (RNS) production form a self-amplifying feed-forward loop that accelerates neuronal injury. In glaucoma, these mechanisms drive intraocular pressure-independent retinal ganglion cell loss. In AMD and DR, lipid dysregulation, complement activation, and chronic hyperglycemia sustain oxidative-inflammatory injury to the retinal pigment epithelium, photoreceptors, and neurovasculature. In AD, retinal amyloid deposition and oxidative stress mirror cortical pathology, positioning the retina as a noninvasive biomarker site.<br><br>CONCLUSIONS: Neuroinflammation and oxidative stress constitute unifying upstream mechanisms across major vision-threatening neurodegenerative diseases. Combination therapeutic strategies that simultaneously modulate glial activation and restore redox homeostasis may offer superior neuroprotective efficacy compared to approaches targeting isolated downstream mediators.}, }
@article {pmid42123125, year = {2026}, author = {Schrittwieser, J and Kuchernig, L and Mares, V and Steiner, I and Birner, K and Frommlet, F and Borrelli, E and Bogunović, H and Sacu, S and Reiter, GS}, title = {Choriocapillaris Flow-Enriched Prediction of Retinal Sensitivity Using OCT-Derived Biomarkers in Intermediate Age-Related Macular Degeneration.}, journal = {Journal of clinical medicine}, volume = {15}, number = {9}, pages = {}, doi = {10.3390/jcm15093392}, pmid = {42123125}, issn = {2077-0383}, abstract = {Objectives: To assess the association of structural biomarkers derived from optical coherence tomography (OCT) and choriocapillaris (CC) flow information with point-wise retinal sensitivity (PWS) measured by microperimetry (MP) in intermediate age-related macular degeneration (iAMD). Methods: Patients with iAMD received imaging with spectral-domain (SD)-OCT (Spectralis, Heidelberg Engineering) and OCT-angiography (OCT-A) (PLEX Elite 9000, ZEISS). In addition, MP examinations in photopic setting (MP-3, NIDEK) and mesopic background illumination (MAIA2, ICare) were performed. The thickness of the ellipsoid-zone (EZ) and the outer nuclear layer (ONL), as well as the volume of drusen and HRF, were segmented using deep-learning (DL)-based approaches. CC flow deficit percentage (FD%) was extracted from OCT-A slabs using a novel binarization method. Semiautomatic co-registration of MP examinations, OCT-A slabs, and OCT volumes was performed. Three exploratory models were calculated using multivariable mixed-effects models: (1) structure-function (SF) using structural OCT biomarkers, (2) flow-function (FF) utilizing OCT-A derived flow information, and (3) structure-flow-function (SFF) incorporating both OCT and OCT-A data. Model performance was evaluated using AIC and BIC criterion. Results: 19 eyes of 19 patients were evaluated, totalling 3297 MP-stimuli, 1873 B-scans, and 19 OCT-A slabs. Mean (SD) age was 76 (7) years, and sensitivity was 26.0 (3.36) dB in the MP-3 and 22.42 (3.64) dB in the MAIA2. Mesopic MAIA2 examinations showed significantly lower PWS values (-3.56 to -3.63 dB; p < 0.001). Drusen and HRF volume decreased PWS (-0.6 [95% CI: -1.04; -0.16] dB/nL; p = 0.007 and -9.56 [95% CI: -12.86; -6.26] dB/nL; p < 0.001), while ONL was positively associated with PWS (0.06 [0.05; 0.07] at an eccentricity of 5.2°; p < 0.001) in the SF model. CC FD% was not significantly associated with PWS in the FF and the SFF model (p > 0.05 in both cases). In the SFF model drusen volume (-1.69 [95% CI: -2.09; -1.29] dB/nL; p < 0.001), EZ (0.04 [95% CI: 0.02; 0.06] dB/µm; p < 0.001), and ONL thickness (0.03 [95% CI: 0.02; 0.04] dB/µm; p < 0.001) were significant predictors for PWS. The SF model exhibited the lowest AIC and BIC indicating best model performance. Conclusions: Structural parameters derived from SD-OCT such as HRF, drusen volume, and outer retinal layer thickness may be more closely associated with PWS, with CC FD% as an OCT-A-derived metric contributing limited additional explanatory benefit in cross-sectional analyses.}, }
@article {pmid42123608, year = {2026}, author = {Alibrandi, S and Donato, L}, title = {Special Issue "Retinal Diseases and Macular Degeneration: Cell Biology and Molecular Genetics".}, journal = {International journal of molecular sciences}, volume = {27}, number = {9}, pages = {}, doi = {10.3390/ijms27094022}, pmid = {42123608}, issn = {1422-0067}, mesh = {Humans ; *Macular Degeneration/genetics/pathology/metabolism ; *Retinal Diseases/genetics/metabolism/pathology ; Animals ; }, abstract = {Retinal diseases and macular degeneration continue to represent major global health challenges, having profound personal, social, and economic implications [...].}, }
@article {pmid42124582, year = {2026}, author = {Nandakumar, S and Farjood, F and Bertucci, T and Lotz, S and Sai, S and Wang, Y and Kozak, JA and Arduini, BL and Stern, JH and Boles, NC and Temple, S}, title = {Single Cell Transcriptomics and Surface Protein Expression Reveal Distinct Cellular and Molecular Phenotypes in Human RPESC-RPE and PSC-RPE.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.02.26.708319}, pmid = {42124582}, issn = {2692-8205}, abstract = {Current retinal pigment epithelium (RPE) cell replacement strategies in trials for age-related macular degeneration (AMD) are based on either pluripotent stem cell (PSC) or adult RPE stem cell (RPESC) sources. We used Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq) to simultaneously assess single-cell transcriptomic and surface protein information, comparing these two RPE sources. Both RPESC-RPE and PSC-RPE expressed key RPE markers and exhibited cellular heterogeneity. However, RPESC-RPE had higher expression of genes related to mature retinal functions, whereas PSC-RPE had greater expression of genes involved in stem cell development and differentiation. We identified two surface proteins that distinguished the cell types. The "don't eat me" signal, CD24, was detected robustly on adult RPESC-RPE cells, while CD57 was detected on most PSC-RPE cells. The differences in gene and surface protein expression suggest that the two RPE sources differ in functional, adhesion, and immunomodulatory properties, which may impact transplantation outcomes.}, }
@article {pmid42125429, year = {2026}, author = {Hiltunen, TO and Kaarniranta, K and Kivinen, N}, title = {Real World Data About the Treatment of Wet Age-Related Macular Degeneration in Kuopio University Hospital During 2019-2021 Using a PRN Regimen.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {595553}, pmid = {42125429}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate the real-world effectiveness of a pro re nata (PRN) anti-vascular endothelial growth factor (anti-VEGF) regimen for neovascular age-related macular degeneration (nAMD) during 2019-2021 at Kuopio University Hospital, including the COVID-19 pandemic period.<br><br>METHODS: This retrospective study included 107 patients (162 eyes) treated with intravitreal anti-VEGF injections for nAMD. The included eyes were not treatment-naive at study entry but had received anti-VEGF treatment before 2019. Annual injection numbers, drug choice (bevacizumab or aflibercept 2 mg), central retinal thickness (CRT), and visual acuity (VA) were analyzed from diagnosis through 2021 using independent-sample t-tests.<br><br>RESULTS: The mean number of injections in the first treatment year was 6.79 &#xb1; 2.32. During 2019-2021, annual means were 5.09 &#xb1; 2.33, 5.40 &#xb1; 2.10, and 4.96 &#xb1; 2.11, respectively. Bevacizumab-treated eyes received significantly more injections than aflibercept-treated eyes across all years (p < 0.01 for 2019; p < 0.05 for 2020-2021). Mean VA declined from 70 &#xb1; 57 ETDRS letters at diagnosis to 62 &#xb1; 57 ETDRS letters by late 2021 (p < 0.0001). In the aflibercept-only subgroup, the decline was smaller and not significant (68 ETDRS letters &#xb1; 55 ETDRS letters to 66 &#xb1; 56 ETDRS letters; p > 0.27). CRT decreased significantly from 388.4 &#xb1; 139.4&#xa0;&#xb5;m at diagnosis to 320.8 &#xb1; 114.7&#xa0;&#xb5;m in 2019 and remained stable thereafter (p < 0.0001 vs. baseline; p > 0.5 between years).<br><br>CONCLUSION: The PRN regimen maintained anatomical outcomes but resulted in gradual visual decline, likely due to fewer injections, particularly during the COVID-19 period. Aflibercept required fewer injections without compromising outcomes. Transitioning toward a treat-and-extend protocol may enhance visual stability and cost-effectiveness in nAMD care.}, }
@article {pmid42125505, year = {2026}, author = {Awan, B and Elsaigh, M and Hesham Gamal, M and Elbahnasawy, SE and Badee, M}, title = {Performance of Artificial Intelligence Systems for Automated Segmentation and Quantification of Retinal Fluid and Pathology in Optical Coherence Tomography Scans: A Systematic Review and Meta-Analysis.}, journal = {Cureus}, volume = {18}, number = {5}, pages = {e108662}, pmid = {42125505}, issn = {2168-8184}, abstract = {Optical coherence tomography (OCT) plays a crucial role in diagnosing retinal diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD), as well as in identifying neurodegenerative biomarkers. Despite advancements in U-Net-based convolutional networks for OCT image segmentation, there is a lack of systematic reviews comparing their performance with expert manual segmentations. This review aims to assess the efficacy of these automated networks in segmenting retinal fluid and pathology in OCT images. By searching three different databases, PubMed, Web of Science, and Scopus, over the past five years, we conducted this systematic review and meta-analysis using data from 16 diagnostic-accuracy studies. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. The analysis used mean and standard deviation for the continuous outcomes and employed a random-effects model. Analyses were performed using Review Manager software version 5.4 (The Cochrane Collaboration, London, UK, 2020). Artificial intelligence (AI) and human Dice scores did not differ significantly (standardized mean difference (SMD) = -0.08; 95% CI: -1.16 to 0.99; p = 0.88), nor did intraclass correlation coefficient (ICC) values (SMD = -0.13; 95% CI: -5.70 to 5.45; p = 0.96). However, very high heterogeneity (I[2] > 90%) limits the reliability of these pooled estimates. AI achieved expert-level Dice scores for subretinal fluid (0.88-0.96) and geographic atrophy (0.94). Intraretinal fluid was more challenging (Dice 0.79-0.89). Volumetric reliability was strong (ICCs > 0.94). Device-dependent variability was substantial; kappa was 0.37 for ZEISS versus 0.73 for Spectralis, indicating a need for device-specific optimization. Volumetric analyses revealed minor systematic overestimation (mean difference: -0.05 mm[2]). Processing times ranged from 100 milliseconds per B-scan to several seconds per volume, representing substantial time savings versus manual segmentation. Fully automated U-Net pipelines reach expert-level accuracy for subretinal fluid and geographic atrophy but remain limited for intraretinal fluid and show marked device-dependent variability. Clinical translation requires four priorities: standardized multi-device benchmarks, domain adaptation for cross-platform robustness, hybrid AI-human workflows pairing automated pre-segmentation with expert oversight, and prospective clinical trials. These steps are needed to move AI segmentation from a research tool to a clinical decision-support system.}, }
@article {pmid42125560, year = {2026}, author = {Robinson, K and Lester, K and Persaud, S and Depry, C and Cooper, S}, title = {Continuing Medical Education as a Tool to Accelerate the Adoption of Extended-Duration Intravitreal Anti-VEGFs.}, journal = {Journal of CME}, volume = {15}, number = {1}, pages = {2669419}, pmid = {42125560}, issn = {2833-8073}, abstract = {PURPOSE: This study evaluated the impact of a comprehensive, curriculum-based continuing education (CE) programme on the adoption of second-generation intravitreal anti-VEGF therapies among ophthalmologists treating patients with diabetic macular oedema (DME) or neovascular age-related macular degeneration (nAMD).<br><br>METHODS: A multimodal educational curriculum was developed for eye care providers, incorporating principles of adult learning and marketing strategies. The curriculum included 14 CE activities (didactic content, case scenarios, live meetings, interprofessional activities, and downloadable resources) delivered from July 2024 through April 2026. Surveys, assessing knowledge, attitudes, and clinical decision-making, were administered before, during, and after participation. Participants were categorised as single-activity learners (one activity) or multiple-activity learners (three or more activities). Statistical analyses compared knowledge acquisition, comfort, and adoption of second-generation anti-VEGF agents between groups.<br><br>RESULTS: As of September 2025, 5,975 providers completed at least one activity; 398 providers, with complete data, were analysed (289 single-activity, 109 multiple-activity learners). Both groups, post education, demonstrated improved knowledge and comfort with second-generation anti-VEGF agents. Multiple-activity learners had higher baseline knowledge and consistently selected second-generation agents more frequently in case scenarios. Single-activity learners showed greater knowledge gains, while multiple-activity learners maintained higher overall knowledge. The curriculum increased preparedness for future use of new therapies, particularly among low-frequency injectors (<9 injections/week), though some barriers to adoption persisted.<br><br>CONCLUSION: A curriculum-based, multimodal CE programme can accelerate the adoption of innovative therapies by improving clinician knowledge, comfort, and clinical decision-making. Iterative, data-driven education is effective in bridging gaps between emerging science and real-world practice, ultimately supporting better patient outcomes in nAMD and DME care.}, }
@article {pmid42127969, year = {2026}, author = {Jensen, N and Ly, K and Kochnev Goldstein, A and Devaud, Q and Palanker, D}, title = {Maximizing the fidelity of a photovoltaic subretinal prosthesis for human patients.}, journal = {Journal of neural engineering}, volume = {}, number = {}, pages = {}, doi = {10.1088/1741-2552/ae6d77}, pmid = {42127969}, issn = {1741-2552}, abstract = {PRIMA subretinal implants provide pros thetic vision to patients blinded by age-related macular degeneration, with acuity closely matching the sampling limit of the pixel pitch: a single 100µm pixel per line of a letter corresponds to 20/420 acuity. Decreasing the pixel size in the same flat geometry is difficult due to the constrained electric field, especially consid ering a 40µm thick debris layer separating the implant from the target neurons. Here we optimize the electrode design to help overcome such limitations. Approach. An end-to-end modeling pipeline combines the retinal photovoltaic implant simulator (RPSim) based on the Xyce circuit simulator with an interface to COMSOL Multiphysics for electric field modelling. It was used to generate and characterize implants in an open-loop sampling based optimization. Implant performance was evaluated with respect to voltage drop across bipolar cells (representing the stimulation strength), pattern contrast, and neural selectivity. Main Results. The highest selectivity in stimulation of bipolar cells was achieved with arrays having active electrodes on pillars and return electrodes connected in a mesh surrounding the photovoltaic pixels in the array. Such a design, even with pixels down to 20µm, provides stimulation strength exceeding, and contrast similar to that of flat 100µm PRIMA pixels. Significance. Using a novel 3-D electrode design, the pitch of the photovoltaic array can be decreased to 20µm, while providing performance that exceeds the flat 100µm PRIMA pixels. In humans, 20µm resolution on the retina corresponds to a visual acuity of 20/80 a five times improvement compared to the current clinical device. .}, }
@article {pmid42114812, year = {2026}, author = {Sánchez-Vela, L and Brosa, H and Martin-Pinardel, R and Bernal-Morales, C and Parrado-Carrillo, A and Moll-Udina, A and Puzo-Bayod, M and Garay-Aramburu, G and Arruabarrena, C and Sararols-Ramsay, L and Calvo-Perez, P and Zapata, MA and Garrido, M and Abraldes, M and Ruiz-Moreno, JM and Broc-Iturralde, L and Velázquez-Villoria, D and Escobar-Barranco, JJ and Gallego-Pinazo, R and Figueroa, MS and García-Layana, A and Figueras-Roca, M and Gillies, MC and Casaroli-Marano, RP and Zarranz-Ventura, J and , }, title = {Vascular endothelial growth factor inhibitors outcomes in good vision eyes with neovascular age-related macular degeneration. Fight Retinal Blindness SPAIN Report 4.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcjo.2026.04.001}, pmid = {42114812}, issn = {1715-3360}, abstract = {PURPOSE: To evaluate the visual outcomes in neovascular age-related macular degeneration (nAMD) eyes initiating anti-vascular endothelial growth factor treatment with baseline visual acuity (VA) ≥70 letters.<br><br>METHODS: Multicentre, real-world, and national database study. Demographics, VA, number of injections, and patient visit data were collected using a validated online tool. Subgroup analysis included 2 nonoverlapping participant groups defined by baseline VA: Good vision eyes (GVE, "70-100 letters") and non-GVE ("0-69 letters") at 12, 24, and 36 months.<br><br>RESULTS: A total of 3 138 eyes (2 520 patients) were included in the analysis, followed up for 12 (n&#x202f;=&#x202f;2 426; 77.3%), 24 (n&#x202f;=&#x202f;1 793; 57.1%), and 36 months (n&#x202f;=&#x202f;1 167; 37.2%). GVE had significantly better 24-month final VA (71.0 &#xb1; 13.8 vs 52.3 &#xb1; 23.2; p < 0.001) than NGVE. Mean VA change (letters) at 12, 24, and 36 months of follow-up was significantly lower in the GVE -2.4 (-3.1, -1.6), -4.5 (-5.6, -3.5), and -7.8 (-9.4, -6.2) than in NGVE +6.7 (5.8, 7.6), +5.0 (3.8, 6.2), and +4.0 (2.5, 5.5) group, respectively. The number of injections and percentage of visits with active lesions were higher in GVE through 36 months.<br><br>CONCLUSIONS: The mean VA of GVE tends to drop, but it is still much higher than NGVE eyes at 12, 24, and 36 months. Early detection and prompt treatment are key and should be considered in treatment access policies, regulatory frameworks, and clinical guidelines, as defining a threshold to start treatment may have a clear impact on final visual function, patient autonomy and legal blindness rates in nAMD patients.}, }
@article {pmid42039665, year = {2026}, author = {Mohan, VB and Yucel, EI and Fine, I and Boynton, G}, title = {Using Virtual Patients to Predict Perceptual Outcomes for Optogenetic Sight Recovery Technologies.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {42039665}, issn = {2692-8205}, abstract = {Optogenetics is emerging as a powerful approach for partial vision restoration, with at least three ongoing clinical trials in humans testing novel light-sensitive proteins (opsins) in patients with inherited retinal degenerative disorders. These therapies aim to restore light responsiveness by introducing opsins into surviving retinal cells, such as bipolar or ganglion cells, enabling them to generate neural activity in response to visual stimuli. One ongoing difficulty in selecting promising opsins for clinical development is that there is no way to predict patient perceptual outcomes from optogenetically evoked neural activity as measured ex vivo. Here, we introduce a virtual patient framework that quantitatively links the sensitivity and speed of opsin-mediated retinal responses to predicted patient outcomes, and show how this framework can predict temporal contrast sensitivity functions - a well-established measure of perceptual performance - from microbial opsin photocurrent responses. Our simulations demonstrate that opsin sensitivity and kinetics jointly determine perceptual outcomes, and that enhancing sensitivity at the expense of temporal resolution can degrade the perception of fast-moving stimuli. This computational platform provides a generalizable tool for comparing and selecting the most effective opsins for clinical translation, thereby guiding the design and optimization of next-generation sight restoration strategies.}, }
@article {pmid42107714, year = {2026}, author = {Grzybowski, A and Liu, TYA and Popovic, MM and Zhao, A and Miyake, M and Takahashi, H and Kawasaki, R and He, M and Gong, X and Goktas, P and Jin, K}, title = {Global approval and certification of ophthalmic AI devices: A comparative regulatory perspective.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {100328}, doi = {10.1016/j.apjo.2026.100328}, pmid = {42107714}, issn = {2162-0989}, abstract = {Artificial intelligence (AI) tools are rapidly reshaping ophthalmology by improving screening and diagnosis for diabetic retinopathy, age-related macular degeneration, glaucoma, and increasingly retina-based systemic risk assessment. This narrative review provides a comparative assessment of regulatory pathways governing ophthalmic AI and software as a medical device (SaMD) across the United States, European Union, United Kingdom, Australia, China, Japan, Canada, India, and selected emerging jurisdictions. We used a structured search of public regulator databases, guidance documents, manufacturer disclosures, and peer-reviewed literature to assemble a representative sample of marketed or authorized devices through August 2025; the device inventory is illustrative rather than exhaustive. Key differences persist in device classification, evidence expectations, change management for adaptive algorithms, and post-market oversight. Examples such as LumineticsCore, EyeArt, DrNoon for CVD, CLAiR, and EyeWisdom illustrate how risk-based approaches vary across jurisdictions. These inconsistencies can delay multi-region deployment and complicate implementation, supporting the need for lifecycle-focused and internationally aligned standards for safe, transparent, and equitable use of ophthalmic AI.}, }
@article {pmid42107776, year = {2026}, author = {Novarese, C and Vyas, C and Berni, A and Bacherini, D and Chaudhary, V and Dolz-Marco, R and Gallego-Pinazo, R and Mastropasqua, R and Reiter, GS and Subhi, Y and Bandello, F and Reibaldi, M and Borrelli, E}, title = {- Systematic Review - Macular Neovascularization in Neovascular AMD: A Systematic Review of OCTA-Based Assessments and Challenges in Standardization.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.05.002}, pmid = {42107776}, issn = {2468-6530}, abstract = {TOPIC: This systematic review evaluates the methodologies employed for assessing the macular neovascularization (MNV) in neovascular age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA). It focuses on identifying methodological heterogeneity in imaging and analysis protocols and its implications for clinical and research applications.<br><br>CLINICAL RELEVANCE: Accurate assessment of MNV is critical for understanding disease activity, monitoring treatment response, and guiding clinical management in AMD. OCTA offers non-invasive, high-resolution visualization of neovascular networks, but variability in device types, scan protocols, segmentation strategies, and post-processing methods hampers reproducibility and comparability across studies.<br><br>METHODS: A systematic literature search was conducted in PubMed (Medline) and the Cochrane Library from inception through April 3, 2025. The review protocol was prospectively registered in PROSPERO (CRD420251046977). Studies included patients with neovascular AMD who underwent OCTA for MNV evaluation, irrespective of device type or scan parameters. Data extraction focused on OCTA technology, scan sizes, segmentation strategies, image processing techniques, quantitative metrics, and approaches to artifact reduction. A descriptive synthesis was performed.<br><br>RESULTS: A total of 155 studies, comprising 9,025 patients (9,669 eyes), were included. MNV subtypes included type 1 (5,059 eyes), type 2 (973 eyes), type 3 (321 eyes), and mixed lesions (138 eyes); 12 studies did not specify subtype. OCTA devices included spectral-domain (86 studies) and swept-source systems (64 studies), with PLEX Elite 9000 and RTVue XR Avanti most frequently used. Scan sizes varied, predominantly 3&#xd7;3 mm and 6&#xd7;6 mm. Segmentation strategies and slab boundaries exhibited marked heterogeneity, with frequent manual corrections required for accurate visualization. Quantitative analyses employed diverse thresholding and binarization techniques, and only a minority of studies addressed projection artifact correction, highlighting substantial variability in methodological approaches across studies.<br><br>CONCLUSION: OCTA provides detailed, non-invasive assessment of MNV in AMD, but methodological heterogeneity-including variability in devices, scan protocols, segmentation, binarization, and artifact management-limits comparability across studies. Standardized imaging and analytical protocols are urgently needed to improve reproducibility, enable reliable biomarker development, and enhance clinical utility in AMD management.}, }
@article {pmid42109964, year = {2026}, author = {Danish, E and Alsulami, R and Baeshen, H}, title = {CDH3 Mutation in Saudi Arabia: A Case of Hypotrichosis With Juvenile Macular Dystrophy.}, journal = {Cureus}, volume = {18}, number = {4}, pages = {e106554}, pmid = {42109964}, issn = {2168-8184}, abstract = {Congenital sparse scalp hair and progressive vision loss are hallmarks of hypotrichosis with juvenile macular dystrophy (HJMD), a rare autosomal recessive condition. We present a rare case of HJMD from Saudi Arabia. A six-year-old Saudi girl, born to first-cousin consanguineous parents, presented with sparse scalp hair growth from birth and decreased night vision from one year of age. Full-field electroretinography (ffERG) suggested cone-rod dysfunction. Fundus photographs showed pigmentary degenerative changes around the macular area and mid-periphery. HJMD was suspected. A homozygous missense mutation, c.1918T>G (p.Cys640Gly), was discovered in exon 4 (NM_001793.5) of the CDH3 gene by whole-exome sequencing. Patients with these clinical characteristics should be evaluated for HJMD, a rare genetic cause of hypotrichosis and macular degeneration. Although several mutations have been reported in Saudi Arabia, the CDH3 c.1918T>G variant identified in this patient further expands the understanding of the genetic spectrum of HJMD in the region.}, }
@article {pmid42110464, year = {2026}, author = {Li, Y and Fu, X and Huang, L and Xiao, L and Chen, D}, title = {Global research trends and hotspots in the pathophysiology, imaging and therapy of type 3 macular neovascularization (MNV3) in age-related macular degeneration (AMD).}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1811978}, pmid = {42110464}, issn = {2296-858X}, abstract = {BACKGROUND: To provide an overview of the research hotspots and directions of type 3 macular neovascularization (MNV3) in age-related macular degeneration by bibliometric analysis.<br><br>METHODS: Publications related to MNV3 were retrieved from two databases, the Science Citation Index-Expanded database of the Web of Science Core Collection (WoSCC) and PubMed. CiteSpace was utilized to analyze country distribution, keyword bursts, and co-cited references. VOSviewer was employed to identify collaborative authors and the keyword co-occurrence network.<br><br>RESULTS: A total of 564 publications were identified from 2001 to 2026. They were performed in 97 countries, with the United States leading the way. Kim JW is the most prolific author, while Yannuzzi LA is the most cited author. Investigative Ophthalmology &amp; Visual Science has published the most papers. Retina-The Journal of Retinal and Vitreous Diseases is the most cited journal. In the keyword co-occurrence network, apart from terms related to MNV3, "ranibizumab," "photodynamic therapy" and "optical coherence tomography" are high-frequency keywords, while terms such as "artificial intelligence," "biomarker," and "microglia" have emerged as more recent research hotspots. Research topics can be categorized into four major clusters: pathogenesis, imaging, therapy, clinical prognosis and long-term management. Meanwhile, highly cited co-cited articles successively addressed risk stratification, early identification, imaging evaluation, and standardized therapeutic regimens of MNV3, providing important references for clinical practice.<br><br>CONCLUSION: This bibliometric analysis elucidates research hotspots and directions in MNV3 across pathophysiology, imaging, and therapy, and outlines the dynamic development of research in this field.}, }
@article {pmid42111215, year = {2026}, author = {Hou, J and Ikeda, SI and Yang, Y and Fukuchi, T and Ikeda, C and Imanishi, S and Ma, Z and Chen, J and Mori, K and Torii, H and Fujii, H and Negishi, K and Tsubota, K and Kurihara, T}, title = {The choroidal macrophage polarization significantly influences myopia development in murine models.}, journal = {iScience}, volume = {29}, number = {5}, pages = {115764}, pmid = {42111215}, issn = {2589-0042}, abstract = {While choroidal macrophages regulate homeostasis in macular degeneration, their role in myopia is unclear. In this study, depleting choroidal macrophages via clodronate liposome injections induced myopia. To further dissect their function, introducing polarized classically activated (M1) or alternatively activated (M2) macrophages into a myopia model revealed that both the presence and polarization of choroidal macrophages affect myopia progression. Further exploration in normal mice showed that choroidal M1 macrophages polarization triggered choroidal thinning and promoted myopia progression, whereas M2 macrophages polarization enhanced choroidal thickening and suppressed myopia development. These opposite effects of M1 and M2 macrophages on choroidal thickness and myopia progression appeared to be related to their differential regulation of inflammatory responses and oxidative stress. Taken together, these results support a role for choroidal macrophages and their polarization states in myopia onset and progression, suggesting potential therapeutic strategies for controlling the development and progression of myopia.}, }
@article {pmid42112359, year = {2026}, author = {Skerka, C and Cochlovius, B and Hüllebrand, JP and Goel, D and Sood, P and Pal, N and Chakravarti, A and Muth, DR and Zeitz, O and Zipfel, PF}, title = {A new perspective on AMD pathogenesis: a sequential Factor H-centered view of complement dysregulation.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1814415}, pmid = {42112359}, issn = {1664-3224}, mesh = {Humans ; *Macular Degeneration/immunology/etiology/metabolism/pathology ; *Complement Factor H/metabolism/immunology/genetics ; Animals ; Complement Activation ; Complement C3b Inactivator Proteins ; Complement System Proteins ; Genome-Wide Association Study ; }, abstract = {Age-related macular degeneration (AMD) is a chronic, progressive, retinal disease that primarily affects older individuals and is one of the leading causes of blindness worldwide. Both genetic predisposition and environmental factors contribute to its development. Landmark genome-wide association studies (GWAS) positioned the complement system at the center of AMD research, opening new avenues for understanding disease mechanisms and developing targeted therapies. Among the key complement regulators, Factor H and its splice variant FHL-1, are best known for their roles in inhibiting the alternative pathway. Recent research has expanded our understanding of Factor H, revealing a range of non-canonical functions beyond complement regulation which might also affect AMD pathology. These new functions include roles in cell signaling, tissue protection, metabolism, homeostasis, and modulation of inflammation. In contrast, the related protein FHR1 which is also associated with AMD, exhibits pro-inflammatory properties, promoting monocyte recruitment and activation to facilitate clearance processes. In this review, we summarize the canonical and non-canonical functions of Factor H, FHL-1, and FHR1, and we show how the coordinated action of these three proteins integrates into the broader scope of AMD pathogenesis, including complement activation, inflammation, and photoreceptor degeneration. We also describe the current status of approved complement inhibitors in AMD and emerging therapeutic targets within the complement cascade.}, }
@article {pmid42112650, year = {2026}, author = {Serrano Martinez, P and Cammeraat, M and Teppema, A and van Noorden, CJF and Schlingemann, RO and Klaassen, I}, title = {Human iPSC-Derived Blood Vessel Organoids for Studying Chronic Hypoxia-Induced Microvascular Dysfunction.}, journal = {The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society}, volume = {}, number = {}, pages = {221554261437861}, doi = {10.1369/00221554261437861}, pmid = {42112650}, issn = {1551-5044}, abstract = {Microvascular dysfunction due to hypoxia is a key contributor in the pathogenesis of many disorders including cancer and retinal and cardiovascular diseases, but relevant human models are missing. Here, we present a robust 3D in vitro method with the use of human induced pluripotent stem cell-derived blood vessel organoids to analyze in vitro microvascular remodeling. We present a detailed practical pipeline combining optical tissue clearing, high-resolution immunofluorescence, and surface marker analysis to quantitatively assess hypoxia-driven changes in endothelial cells, pericytes, and the basal lamina. Exposure of these blood vessel organoids to chronic hypoxia (1% O2) for 1 week recapitulated key pathological features, including structural remodeling and a dysregulated secretome with altered vascular endothelial growth factor signaling. This approach establishes a versatile and human-relevant platform to study microvascular remodeling induced by chronic hypoxia and other pathological stimuli and their contribution to microvascular-related diseases.}, }
@article {pmid42113424, year = {2026}, author = {Elham, A and Liu, H and Li, W and Zhao, J and Yang, X and Zeng, C and Meng, X}, title = {Real-World Persistence with Anti-VEGF Therapy in Neovascular Age-related Macular Degeneration.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42113424}, issn = {2193-8245}, abstract = {INTRODUCTION: The purpose of this study was to quantify real-world non-persistence and non-adherence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy among Chinese patients with neovascular age-related macular degeneration (nAMD) and to identify factors associated with treatment continuity in routine practice.<br><br>METHODS: This single-center retrospective cohort study was conducted at a one-stop intravitreal injection (IVI) clinic (Dalian University Affiliated Zhongshan Hospital) and included consecutive patients initiating anti-VEGF therapy between 1 August 2022 and 1 August 2024 (N&#x2009;=&#x2009;179). Non-persistence was defined as no visit or treatment for&#x2009;&#x2265;&#x2009;6&#xa0;months. Among patients remaining on therapy, non-adherence was defined as&#x2009;&#x2265;&#x2009;2 visit or injection gaps&#x2009;>&#x2009;16&#xa0;weeks within any 12-month window. Cox proportional-hazards models were used for time-to-event analyses.<br><br>RESULTS: The median age was 78&#xa0;years (IQR 71-86 years), and 26% of patients received bilateral injections. Over a median follow-up of 383&#xa0;days, 117 of 179 patients (65.4%) became non-persistent. Completion of the initial loading phase was associated with a lower hazard of discontinuation (adjusted HR 0.61, 95% CI 0.38-0.98), with similar estimates in prespecified sensitivity analyses. Among patients remaining on therapy (n&#x2009;=&#x2009;62), 32.3% met criteria for non-adherence. In parsimonious models, increasing age was associated with a higher likelihood of extended treatment gaps, although this secondary finding was exploratory.<br><br>CONCLUSION: In this pro re nata (PRN)-managed cohort, loss to follow-up was frequent, and one-third of persistent patients experienced clinically meaningful schedule deviations. Early treatment regularity-particularly completion of the loading phase-was the most actionable factor associated with improved persistence. Associations between older age and non-adherence highlight the need to address age-related barriers to sustained care, but should be interpreted cautiously given the exploratory nature of this secondary endpoint. Strategies focusing on early phase support and burden reduction may help narrow the real-world efficacy gap in nAMD management.}, }
@article {pmid42114678, year = {2026}, author = {Borrelli, E and Bandello, F and Bhutto, IA and Reibaldi, M and Edwards, MM}, title = {Tracing the Journey from Histology to Imaging: Exploring the Retina and Choroid in Age-related Macular Degeneration.}, journal = {Progress in retinal and eye research}, volume = {}, number = {}, pages = {101475}, doi = {10.1016/j.preteyeres.2026.101475}, pmid = {42114678}, issn = {1873-1635}, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss worldwide, driven by complex interactions within the photoreceptor-retinal pigment epithelium (RPE)-choroid unit. Understanding these processes requires integrating in vivo imaging with histopathological evidence, as each provides complementary insights into disease mechanisms. Historically, landmark discoveries-including the characterization of drusen, RPE alterations, and the introduction of optical coherence tomography (OCT)-have led to major paradigm shifts in the diagnosis and management of AMD. Recent advances in multimodal imaging, particularly OCT and OCT angiography (OCTA), have enabled high-resolution, non-invasive visualization of structural and vascular changes, facilitating the identification of clinically relevant biomarkers. When interpreted in the context of histology, these imaging findings have significantly advanced our understanding of AMD pathogenesis, revealing dynamic interactions between neuronal degeneration, outer retinal dysfunction, and vascular impairment. In this review, we synthesize key imaging features of AMD alongside their histopathological correlates, highlighting how this integrative approach has refined disease classification, improved prognostic assessment, and informed therapeutic strategies. We further discuss emerging imaging technologies and their potential to bridge the gap between tissue-level pathology and clinical practice. By linking historical insights with contemporary advances, this review provides a comprehensive framework for understanding AMD and its management.}, }
@article {pmid42104267, year = {2026}, author = {Okonkwo, ON and Hassan, AO and Oronsaye, DA and Emelumadu, C and Akanbi, T and Agweye, C}, title = {Compliance to intravitreal anti-vascular endothelial growth factors for treatment of retinal diseases in Nigerians: a retrospective multicenter study.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04880-z}, pmid = {42104267}, issn = {1471-2415}, abstract = {BACKGROUND: Little is known about compliance with intravitreal anti-vascular endothelial growth factor (VEGF) therapy for the treatment of macular and retinovascular diseases among Nigerians and Africans. The objective of this study is to measure compliance to 3 or more and 6 or more intravitreal anti-VEGF injections for common macular and retinovascular diseases in Nigerian clinics and evaluate the impact on visual outcomes.<br><br>METHOD: Retrospective multicenter chart review of 622 eyes/ 528 patients diagnosed with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusions (RVOs), including branch, central, and hemiretinal (BRVO, CRVO, and HRVO), and non-AMD Choroidal Neovascular Membrane (CNVM) from five clinics (urban, semi-urban, and rural), collecting demographics, diagnosis, injection type/number, pre-/post-BCVA (converted to LogMAR), and follow-up. Treatments were intravitreal Bevacizumab (Avastin), Ranibizumab (Patizra), and Aflibercept (Eylea). Definitions of compliance: compliant; &#x2265;3 injections (standard loading), also &#x2265;&#x2009;6 injections.<br><br>RESULTS: For all 622 eyes, presenting BCVA: 1.21&#x2009;&#xb1;&#x2009;0.84 and the final BCVA: 0.91&#x2009;&#xb1;&#x2009;0.80 (P&#x2009;=&#x2009;<&#x2009;0.001). Overall compliance with &#x2265;&#x2009;3 injections was 47.5%, and with &#x2265;&#x2009;6 injections, 10.1%. Compliance to &#x2265;&#x2009;3 injections by diagnosis was as follows: AMD 50.4%, Non-AMD CNVM 58.2%, BRVO 44.8%, CRVO 44.0%, HRVO 46.7%, DME 40.6%. Age (P&#x2009;=&#x2009;0.264) and sex (P&#x2009;=&#x2009;0.870) did not affect compliance to &#x2265;&#x2009;3 injections. Clinic location significantly influenced compliance with &#x2265;&#x2009;3 injections (P&#x2009;=&#x2009;0.000), but not with 6 injections (P&#x2009;=&#x2009;0.173). The highest rates of compliance with &#x2265;&#x2009;3 injections were observed in urban tertiary centers. Injection type and cost were not significant factors (P&#x2009;=&#x2009;0.36). Eyes with &#x2265;&#x2009;3 injections achieved better vision (&#x2265;&#x2009;6/18) across all diagnoses; the most notable improvements were in non-AMD CNVM (+&#x2009;41.4%) and BRVO (+&#x2009;35%). Statistically significant LogMAR improvements were seen in CRVO (p&#x2009;=&#x2009;0.049) and DME (p&#x2009;=&#x2009;0.043). Postoperative endophthalmitis occurred in 2/622 eyes (0.0032) (both Avastin); no other serious adverse event was recorded.<br><br>CONCLUSIONS: Real-world compliance is significantly lower than ideal. Urban and tertiary clinics show better adherence. Receiving the recommended loading doses is associated with improved visual outcomes for most diagnoses. Understanding the reasons for non-compliance, using a prospective approach, and addressing them will improve treatment outcomes for more Nigerian and presumably African patients receiving anti-VEGF drugs.}, }
@article {pmid42104825, year = {2026}, author = {Gama-Castro, A and Ferrão-Mendes, A and Rodrigues, R and Figueiredo, I and Bragança, F and Laiginhas, R and Cunha, AM and Lume, M and Silva, R and Carneiro, &#xc2;}, title = {[Value-Based Healthcare in the Treatment of Age-Related Macular Degeneration: Clinical and Patient-Reported Outcomes from a Portuguese Multicenter Study].}, journal = {Acta medica portuguesa}, volume = {39}, number = {5}, pages = {332-339}, doi = {10.20344/amp.24246}, pmid = {42104825}, issn = {1646-0758}, mesh = {Humans ; Female ; Prospective Studies ; Male ; Aged, 80 and over ; *Patient Reported Outcome Measures ; *Macular Degeneration/drug therapy/therapy ; Aged ; Portugal ; Intravitreal Injections ; Value-Based Health Care ; }, abstract = {INTRODUCTION: This study aimed to describe and compare patient-reported outcome measures (PROMs) and objective clinical outcome measures (CROMs) in the treatment of age-related macular degeneration (AMD), exploring the concordance between these measures within a value-based healthcare (VBH) framework.<br><br>METHODS: This prospective, multicenter, observational, real-world study was conducted at three tertiary referral hospitals specializing in the treatment of neovascular AMD. Clinical outcomes (CROMs) and patient-reported outcomes (PROMs) were analyzed using the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) questionnaire as a functional assessment tool. Data were collected at baseline and at three, six, and 12 months following initiation of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Statistical analysis was primarily descriptive. The comparison between baseline and 12 months in the global NEI VFQ-25 score was performed using the Wilcoxon signed-rank test for paired samples. Concordance between CROMs and PROMs was assessed using the intraclass correlation coefficient (ICC).<br><br>RESULTS: A total of 235 eyes were included, receiving 2338 intravitreal injections. The mean age of participants was 81 years (SD = 8.57), and 55.8% were female. The mean baseline NEI VFQ-25 score was 67.83 (SD = 10.39). The median best-corrected visual acuity was 63 ETDRS letters (interquartile range [P25 - P75]: 41 - 75) at baseline, increasing to 65 letters at three months and remaining stable through 12 months of follow-up. The comparison between baseline and 12 months revealed a statistically significant difference in visual acuity (Wilcoxon signed-rank test, Z = 4.2; p < 0.001). A reduction in the proportion of patients classified as legally blind was observed, together with an increase in the proportion of patients in the reading-vision and driving-vision categories. At 12 months, 58.7% of patients reported stabilization or improvement in visual function on the NEI VFQ-25 questionnaire. Concordance between the variation in visual acuity and the variation in the global NEI VFQ-25 score showed good agreement between CROMs and PROMs (ICC = 0.76; p < 0.001).<br><br>CONCLUSION: The integrated analysis of CROMs and PROMs suggests that anti-VEGF treatment for neovascular AMD is associated with stabilization or improvement in visual acuity and patients' perceived visual function. The implementation of the VBH-AMD model proved feasible in a real-world clinical setting, reinforcing the importance of integrating patient-centered measures into the evaluation of therapeutic outcomes.}, }
@article {pmid42105087, year = {2026}, author = {Avram, O and Shwartz, Y and Green, A and Bloom, R and Corradetti, G and Wu, A and Chen, ZJ and Lior, TE and Durmus, B and Rudas, A and Pal, R and Rakocz, N and Soylu, C and Alhelaly, M and Boscia, G and Wykoff, CC and Cannesson, M and Sadda, SR and Levy, J and Halperin, E and Chiang, JN and Chowers, I and Tiosano, L}, title = {A deep learning model for automated identification of age-related macular degeneration atrophy.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42105087}, issn = {1435-702X}, abstract = {Age-related macular degeneration (AMD), a leading cause of visual impairment and blindness among the elderly, is projected to affect 288 million individuals globally by 2040. Advanced AMD, including complete retinal pigment epithelium and outer retinal atrophy (cRORA), pose significant challenges for diagnosis and monitoring due to the labor-intensive, costly, and variable nature of manual annotation of volumetric optical coherence tomography (OCT) scans. Automating cRORA diagnosis offers the potential to improve annotation consistency and reduce clinical burden, which could facilitate, for example, the evaluation of recently FDA-approved treatments that delay disease progression. In this study, we compiled two large independent cohorts totaling nearly 5,000 3D OCT scans, labeled them for cRORA presence, and developed a deep learning model for cRORA automated detection. The model achieved state-of-the-art performance, with a ROC AUC of 0.97 on internal validation, and demonstrated robust translatability (zero-shot learning) with a ROC AUC of 0.88 on external evaluation. Notably, it exhibited high accuracy for both non-neovascular (non-nv) and neovascular (nv) AMD subgroups (ROC AUC 0.98 and 0.93, respectively), including complex cases with exudation. This model and dataset combination could facilitate clinical research and trial analyses by providing scalable, standardized assessments across non-nv and nv AMD patient subgroups.}, }
@article {pmid42105126, year = {2026}, author = {Turan, L and Bjerager, J and Subhi, Y and Klefter, ON and Hajari, JN and Schneider, M}, title = {Durability of Three Monthly Loading Doses with Faricimab in Treatment-Naïve Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42105126}, issn = {2193-8245}, abstract = {INTRODUCTION: Understanding the durability of faricimab with three monthly loading injections in a real-world clinical setting is important for optimizing treatment intervals and reducing the treatment burden. The aim of this study was to evaluate the durability and visual outcomes of a loading dose regimen consisting of three consecutive monthly faricimab injections in treatment-naïve patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This is a retrospective, single-center cohort study using chart review and an electronic injection database, including treatment-na&#xef;ve patients with nAMD aged 50 years or older who received three monthly faricimab injections between 1 November 2023 and 31 August 2024.<br><br>RESULTS: Overall, 827 eyes of 742 patients were included in the study. Following the loading dose, the median injection-free interval was 15.0&#xa0;weeks (95% confidence interval [CI] 13.1 to 16.6). The estimated injection-free survival probabilities at 4, 6, 8, 10, 12, 14, 16, and 24&#xa0;weeks were 90.9%, 81.1%, 79.1%, 75.5%, 57.1%, 51.1%, 48.6%, and 29.4%, respectively. At 180&#xa0;days, 28.4% (n&#x2009;=&#x2009;235) of eyes remained injection-free, and 21.6% (n&#x2009;=&#x2009;179) were discharged from hospital-based care. At 4&#xa0;weeks post-loading, 42.6% of eyes showed improved best-corrected visual acuity (BCVA), 46.3% were stable, and 11.1% declined. The mean BCVA change was -0.082 logarithm of the minimum angle of resolution (logMAR) (95% CI -0.097 to -0.067; p&#x2009;<&#x2009;0.001), corresponding to a gain of approximately 4 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters.<br><br>CONCLUSIONS: A three-injection loading dose regimen of faricimab demonstrated favorable durability, with most eyes maintaining a long injection-free interval and experiencing visual improvement or stability. A routine follow-up at 4&#xa0;weeks after loading may be unnecessary in many patients, whereas 8&#xa0;weeks appear adequate. Treatment after loading can be paused for an extended period in a substantial subset of patients. Faricimab may reduce treatment burden early, while providing stabilization or improvement of visual acuity for the majority of patients with nAMD in clinical practice.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov registration no. NCT06890026; date of registration: 16 March 2025 (retrospectively registered).}, }
@article {pmid42105376, year = {2026}, author = {Mang, K and Eichenbaum, D and Vakharia, P}, title = {Geographic atrophy: From slowing lesions to preserving vision.}, journal = {Current opinion in ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICU.0000000000001224}, pmid = {42105376}, issn = {1531-7021}, abstract = {PURPOSE OF REVIEW: Geographic atrophy, the advanced form of dry age-related macular degeneration (AMD), has historically been evaluated using structural endpoints and best-corrected visual acuity (BCVA). This review examines the growing rationale for a function-first approach.<br><br>RECENT FINDINGS: Emerging data demonstrate that functional deficits often decline earlier and more profoundly than BCVA. Recently approved complement inhibitors have shown slowing of geographic atrophy lesion growth but without consistent improvements in traditional visual acuity endpoints. Extension studies and post hoc analyses suggest some functional benefits. Next-generation therapies are increasingly incorporating functional endpoints into trial design.<br><br>SUMMARY: Structural slowing alone does not fully capture therapeutic value in geographic atrophy. Functional measures provide a more sensitive and patient-centered assessment of disease progression and treatment impact.}, }
@article {pmid42106176, year = {2026}, author = {Joo, JH and Jidigam, V and Rao, S}, title = {Retinal angiogenesis: Development and pathophysiology.}, journal = {Handbook of clinical neurology}, volume = {217}, number = {}, pages = {179-201}, doi = {10.1016/B978-0-443-22193-4.00005-6}, pmid = {42106176}, issn = {0072-9752}, mesh = {Humans ; Animals ; *Retinal Neovascularization/physiopathology/pathology ; *Retinal Vessels/physiopathology/pathology ; *Retina/growth &amp; development/pathology/physiopathology ; *Neovascularization, Pathologic/physiopathology/pathology ; Angiogenesis ; }, abstract = {Retinal angiogenesis is the process of new blood vessel formation within the retina, the light-sensitive tissue located at the back of the eye. It is a tightly regulated physiologic process essential for supplying oxygen and nutrients to retinal cells, supporting their metabolic needs, and maintaining overall retinal function. During retinal angiogenesis, new blood vessels sprout from pre-existing vessels in response to specific signals and cues within the retinal microenvironment. The process involves a series of coordinated events, including endothelial cell proliferation, migration, tube formation, and vessel maturation. The process of retinal angiogenesis is tightly regulated by a complex interplay of proangiogenic and antiangiogenic factors, including growth factors, cytokines, extracellular matrix components, and cell-cell signaling pathways. In addition to its role in normal retinal development, angiogenesis in the retina can also occur under pathologic conditions, leading to the formation of abnormal blood vessels. Conditions such as diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration are characterized by aberrant retinal angiogenesis, which can result in vision-threatening complications. Understanding the mechanisms that regulate retinal angiogenesis is essential for developing novel therapeutic strategies aimed at promoting normal vascular development, inhibiting pathologic angiogenesis, and preserving vision in patients with retinal vascular disorders.}, }
@article {pmid42106177, year = {2026}, author = {Navratil, EM and Mullins, RF}, title = {Vasculature: Choroid.}, journal = {Handbook of clinical neurology}, volume = {217}, number = {}, pages = {203-217}, doi = {10.1016/B978-0-443-22193-4.00003-2}, pmid = {42106177}, issn = {0072-9752}, mesh = {Humans ; *Choroid/blood supply/anatomy &amp; histology ; Animals ; }, abstract = {The choroid is the highly vascularized connective tissue compartment exterior to the outer blood retinal barrier, which resides between the RPE and the sclera and is the main vascular supply for the retinal pigment epithelium and photoreceptor cells. This review summarizes the structure, innervation, vascular supply, and cell types of the human choroid in both healthy and disease eyes. Special attention is paid to the choriocapillaris and its biochemical and molecular changes in aging and atrophic macular degeneration.}, }
@article {pmid42106178, year = {2026}, author = {Zaydon, Y and Ahmed, F and Tsang, S}, title = {Genetics of the retina.}, journal = {Handbook of clinical neurology}, volume = {217}, number = {}, pages = {21-33}, doi = {10.1016/B978-0-443-22193-4.00012-3}, pmid = {42106178}, issn = {0072-9752}, mesh = {Humans ; *Retina/pathology ; *Retinal Diseases/genetics ; *Mutation/genetics ; Animals ; }, abstract = {The retina is a vital component of the visual system, converting light into neural signals processed by the brain. Its structure includes photoreceptors, bipolar cells, and ganglion cells, each contributing to vision. Genetics play a critical role in retinal development and health, with mutations in over 270 genes linked to inherited retinal diseases, such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), and Leber congenital amaurosis (LCA). These conditions range from mild visual impairment to complete blindness, reflecting the genetic diversity underlying retinal diseases. Progress in molecular biology has improved understanding of how genetic mutations disrupt retinal function. For example, RP involves mutations in RHO, USH2A, and RPGR, leading to progressive photoreceptor degeneration. AMD is associated with variations in CFH and ARMS2, driven by both genetic and environmental factors. Next-generation sequencing and gene therapy have enabled more targeted treatments. Continued research into retinal implants, pharmacologic interventions, and mitochondrial therapies is expanding therapeutic options, providing hope for improved outcomes and preservation of vision in individuals with these genetic conditions.}, }
@article {pmid42106184, year = {2026}, author = {Liu, T and Tsui, JC and Vanderbeek, BL}, title = {Epidemiology of retinal disease.}, journal = {Handbook of clinical neurology}, volume = {217}, number = {}, pages = {3-19}, doi = {10.1016/B978-0-443-22193-4.00009-3}, pmid = {42106184}, issn = {0072-9752}, mesh = {Humans ; *Retinal Diseases/epidemiology ; Risk Factors ; Prevalence ; Incidence ; }, abstract = {Age-related macular degeneration (AMD), diabetic retinal disease (DRD), retinal vascular occlusion, retinal detachment, pathologic myopia, macular hole, and epiretinal membrane are major causes of blindness and visual impairment globally. Studies on the epidemiology of these retinal diseases exhibit significant heterogeneity in terms of study design, population, timeframe, and disease definition. Recent data suggest increases in the prevalence and/or incidence of AMD, DRD, retinal vein occlusion, and pediatric myopia, but projecting the future epidemiologic burden of these disorders is difficult due to the disparate impact of demographic, diagnostic, and treatment-associated changes. This chapter reviews the epidemiology of these major retinal diseases with a focus on prevalence, incidence, risk factors, and associations, and highlights areas of need for further research.}, }
@article {pmid42106387, year = {2026}, author = {Balaha, HM and Azam, MT and Mahmoud, A and Ghazal, M and El-Baz, A}, title = {Advanced computer-aided diagnosis for age-related macular degeneration: integrating segmentation and feature extraction for precise diagnosis.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-46569-9}, pmid = {42106387}, issn = {2045-2322}, abstract = {Age-related Macular Degeneration (AMD) is a leading cause of vision loss globally; necessitating early detection and precise diagnosis for effective intervention. This study presents a computer-aided diagnosis (CAD) system for AMD detection and diagnosis over two main stages; that are SegNet-MobileNet for segmentation and feature extraction for classification. The SegNet-MobileNet architecture merges the SegNet's precise segmentation with the MobileNet's efficacy; achieving high accuracy in delineating AMD lesions from retinal images. Also, the features extracted from regions of interest (ROIs) capture diverse aspects of retinal structure and texture mandatory for the AMD diagnosis. A dataset of 864 retinal images (accompanied by detailed demographic and clinical information) was collected and analyzed. Through the proper evaluation of ML algorithms, we reported that ensemble methods (such as CatBoost, Extra Trees, and XGBoost) demonstrate superior performance in distinguishing AMD cases, with accuracies exceeding 97%. Model explainability is utilized through the SHapley Additive exPlanations (SHAP) technique; providing insights into feature importance and model decision-making. This study demonstrates the potential of advanced methodologies in contributing to AMD diagnosis and laying the groundwork for future research directions in the ophthalmic imaging and diagnostic field. While promising, these results indicate the need for larger, multi-center validation to ensure generalizability.}, }
@article {pmid42106726, year = {2026}, author = {Saturno, MC and Gagliardi, OM and La Cava, M and Armentano, M and Alisi, L and Giovannetti, F and Iannetta, D}, title = {Fellow-eye herpes simplex virus type 1 uveitis after intravitreal bevacizumab: a case report.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04872-z}, pmid = {42106726}, issn = {1471-2415}, abstract = {BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is widely used for neovascular retinal diseases. Intraocular inflammation is a recognized adverse event and typically occurs in the injected eye. Inflammation in the fellow, uninjected eye is exceptionally rare and may be misinterpreted as sterile immune-mediated inflammation, potentially delaying appropriate treatment. We report a case of polymerase chain reaction (PCR)-confirmed herpes simplex virus type 1 (HSV-1) uveitis presenting in the fellow eye shortly after intravitreal bevacizumab administration.<br><br>CASE PRESENTATION: An 84-year-old man with well-controlled type 2 diabetes mellitus received intravitreal bevacizumab (1.25&#x2009;mg) in the left eye for neovascular age-related macular degeneration. Three days later, he developed acute granulomatous anterior uveitis with dense vitritis in the right, uninjected eye, while the treated eye remained quiescent. Best-corrected visual acuity decreased to 20/400. Given the severity of inflammation and limited fundus visualization, viral retinitis was suspected. Empirical systemic valacyclovir and topical corticosteroids were initiated. Aqueous humor PCR detected HSV-1 DNA, confirming herpetic uveitis. Inflammation resolved within 40&#x2009;days with recovery of visual acuity to 20/20 and no progression to acute retinal necrosis. The patient remained recurrence-free under antiviral prophylaxis at last follow-up.<br><br>CONCLUSIONS: Severe fellow-eye inflammation following intravitreal bevacizumab may reflect viral reactivation rather than sterile inflammation. Early diagnostic evaluation, including aqueous humor PCR when clinically indicated, is essential to guide appropriate therapy and prevent sight-threatening complications.}, }
@article {pmid42106786, year = {2026}, author = {Hall, JC and Krishna Sudhakar, K and Daniszewski, M and Senabouth, A and Abbott, CJ and Liang, HH and Kumar, H and Lidgerwood, GE and Mirzaei, M and Ma, JY and Atkeson, T and Hirokawa, Y and Nandrot, EF and Barnett, A and Cazevieille, C and Manes, G and Mountford, S and Thompson, P and Fletcher, EL and Wu, Z and Bahlo, M and Ansell, BRE and Paull, D and Hewitt, AW and Guymer, RH and Powell, JE and Pébay, A}, title = {Patient induced pluripotent stem cells identify specificities of a reticular pseudodrusen phenotype in age-related macular degeneration.}, journal = {Genome medicine}, volume = {18}, number = {1}, pages = {}, pmid = {42106786}, issn = {1756-994X}, }
@article {pmid42103449, year = {2026}, author = {Riedl, S and Mai, J and Enzendorfer, ML and Nugawela, MD and Fritsche, L and Prevost, T and Rueckert, D and Menten, M and Scholl, H and Sivaprasad, S and Lotery, A and Bogunovic, H and Sacu, S and Schmidt-Erfurth, U}, title = {OCT-based AI-assisted phenotyping of intermediate AMD in the prospective PINNACLE trial: PINNACLE Study Report 9.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-327938}, pmid = {42103449}, issn = {1468-2079}, abstract = {BACKGROUND/AIMS: PINNACLE is one of the largest prospective multicentre observational studies evaluating the progression of intermediate age-related macular degeneration (iAMD). This paper aims to provide an optical coherence tomography (OCT)-based qualitative and quantitative characterisation of the cohort's baseline morphology.<br><br>METHODS: Based on expert grader readings and artificial intelligence (AI)-based image analysis, we report the prevalence, quantitative measurements, topographic distribution and intercorrelation of characteristic iAMD features including drusen, drusen subtypes, subretinal drusenoid deposits (SDD), hyperreflective foci (HRF), double layer sign and various measurements of outer retinal condition, such as ellipsoid zone (EZ) and outer nuclear layer (ONL) thicknesses, incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and a semi-automated atrophic marker including EZ loss and choroidal hypertransmission (EZLHT).<br><br>RESULTS: Drusen accumulate within the central 3&#x2009;mm while SDD predominantly occurs in the superior perifoveal quadrant. Whereas higher drusen volume was associated with the presence and volume of HRF, it was inversely correlated with SDD presence. Thickness measurements of the EZ and ONL demonstrate outer retinal thinning, indicating photoreceptor compromise in iAMD, more pronounced in eyes showing atrophic features such as iRORA or EZLHT.<br><br>CONCLUSION: This work combines expert grader readings with AI-based image analyses, applied on the largest prospectively, densely OCT-imaged cohort of iAMD reported on so far. The results show feature distribution comparable to previous reports. They substantially contribute to the comprehensive morphological characterisation of iAMD. This data is relevant for the interpretation of longitudinal data, refining inclusion criteria for future clinical trials and for providing a reference to other trials in the field.}, }
@article {pmid42095312, year = {2026}, author = {Wartenberg, PJ and Jensen, AN and Thomsen, AK and Sørensen, TL}, title = {Geographical disparities in visual acuity at diagnosis among patients with neovascular age-related macular degeneration.}, journal = {Danish medical journal}, volume = {73}, number = {5}, pages = {}, doi = {10.61409/A05250419}, pmid = {42095312}, issn = {2245-1919}, mesh = {Humans ; Male ; Female ; Retrospective Studies ; *Visual Acuity ; Denmark/epidemiology ; Aged ; Aged, 80 and over ; Middle Aged ; *Macular Degeneration/diagnosis ; *Wet Macular Degeneration/diagnosis/physiopathology ; }, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) affects approximately 8% of the global population. While socioeconomic and geographical disparities have been increasingly studied in Denmark, geographical disparity in best corrected visual acuity (BCVA) at the time of diagnosis in nAMD remains understudied. This study aimed to investigate possible geographical disparity in BCVA at the time of diagnosis in nAMD patients in Region Zealand, Denmark.<br><br>METHODS: This was a retrospective study using data from the database "Bedre Oftalmologi for Brugere" from 2011 to 2021. BCVA was extracted for patients at the time of diagnosis with nAMD. Patients were grouped geographically by postal code and municipality. Data were analysed using the Kruskal-Wallis test to investigate geographical disparity and stratified by sex.<br><br>RESULTS: A total of 4,266 eyes with nAMD were included. Variations in BCVA at the time of nAMD diagnosis were found between geographical regions in Region Zealand at postal code level and at municipality level. Furthermore, we found a disparity between municipalities among males and females. However, no statistically significant disparity between postal codes was found among males or females.<br><br>CONCLUSIONS: There was a significant geographical disparity in BCVA at the time of diagnosis in nAMD patients, inviting further investigation to determine the extent and roots of this disparity.<br><br>FUNDING: None.<br><br>TRIAL REGISTRATION: Not relevant.}, }
@article {pmid42097863, year = {2026}, author = {Chi, K and He, Y and Zuo, X and Lai, C and Cao, J and Ying, Y and Zhang, B and Li, R and Chen, M and Tan, X and Li, Q and Wang, S and Wu, Q and He, J and Liu, L and Hu, Y and Zhu, Z and Zhang, X and Yu, H}, title = {Linking accelerated biological ageing to cataract susceptibility: evidence from cross-cohort analysis.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-329061}, pmid = {42097863}, issn = {1468-2079}, abstract = {PURPOSE: The cross-sectional and longitudinal associations between accelerated biological ageing and the risk of cataract and other blinding eye diseases (including glaucoma and age-related macular degeneration (AMD)) remain unclear.<br><br>METHODS: We included participants aged 40 and above with biological ages, including phenotypic age (PhenoAge), Klemera-Doubal method (KDMAge) and retinal age (RetiAge), from the US National Health and Nutrition Examination Survey (NHANES) and UK Biobank. The cross-sectional analyses were conducted to identify associations of PhenoAge or KDMAge acceleration with cataract and other blinding eye diseases using logistic regression. In a prospective UK cohort, we explored the relationships between the acceleration of PhenoAge, KDMAge or RetiAge and cataract and other blinding eye diseases using the Cox proportional hazards model.<br><br>RESULTS: This study consisted of 5433 participants from the US NHANES and 269 615 participants from the UK Biobank. In both cross-sectional and longitudinal analyses, accelerated biological ageing was positively associated with an increased risk of cataract (all p<0.05). In a longitudinal cohort, RetiAge acceleration demonstrated the larger effect size estimates (HR 1.54 (95% CI 1.38 to 1.73)) compared with PhenoAge acceleration (HR 1.05 (95% CI 1.03 to 1.08)) and KDMAge acceleration (HR 1.06 (95% CI 1.04 to 1.08)). Only in the UK population, risks of glaucoma showed stronger links with KDMAge acceleration (HR 1.06 (95% CI 1.01 to 1.11)), while AMD showed more pronounced associations with PhenoAge acceleration (HR 1.08 (95% CI 1.02 to 1.14)).<br><br>CONCLUSIONS: Accelerated biological ageing might represent a potential target of assessment and intervention for cataract.}, }
@article {pmid42100539, year = {2026}, author = {Zou, H and Li, D and Wang, X and Yu, L and Yang, B and Luo, L and Xiao, J}, title = {Knowledge, attitude and practice of patients and their family members regarding age-related macular degeneration: a cross-sectional study.}, journal = {Frontiers in public health}, volume = {14}, number = {}, pages = {1811521}, pmid = {42100539}, issn = {2296-2565}, mesh = {Humans ; Cross-Sectional Studies ; *Health Knowledge, Attitudes, Practice ; *Macular Degeneration/therapy/psychology ; Female ; Male ; *Family/psychology ; Aged ; Surveys and Questionnaires ; Middle Aged ; Adult ; Aged, 80 and over ; China ; }, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the older adults, and understanding the knowledge, attitudes, and practices (KAP) of patients and their family members is essential for improving disease management and patient education. This study aimed to assess the knowledge, attitudes, and practices (KAP) of patients with age-related macular degeneration (AMD) and their family members.<br><br>METHODS: A cross-sectional survey was conducted between April and July 2023 at the Department of Ophthalmology, the Second Hospital of Jilin University, using a self-administered questionnaire.<br><br>RESULTS: A total of 538 valid questionnaires were included in the analysis, comprising 325 patients (60.41%) and 213 family members (39.59%). Among all participants, 495 (92.01%) reported having undergone intraocular injection therapy, while 43 (7.99%) had not received such treatment. The mean KAP scores were 10.99 &#xb1; 1.30 for knowledge, 43.05 &#xb1; 3.48 for attitude, and 22.36 &#xb1; 3.96 for practice. Significant positive correlations were observed between knowledge and attitude, knowledge and practice, and attitude and practice. Structural equation modeling further demonstrated that knowledge had a significant direct effect on attitude, and attitude had a significant direct effect on practice, with attitude fully mediating the relationship between knowledge and practice.<br><br>DISCUSSION: Overall, patients and their family members exhibited adequate knowledge of AMD, whereas attitude and practice levels were moderate. These findings highlight the need for targeted educational interventions to enhance AMD-related knowledge, foster positive attitudes through supportive patient-family interactions, and facilitate the translation of knowledge and attitudes into appropriate health-related behaviors, with particular emphasis on timely medical consultation and adherence to treatment.}, }
@article {pmid42100984, year = {2026}, author = {Wolf, A and Clahsen, T and Langmann, T}, title = {The role of human complement factor H in retinal immune response and the prospects for targeted therapy for age-related macular degeneration (AMD).}, journal = {Expert opinion on therapeutic targets}, volume = {}, number = {}, pages = {}, doi = {10.1080/14728222.2026.2671685}, pmid = {42100984}, issn = {1744-7631}, }
@article {pmid42102824, year = {2026}, author = {Brennan, K and Ozaki, E and Noone, E and Palko, S and Byrne, KP and Roche, F and McElheron, M and Byrne, K and Gibbons, L and Robb, K and Aktas, S and Connolly, E and Hudson, N and O'Riordan, MM and O'Boyle, D and Dalton, R and Zoller, A and Fahey, E and Hokamp, K and Feenstra, D and Bourke, N and Campbell, M and Finlay, D and Mulfaul, K and Mullins, RF and Kenny, RA and Cahill, MT and Doyle, SL}, title = {Circulating natural killer cells are phenotypically and functionally altered in age-related macular degeneration.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {102792}, doi = {10.1016/j.xcrm.2026.102792}, pmid = {42102824}, issn = {2666-3791}, abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible central blindness and can result in pathological neovascularization. Using a "human-first" approach, we identify immunotherapy as a disease modifier in models of neovascular AMD (nAMD). Plasma cytokine analysis in a large population cohort reveals an imbalance of lymphocytic cytokines associated with severity of AMD, leading to discovery of a skewed peripheral natural killer (NK) cell phenotype in individuals with AMD. Peripheral NK cells are rapidly activated in nAMD models, and single-cell RNA sequencing demonstrates expansion of activated cytolytic NK cells within neovascular lesions during resolution. NK cells localize to neovessels in human AMD donor eyes; however, they exhibit markers of terminal differentiation and quiescence. Adoptive transfer of pre-activated NK cells reduces neovascularization and restores barrier integrity. Our data identify a distinct, functionally altered NK cell phenotype in nAMD and suggests harnessing NK cells represents an immunotherapeutic alternative for the treatment of nAMD.}, }
@article {pmid42103030, year = {2026}, author = {Sadek, K and Yu, P and Al-Burak, SA and Osman, R and Tao, BK and Al-Ani, A and Ghaseminejad, F and Khan, H and Arjmand, P and Hutnik, C and Navajas, EV}, title = {The role of adjunctive aqueous suppressants for anti-vascular endothelial growth factor therapy: A systematic review.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.04.007}, pmid = {42103030}, issn = {1879-3304}, abstract = {Our goal is to determine whether adjunctive aqueous suppressants (topical β-blockers, carbonic anhydrase inhibitors, or oral acetazolamide) enhance outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME), retinal vein occlusion (RVO), and neovascular age-related macular degeneration (nAMD), focusing on retinal thickness, visual acuity, injection burden, intraocular pressure (IOP), and safety. DME, RVO, and nAMD are leading causes of vision loss treated with repeated intravitreal injections, yet many eyes show persistent fluid. Aqueous suppressants are inexpensive and widely available, with potential to prolong intravitreal drug residence and improve outcomes, but their clinical value remains uncertain. Following a registered protocol, we searched 4 databases (January, 2000 toMay, 2025) for randomized and comparative studies evaluating adjunct aqueous suppressants with anti-VEGF therapy. Primary outcome was change in retinal thickness; secondary outcomes included visual acuity, injection burden, IOP, and adverse events. Risk of bias was assessed and findings synthesized narratively. Twelve studies (7 randomized trials; 495 eyes) met inclusion criteria. In DME, 3 of 4 trials showed greater thickness reduction with adjunctive dorzolamide (±timolol), although visual gains were inconsistent. In RVO, 1 trial suggested transient anatomical benefit, whereas oral acetazolamide showed no added effect. In nAMD, adjunctive dorzolamide-timolol reduced residual fluid in refractory cases without visual or treatment-sparing benefit. Topical therapy produced modest IOP reductions without serious adverse events. Adjunct aqueous suppressants may provide limited short-term anatomical benefit, particularly in DME and refractory nAMD, but consistent functional or durability effects are not found in this study. Larger, longer-term randomized studies are needed.}, }
@article {pmid42091216, year = {2026}, author = {Huang, Z and Su, K and Zhou, L and Du, Y and Li, Y and Zhu, X}, title = {Systemic inflammatory biomarkers as risk factors for age-related ocular diseases: a large-scale prospective cohort study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328553}, pmid = {42091216}, issn = {1468-2079}, abstract = {AIMS: To evaluate associations between systemic inflammation biomarkers and incident age-related ocular diseases while also investigating their correlations with retinal structures.<br><br>METHODS: This population-based prospective cohort study analysed 415&#x2009;599 UK Biobank participants. Systemic immune-inflammation index (SII) and low-grade inflammation score (INFLA-score) were calculated from baseline haematological parameters. Primary outcomes were incident diagnoses of cataract, primary open-angle glaucoma (POAG), age-related macular degeneration (AMD) and diabetic retinopathy (DR). Multivariable Cox proportional hazards models estimated HRs with 95% CIs. Secondary analyses assessed the associations with optical coherence tomography-derived retinal layer thicknesses and vascular features.<br><br>RESULTS: Over a median 13.0-year follow-up, we identified 44&#x2009;906 cataract, 5803 POAG, 7388 AMD and 3319 DR incident cases. Both SII and INFLA-score demonstrated significant, dose-dependent associations with all ocular outcomes (all p<0.05). Distinct exposure-response patterns emerged: J-shaped relationships for cataract and POAG (SII threshold >500; INFLA-score threshold >0), versus monotonically positive associations for AMD and DR. Elevated inflammatory markers also correlated with retinal thinning, especially in photoreceptor layers.<br><br>CONCLUSIONS: Systemic inflammation biomarkers could predict incident age-related ocular diseases with disease-specific patterns while concurrently associating with quantifiable retinal structural and vascular pathologies. These findings suggest that anti-inflammatory strategies might have potential to mitigate ocular ageing processes, although further evidence on causal mechanisms and interventions is warranted.}, }
@article {pmid42091217, year = {2026}, author = {Li, Y and Tan, S and Xiong, R and Li, H and Zhu, Z and Chen, S and Wang, W}, title = {Posterior staphyloma and long-term structural and visual trajectories in high myopia.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2026-329468}, pmid = {42091217}, issn = {1468-2079}, abstract = {PURPOSE: To determine whether posterior staphyloma (PS) is associated with long-term trajectories of ocular structural changes, myopia-related complications and visual outcomes in high myopia.<br><br>METHODS: This prospective longitudinal cohort study included 614 highly myopic eyes from the Zhongshan High Myopia Cohort Study, followed for up to 12 years. Eyes were categorised by PS status: baseline PS (n=46), new-onset PS (n=94) or no PS (n=474). The associations between PS and myopic macular degeneration (MMD) progression, myopic traction maculopathy (MTM) and plus lesions incidence, longitudinal changes in ocular parameters and incident moderate-to-severe visual impairment (MSVI) were assessed.<br><br>RESULTS: PS was independently associated with increased risks of MMD progression (OR 3.39, 95%&#x2009;CI 1.81 to 6.35, p<0.001), MTM (OR 2.25, 95%&#x2009;CI 1.06 to 4.77, p=0.034) and incident plus lesions (OR 3.15, 95%&#x2009;CI 1.16 to 8.57, p=0.024). The highest risks of MTM and plus lesions were observed in eyes with new-onset PS. Eyes with PS demonstrated significantly faster axial elongation (mean annual rate: baseline PS, 0.120 mm (95% CI 0.099 to 0.142); new-onset PS: 0.129&#x2009;mm (95% CI 0.114 to 0.145); no PS: 0.066&#x2009;mm (95% CI 0.060 to 0.073), p<0.001) and a fivefold higher risk of MSVI (95% CI 1.36 to 18.45, p=0.016).<br><br>CONCLUSIONS: PS marks a pivotal structural transition in high myopia, identifying a phase of accelerated axial elongation, increased risk of complications and worse visual outcomes, and may serve as a key marker for risk stratification and an important target for early intervention.}, }
@article {pmid42093552, year = {2026}, author = {Huang, Y and Zhu, X and Lu, R and Jiang, K and Zhu, L and Zhou, X and Hong, J and Zhang, C}, title = {Retina-targeted siRNA delivery via exosome-liposome hybrid vesicles for AMD treatment.}, journal = {Biomaterials science}, volume = {}, number = {}, pages = {}, doi = {10.1039/d6bm00090h}, pmid = {42093552}, issn = {2047-4849}, abstract = {Effective treatment of neovascular age-related macular degeneration (AMD) requires targeted inhibition of vascular endothelial growth factor (VEGF) within the retina. However, delivering therapeutic siRNA to the retinal pigment epithelium (RPE), a key source of pathogenic VEGF, remains a major challenge due to ocular barriers and poor cellular tropism. To address this, we developed a retina-targeted delivery system by engineering exosome-liposome hybrid vesicles that encapsulate VEGF-silencing siRNA (Hybrid-siVEGF). The hybrid design leverages the innate homing capability of RPE-derived exosomes for retinal targeting, combined with the high siRNA loading capacity of synthetic liposomes. In vitro, Hybrid-siVEGF showed significantly enhanced uptake by human RPE cells compared to conventional liposomes, leading to the potent and specific knockdown of VEGF expression and the subsequent inhibition of endothelial cell proliferation. In vivo, a single intravitreal injection of Hybrid-siVEGF in a laser-induced choroidal neovascularization mouse model resulted in efficient accumulation within the retina, significant suppression of pathological angiogenesis, preservation of retinal morphology, and restoration of visual function. Our work establishes exosome-liposome hybrids as an effective and targeted platform for ocular siRNA delivery, offering a promising strategy for RNAi-based therapy for AMD and other retinal disorders.}, }
@article {pmid42094155, year = {2026}, author = {Sun, X and You, S and Sun, S and Cai, CX and Abraham, J and Yen, PY and Zhang, L}, title = {One Size Fits All? Comparing Foundation and Task-specific Models for Retinal Fluid Segmentation.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.04.26.26351792}, pmid = {42094155}, abstract = {Retinal fluids, detectable through optical coherence tomography (OCT), are key biomarkers for retinal diseases such as diabetic macular edema and age-related macular degeneration, guiding treatment decisions and monitoring response to therapy. Automated segmentation of retinal fluids could support large-scale clinical research and the development of clinical decision support tools. Recent ophthalmic foundation models trained on massive retinal imaging datasets show promise across many downstream tasks, including disease risk prediction and biomarker segmentation, but their performance relative to task-specific models for specialized clinical tasks remains unclear. We compared a task-specific segmentation model (RetiFluidNet) and an ophthalmic foundation model (VisionFM) using a standard benchmarking dataset containing 4,248 OCT images from 48 patients with three retinal diseases. Models were evaluated using three-fold cross-validation and assessed for pixel-level segmentation accuracy and patient-level fluid burden estimation. The task-specific model achieved higher segmentation performance and more consistent fluid quantification across devices. These findings suggest that, for retinal fluid segmentation, specialized task-specific models currently remain more reliable than general-purpose foundation models, highlighting the need for targeted adaptation before clinical deployment.}, }
@article {pmid42086315, year = {2026}, author = {Cheng, S and Han, R and Zhang, W and Meng, L and Gu, X and Zhao, X and Chen, Y}, title = {Development and validation of a machine learning model to predict recurrence in polypoidal choroidal vasculopathy: a multicentre prospective study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328228}, pmid = {42086315}, issn = {1468-2079}, abstract = {AIM: This study aims to develop and validate machine learning models for predicting recurrence in polypoidal choroidal vasculopathy (PCV) patients using optical coherence tomography (OCT) and OCT angiography (OCTA) biomarkers.<br><br>METHODS: This multicentre prospective study was conducted at 14 hospitals between June 2019 and December 2023. Patients who achieved remission after anti-vascular endothelial growth factor treatment were followed up for at least 1 year with serial OCT/OCTA imaging. Predictive features were selected using the least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation. Five classifiers (logistic regression, support vector machine, random forest, k-nearest neighbours and extreme gradient boosting (XGBoost)) were developed and evaluated using area under the curve (AUC), accuracy, sensitivity and specificity. Shapley additive explanations (SHAP) were applied for model interpretation and feature ranking.<br><br>RESULTS: A total of 204 eyes were included, with 125 from Peking Union Medical College Hospital (training set) and 79 from 13 other centres across China (external validation set). Ten features were selected for model development. In the external validation set, AUCs ranged from 0.801 to 0.861, with the XGBoost model achieving the highest AUC (0.861). SHAP analysis revealed that the percent change in polyp height, the change in branching neovascular network area and the change in subfoveal choroidal thickness were the top three significant predictors.<br><br>CONCLUSION: The XGBoost model demonstrated the best predictive performance, providing a reliable tool for recurrence prediction, aiding personalised treatment decisions and optimising clinical resources.}, }
@article {pmid42086316, year = {2026}, author = {Shah, P and Farah, HA and Wisotsky, DJ and Nawani, P and Hariharan, S and Satasia, A and Muir, ER and Mian, UK and Duong, TQ}, title = {Classification of retinal diseases based on optical coherence tomography angiography using cross-modal transfer learning of domain-specific foundation AI models.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-329249}, pmid = {42086316}, issn = {1468-2079}, abstract = {AIMS: This study evaluated the use of ophthalmic foundation deep-learning models with cross-modal transfer learning to classify multiple diseases on optical coherence tomography angiography (OCTA) with limited sample size.<br><br>METHODS: The OCTA-500 dataset (n=500 subjects) was split into an 85% training/validation set for fivefold cross-validation and a 15% held-out test set. Superficial and deep projections from OCTA were combined using intermediate fusion. Outcomes were multi-disease classification of normal, diabetic retinopathy, age-related macular degeneration and 'other'. Transfer-learning from colour fundus photography was used to overcome the limitation of small sample sizes. Vision-Transformer-VisionFM and Vision-Transformer-RETFound domain-specific foundation models with cross-modal transfer learning were evaluated. Comparison was made with Vision-Transformer-ImageNet, a non-domain-specific model. Performance was evaluated using accuracy, F1-score, precision, recall and area under the receiver operating characteristic curve. Saliency maps were also computed.<br><br>RESULTS: VisionFM with cross-modal transfer learning outperformed ImageNet in classifying different diseases on OCTA (accuracy: 0.8133&#xb1;0.0470&#x2009;vs 0.7600&#xb1;0.0502). RETFound with cross-modal transfer learning outperformed ImageNet in classifying different diseases on OCTA (accuracy: 0.8000&#xb1;0.0507&#x2009;vs 0.7600&#xb1;0.0521). Similar conclusions were reached with other performance metrics. Saliency maps from VisionFM and RETFound yielded attention patterns that localised pathology to relevant retinal structures on superficial and deep projections from OCTA, comparing favourably with those from ImageNet models.<br><br>CONCLUSIONS: Retinal foundation models with cross-modal transfer learning enable accurate multi-class classification using OCTA data, which had small sample size. Results from domain-specific foundation models compared favourably with a non-domain-specific model. Saliency analysis showed attention patterns of pathology localised to anatomically relevant retinal structures.}, }
@article {pmid42088264, year = {2026}, author = {Wickman, I and Huzevkova, I and Schroeder, M and Granstam, E and Kjellström, U and Lövestam-Adrian, M}, title = {Visual Acuity and Intraretinal Fluid as Predictive Factors for Legal Blindness and Macular Atrophy in Neovascular AMD Eyes Treated with Anti-VEGF: A Swedish Real-World Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {579968}, pmid = {42088264}, issn = {1177-5467}, abstract = {PURPOSE: Ocular coherence tomography (OCT) biomarkers have previously been able to predict low visual acuity (VA). The purpose of this study was to identify other OCT predictors for a final VA ≤35 and risk factors for macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This retrospective observational study included 107 treatment na&#xef;ve nAMD eyes who initiated treatment and were followed for 3 years &#xb1; 2 months or until VA deterioration to or below 35 ETDRS letters. Eyes with final VA &#x2264;35 letters (low VA group) were compared with those with a final VA >35 letters (maintenance group). Swedish Macula Register (SMR) data and OCT images were analyzed to identify risk factors for MA development and low VA. MA was defined according to the criteria for Complete Retinal Pigment Epithelium and Outer Retinal Atrophy (cRORA), which was based on OCT parameters.<br><br>RESULTS: Twenty eyes (19%) were presented with a final VA &#x2264;35 ETDRS letters. Mean time from baseline to &#x2264;35 ETDRS letters was 587.7 &#xb1; 330.4 days, with a mean 9.7 &#xb1; 5.3 injections during that period. Mean baseline VA in the maintenance group vs the low VA group were 65.4 &#xb1; 10.8 and 52.0 &#xb1; 10.6, respectively; p <0.001. Lower baseline VA was a predictor for low final VA. At baseline, 87% did not have MA on OCT. Among eyes with at least 1 OCT follow-up value in this group, 25% developed MA during the 3-year period. The presence of intraretinal fluid (IRF) at baseline was a predictor for MA development within 3 years in this subgroup.<br><br>CONCLUSION: After 3 years, 19% had declined to VA &#x2264;35 ETDRS letters. About 25% with &#x2265;1 available OCT follow-ups developed MA. Lower baseline VA predicted a final VA &#x2264;35 ETDRS letters in nAMD eyes. IRF at baseline predicted MA. The high prevalence of missing VA values emphasizes the importance of increasing the frequency of VA testing.}, }
@article {pmid42082325, year = {2026}, author = {Karri, R and Sousa, DC and Hadoux, X and Al-Qureshi, S and Harper, CA and Cohn, AC and Fagan, XJ and Chong, E and Edwards, TL and Lin, ML and Wickremasinghe, S and Chiu, D and Arnold, JJ and Kwan, AS and Campbell, TG and Durkin, SR and Mehta, H and Fraser-Bell, S and Razavi, H and Korobelnik, JF and Lanzetta, P and Holz, FG and Cheung, CMG and Boyer, DS and Balaratnasingam, C and Allen, PJ and Lim, LL and Guymer, R and Van Wijngaarden, P}, title = {Expert consensus on fundus fluorescein angiography reporting in ophthalmology: a Delphi study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328870}, pmid = {42082325}, issn = {1468-2079}, abstract = {PURPOSE: Fundus fluorescein angiography (FFA) is an important tool in evaluating retinal vascular disease. In the era of optical coherence tomography angiography (OCTA), however, expert preferences regarding the comparative utility of FFA and OCTA remain unclear. Additionally, despite FFA's widespread use, variability exists in the terminology used to describe angiographic findings. This study aimed to establish expert consensus on clinical indications for FFA versus OCTA and to provide consensus definitions of key angiographic terms.<br><br>METHODS: Using a two-round modified Delphi process, 25 retinal subspecialists provided perspectives on the clinical indications for FFA in the assessment of a range of retinal vascular conditions. They also evaluated proposed definitions for FFA findings in retinal vascular diseases. Consensus was defined as &#x2265;80% agreement and near consensus as 70%-79%.<br><br>RESULTS: Experts agreed that FFA is preferable for the diagnosis of retinal vasculitis, ocular ischaemic syndrome and proliferative diabetic retinopathy, even when OCTA is available. Furthermore, FFA was the favoured imaging modality to guide laser photocoagulation in branch retinal vein occlusion. Conversely, FFA was considered non-essential in evaluating neovascular age-related macular degeneration and mild-to-moderate non-proliferative diabetic retinopathy. Finally, definitions were agreed on for seven FFA terms used in the evaluation of retinal vascular diseases. These were non-perfusion, capillary dropout, window defect, pooling, leakage, neovascularisation and staining.<br><br>CONCLUSION: This study presents contemporary perspectives on the clinical indications for FFA in an era in which OCT and OCTA are widely available. It also provides a lexicon for FFA reporting in retinal vascular diseases based on expert consensus.}, }
@article {pmid42082781, year = {2026}, author = {Biagioni, F and Forte, M and di Nonno, F and Busceti, CL and Pinelli, R and Bumah, VV and Ferrucci, M and Lazzeri, G and Sciarretta, S and Frati, G and Fornai, F}, title = {Spontaneous whole retinal degeneration in aged Beclin1 heterozygous mice.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {42082781}, issn = {1435-1463}, abstract = {Retinal degenerative diseases range from rare inherited forms to common multifactorial disorders such as age-related macular degeneration, which is the leading cause of blindness in developed countries. Recent evidence identifies impaired autophagy as a key pathogenetic mechanism. In the disease process alterations of the outer retina start from the retinal pigment epithelium (RPE), to progress downstream in the inner retina leading to widespread whole retinal degeneration. Recent studies indicate that among autophagy-related proteins Beclin1 plays a relevant effect in sustaining retinal integrity, since it is induced by light exposure and it is placed at the intersection between mitophagy, lipophagy, and glycophagy, which are involved during retinal degeneration. The present study was carried out by profiting of BECN1 heterozygous aged mice (BECN+/-), where RT-PCR and western blotting analysis confirmed the loss of both the primary transcript (BECN1) and protein (Beclin1) in the whole retina. Multiple converging techniques indicate a marked degeneration of RPE and photoreceptor layer, where a dismantling of proteins forming tight junction was documented. Inner retinal degeneration was extended within outer and inner nuclear layer. In the inner retina the expression of the detrimental protein alpha synuclein was increased concomitantly with a defect of autophagy markers. The study indicates a seminal role of Beclin1 in maintaining retinal integrity and it defines the vulnerability of various retinal layers in the spreading of Beclin1-dependent retinal degeneration. The potential of increasing the expression of Beclin1 through photobiomodulation is discussed, since it supports retinal integrity when amber/red light-induced stimulation occurs.}, }
@article {pmid42084617, year = {2026}, author = {Swarn, S and Singh, RK and Sharma, SK and Nasir, N and Wahab, S and Kapoor, DU}, title = {Nanoparticle-mediated targeted delivery of lutein for retinal protection: emerging strategies in ocular drug targeting.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {42084617}, issn = {1432-1912}, support = {RGP1/44/46//Deanship of Research and Graduate Studies at King Khalid University for funding this work through Small Research Project/ ; }, abstract = {Lutein, a key macular carotenoid with potent antioxidant and blue-light-filtering properties, plays a crucial role in maintaining retinal integrity and preventing vision-threatening ocular disorders. However, its clinical efficacy is limited by poor aqueous solubility, instability, low bioavailability, and restricted penetration across ocular barriers. Recent advances in nanotechnology have enabled the development of lutein-loaded nanoparticle systems that significantly improve its stability, solubility, controlled release, and targeted delivery to anterior and posterior eye segments. This review comprehensively summarizes the physicochemical properties of lutein and the limitations of conventional lutein supplementation. The review entails diverse nanocarrier platforms including liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanoemulsions, micelles, and cubosomes highlights their mechanisms of ocular transport, formulation variables, and therapeutic relevance. Emerging evidence demonstrates that lutein-loaded nanoparticles unveil enhanced antioxidant, anti-inflammatory, anti-angiogenic, and cytoprotective effects across multiple ocular pathologies such as age-related macular degeneration, cataract, dry eye disease, blue light-induced retinal degeneration, and retinal pigment epithelial cell injury. Preclinical studies reveal improved retinal uptake, prolonged retention, and superior biological activity compared to free lutein. The lutein-loaded nanoparticles represent a promising next-generation strategy for efficient ocular delivery and targeted management of degenerative and oxidative eye diseases.}, }
@article {pmid42069635, year = {2026}, author = {Xu, Q and Li, M and Li, D and Dai, X and Zhang, Y and Qu, Y}, title = {3D spheroids of umbilical cord-derived MSCs protect retinal pigment epithelium against oxidative and inflammatory injury by activating autophagy.}, journal = {Stem cell research &amp; therapy}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13287-026-05043-z}, pmid = {42069635}, issn = {1757-6512}, support = {#ZR2025QC1712//Shandong Provincial Natural Science Foundation/ ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is characterized by progressive retinal pigment epithelium (RPE) dysfunction driven by oxidative stress and chronic inflammation, in which NLRP3 inflammasome activation plays a critical role. Mesenchymal stem cells (MSCs) exhibit therapeutic potential, but their efficacy is limited by poor survival and reduced paracrine activity in hostile microenvironments. Here, we investigated whether three-dimensional (3D) spheroid culture enhances the protective effects of umbilical cord-derived MSCs (UC-MSCs) on RPE cells by promoting autophagy and suppressing inflammasome activation.<br><br>METHODS: Human UC-MSCs were cultured as 3D spheroids or conventional 2D monolayers and applied in sodium iodate (NaIO3)-induced oxidative injury models both in vitro and in vivo. Retinal morphology and function were assessed via histology and electroretinography, while NLRP3/caspase-1 activation, LC3-II/I ratios, and autophagy flux were quantified using immunofluorescence and Western blot. GO/KEGG enrichment was performed to identify pathways associated with 3D MSCs efficacy. Mechanistic involvement of autophagy was validated using 3-methyladenine (3-MA) and rapamycin.<br><br>RESULTS: 3D MSCs formed compact spheroids exhibiting enhanced paracrine potential and significantly outperformed 2D MSCs in protecting RPE cells against NaIO3-induced injury. In vivo, 3D MSC treatment preserved retinal structure, reduced RPE cell loss, and improved retinal function. In vitro, co-culture with 3D MSCs markedly improved ARPE-19 viability, reduced apoptosis, and modulated autophagy-related marker expression, as evidenced by increased LC3-II/I ratios. 3D MSCs significantly inhibited NLRP3 inflammasome activation and pro-inflammatory cytokine release, effects reversed by 3-MA and further enhanced by rapamycin.<br><br>CONCLUSIONS: 3D spheroid culture substantially augments the therapeutic efficacy of UC-MSCs by boosting autophagy and suppressing NLRP3 inflammasome signaling, resulting in enhanced protection of RPE cells from oxidative and inflammatory injury. These findings provide preclinical evidence supporting 3D MSCs as a promising therapeutic strategy for AMD.}, }
@article {pmid42070018, year = {2026}, author = {Agarwal, R and Iezhitsa, I and Hombrebueno, JR and Agarwal, P}, title = {Retinal organoids: current status of development and new avenues for application in disease modeling, drug discovery and therapeutics.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00846-x}, pmid = {42070018}, issn = {2056-9920}, abstract = {Visual impairment affects over 2.2 billion people worldwide and the major causes include age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy. For research in these areas, although animal models offer a more physiologically complex system than in vitro approaches, their use raises ethical considerations, and species-specific differences such as variations in protein sequences and signaling pathways. This can limit the direct translatability of the outcomes. Traditional 2-D cell cultures, in contrast, lack the multicellular organization and dynamic microenvironment necessary to replicate human retinal complexity. Retinal organoids (ROs), three-dimensional tissue constructs derived from pluripotent stem cells, have emerged as a promising model due to their human origin and complex cellular interactions that cannot be achieved in conventional 2-D/3-D co-culture models. In this review, we provide a brief overview of the evolution from 2-D to 3-D retinal models, highlight the structural and functional features of ROs including the presence of layered retinal architecture, photoreceptor outer segment formation, and light-responsive electrophysiological activity and summarize their applications in disease modeling, drug discovery, and gene and cell therapy. ROs represent a significant advancement over traditional models by enabling the recapitulation of human-specific retinal development, facilitating the study of patient-derived disease phenotypes, and providing a platform for personalized therapeutic screening. Their development has deepened understanding of pathological mechanisms in conditions such as retinitis pigmentosa and AMD, while enabling preclinical testing of targeted interventions like CRISPR-based gene editing and photoreceptor cell replacement. Nonetheless, challenges remain in fully replicating retinal vascularization, long-term functional maturation, and synaptic connectivity, underscoring the need for continued refinement and integration with complementary model systems.}, }
@article {pmid42072143, year = {2026}, author = {Maggi, MA and Mastromartino, R and Piccardi, M and Minnella, AM and Marangoni, D and Di Marco, S and Falsini, B and Bisti, S}, title = {Saffron as a Retinal Neuroprotectant: A Narrative Review of Preclinical Studies and Clinical Results.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {4}, pages = {}, doi = {10.3390/antiox15040501}, pmid = {42072143}, issn = {2076-3921}, abstract = {The present narrative review reports the main preclinical and clinical results obtained by using supplementation of saffron or its pure components in neurodegeneration, with special emphasis on age-related macular degeneration. Beyond that, this article will address shared pathways between neurodegenerative diseases of the eye and the brain. It will be shown that saffron treatment might counteract oxidative damage in the retina and brain, as well as inflammation and inflammatory mediators that induce neuronal degeneration and death. The ways of action are multiple, and saffron chemical components appear to act in a synergistic manner, inducing tissue resilience. These effects critically depend upon the saffron chemical composition and structure. A well-defined ratio among molecules is linked to a patented batch known as Repron[®] and offers the maximum protection against neurodegeneration.}, }
@article {pmid42072148, year = {2026}, author = {Wiciński, M and Fajkiel-Madajczyk, A and Kurant, Z and Rzepiński, &#x141; and Słupski, M}, title = {Review of Therapeutic Potential of Coenzyme Q10 in Ophthalmology: Focus on Age-Related Macular Degeneration, Glaucoma, and Retinitis Pigmentosa.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {4}, pages = {}, doi = {10.3390/antiox15040506}, pmid = {42072148}, issn = {2076-3921}, abstract = {Coenzyme Q10 (CoQ10), a natural antioxidant produced by the human body, has strong anti-inflammatory properties, reduces oxidative stress, and improves mitochondrial function. It is also known for its strong neuroprotective effects. With age, endogenously produced CoQ10 levels decline, contributing to the development of chronic diseases, including eye disorders. Irreversible ocular diseases that result in blindness present a significant challenge in contemporary medicine, as no fully effective cure exists; current treatments primarily aim to decelerate disease progression, manage symptoms, and preserve residual vision. Our study reviews research on the use of CoQ10 in eye diseases like age-related macular degeneration (AMD), retinitis pigmentosa (RP), and glaucoma, which can cause permanent vision loss and are linked to oxidative stress and mitochondrial dysfunction. This article explores whether CoQ10 can be a safe and effective addition to treatment for these conditions. We also outline directions for future research and explain how CoQ10 functions in the studies discussed in this review.}, }
@article {pmid42072314, year = {2026}, author = {Menna, F and De Luca, L and Meduri, A and Baldascino, A and Lupo, S and Vingolo, EM}, title = {New Clinical Trials and Therapeutic Advances with Faricimab and Aflibercept 8 mg in Neovascular Age-Related Macular Degeneration: A Durability-Oriented Comparative Perspective.}, journal = {Biomedicines}, volume = {14}, number = {4}, pages = {}, doi = {10.3390/biomedicines14040773}, pmid = {42072314}, issn = {2227-9059}, abstract = {Neovascular age-related macular degeneration (nAMD) remains a major cause of visual morbidity worldwide, although its contribution to blindness in developed healthcare systems has declined in the era of anti-VEGF therapy. Although randomized clinical trials have consistently demonstrated meaningful visual gains under structured retreatment protocols, real-world outcomes frequently decline over time due to undertreatment, limited durability, and persistent disease activity. Recent therapeutic advances have shifted the focus from maximizing short-term efficacy to engineering sustained disease control. Faricimab, a bispecific antibody targeting both VEGF-A and angiopoietin-2, introduces dual-pathway vascular modulation, while high-dose aflibercept (8 mg) enhances VEGF suppression through pharmacokinetic intensification. This perspective critically examines the biological rationale, clinical evidence, real-world implications, and strategic positioning of these agents, proposing a durability-centered framework for next-generation management of nAMD.}, }
@article {pmid42072323, year = {2026}, author = {Menna, F and Pinelli, C and De Luca, L and Meduri, A and Baldascino, A and Lupo, S and Vingolo, EM}, title = {From Genetic Diagnosis to Therapeutic Implementation in Retinal Diseases: Translational Advances and Persistent Bottlenecks.}, journal = {Biomedicines}, volume = {14}, number = {4}, pages = {}, doi = {10.3390/biomedicines14040782}, pmid = {42072323}, issn = {2227-9059}, abstract = {Background: Retinal and optic nerve disorders are a leading cause of irreversible visual impairment worldwide. Advances in molecular genetics-including next-generation sequencing, genome-wide association studies, and gene-based therapeutic technologies-have reshaped understanding of both inherited and complex retinal diseases. However, translating genetic discovery into sustained clinical benefit remains biologically and practically constrained. Methods: A structured literature search was conducted using PubMed and Scopus to identify relevant studies published between 2015 and 2025. The search focused on molecular genetics, epigenetic modulation, mitochondrial biology, and translational applications in inherited retinal dystrophies and selected complex retinal diseases, prioritizing high-impact original research and systematic reviews addressing diagnostic innovation and therapeutic development. Results: Inherited retinal dystrophies represent the most advanced model of precision ophthalmology, with diagnostic yields approaching 70-80% in well-characterized cohorts. Gene augmentation and genome-editing strategies have demonstrated proof-of-concept efficacy, yet clinical benefit depends on residual cellular viability, delivery efficiency, and durability of expression. Emerging platforms include AAV-mediated gene transfer, in vivo CRISPR-based editing, RNA-directed splice modulation, and mitochondrial-targeted approaches. Persistent barriers include unresolved non-coding and structural variants, variant interpretation uncertainty, and endpoint selection in clinical trials. In contrast, complex retinal diseases such as glaucoma, age-related macular degeneration, and pathological myopia reflect polygenic susceptibility interacting with environmental and aging-related factors. Although polygenic risk scores refine probabilistic prediction, their utility is limited by ancestry bias and incomplete predictive performance. Epigenetic and mitochondrial mechanisms further modulate disease expression but remain largely non-actionable in routine practice. Conclusions: Retinal genetics has progressed from gene discovery to early therapeutic implementation. Future advances will depend on improved variant detection, functional validation, biomarker-guided staging, and integration of genomics with imaging and longitudinal modeling to achieve durable and equitable precision ophthalmology.}, }
@article {pmid42072770, year = {2026}, author = {Unlu, BH and Durmaz Engin, C and Ozturk, AT}, title = {The Role of Systemic Inflammation in Age-Related Macular Degeneration Subtypes: Exploring Novel Biomarkers.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {8}, pages = {}, doi = {10.3390/diagnostics16081144}, pmid = {42072770}, issn = {2075-4418}, abstract = {Background/Objectives: This study aimed to compare hematological and inflammatory markers among patients with dry and wet age-related macular degeneration (AMD) and healthy controls, and to evaluate the influence of geographic atrophy (GA) in dry AMD and treatment response (TR) in wet AMD on these markers. Methods: The study included patients with dry AMD (n = 54), wet AMD (n = 53), and age- and sex-matched controls (n = 55). Hematological parameters, serum albumin, and systemic inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), pan-immune-inflammation value (PIV), and hemoglobin, albumin, lymphocyte, and platelet index (HALP), were compared among the groups. Results: Age and sex distributions did not differ significantly between groups. Compared to controls, the wet AMD group had significantly higher neutrophil counts (p = 0.013), red cell distribution width (RDW) (p = 0.033), and inflammatory indices, including NLR, PLR, SII, SIRI, and PIV (all p < 0.01). HALP levels were significantly lower in wet AMD (p < 0.001). Dry AMD patients also had higher PLR (p = 0.045) and RDW (p = 0.005) than controls. When comparing wet and dry AMD groups directly, SIRI (p = 0.041) and PIV (p = 0.029) were significantly elevated in wet AMD, indicating stronger systemic inflammatory burden. In the dry AMD subgroup, patients with GA had significantly lower hemoglobin (p = 0.002) and erythrocyte counts (p = 0.039) than those without GA. No significant differences were observed between TR-positive and TR-negative wet AMD patients. Conclusions: Patients with wet AMD exhibit a more pronounced systemic inflammatory profile than both dry AMD patients and healthy controls. These findings support the hypothesis that systemic inflammation may contribute to AMD pathogenesis. Geographic atrophy in dry AMD may also be associated with additional hematologic alterations, whereas treatment response in wet AMD is not reflected in systemic markers.}, }
@article {pmid42074336, year = {2026}, author = {Bruzaite, A and Vilkeviciute-Petraite, A and Cebatoriene, D and Zaliuniene, D and Ciapiene, I and Smalinskiene, A and Kriauciuniene, L and Liutkeviciene, R}, title = {Metabolic and Genetic Alterations in Early and Exudative Age-Related Macular Degeneration: Inosine, Amino Acids, and COL2A1 Gene Variant.}, journal = {International journal of molecular sciences}, volume = {27}, number = {8}, pages = {}, doi = {10.3390/ijms27083697}, pmid = {42074336}, issn = {1422-0067}, support = {S-MIP-23-96//Research Council of Lithuania/ ; }, mesh = {Humans ; Female ; Male ; Aged ; *Polymorphism, Single Nucleotide ; *Macular Degeneration/genetics/metabolism ; *Inosine/metabolism ; *Amino Acids/metabolism ; *Collagen Type II/genetics/metabolism ; Genetic Predisposition to Disease ; Middle Aged ; Genotype ; Case-Control Studies ; Alleles ; Aged, 80 and over ; }, abstract = {Age-related macular degeneration (AMD) is a complex retinal disease influenced by genetic and metabolic factors. Genetic variants impact disease susceptibility, while alterations in amino acid and purine metabolism are involved in AMD development. This study aimed to examine the association between the COL2A1 rs1635529 polymorphism and AMD, as well as its relation to specific metabolites. The study comprised 919 participants: 261 with early AMD, 229 with exudative AMD, and 429 controls. DNA was extracted using the salting-out method, and genotyping was performed using real-time PCR. Metabolite levels were analysed with liquid chromatography-mass spectrometry. Statistical analysis was conducted using IBM SPSS Statistics 27.0. Logistic regression revealed that carriers of the GT + TT genotypes had a 1.63-fold higher risk of early AMD (p = 0.046). The T allele was also linked to a 1.67-fold elevated risk (p = 0.033). No significant associations were observed in exudative AMD. Furthermore, lower leucine levels were noted in exudative AMD patients, and inosine levels were reduced in GT genotype carriers within the early AMD group. The COL2A1 rs1635529 polymorphism showed a nominal association with early AMD, but not exudative AMD. Differences in leucine and inosine levels were observed, suggesting a potential link between genetic variation and metabolic alterations. These findings indicate possible involvement of collagen-related and metabolic pathways in early disease development; however, the results should be interpreted with caution and require validation in larger studies.}, }
@article {pmid42074510, year = {2026}, author = {Rowe, LW and Becerra, SP and MacLaren, RE and Avery, RL and Wykoff, CC and Ho, AC and Regillo, CD and Eliott, D and Osborne, A and Binley, KM and Ciulla, TA}, title = {Gene-Agnostic Therapeutic Strategies for Inherited Retinal Diseases: Neuroprotection and Immunomodulation.}, journal = {Genes}, volume = {17}, number = {4}, pages = {}, doi = {10.3390/genes17040392}, pmid = {42074510}, issn = {2073-4425}, mesh = {Humans ; *Genetic Therapy/methods ; *Retinal Diseases/genetics/therapy ; *Neuroprotection/genetics ; *Immunomodulation/genetics ; Animals ; Nerve Growth Factors/genetics ; }, abstract = {Background/Objectives: Inherited retinal diseases (IRDs) represent a genetically heterogeneous group of disorders caused by mutations in over 280 genes with more than 3100 identified variants. While gene-specific replacement therapies have achieved landmark success with voretigene neparvovec (Luxturna) for biallelic RPE65-associated retinal dystrophy, developing individual therapies for each genetic subtype remains impractical. This review examines gene-agnostic therapeutic approaches utilizing neuroprotection and immunomodulation that target common pathophysiological mechanisms shared across multiple IRD genotypes. Methods: We reviewed the literature on neuroprotective and immunomodulatory gene therapy strategies for IRDs, focusing on neurotrophic factors and complement system modulation. Results: Neuroprotective approaches delivering neurotrophic factors-including pigment epithelium-derived factor (PEDF), ciliary neurotrophic factor (CNTF), rod-derived cone viability factor (RdCVF), brain-derived neurotrophic factor (BDNF), fibroblast growth factors (FGFs), glial cell line-derived neurotrophic factor (GDNF), and proinsulin-have demonstrated photoreceptor preservation across multiple preclinical IRD models regardless of the underlying genetic mutation. The recent FDA approval of CNTF cell-based gene therapy (Encelto) for macular telangiectasia type 2 validates this therapeutic paradigm. Complement system inhibition represents another gene-agnostic strategy, with intravitreal complement inhibitors approved for geographic atrophy secondary to age-related macular degeneration and gene therapy approaches targeting C3, C5, or delivering soluble complement regulators under investigation for IRDs. Combination strategies simultaneously addressing multiple pathogenic pathways may offer synergistic benefits. Conclusions: Gene-agnostic approaches targeting neuroprotection and immunomodulation offer a therapeutic paradigm capable of benefiting patients across the spectrum of IRD genotypes, potentially transforming treatment for conditions where mutation-specific therapies remain unavailable.}, }
@article {pmid42074639, year = {2026}, author = {Kamao, H and Goto, K and Mizukawa, K and Hiraki, R and Miki, A and Kimura, S}, title = {Five-Year Changes in Pachydrusen with Late-Phase Hyperfluorescence on Indocyanine Green Angiography.}, journal = {Journal of clinical medicine}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/jcm15082836}, pmid = {42074639}, issn = {2077-0383}, abstract = {Background/Objectives: Pachydrusen are a drusen subtype associated with the pachychoroid disease spectrum; however, their long-term natural history and pathophysiological significance remain unclear. We investigated 5-year morphological and topographic changes in pachydrusen using diagnostic criteria incorporating late-phase indocyanine green angiography (ICGA) hyperfluorescence. Methods: This retrospective observational study included fellow eyes with pachydrusen from patients with unilateral neovascular age-related macular degeneration. Pachydrusen were defined as sub-retinal pigment epithelium (RPE) deposits ≥ 125 µm in size with corresponding hyperfluorescence on late-phase ICGA. Lesion number, size, and spatial distribution (ETDRS grid and quadrant-based classification) were evaluated at baseline and 5 years. The incidence of macular neovascularization (MNV) and its colocalization with pachydrusen were assessed. Results: Among 57 fellow eyes with pachydrusen, incident MNV developed in 8 eyes (14.0%) during follow-up; the mean time to onset was 25.6 ± 16.3 months. No clear colocalization between pachydrusen and incident MNV was observed. Nineteen eyes completed the 5-year follow-up period. Pachydrusen were predominantly located outside the 6000 µm ETDRS grid at baseline (63.4%) and 5 years (66.3%), significantly exceeding the expected proportion based on the area ratio (p < 0.001). The lesions were most frequently observed in the superotemporal quadrant (52.6%). Over 5 years, 19.8% of the lesions increased in size, 67.2% remained stable, and 12.9% regressed; none of the regressed lesions were accompanied by RPE atrophy. Conclusions: Pachydrusen, defined as late-phase ICGA hyperfluorescence, was predominantly distributed outside the ETDRS grid with a superotemporal predilection and could increase or decrease over a 5-year follow-up period. No colocalization with MNV was observed, and no accompanying RPE atrophy after pachydrusen regression was identified, suggesting that late-phase ICGA-hyperfluorescent pachydrusen may represent a pathophysiology distinct from that of soft drusen.}, }
@article {pmid42074670, year = {2026}, author = {Sanders, FWB and Acton, JH and Ryan, B and McAlinden, C}, title = {Psychometric Assessment of the Metamorphopsia Questionnaire in Patients with Macular Diseases Receiving Anti-Vascular Endothelial Growth Factor Treatment.}, journal = {Journal of clinical medicine}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/jcm15082867}, pmid = {42074670}, issn = {2077-0383}, support = {2023/2024(ER)-ER-23-07-Dr Francis William Barwise Sanders//HCRW/ ; }, abstract = {Background: The metamorphopsia questionnaire (MeMoQ) is an established patient-reported outcome measure (PROM) in the context of macular disease. However, its performance has not been proved in those being treated for various macular conditions with intravitreal anti-vascular endothelial growth factor (Anti-VEGF). The objective was to eliminate misfitting items, enhance measurement precision, and ensure optimal response categorisation. Methods: Rasch analysis was performed iteratively on 2286 responses from patients with macular diseases being treated with Anti-VEGF to optimise the MeMoQ. Fit statistics, reliability indices, person and item separation measures, and principal component analysis (PCA) of residuals were assessed to determine the optimal model. This study was conducted in an outpatient clinic specialising in retinal diseases in Hywel Dda University Health Board. Results: Misfitting items were removed in successive iterations, leading to optimised category probability curves and stable fit statistics for the MeMoQ. The resulting model for all responses included two final items, with person separation remaining inadequate reducing from 1.23 to 1.12 and reliability from 0.60 to 0.56. Category probability curves demonstrated good ordering of response variables with Andrich thresholds separated by >1.2 logits. In the subgroups of neovascular age-related macular degeneration and diabetic macular oedema person separation remained below two and reliability remained low. Conclusions: Rasch analysis demonstrated that the MeMoQ was not a valid or reliable PROM in this patient population. Therefore, the MeMoQ may not provide a reliable index of patient's perception and visual experience when undergoing Anti-VEGF treatment.}, }
@article {pmid42074763, year = {2026}, author = {Dmoch, W and Sawicka, J and Żelichowska, N and Kępczyńska, Z and Maciejewicz, P and Kęcik, D}, title = {Statins and Fibrates in Age-Related Macular Degeneration: A Contemporary Clinical Narrative Review (2020-2025).}, journal = {Journal of clinical medicine}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/jcm15082960}, pmid = {42074763}, issn = {2077-0383}, abstract = {Age-related macular degeneration (AMD) remains the leading cause of irreversible central vision loss in the elderly. Increasing attention has been directed toward lipid metabolism as a potential contributor to disease onset and progression. The overlap between AMD and atherosclerosis-particularly regarding lipid accumulation, endothelial dysfunction, and chronic inflammation-has prompted interest in lipid-lowering therapies. This narrative review synthesizes the clinical evidence published between 2020 and 2025 on the potential role of statins and fenofibrate in AMD risk modification and disease progression. A structured literature search was conducted in PubMed, Scopus, and Web of Science using combined MeSH and free-text terms related to lipid-lowering agents and AMD. Human studies evaluating clinical incidence or progression outcomes were considered alongside contextual evidence from prior evidence syntheses. Overall, findings remain heterogeneous. Most studies did not demonstrate a consistent association between statin therapy and AMD incidence or progression in unselected populations. However, selected reports suggested a potential delay in dry AMD onset or slower disease progression among patients receiving prolonged or higher-intensity statin treatment. Evidence regarding fenofibrate was more limited and heterogeneous, with only a tentative protective signal observed in adherent users, particularly for non-exudative AMD. The current literature does not support lipid-lowering therapy as a universal preventive strategy for AMD. Nonetheless, subgroup-specific benefits cannot be excluded, especially in early disease stages or metabolically high-risk populations. Further well-designed prospective and randomized studies are needed to clarify therapeutic relevance and identify the patients who are most likely to benefit.}, }
@article {pmid42074798, year = {2026}, author = {Nagano, N and Kanemori, E and Hirano, Y and Hojo, T and Sakaeda, Y and Yuguchi, T and Kuwayama, S and Ogura, S and Kimura, M and Morita, H and Uemura, K and Yasukawa, T}, title = {Assessing the Validity of the Fellow Eye as an Internal Control in Early-Phase Clinical Trials for Myopic Chorioretinal Atrophy.}, journal = {Journal of clinical medicine}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/jcm15082997}, pmid = {42074798}, issn = {2077-0383}, support = {Not applicable//PharmaBio Corporation/ ; }, abstract = {Background/Objectives: Age-related macular degeneration, particularly geographic atrophy, is a major cause of irreversible vision loss and shares pathological features with myopic chorioretinal atrophy (CRA). This study was designed as an exploratory methodological analysis to evaluate the feasibility of using the fellow eye as an internal control in early-phase clinical trials for myopic CRA. Methods: This exploratory and methodological retrospective study included eight patients (16 eyes) with myopic CRA who visited the Department of Ophthalmology at Nagoya City University Hospital between January 2010 and August 2023. Atrophic areas in both eyes were measured, and the longitudinal changes were analyzed. Three mixed-effects models were compared to assess the impact of inter-individual and inter-ocular variability on atrophic area progression. Subsequently, fixed-effects and mixed-effects models were compared using the Akaike Information Criterion (AIC). Finally, the square root of the variance ratio was calculated to quantify the contribution of inter-ocular variability to atrophic area progression. Results: In all eyes, the square root of the atrophic area increased over time. The model including random intercepts and slopes for each eye nested within patients had the lowest AIC of 69.4, suggesting that accounting for both inter-individual and inter-ocular variability improved model accuracy. The mixed-effects model had a lower AIC than the fixed-effects model, indicating a better fit. The square root of the variance ratio was 0.34 in the mixed-effects model, indicating that the inter-ocular variability was lower than the inter-individual variability, though it remained appreciable. Conclusions: This study quantitatively supports the feasibility and methodological validity of inter-ocular comparison designs for early-phase clinical trials in myopic CRA.}, }
@article {pmid42074899, year = {2026}, author = {Ahmad, NU and Mir, TA}, title = {Advances in Gene Therapy for Age-Related Macular Degeneration: A Narrative Review.}, journal = {Journal of clinical medicine}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/jcm15083097}, pmid = {42074899}, issn = {2077-0383}, abstract = {Age-related macular degeneration (AMD) is the most common cause of blindness and vision impairment in individuals over 60 years of age in the United States (US). Despite this, current treatment options have limitations related to drug efficacy and durability. Gene therapy provides a potential solution by providing a more durable and longer- acting treatment option that can decrease treatment burden and improve long-term visual outcomes. This review presents the current treatment approaches, routes of administration, and vectors being investigated for gene therapy delivery in AMD. It also provides an update on the ongoing gene therapy clinical trials for dry and wet AMD. As these therapies advance into later-stage clinical trials, ophthalmologists need to be mindful of the many challenges pertaining to gene therapy delivery, including safety, limitations related to immunogenicity, long-term ocular and systemic side effects, and potential barriers to drug manufacturing and access. Continued efforts are required to improve precision, safety, and efficacy, including identifying the safest and most effective vectors and delivery routes, and minimizing potential adverse effects. In addition, guidelines need to be established to guide appropriate patient selection before gene therapy can be integrated into clinical practice.}, }
@article {pmid42079735, year = {2026}, author = {Yu, B and Liu, L and Yang, N and Xu, L and Wu, H}, title = {Visual acuity and stereopsis across the parafoveal and perifoveal retina in young adults: an eccentricity and meridian analysis.}, journal = {PeerJ}, volume = {14}, number = {}, pages = {e21251}, pmid = {42079735}, issn = {2167-8359}, mesh = {Humans ; *Visual Acuity/physiology ; Male ; Female ; Adult ; *Depth Perception/physiology ; Young Adult ; *Retina/physiology ; *Fovea Centralis/physiology ; Vision, Binocular/physiology ; }, abstract = {BACKGROUND: Visual acuity (VA) and stereoacuity (SVA) are fundamental visual functions that decline with increasing retinal eccentricity. Patients with macular degeneration and other central vision disorders often rely on paracentral vision, yet location-specific reference data for VA and SVA across the parafoveal and perifoveal retina remain limited. This study aimed to quantify the distribution of binocular VA and SVA across eccentricity and meridian in young adults, develop prediction equations with 95% prediction intervals, and examine the relationship between these two visual functions in the paracentral retina.<br><br>METHODS: Thirty-five healthy young adults (13 males, 22 females; mean age 27.23&#xa0;&#xb1;&#xa0;2.43 years) were recruited. Binocular VA and SVA were measured at 48 test positions across eight meridians (0&#xb0;, 45&#xb0;, 90&#xb0;, 135&#xb0;, 180&#xb0;, 225&#xb0;, 270&#xb0;, 315&#xb0;) and six eccentricities (2.5&#xb0; to 15&#xb0; in 2.5&#xb0; increments) using a polarized 3D display system. A four-alternative forced-choice task was employed with tumbling E optotypes for VA and random-dot stereograms for SVA. Eye tracking ensured fixation stability throughout testing. Generalized estimating equations were used to analyze the effects of eccentricity and meridian. Linear mixed-effects models and Bayesian Tobit models were employed to develop prediction equations. Ten-fold cross-validation assessed model generalizability.<br><br>RESULTS: Both VA and SVA significantly declined with increasing eccentricity (P&#xa0;<&#xa0;0.001). VA decreased from a median of 0.40 logMAR at 2.5&#xb0; to 1.20 logMAR at 15.0&#xb0;, at a rate of 0.057 logMAR per degree. SVA increased from 2.1 log arcsec at 2.5&#xb0; to 2.9 log arcsec at 7.5&#xb0;, declining approximately three times faster than VA (0.154 log arcsec per degree). Both functions showed significant meridional anisotropy (P&#xa0;<&#xa0;0.001), with the horizontal meridian demonstrating 0.058 logMAR better VA and 0.106 log arcsec better SVA compared to the vertical meridian. Despite parallel declines with eccentricity, no significant correlations were observed between VA and SVA at any test position within 7.5&#xb0; eccentricity (P&#xa0;>&#xa0;0.05).<br><br>CONCLUSIONS: VA and SVA deteriorate with increasing eccentricity in the paracentral retina, with stereopsis declining approximately three times faster and demonstrating a more pronounced horizontal-over-vertical advantage. The absence of correlation between VA and SVA suggests distinct neural mechanisms underlying these functions. The prediction equations with 95% prediction intervals provide reference benchmarks for healthy young adults, facilitating clinical interpretation of patient measurements and enabling objective assessment of disease-related changes in paracentral visual function.}, }
@article {pmid42079755, year = {2026}, author = {Zhu, S and Yang, T and Sheng, L and Shi, L}, title = {TREM2 in age-related macular degeneration: a microglia-centered perspective in the retinal myeloid landscape.}, journal = {Frontiers in ophthalmology}, volume = {6}, number = {}, pages = {1804578}, pmid = {42079755}, issn = {2674-0826}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in older adults. Advanced AMD comprises an atrophic ("dry") form characterized by retinal pigment epithelium (RPE) and photoreceptor degeneration and a neovascular ("wet") form driven by choroidal neovascularization (CNV). Beyond genetic predisposition and environmental stressors, chronic dysregulation of innate immunity is increasingly recognized as a convergent mechanism linking drusen/Bruch's membrane alterations to outer retinal cell death and pathological angiogenesis. Retinal myeloid cells-including resident microglia and, in specific disease contexts, recruited monocyte-derived macrophages-can support homeostasis by clearing lipids and cellular debris, yet may also exacerbate inflammation, matrix remodeling, and neovascularization. Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed by microglia and other myeloid cells that regulates phagocytosis, lipid handling, migration, survival, immunometabolism, and inflammatory tone. Recent retinal studies suggest that TREM2-associated programs can restrain lesion expansion in outer retinal degeneration models and modulate CNV severity in experimental neovascularization; however, interpretation remains limited by disease stage, anatomical niche, and the difficulty of cleanly separating microglia from infiltrating macrophages in vivo. Here, we synthesize current evidence on retinal myeloid contributions to dry and neovascular AMD, provide an updated mechanistic framework for TREM2 signaling, and discuss therapeutic strategies and translational challenges for targeting TREM2 in AMD.}, }
@article {pmid42080790, year = {2026}, author = {Piroozmand, S and Latifi-Navid, H and Soheili, ZS and Hosseinkhani, S and Samiei, S and Barzegar Behrooz, A and Ahmadieh, H and Leonardi, A and Ghavami, S and Sheibani, N}, title = {Suboptimal Responses to Anti-VEGF in Retinal Neurovascular Diseases: Linking Aging and Alternative Angioinflammatory Pathways.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {5}, pages = {4}, doi = {10.1167/iovs.67.5.4}, pmid = {42080790}, issn = {1552-5783}, mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Aging/physiology ; Signal Transduction ; *Retinal Diseases/drug therapy/metabolism ; }, abstract = {PURPOSE: Vision-threatening ocular diseases are impacted by aging-associated molecular changes, including mitochondrial dysfunction, cellular senescence, and chronic inflammation. Anti-VEGF therapies targeting VEGF-A/VEGFR2 signaling remain the frontline standard of care, but many patients exhibit suboptimal or nondurable responses, often due to compensatory and/or compromised antiangiogenic and anti-inflammatory pathways. We aimed to elucidate shared mechanisms underlying treatment failure and disease progression.<br><br>METHODS: We applied an integrative systems biology framework that combined multiomics datasets, network-based machine learning, and disease-specific pathway mapping. A comprehensive literature review of conditions, including diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and aging, identified 14 core genes consistently associated with angiogenesis, inflammation, and immune signaling. Multialgorithm centrality and enrichment analyses reconstructed disease-specific interaction networks, revealing consensus mechanistic axes. Integration of cell-type-specific single-cell RNA sequencing data from AMD-RPE clusters identified cluster-specific gene hubs and vertical signaling axes, leading to VEGF blockade failure.<br><br>RESULTS: EGFR, HSP90AA1, SIRT1, and STAT3 emerged as central resistance hubs linking angiogenesis and inflammatory processes. Pathway enrichment analyses revealed 21 conserved core signaling cascades, grouped into six functional categories, with AGE-RAGE, PI3K-Akt, HIF-1, MAPK, and chemokine pathways playing central roles. A MiRGD-based peptide nanocomplex delivering htsFLT01 achieved efficient RPE transfection and controlled gene activation under basal conditions.<br><br>CONCLUSIONS: This systems-level framework clarifies mechanisms of VEGF blockade resistance and provides a rational basis for next-generation, combinatorial therapeutic strategies requiring validation in disease-relevant models.}, }
@article {pmid42080917, year = {2026}, author = {Haroon, MM and Akram, L and Jalal, L and Ahmed, A and Haider, S}, title = {Granzyme B in age-related macular degeneration: mechanistic insights and therapeutic perspectives.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42080917}, issn = {1435-702X}, abstract = {Granzyme B (GzmB), beyond its established role in corneal and conjunctival disease, is increasingly recognized in the retinal and choroidal distribution of several pathologies. GzmB targets tight-junction proteins (e.g., ZO-1, JAM-A) and extracellular proteins such as fibronectin and laminin within the retinal pigment epithelium (RPE) and Bruch's membrane, thereby disrupting the outer blood-retinal barrier and contributing to the pathogenesis of age-related macular degeneration (AMD) and Macular neovascularization (MNV). This mini review highlights recent mechanistic insights into how GzmB drives extracellular matrix breakdown, inflammation, and angiogenesis; summarizes experimental and clinical evidence supporting its role in AMD; and discusses emerging therapeutic approaches, limitations, and translational potential for targeted therapy.}, }
@article {pmid42081160, year = {2026}, author = {Lin, Y and Han, Z and Zhang, Y and Yuan, R and Huang, M and Liu, Y and Wang, J and Xu, C and Liu, L and Yu, P and Yang, Q and Zeng, L and Li, S}, title = {The aging eye: navigating molecular mechanisms and innovative interventions.}, journal = {Biogerontology}, volume = {27}, number = {3}, pages = {}, pmid = {42081160}, issn = {1573-6768}, mesh = {Humans ; *Aging/pathology/metabolism ; Oxidative Stress ; Animals ; Cellular Senescence ; *Eye/metabolism/pathology ; *Eye Diseases/therapy/metabolism ; Autophagy ; }, abstract = {The global demographic shift toward aging has precipitated a surge in age-related ocular pathologies, imposing a formidable public health challenge that demands urgent intervention. Blinding disorders such as age-related macular degeneration (AMD), cataracts, and dry eye disease exemplify this crisis, with their pathogenesis being intrinsically linked to tissue-specific aging processes in the eye. At the molecular level, core pathways including telomere attrition, oxidative stress, cellular senescence, and autophagic dysregulation orchestrate this degenerative cascade. This review systematically delineates the dynamic interplay network of these pathways during ocular aging, with particular emphasis on four pivotal mechanisms: oxidative stress-driven reactive oxygen species (ROS) accumulation, senescence-associated secretory phenotype (SASP)-mediated inflammatory cascades, autophagic flux dysfunction, and epigenetic remodeling aberrations. We further evaluate recent advancements in translational therapies, emphasizing the clinical potential of targeted gene-editing technologies, stem cell-derived regenerative approaches, and novel senolytic agents. Additionally, artificial intelligence (AI) -assisted diagnostics are explored as pivotal tools for precision medicine, particularly in early disease detection via retinal imaging and biomarker analysis. Future research priorities should focus on the integration of aging-specific biomarkers including methylation signatures, the advancement of tissue-selective drug delivery systems tailored to anterior and posterior ocular compartments. Collectively, these initiatives will propel the development of targeted interventions to address age-related visual decline, positioning precision medicine as the cornerstone of next-generation geriatric ophthalmic care.}, }
@article {pmid42081293, year = {2026}, author = {Procyk, CA and Melati, A and Tariq, M and Liu, J and Branch, MJ and Delicata, JD and Harding, P and Khazim, M and Moshtagh Khorasani, M and Ladino, B and Lanning, EP and Margari, M and Mahamoud, I and Mofidi, C and Kumar, KN and Van Heerden, S and Smith, AJ and West, EL and Ali, RR and Pearson, RA}, title = {Transplantation of human stem cell-derived cone photoreceptors partially restores vision in aged rd1 mice with advanced retinal degeneration.}, journal = {Stem cells (Dayton, Ohio)}, volume = {}, number = {}, pages = {}, doi = {10.1093/stmcls/sxag023}, pmid = {42081293}, issn = {1549-4918}, abstract = {Targeted photoreceptor replacement therapy is a promising, potentially disease-agnostic approach for reversing sight-loss associated with advanced retinal degenerations, including age-related macular degeneration. We have previously shown that transplantation of human stem cell-derived cone photoreceptors (hCones) into young adult (3-month-old) mouse models of advanced retinal degeneration can restore retinal function. However, substantial remodeling of the remaining inner retinal circuitry continues long after complete photoreceptor loss, raising the critical question of whether photoreceptor transplantation can effectively rescue function at very late-stage degeneration. rd1 mice received transplants at 12-15 months of age and were examined ∼3 months later. Transplanted hCones survived in large numbers, while host inner retinal neurons exhibited significant plasticity, extending dendrites to transplanted hCones, and making synapse-like contacts. Host Müller glia undergo notable remodeling, apparently incorporating the donor cells within the retinal structure. Multielectrode array recordings showed robust rescue of light-evoked activity across the normal photopic range intensities and evidence of inner retinal processing, while some treated mice showed improvements in visually-evoked optokinetic head tracking behavior. Together, these data indicate that effective rescue following photoreceptor replacement therapy is feasible long after complete photoreceptor loss and extensive inner retinal remodeling.}, }
@article {pmid42082070, year = {2026}, author = {Tran, J and Chhablani, J}, title = {Unsuccessful Clinical Trials in Retina: Lessons Learned.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.04.028}, pmid = {42082070}, issn = {1879-1891}, abstract = {OBJECTIVE: To analyze patterns of non-success in phase 2 and 3 interventional retinal clinical trials conducted in the United States between 2015 and 2025.<br><br>DESIGN: Perspective based on retrospective analysis of unsuccessful clinical trials.<br><br>METHODS: Unsuccessful trials that were terminated, withdrawn, or completed without meeting primary endpoints were evaluated across indications, trial phases, intervention classes, and mechanisms of action to identify recurring design, feasibility, and operational challenges.<br><br>RESULTS: High attrition rates were observed across diabetic macular edema, diabetic retinopathy, neovascular age-related macular degeneration, and geographic atrophy. Phase 2 trials were more frequently discontinued following interim analyses, whereas phase 3 trials more often failed to meet primary efficacy endpoints. Later-phase studies were associated with increased sample size, geographic dispersion, follow-up duration, and assessment burden. Differences in endpoint selection, comparator choice, and population heterogeneity may contribute to attenuation of treatment effects. Operational and sponsor-level factors, including strategic and financial considerations, were also associated with trial discontinuation.<br><br>CONCLUSION: Translating early-stage findings into successful late-phase outcomes remains challenging in retinal drug development. Improved alignment of biological rationale, endpoint selection, and operational feasibility may enhance trial success.}, }
@article {pmid42082131, year = {2026}, author = {Duo, L and Cheng, P and Jiang, W and Lin, Q}, title = {Free-standing chondroitin sulfate/collagen multilayered films as preliminary Bruch's membrane-mimetic platform for retinal pigment epithelial cell culture.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {152359}, doi = {10.1016/j.ijbiomac.2026.152359}, pmid = {42082131}, issn = {1879-0003}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness, primarily associated with retinal pigment epithelial (RPE) cell degeneration. Although RPE cell therapy has emerged as a promising strategy for AMD, maintaining RPE cell attachment, organization, and functional characteristics remains a major challenge. In this study, free-standing chondroitin sulfate (CS)/collagen (Col) multilayered films were fabricated via spin-coating-assisted layer-by-layer (LbL) assembly and evaluated in vitro as preliminary Bruch's membrane (BM)-mimetic platform for supporting RPE growth and preserving cellular functionality. Genipin cross-linking improved the mechanical stability of the films and reduced their swelling behavior. ARPE-19 cells cultured on the 2 h cross-linked films showed improved attachment and proliferation compared with uncross-linked films, together with detectable RPE65 expression and several RPE-related functional features, including apical-basal differences in pigment epithelium-derived factor (PEDF) secretion, phagocytosis of labeled photoreceptor outer segments (POS), and formation of microvilli-like structures. Collectively, these findings suggest that CS/Col free-standing films can support ARPE-19 cell growth and maintain several RPE-related phenotypic and functional features in vitro, providing a preliminary BM-mimetic platform for future RPE culture studies.}, }
@article {pmid42082322, year = {2026}, author = {Kortuem, KU and Zarranz-Ventura, J and Bandello, F and Duval, R and O'Toole, L and De Zanet, S and Blair, JPM and Seaman, J and Zvolanek, M and Jaeger, K and Gmeiner, B and Holz, FG}, title = {Impact of AI-enhanced three-dimensional OCT scans on disease activity assessment in patients with nAMD: the RAZORBILL study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2024-327060}, pmid = {42082322}, issn = {1468-2079}, abstract = {BACKGROUND: The standard of care for neovascular age-related macular degeneration (nAMD) is repeated intravitreal injection with anti-vascular endothelial growth factor agents. Real world evidence suggests that some patients are undertreated, which might be linked with the retreatment decisions made by physicians. Therefore, this multicentre observational study aimed to investigate the extent to which enrichment of optical coherence tomography (OCT) images with segmentation information could influence and support disease activity assessment (DAA) in patients treated for nAMD.<br><br>METHODS: Descriptive statistics were tabulated for the demographic and clinical characteristics and outcome variables. To assess the influence of automated OCT image enrichment with segmentation information on DAA, a generalised linear mixed model was employed. The degree of agreement in classification of disease activity across reviewers was assessed by Krippendorff's alpha.<br><br>RESULTS: The odds estimate for DAA regarding enriched OCT images was 0.759 and for non-enriched OCT images 0.772. The OR for enriched versus non-enriched OCT images was 1.078 with a p value of 0.229. No difference in the odds of DAA between automated OCT image enrichment with segmentation and DAA was noted. Krippendorff's alpha coefficient was 0.416 for enriched and 0.402 for non-enriched OCT images. Thus, the inter-reviewer reliability/agreement was similarly low between enriched and non-enriched OCT images.<br><br>CONCLUSIONS: OCT image enrichment did not appear to impact the likelihood of adequately detecting disease activity, nor did it have an impact on agreement between reviewers of images in this study. No new safety signals in products involved in the study were detected.<br><br>TRIAL REGISTRATION NUMBER: NCT04662944.}, }
@article {pmid42066985, year = {2026}, author = {Cui, X and Zhao, Q and Yuan, J and Yu-Wai-Man, P}, title = {Integrated plasma proteomics and metabolomics reveal immunometabolic pathways and predictive signatures for age-related eye diseases.}, journal = {Metabolism: clinical and experimental}, volume = {180}, number = {}, pages = {156624}, doi = {10.1016/j.metabol.2026.156624}, pmid = {42066985}, issn = {1532-8600}, abstract = {BACKGROUND AND AIMS: Age-related eye diseases (AREDs) share aging as a major risk factor, but the systemic molecular changes preceding disease onset remain incompletely understood. We aimed to define the shared and disease-specific immunometabolic architecture of major AREDs and to examine how circulating molecular features relate to retinal phenotypes, pre-diagnostic patterns, and disease risk.<br><br>METHODS: We performed a large-scale prospective multi-omics study in the UK Biobank integrating baseline plasma proteomics, metabolomics, retinal imaging-derived phenotypes, and longitudinal follow-up across five major AREDs: age-related macular degeneration, cataract, diabetic retinopathy, glaucoma, and retinal vascular occlusion. Cox regression, functional enrichment, protein-metabolite correlation, mediation analysis, trajectory analysis, and machine-learning models were applied.<br><br>RESULTS: Proteome-wide analyses identified both shared and disease-specific circulating signatures, mainly involving immune, extracellular matrix, vascular, and stress-response pathways. Reconstructed population-level molecular patterns diverged from controls up to 15&#xa0;years before diagnosis, with marked heterogeneity across diseases. Integration with retinal imaging linked immune- and matrix-related proteins to retinal neurodegenerative and microvascular phenotypes. Metabolite clustering and mediation analyses highlighted recurrent lipoprotein-related pathways, particularly HDL-related structure and composition, as cross-layer features associated with systemic protein signals, metabolic states, and disease risk. Combined proteomic-metabolomic models improved prediction of incident disease compared with protein-only models.<br><br>CONCLUSIONS: Major AREDs share a systemic immunometabolic aging architecture while retaining substantial disease-specific molecular features. Circulating molecular alterations are detectable years before clinical onset and may support future biological stratification and risk prediction.}, }
@article {pmid42067026, year = {2026}, author = {González Escobar, AB and Baquero Aranda, IM and Valera Ávila, JC and Barco Moreno, E and Galván Cano, JM and Luque Aranda, R}, title = {Bilateral peripheral exudative hemorrhagic chorioretinopathy treated with intravitreal injections of ranibizumab.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502539}, doi = {10.1016/j.oftale.2026.502539}, pmid = {42067026}, issn = {2173-5794}, abstract = {Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a rare entity consisting of lesions similar to those of age-related macular degeneration (AMD) and type 1 aneurysmal neovascularization (N1a), but located outside the macular region in the peripheral retina. We present the case of an 89-year-old woman who presented to the emergency department with loss of visual acuity (VA) in both eyes (OU) due to a massive macular subretinal hemorrhage in the right eye (OD) and a vitreous hemorrhage in her left eye (OS), accompanied in both eyes by peripheral hemorrhagic retinal pigment epithelium detachments (HPED). Ophthalmological examination and multimodal imaging led to the diagnosis of PEHCR. This case highlights the importance of the differential diagnosis of PEHCR from other vascular and neoplastic pathologies in order to avoid unnecessary tests and treatments. Early recognition and diagnosis are essential for establishing appropriate management, with intravitreal injections of anti-vascular endotelial groth factors (anti-VEGF) being recommended in cases with loss of VA or threat thereof. This case also contributes to the limited published literature on bilateral PEHCR, reinforcing the need to consider this pathology in elderly patients with peripheral hemorrhagic lesions.}, }
@article {pmid42068401, year = {2026}, author = {Kaplan, E and Segal, O and Moisseiev, E and Allon, G}, title = {Switch to faricimab in various retinal diseases: real-world data.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {42068401}, issn = {1573-2630}, mesh = {Humans ; Male ; Female ; Intravitreal Injections ; *Retinal Diseases/drug therapy/diagnosis ; Aged ; Retrospective Studies ; *Visual Acuity ; Middle Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence ; Treatment Outcome ; Fluorescein Angiography ; *Drug Substitution ; Aged, 80 and over ; Fundus Oculi ; Follow-Up Studies ; Antibodies, Bispecific ; }, abstract = {OBJECTIVE: To evaluate the efficacy of faricimab in various retinal conditions in previously treated patients.<br><br>METHODS: This study included patients who received at least three faricimab injections at a large medical center between April 2023 and October 2024, all of whom were not naive to treatment.<br><br>RESULTS: A total of 242 eyes from 219 patients were included in the analysis. The diagnoses were: 139 eyes with neovascular age-related macular degeneration (NVAMD), 63 eyes with diabetic macular edema (DME), 24 eyes with polypoidal choroidal vasculopathy (PCV), 5 eyes with choroidal neovascularization (CNV) secondary to central serous retinopathy (CSR), 5 eyes with branch retinal vein occlusion (BRVO) accompanied by cystoid macular edema (CME), 3 eyes with central retinal vein occlusion (CRVO) with CME, and 3 eyes with myopic CNV. Patients had previously received intravitreal injections of medications including bevacizumab, ranibizumab, aflibercept 2&#xa0;mg, brolucizumab, triamcinolone, and Ozurdex. Following treatment with faricimab, the proportion of eyes with no intraretinal or subretinal fluid increased across all retinal diseases. Additionally, the average central subfield thickness decreased, the interval between injections was extended, and average visual acuity improved in every retinal condition. The average height of the pigment epithelium detachment (PED) decreased in cases of NVAMD and PCV.<br><br>CONCLUSIONS: Faricimab appears to be effective after the failure of other treatment options.}, }
@article {pmid42068868, year = {2026}, author = {Hammond, BR and Buch, J}, title = {The evidentiary basis and challenges associated with studying the role of light damage on ocular health.}, journal = {Journal of optometry}, volume = {19}, number = {3}, pages = {100616}, doi = {10.1016/j.optom.2026.100616}, pmid = {42068868}, issn = {1989-1342}, abstract = {The interaction between light and the eye is both essential and potentially harmful. Light regulates ocular development, supports vision, and influences systemic physiology, yet it can also induce photochemical damage. Determining whether chronic exposure to high-energy visible (HEV) light contributes to age-related ocular disease remains challenging. Randomized clinical trials, the gold standard for medical evidence, are largely infeasible for exposures that are lifelong, ubiquitous, and potentially harmful. Instead, researchers rely on a spectrum of evidence, from cellular and animal models to case studies, cohort studies, and expert consensus, each with unique advantages and limitations. This review categorizes existing evidence according to study design, evaluates its strengths and weaknesses, and considers how converging findings might inform clinical practice. We conclude that while acute light injury is well established, the long-term impact of low-level HEV exposure remains largely and necessarily inferential. Definitive evidence is difficult to obtain but improvements in exposure assessment and integration across different categories of evidence have led to a cautious but reasonable conclusion on the potential harms of long-term exposure.}, }
@article {pmid42069034, year = {2026}, author = {Hekimsoy, HK and Şekeroğlu, MA and Ateşoğlu, H&#x130; and Doğuizi, S}, title = {The Foveal Microvasculature of Adult Offspring of Patients with Neovascular Age-Related Macular Degeneration.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {}, number = {}, pages = {105497}, doi = {10.1016/j.pdpdt.2026.105497}, pmid = {42069034}, issn = {1873-1597}, abstract = {AIM: To assess the foveal microvasculature in adult offspring of patients with neovascular age-related macular degeneration (nAMD) who exhibit no clinical or imaging signs of AMD, and to compare these parameters with those of healthy controls without a family history of AMD.<br><br>METHODS: This cross-sectional study included 82 adult offspring of patients with nAMD and 85 age- and sex-matched controls. Optical coherence tomography angiography (OCTA) was used to evaluate vessel densities of the superficial and deep capillary plexuses (SCP and DCP), the foveal avascular zone (FAZ), outer retinal flow, and choriocapillaris (CCP) flow area.<br><br>RESULTS: There were no significant differences in demographic or visual parameters between groups, nor in FAZ area, perimeter, or acircularity index. However, vessel densities in all SCP and DCP zones, as well as outer retinal and CCP flow areas, were significantly reduced in the nAMD offspring group (all p < 0.05).<br><br>CONCLUSION: Subclinical microvascular alterations in SCP, DCP, and CCP were identified in clinically unaffected adult offspring of patients with nAMD. These findings suggest a potential heritable vascular component in early AMD pathogenesis and support the use of OCTA as a tool for risk stratification.}, }
@article {pmid42062331, year = {2026}, author = {Zhong, L and Liu, S and Lu, W and Wu, Q and Lv, Y and Yi, S and Wang, X and Wu, Z and Yan, J}, title = {Assessment of quality, reliability, and interactive characteristics of age-related macular degeneration short videos on TikTok: a cross-sectional study.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-44509-1}, pmid = {42062331}, issn = {2045-2322}, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. Short-video platforms like TikTok are increasingly important sources of health information, yet concerns persist regarding content quality and reliability. To systematically evaluate the quality, reliability, and user engagement characteristics of AMD-related videos on TikTok. We systematically searched TikTok for AMD-related videos. Quality and reliability were assessed using JAMA benchmark, modified DISCERN, Global Quality Scale (GQS), and Patient Education Materials Assessment Tool (PEMAT). Entropy weight method and cluster analysis were applied to engagement data. Among 145 videos, overall quality was poor. Median scores were 1 for JAMA, 2 for mDISCERN, and 3 for GQS. Understandability was limited (median PEMAT-U: 43%), while actionability was moderate (median PEMAT-A: 60%). High-quality videos were characterized by creation by Western medicine ophthalmologists, inclusion of prognostic information, and monologue narration; physician title showed no association with quality. "Saves" carried the highest engagement weight (35.71%). "Self-test and screening" themes achieved the highest engagement rate (62.5%). Media accounts attained the highest PEMAT-U scores and interaction metrics. Video format and presenter attire showed no significant impact on quality or engagement. AMD-related health information on TikTok is generally poor quality. Information quality and user engagement are driven by distinct factors, highlighting the need for targeted strategies to improve content accuracy and understandability.}, }
@article {pmid42063159, year = {2026}, author = {Yuan, XL and Hughes, D and Cui, X and Zhou, R and Qi, J and Yi, C and Liu, J and McFetridge, S and Silva, JD and Naderi-Meshkin, H and Krasnodembskaya, AD and Xu, H and Chen, M}, title = {MSC-EVs attenuate subretinal fibrosis in choroidal neovascularization through miR-21-5p-mediated inhibition of EMT and MMT and suppression of inflammation.}, journal = {Journal of neuroinflammation}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12974-026-03836-w}, pmid = {42063159}, issn = {1742-2094}, support = {AIM2301D02//Science Research Foundation of Aier Eye Hospital Group/ ; KY24002//Philanthropy Foundation of Xiangjiang Public Welfare Fund/ ; 2023JJ70047//Hunan Provincial Natural Science Fund/ ; }, abstract = {BACKGROUND: Subretinal fibrosis causes irreversible vision loss in neovascular age-related macular degeneration (nAMD). Sustained macular inflammation drives the initiation and progression of fibrosis by activating profibrotic cells and perpetuating tissue damage. This study investigated the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in mitigating nAMD-associated subretinal fibrosis.<br><br>METHODS: MSC-EVs were prepared from human bone marrow-derived MSCs and characterized using nanoparticle tracking analysis, transmission electron microscopy, and Western Blotting. Subretinal fibrosis was induced in C57BL/6J mice using the two-stage laser-induced model. MSC-EVs were injected either intravitreally (1&#x2009;&#xd7;&#x2009;10[8] particles/eye, single injection) or retro-orbitally (1&#x2009;&#xd7;&#x2009;10[8] particles, two injections four days apart) immediately after the second laser. Eyes were collected 10 days post-second laser for immunostaining of collagen-1 and CD31 or iso-lectin B4. In vitro, primary human RPE and ARPE-19 cells were treated with TGF-&#x3b2;2 (10 ng/mL) to induce epithelial-mesenchymal transition (EMT); peritoneal macrophages were treated with TGF-&#x3b2;1 (10 ng/mL) to induce macrophage-to-myofibroblast transition (MMT). After 48&#xa0;h, cells were treated with MSC-EVs (cell-to-MSC-EV ratio&#x2009;=&#x2009;1:2000) for 3 days. Myofibroblast markers (&#x3b1;SMA, fibronectin, and collagen-1) were examined by immunocytochemistry and quantitative PCR (qPCR). Human iPCS-derived macrophages (iMACs), bone-marrow-derived macrophages, peritoneal macrophages, and BV2 microglia were treated with LPS (100 ng/mL) and IFN-&#x3b3; (20 ng/mL) for 24&#xa0;h with or without MSC-EVs (1:2000). Small RNA sequencing was used to identify specific functional molecules within MSC-EVs. Immune-related gene expressions were evaluated by qPCR.<br><br>RESULTS: Intravitreal and retroorbital administration of MSC-EVs reduced collagen-1[+] fibrotic lesions by 46% and 30%, respectively, and significantly inhibited infiltrating Iba-1[+] cells. In vitro, MSC-EVs attenuated TGF-&#x3b2;2-induced upregulation of &#x3b1;SMA, fibronectin, and collagen-1 at both protein and mRNA levels in RPE cells. Similarly, the expression of Acta2, Fn1, and Col1a1 in TGF-&#x3b2;1-treated macrophages was also significantly reduced following MSC-EV treatment. In LPS&#x2009;+&#x2009;IFN-&#x3b3;-stimulated immune cells, MSC-EVs significantly suppressed the expression of Il6 and Il1b in all cell types, and reduced the expression of Inos, Tnfa, and Cd86 in iMACs, peritoneal macrophages, and BV2 cells. Enriched hsa-miR-21-5p was identified in MSC-EVs and involved in the TGF-&#x3b2;-related signaling pathway. Overexpression of miR-21-5p mimic abrogated the TGF-&#x3b2;1-driven upregulation of pro-fibrotic markers in RPE and macrophages.<br><br>CONCLUSIONS: Local administration of MSC-EVs effectively mitigated subretinal fibrosis and reduced inflammation in the mouse model of nAMD, potentially via miR-21-5p-mediated attenuation of EMT and MMT, and suppression of inflammation. MSC-EVs represent a novel cell-free therapeutic strategy for macular fibrosis in nAMD.}, }
@article {pmid42063162, year = {2026}, author = {Huang, M and Lin, Y and Zhang, H and Yuan, R and Zeng, L and Li, S and Yang, Q and Gong, M and Xiao, R and Jia, P and Yuan, L and Guo, Q and Han, Z and Xie, L}, title = {The role of autophagy in ocular health: mechanisms, pathologies, and therapeutic strategies.}, journal = {Biology direct}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13062-026-00821-4}, pmid = {42063162}, issn = {1745-6150}, abstract = {Autophagy is a self-digestive process in which cellular components are degraded and recycled to maintain homeostasis and cope with stress. When cells are in a state of stress, autophagy will degrade proteins, lipids and damaged organelles, and convert them into key nutrients and building cornerstones needed to maintain cell homeosis. More and more evidence shows that there is a link between autophagy process damage and the development of a variety of ophthalmic diseases that seriously threaten vision, including age-related macular degeneration, glaucoma and the formation of cataracts. Through a systematic review, we integrate experimental data covering basic biological mechanisms, genetic models and clinical evidence to clarify these pathological associations. With a focus on the mechanisms and regulation of autophagy in various ocular tissues and diseases, we analyzed research on autophagy in the lens, retina, cornea, and trabecular meshwork. Key findings elucidate the specific mechanisms of autophagy in maintaining lens transparency, promoting retinal ganglion cell survival, and regulating ocular immunity, demonstrating its critical role in preserving cellular equilibrium in ocular tissues. Furthermore, we evaluated potential therapeutic strategies targeting autophagic pathways, including mammalian target of rapamycin (mTOR) inhibition, transcription factor EB(TFEB) activation, noncoding RNA regulation, gene editing, and artificial intelligence-assisted diagnostics, which show significant promise for modulating autophagy to treat ocular diseases. The results of this review underscore the importance of autophagy in ocular health and disease.}, }
@article {pmid42063165, year = {2026}, author = {Ruiz-Medrano, J and Su, A and Mao, Z and Akiba, M and Ruiz-Moreno, JM}, title = {Exploratory study on a novel automatic quantification software by artificial intelligence for geographic atrophy associated to age-related macular degeneration.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00862-x}, pmid = {42063165}, issn = {2056-9920}, }
@article {pmid42064470, year = {2026}, author = {Afridi, R and Senaldi, G and Hwang, JJ and Nguyen, N and Inoue, T and Berger, B and Patel, S and Fazal, ZZ and Nguyen, QD and Sepah, Y}, title = {Assessing the Safety and Efficacy of Agonistic Monoclonal Antibody against Robo4 versus Ranibizumab in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Phase I, Open-Label, Multicenter Study.}, journal = {Ophthalmology science}, volume = {6}, number = {5}, pages = {101084}, pmid = {42064470}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the safety and efficacy of agonistic monoclonal antibody against roundabout receptor 4 (DS-7080a) in eyes with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) alone or in combination with ranibizumab.<br><br>DESIGN: This was a phase I dose escalation and expansion study registered on clinicaltrials.gov (NCT02530918) and conducted in 3 parts. Parts 1 (first phase of the study [P1]) and 2 (second phase of the study [P2]) involved dose escalation and expansion for patients with nAMD, while part 3 (third phase of the study [P3]) involved dose expansion only for DME subjects.<br><br>SUBJECTS: Patients with nAMD or DME.<br><br>METHODS: In P1, eligible patients were randomized into 3 sequential dose-level cohorts to establish a maximum tolerated dose for DS-7080a as 4.0 mg and assess its safety and tolerability. The study then proceeded to P2, where 27 nAMD subjects were randomized to one of the 3 treatment arms: DS-7080a, 4.0 mg only; ranibizumab, 0.5 mg only; or DS-7080a, 4.0 mg plus ranibizumab, 0.5 mg. In P3, 20 subjects with DME were randomized to one of the 2 arms: DS-7080a, 4.0 mg or ranibizumab, 0.3 mg injected thrice. The treatment period was 12 weeks.<br><br>MAIN OUTCOME OUTCOMES: The primary endpoints were treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). The secondary endpoints were changes in central retinal thickness (central subfield thickness [CST]) and best-corrected visual acuity (BCVA).<br><br>RESULTS: A total of 56 patients were enrolled. Agonistic monoclonal antibody against Robo4, administered as monotherapy or in combination with ranibizumab, was generally well tolerated. Six drug-related TEAEs were observed, 4 of which were ocular events that led to treatment discontinuation. No drug-related SAEs or deaths occurred. As expected, ranibizumab was associated with improvements in BCVA and CST, whereas DS-7080a, alone or in combination, did not show clinically meaningful functional or anatomical benefit.<br><br>CONCLUSIONS: Agonistic monoclonal antibody against Robo4 was generally well tolerated in eyes with nAMD and DME; however, drug-related TEAEs, including ocular events leading to discontinuation, were observed. In terms of efficacy outcomes, DS-7080a does not show BCVA improvement and CST decrease when administered alone or in conjunction with ranibizumab. These findings are inconsistent with nonclinical studies supporting DS-7080a as a therapeutic agent for nAMD and DME.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42058402, year = {2026}, author = {Ameli, S and Ní Dhubhghaill, S and Vidal-Aroca, F and Fasolino, G}, title = {Surgical repositioning of a SING IMT following haptic dislocation: Restoration of alignment and visual function.}, journal = {American journal of ophthalmology case reports}, volume = {42}, number = {}, pages = {102583}, pmid = {42058402}, issn = {2451-9936}, abstract = {PURPOSE: The Smaller-Incision New-Generation Implantable Miniature Telescope (SING IMT) is an IOL designed to enhance central vision in patients with bilateral late-stage AMD. This report describes a case of successful surgical repositioning of a tilted SING IMT following haptic displacement out of the capsular bag.<br><br>OBSERVATIONS: A 77-year-old man with bilateral geographic atrophy and baseline CDVA (Corrected Distance Visual Acuity) of logMAR 0.96 (Snellen 20/200) underwent uncomplicated implantation of a SING IMT in the right eye. Six weeks postoperatively, CDVA showed no improvement, and the patient reported monocular diplopia with off-axis visual perception. Retinal morphology remained stable. Slit-lamp and anterior segment OCT revealed pronounced optic tilt caused by inferior haptic dislocation out of the capsular bag. The haptic was successfully repositioned by performing superior traction with a push-pull hook, resulting in restoration of straight, diplopia-free vision and an improvement in CDVA to logMAR 0.52 (Snellen 20/63).<br><br>CONCLUSIONS AND IMPORTANCE: Prompt surgical correction of haptic displacement may fully restore the optical and functional benefits of the SING IMT without compromising corneal health.}, }
@article {pmid42058595, year = {2026}, author = {Bettelheim, EC and Liu, J and Dazzan, P and Turkheimer, F}, title = {Self images: an empirical enquiry into Rembrandt's self-portraits.}, journal = {Frontiers in psychiatry}, volume = {17}, number = {}, pages = {1631373}, pmid = {42058595}, issn = {1664-0640}, abstract = {Many have speculated that events of personal and financial loss in the life of Rembrandt van Rijn (Rembrandt) caused depression and that this is revealed by examination of his work particularly self-portraits painted in old age. Some report detecting various physiological diseases associated with aging, including vision impairment, which may have affected his mood and work. Aging and neurodegenerative disease which often accompanies it, are both associated with depression. Depression is characterised by visual deficits including perception of reduced contrast and colour. Age-related neurological disorders are associated in artists with reduced complexity. Recent advances in imaging and computer technology make it possible to empirically examine changes in artistic style which can contribute to understanding artists' physical and mental health. Previous studies have identified associations between adverse events in artists' lives and altered contrast and colour in their self-portraits. In the current study changes in contrast, colour and fractal dimension were measured in the entire corpus of Rembrandt's painted self-portraits and portraits to determine whether changes in style indicate depression, cognitive decline, or neurological disease and whether differences in style can be detected between self-portraits and portraits of related and unrelated others. Productivity was also examined as an indirect indicator. The results suggest that it is unlikely that Rembrandt suffered from unipolar or bipolar depression, age-related cognitive decline, or neurodegenerative disease. The data are consistent with someone experiencing episodes of low mood associated with normal grieving and adversity followed by resilient recovery. There is evidence of a gradient in saliency and complexity between self-portraits and related and unrelated portraits and of a 'late' style identified by leading art historians consistent with macular degeneration.}, }
@article {pmid42059115, year = {2026}, author = {Song, SJ and Kim, E}, title = {Glucagon-Like Peptide-1 Receptor Agonists and Ocular Outcomes: Metabolic Transition, Retinal Vulnerability, and Risk-Stratified Monitoring.}, journal = {Journal of obesity &amp; metabolic syndrome}, volume = {35}, number = {2}, pages = {164-175}, doi = {10.7570/jomes26012}, pmid = {42059115}, issn = {2508-7576}, abstract = {Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual incretin-based therapies provide marked reductions in glycosylated hemoglobin (HbA1c), body weight, and cardiovascular risk. As global adoption expands and recognition of their broad metabolic benefits grows, clinical attention is shifting toward potential secondary complications, including ocular manifestations, during rapid metabolic improvement. This narrative review synthesizes evidence from randomized trials, meta-analyses, and observational studies up to 2026 to evaluate the effects of GLP-1-based therapies on various ocular outcomes. Recent meta-analyses demonstrate an overall neutral long-term risk for diabetic retinopathy (DR) and macular edema. Transient early worsening of DR occurs primarily in patients with advanced baseline disease and rapid HbA1c reductions, reflecting a metabolic transition phenomenon rather than intrinsic retinal toxicity. This interpretation is supported by 2024 cardiovascular outcome data in a non-diabetic population (e.g., Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity [SELECT] trial) that showed no increased ocular risk. Observational data suggest protective associations with glaucoma via intraocular pressure-independent neuroprotection and a reduced risk of incident age-related macular degeneration, but a potential safety signal for nonarteritic anterior ischemic optic neuropathy has emerged in recent datasets. Although the absolute incidence remains low, risk with a delayed temporal pattern appears to be increased in specific cohorts. Emerging evidence also suggests potential benefits in ocular surface homeostasis and uveitis. Accordingly, following a 2025 multidisciplinary expert consensus, risk-stratified ophthalmic monitoring, rather than routine treatment avoidance, is recommended during the early metabolic transition in high-risk diabetic patients.}, }
@article {pmid42059902, year = {2026}, author = {Vahldiek, B and Heine, L and Vahldiek, A and Schröter, J and Wolf, JN and Swora, M and Reissberg, L and Pauleikhoff, L and Kleesiek, J and Pauleikhoff, D}, title = {Choroidal vascularity across aging and the spectrum of age-related macular degeneration: an AI-based OCT study.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42059902}, issn = {1435-702X}, abstract = {PURPOSE: To characterize the choroidal morphology across a spectrum of participants affected by normal aging as well as age-related macular degeneration (AMD) using various metrics.<br><br>METHODS: Four cohorts were analyzed: healthy young (n&#x2009;=&#x2009;42), healthy elderly (n&#x2009;=&#x2009;19), iAMD (n&#x2009;=&#x2009;20), and treatment-naive nAMD eyes (n&#x2009;=&#x2009;79). Quantification of choroidal volume (CV) and choroidal vessel volume (VV) resulting in choroidal vascularity index (CVI) as well as mean choroidal thickness (CT), vessel thickness (VT) and foveal vessel area (FVA) and vessel count (FVC) were derived from spectral-domain optical coherence tomography using an artificial intelligence (AI)-based semantic segmentation model with manual validation. Cohort differences were statistically assessed.<br><br>RESULTS: All choroidal parameters were reduced in healthy elderly, iAMD and nAMD eyes compared with young controls. While most of these reduced choroidal measurements were largely similar between healthy elderly, iAMD and nAMD eyes, only CVI and FVA showed a specific reduction in nAMD eyes.<br><br>CONCLUSIONS: This study demonstrates a decline in several choroidal parameters with age, which can be quantified using AI-based segmentations. While age-related reductions were comparable between elderly and iAMD eyes, a significantly higher reduction of the CVI and FVA was observed in eyes with nAMD which may indicate a more pronounced alteration of choroidal structure in this condition.}, }
@article {pmid42060220, year = {2024}, author = {Kim, BS and Choi, RY and Kweon, H and Lee, JH and Kim, IW and Seo, M}, title = {Oxya chinensis sinuosa (OC) Extracts Protects ARPE-19 Cells against Oxidative Stress via Activation of the Mitogen-Activated Protein Kinases (MAPKs)/ Nuclear Factor-κB (NF-κB) Pathway.}, journal = {Food science of animal resources}, volume = {44}, number = {3}, pages = {699-709}, doi = {10.5851/kosfa.2024.e15}, pmid = {42060220}, issn = {2636-0780}, abstract = {Oxya chinensis sinuosa (OC) is a well-known edible insect. Several researches on the health benefits of OC consumption have been performed to date; however, their effect on eye health remains largely unknown. This study aimed to assess the protective effects of OC extracts on the oxidative stress on the retinal pigment epithelium (RPE) cells. Oxidative damage has been identified as one of the key regulatory factors in age-related macular degeneration. H2O2-induced reactive oxygen species (ROS) production, a well-known oxidative stress factor, can cause cell death in retinal pigment epithelia cells. In this study, we found that three OC extracts effectively prevented H2O2-induced ROS production and subsequent death of ARPE-19 cells in a dose-dependent manner. In addition, the OC extracts inhibited the phosphorylation of mitogen-activated protein kinases including p38, JNK, and ERK. The OC extracts restored IκBα degradation induced by H2O2, indicating that OC extracts suppressed the activation of nuclear factor-κB. Furthermore, the three OC extracts were shown to have antioxidant effects by up-regulating the intracellular expression of key antioxidant proteins such as SOD, NQO, and HO-1. Here we demonstrated the antioxidant and anti-apoptotic effects of the OC extracts on ARPE-19, indicating their potential role in improving eye health. These results suggest that three OC extracts plays a critical role in oxidative stress-induced cell death protects in ARPE-19 cells.}, }
@article {pmid42060349, year = {2026}, author = {Verma, L and Singh, S and Ramachandran, O}, title = {Peep into anti-vascular endothelial growth factor.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {5}, pages = {635-638}, doi = {10.4103/IJO.IJO_385_26}, pmid = {42060349}, issn = {1998-3689}, mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Receptors, Vascular Endothelial Growth Factor ; Ranibizumab/therapeutic use ; }, abstract = {Anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed the management of retinal vascular diseases over the past two decades. Beginning with the foundational identification of VEGF as the principal driver of ocular neovascularization, the field has evolved from early agents such as pegaptanib and bevacizumab to more potent molecules including ranibizumab, aflibercept, brolucizumab, and faricimab. In India, the landscape is shaped by unique economic and epidemiological factors, including a high burden of diabetic retinopathy and age-related macular degeneration, limited healthcare reimbursement, and the significant role of biosimilar ranibizumab products in expanding access. This article provides a comprehensive overview of the historical development, pharmacology, regulatory milestones, safety considerations, and current clinical use of anti-VEGF agents in the Indian context, with emphasis on strategies to deliver equitable, high quality retinal care across a diverse population.}, }
@article {pmid42060351, year = {2026}, author = {Sharma, D and Gupta, T}, title = {Anti-vascular endothelial growth factor therapy in clinical practice: Real-world scenarios, limitations, and outcomes.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {5}, pages = {643-652}, doi = {10.4103/IJO.IJO_185_26}, pmid = {42060351}, issn = {1998-3689}, mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; *Visual Acuity ; *Retinal Vein Occlusion/drug therapy ; *Macular Edema/drug therapy ; *Diabetic Retinopathy/drug therapy ; *Wet Macular Degeneration/drug therapy ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {This narrative review examines the "efficacy-effectiveness gap" in anti-vascular endothelial growth factor (anti-VEGF) therapy by comparing outcomes from randomized controlled trials (RCTs) with global and Indian real-world evidence (RWE) in neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Across all three conditions, real-world outcomes consistently fall short of those observed in RCTs. In nAMD, studies such as AURA report minimal visual gains by Year 2 (+0.6 letters) compared to +8 to +10 letters in RCTs, largely attributable to fewer injections administered in practice. Indian data, including the ARMOUR study, reflect similarly reduced injection frequencies alongside issues such as delayed presentation. For DME, global RWE demonstrates modest improvements in visual acuity with fewer injections per year than in RCTs, while Indian cohorts show even lower treatment intensity, resulting in anatomical stabilization without meaningful visual gains. Outcomes in RVO are also compromised by incomplete loading doses and inadequate follow-up. The primary drivers of this gap include undertreatment, variability in patient populations, and socioeconomic barriers that affect adherence and access to care. Overall, the discrepancy appears to stem more from real-world treatment challenges than from limitations of the therapies themselves. Addressing this gap will require practical approaches such as implementing Treat-and-Extend regimens, promoting earlier diagnosis and intervention, enhancing patient engagement, and increasing the use of cost-effective or longer-acting treatment options, particularly in resource-constrained settings like India.}, }
@article {pmid42060352, year = {2026}, author = {Singh, S and Kala, U and Bamel, A and Agarwal, M}, title = {Expanding horizons of intravitreal anti-vascular endothelial growth factor therapy in retinal diseases.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {5}, pages = {661-668}, doi = {10.4103/IJO.IJO_3035_25}, pmid = {42060352}, issn = {1998-3689}, mesh = {Humans ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Retinal Diseases/drug therapy/diagnosis ; }, abstract = {Vascular endothelial growth factor (VEGF) plays a central role in the pathogenesis of retinal and choroidal neovascularization, as well as macular edema (ME), in retinal disorders such as diabetic retinopathy, retinal vein occlusion (RVO), and age-related macular degeneration (ARMD). The advent of intravitreal anti-VEGF therapy has revolutionized their management. More recently, these agents have been explored in several other retinal pathologies characterized by secondary neovascularization, either in vascular or non-vascular disorders. This review summarizes current evidence on the role of anti-VEGF agents in retinal disorders other than ARMD, including central serous chorioretinopathy (CSCR), macular telangiectasia type 2 (MacTel), choroidal osteoma, retinopathy of prematurity (ROP), tubercular granuloma, inherited retinal dystrophies, Coats' disease, angioid streaks, and retinal vasoproliferative tumors (RVPTs).}, }
@article {pmid42061620, year = {2026}, author = {Zieneldien, T and Ma, S and Kim, J and Grant-Kels, JM}, title = {Dermatologic Care Amid Vision Loss: Preventing Harm While Preserving Autonomy.}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2026.04.1969}, pmid = {42061620}, issn = {1097-6787}, }
@article {pmid42050639, year = {2026}, author = {Rezende, MP and Faria, FA and Beraldo, DP and Polido, J and Belfort, R and Cabral, T}, title = {Correlations between SS-OCT and OCT angiography biomarkers in treatment-naïve neovascular AMD during aflibercept therapy: a prospective study.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00854-x}, pmid = {42050639}, issn = {2056-9920}, }
@article {pmid42050899, year = {2026}, author = {Sano, H and Yanai, R and Mitamura, Y}, title = {Hemolytic Glaucoma Following Intravitreal Aflibercept Injection for Age-Related Macular Degeneration: A Case Report.}, journal = {The American journal of case reports}, volume = {27}, number = {}, pages = {e952247}, doi = {10.12659/AJCR.952247}, pmid = {42050899}, issn = {1941-5923}, mesh = {Humans ; Male ; *Recombinant Fusion Proteins/adverse effects/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Middle Aged ; Intravitreal Injections/adverse effects ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; *Glaucoma/etiology/chemically induced ; *Macular Degeneration/drug therapy ; *Hemolysis ; }, abstract = {BACKGROUND Intraocular pressure (IOP) elevation secondary to intraocular hemorrhage after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection for age-related macular degeneration (AMD) is exceedingly rare. Although mild, transient hyphema has been reported, secondary glaucoma caused by hemolysis or ghost cell formation has not previously been documented in this setting. CASE REPORT A 54-year-old man presented with decreased vision and was diagnosed with exudative AMD in the right eye. Baseline evaluation showed subretinal hemorrhage and macular neovascularization, and intravitreal aflibercept injections were initiated and continued for 1 year. Three days after the tenth injection, the patient developed blurred vision, progressing to hand-motion vision by day 4. Slit-lamp examination revealed hyphema with a fluid level, and IOP increased to 50 mmHg despite conservative therapy. The patient underwent anterior chamber irrigation and phacoemulsification with pars plana vitrectomy. Intraoperatively, mild vitreous hemorrhage was observed, and temporal scleral indentation revealed a localized blood clot adherent to the pars plana and vitreous base at the injection site. Postoperatively, IOP normalized, without recurrence of vitreous hemorrhage or exudative activity during 1-year follow-up. CONCLUSIONS This case demonstrates that hemolytic glaucoma can develop even after intravitreal anti-VEGF injection in AMD, a context in which intraocular bleeding is uncommon. Clinicians should remain vigilant to postinjection IOP elevation, and timely surgical intervention can yield favorable visual and pressure outcomes.}, }
@article {pmid42051690, year = {2026}, author = {Reiter, RJ and Sharma, R and Blasiak, J and Rosales-Corral, S and Loh, D}, title = {Retinal pigment epithelium pathology in age-related macular degeneration: mitigation with melatonin.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1813015}, pmid = {42051690}, issn = {2296-858X}, abstract = {Approximately 1.5 million Americans over the age of 40 suffer from vision-threatening age-related macular degeneration (AMD), a number expected to rise with aging demographics. AMD exists in two defined forms: dry (non-exudative) which accounts for up to 90% of cases, and wet (exudative). Dry AMD is characterized by the slow buildup of drusen under the retina, eventually leading to geographical atrophy. Wet AMD involves vascular endothelial growth factor (VEGF)-induced blood vessel formation from the choriocapillaris into the subretinal space, a process referred to as neovascularization. These newly formed blood vessels leak fluid into the subretinal space leading to atrophy of the retinal pigment epithelium (RPE) and associated photoreceptors. Despite clinical distinctions, dry and wet AMD share overlapping pathophysiological features, marked by degeneration of the RPE and the overlying photoreceptors. A major feature of the RPE and photoreceptors are their high metabolically activity and their large numbers of mitochondria, which generate reactive oxygen species (ROS) during ATP production. ROS-induced oxidative stress damages lipids, proteins and DNA, resulting in cellular degradation which contributes to AMD. Because of the elevated oxidative stress levels, antioxidants which neutralize ROS are often recommended as a treatment for AMD. A major objective of this review is to examine the role of melatonin, a powerful and multifunctional antioxidant, in altering the trajectory of AMD progression. Melatonin is synthesized in the RPE and photoreceptors of young individuals but its expression declines with age. As shown in an epidemiological report, its loss contributes to age-related degeneration of the RPE and photoreceptors. Moreover, melatonin inhibits VEGF, suggesting that it would be useful as a treatment for wet AMD. This review explores melatonin-mediated protective mechanisms in the retina, a likely mechanistic basis for the already published findings showing that melatonin use by humans is associated with delayed AMD, and potential clinical applications.}, }
@article {pmid42052023, year = {2026}, author = {Tang, M and Liu, Y and Dong, L}, title = {Unveiling the non-linear synergistic effects of smoking and aging on cataract-AMD comorbidity: an explainable artificial intelligence approach.}, journal = {Frontiers in public health}, volume = {14}, number = {}, pages = {1784189}, pmid = {42052023}, issn = {2296-2565}, mesh = {Humans ; *Cataract/epidemiology ; Male ; Female ; *Macular Degeneration/epidemiology ; Aged ; Retrospective Studies ; Case-Control Studies ; Comorbidity ; *Smoking/adverse effects/epidemiology ; *Artificial Intelligence ; Risk Factors ; *Aging/physiology ; Middle Aged ; Machine Learning ; Aged, 80 and over ; }, abstract = {BACKGROUND: The comorbidity of cataract and age-related macular degeneration (AMD) poses a significant public health burden. Traditional linear statistical models often fail to capture complex, non-linear interactions among risk factors. This study aimed to develop an interpretable machine learning framework to predict comorbidity risk and elucidate the synergistic effects of systemic and ocular factors.<br><br>METHODS: A retrospective case-control study was conducted involving 640 participants (264 comorbidity cases and 376 controls). Fifteen multi-dimensional clinical features were extracted. Four machine learning algorithms-Logistic Regression, Random Forest, SVM, and XGBoost-were trained and validated. Model performance was assessed via AUROC, AUPRC, and calibration curves. SHapley Additive exPlanations (SHAP) and LIME were employed to visualize global and local interpretability.<br><br>RESULTS: The XGBoost model demonstrated robust discriminative performance (AUC = 0.895, 95% CI: 0.85-0.93) and calibration compared to other algorithms. SHAP analysis identified drusen severity and lens opacity (LOCS III) as dominant ocular predictors, while C-reactive protein (CRP) and smoking were critical systemic contributors. Notably, interaction analysis revealed a non-linear synergistic effect: smoking was associated with an exponentially higher comorbidity risk in individuals aged >75 years, whereas CRP exhibited a distinct saturation threshold effect. Decision curve analysis confirmed the model's high net clinical benefit across a wide range of threshold probabilities.<br><br>CONCLUSION: This study establishes a robust, clinically applicable risk stratification tool for cataract and AMD comorbidity. By uncovering non-linear interactions between aging, lifestyle, and inflammation, it provides valuable evidence-based support for personalized screening and preventive intervention.}, }
@article {pmid42052781, year = {2026}, author = {Chen, X and Hao, P and Lu, P and Han, R and Jiang, Z and Jiang, L and Wang, L and Liu, Z and Li, X}, title = {Proteomic insights into nepetin-mediated protection against oxidative stress in ARPE-19 cells.}, journal = {Free radical research}, volume = {}, number = {}, pages = {1-19}, doi = {10.1080/10715762.2026.2667438}, pmid = {42052781}, issn = {1029-2470}, abstract = {Oxidative stress is one of the crucial factors associated with the pathogenesis of age-related macular degeneration (AMD), particularly the degeneration of retinal pigment epithelium (RPE) cells. In this study, we identified nepetin, a natural flavonoid compound, as a potential inhibitor of hydrogen peroxide (H2O2)-induced ARPE-19 cell death. Pretreatment of nepetin significantly reduced intracellular generation of reactive oxygen species (ROS). Quantitative proteomics was applied to explore the underlying molecular response, revealing that 77 proteins were up-regulated, and 198 proteins were down-regulated significantly after nepetin treatment. Gene ontology (GO) analysis and the protein-protein interaction (PPI) network analysis showed that heme oxygenase 1 (HO-1), Kelch-like ECH-associated protein 1 (KEAP1), Sequestosome 1 (SQSTM1)/p62, and glucose-regulated protein 78 (GRP78) were associated with nepetin-mediated antioxidative responses. Western blotting confirmed the altered expression of these key proteins, with HO-1, p62, and GRP78 being upregulated and KEAP1 being downregulated. Immunofluorescence further showed nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, suggesting the involvement of Nrf2-related antioxidant signaling in nepetin-treated ARPE-19 cells. Although direct causal interactions were not established, the proteomic and bioinformatic analyses provide correlative and suggestive evidence that nepetin modulates key proteins within the oxidative stress response network. Based on our previous research and the current study, nepetin exhibits both anti-inflammatory and antioxidative properties in RPE cells, and may have potential implications for the prophylaxis and treatment of AMD, particularly dry AMD.}, }
@article {pmid42052818, year = {2026}, author = {Zhao, TT and Chang, MK and Shen, BY and Guo, HR and Han, YT and Wang, WF}, title = {Effect of Endogenous FGF21 Deficiency on the Inflammatory Microenvironment of the Retina.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {31}, number = {4}, pages = {47702}, doi = {10.31083/FBL47702}, pmid = {42052818}, issn = {2768-6698}, support = {2025GXNSFAA069182//Guangxi Natural Science Foundation Project/ ; 2023JJ70050//Natural Science Foundation of Hunan Province/ ; Z-A20251080//Guangxi Zhuang Autonomous Region Health Commission Self-funded Scientific Research Project/ ; }, mesh = {Animals ; *Fibroblast Growth Factors/deficiency/genetics ; Mice, Knockout ; Mice ; *Retina/metabolism/immunology/pathology/diagnostic imaging ; *Inflammation/genetics/metabolism/pathology ; Macrophages/immunology/metabolism ; Mice, Inbred C57BL ; Transcriptome ; *Cellular Microenvironment ; Tomography, Optical Coherence ; Signal Transduction ; Gene Expression Profiling ; }, abstract = {BACKGROUND: While the systemic metabolic role of fibroblast growth factor 21 (FGF21) is well-established, its function in retinal homeostasis and its link to retinal diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR) remains poorly understood. This study investigated the impact of endogenous FGF21 deficiency on the retinal immune microenvironment.<br><br>METHODS: Retinal structure was assessed in FGF21 KO and wild-type mice using spectral-domain optical coherence tomography. Transcriptomic profiles of the retina/choroid were analyzed by RNA-seq. Differentially expressed genes (DEGs) were identified (DESeq2, FDR <0.05), clustered, and interrogated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Immune-cell composition was inferred with ImmuCellAI.<br><br>RESULTS: FGF21 KO mice showed no overt retinal structural defects under baseline conditions. Nevertheless, 449 DEGs were identified (293 up, 156 down in knockout). Pathway analysis revealed significant enrichment of cytokine-cytokine receptor interaction, chemokine signaling, and Jak-STAT cascades. Immune deconvolution indicated a significant increase in M2-polarised macrophages (p < 0.01) without change in total macrophage number. Expression of key inflammatory mediators including Il1b was concordantly altered.<br><br>CONCLUSIONS: This work establishes endogenous FGF21 as a crucial local immunomodulator and defines a novel mechanistic link to retinal disease susceptibility, supporting its further exploration as a therapeutic target.}, }
@article {pmid42052823, year = {2026}, author = {Ke, X and Liang, S and Qu, T and Li, S and Lei, J and Han, H and Guo, Y and Xing, M and Wang, X and He, S and Liao, M and Zhou, D and Yan, H}, title = {Platelet Factor 4: A Novel Therapeutic Inhibitor for Experimental Neovascular Age-Related Macular Degeneration.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {31}, number = {4}, pages = {49564}, doi = {10.31083/FBL49564}, pmid = {42052823}, issn = {2768-6698}, support = {82530032//National Natural Science Foundation of China/ ; 82330031//National Natural Science Foundation of China/ ; 82401296//National Natural Science Foundation of China/ ; 25JCZDJC00390//Natural Science Foundation of Tianjin/ ; 25JCQNJC00680//Natural Science Foundation of Tianjin/ ; 23JCQNJC01180//Natural Science Foundation of Tianjin/ ; TJYXZDXK-3-004A//Tianjin Key Medical Discipline Construction Project/ ; }, mesh = {Animals ; Humans ; *Choroidal Neovascularization/drug therapy/metabolism/pathology ; Mice ; *Platelet Factor 4/pharmacology/therapeutic use/metabolism/administration &amp; dosage/genetics ; Disease Models, Animal ; *Macular Degeneration/drug therapy/metabolism/pathology ; Vascular Endothelial Growth Factor A/metabolism ; Cell Proliferation/drug effects ; Mice, Knockout ; *Angiogenesis Inhibitors/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Cell Movement/drug effects ; Signal Transduction/drug effects ; Endothelial Cells/drug effects/metabolism ; Male ; Intravitreal Injections ; Receptors, LDL ; }, abstract = {BACKGROUND: Platelet factor 4 (PF4/CXCL4) is a chemokine with reported anti-angiogenic and immunomodulatory properties; however, the role of PF4 in neovascular age-related macular degeneration (nAMD) remains unclear. Thus, this study aimed to evaluate the therapeutic potential of PF4 in experimental models of ocular pathological neovascularization and explored the underlying mechanisms.<br><br>METHODS: PF4 expression was assessed in a laser-induced choroidal neovascularization (CNV) mouse model using quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. Recombinant PF4 was administered intravitreally in laser-induced CNV mice and very low-density lipoprotein receptor knockout (Vldlr&#x207b;/&#x207b;) mice, a model of spontaneous retinal neovascularization with retinal angiomatous proliferation (RAP)-like lesions. Pathological neovascularization and vascular leakage were quantified by fundus fluorescein angiography and choroidal/retinal flat-mount analyses. Immunofluorescence, qRT-PCR, and RNA sequencing were employed to evaluate inflammatory responses. Moreover, the effects of PF4 on vascular endothelial growth factor (VEGF)-induced proliferation, migration, and tube formation of human retinal microvascular endothelial cells were examined in vitro, and VEGF-mediated signaling was analyzed by Western blotting. Ocular safety was assessed by optical coherence tomography (OCT), electroretinography (ERG), hematoxylin and eosin (H&amp;E) staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.<br><br>RESULTS: Intravitreal PF4 significantly reduced pathological neovascularization and vascular leakage in both models and attenuated intraocular inflammation, as indicated by decreased expression of proinflammatory cytokines and reduced microglial/macrophage recruitment. PF4 inhibited VEGF-induced endothelial cell proliferation, migration, and tube formation in vitro. Mechanistically, PF4 downregulated VEGF expression in CNV lesions in vivo and suppressed VEGF-induced activation of vascular endothelial growth factor receptor 2 (VEGFR2) and downstream extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and signal transducer and activator of transcription 3 (STAT3) signaling in vivo and in vitro. PF4 administration was well tolerated, with no detectable adverse effects on retinal structure or function.<br><br>CONCLUSIONS: PF4 effectively inhibits ocular pathological neovascularization and inflammation by modulating the VEGF/VEGFR2 signaling pathway. These findings support PF4 as a promising therapeutic candidate for nAMD and warrant further investigation.}, }
@article {pmid42053093, year = {2026}, author = {Li, H and Xu, J and Wang, J and Cheng, L and Fan, J}, title = {Mapping ophthalmic research on glycosylation and glycation: a PRISMA-compliant bibliometric and co‑citation analysis.}, journal = {Future science OA}, volume = {12}, number = {1}, pages = {2663167}, doi = {10.1080/20565623.2026.2663167}, pmid = {42053093}, issn = {2056-5623}, abstract = {BACKGROUND: Enzymatic glycosylation and non-enzymatic glycation contribute significantly to the pathogenesis of major ocular diseases, particularly diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, and cataract. However, the knowledge structure and developmental trajectory of glycosylation-related research in ophthalmology remain unclear.<br><br>METHODS: The literature on the role of enzymatic glycosylation and non-enzymatic glycation modification in ophthalmic diseases from 1997 to 2024 was searched in the core database of Web of Science. Bibliometrics analysis software VOS viewer (version 1.6.20), Citespace (version 6.1.R1), Scimago Graphica (version 6.1.R1), Microsoft Excel 2021.<br><br>RESULTS: This study analyzed 3,221 publications, all results are available on January 4, 2025. Biochemistry &amp; Molecular Biology was the primary subject area. Research has evolved from early exploration of advanced glycation end products and protein kinase C pathways toward inflammation, biomarker discovery, and risk prediction in specific ocular disorders. Increasing attention has also been directed toward glycosylation-based diagnostic markers and potential therapeutic targets.<br><br>CONCLUSION: This bibliometric analysis provides an ophthalmology-centered overview of glycosylation and glycation research, identifying DR as the primary research hub while highlighting emerging translational directions in retinal and other ocular diseases.}, }
@article {pmid42053221, year = {2026}, author = {Nitzan, I and Jaskoll, S and Kramer, A and Shmueli, O and Levy, J and Chowers, I}, title = {High-Density Lipoprotein Cholesterol Levels and Risk of Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {69}, doi = {10.1167/iovs.67.4.69}, pmid = {42053221}, issn = {1552-5783}, mesh = {Humans ; Retrospective Studies ; Female ; Male ; *Cholesterol, HDL/blood ; Aged ; *Macular Degeneration/blood/epidemiology ; Risk Factors ; Middle Aged ; Incidence ; Follow-Up Studies ; United States/epidemiology ; Aged, 80 and over ; Biomarkers/blood ; }, abstract = {PURPOSE: To evaluate the association between high-density lipoprotein cholesterol (HDL-C) levels and incident age-related macular degeneration (AMD) in a large cohort.<br><br>METHODS: This retrospective cohort study used electronic health records from 70 U.S. healthcare organizations in the TriNetX network from 2005 to 2025. Adults with at least two HDL-C measurements obtained at least three months apart were classified as having high HDL-C (all values &#x2265;60 mg/dL) or low HDL-C (all values &#x2264;39 mg/dL). Groups were matched 1:1 on demographics, comorbidities, medications, laboratory values, and healthcare utilization. Follow-up began at the second qualifying HDL-C measurement and continued for up to 10 years. Incident nonexudative and exudative AMD were evaluated using Kaplan-Meier and Cox proportional hazards analyses, with robustness assessed through nested matching, subgroup and sensitivity analyses, and positive and negative control outcomes.<br><br>RESULTS: Over 1.29 million person-years of follow-up, high HDL-C was associated with increased risk of nonexudative AMD (hazard ratio [HR] = 1.53; 95% confidence interval [CI], 1.32-1.78) and exudative AMD (HR = 1.37; 95% CI, 1.09-1.73). For nonexudative AMD, risk was elevated across early (HR = 1.55; 95% CI, 1.26-1.91), intermediate (HR = 1.82; 95% CI, 1.42-2.33), and advanced atrophic (HR = 1.85; 95% CI, 1.16-2.97) stages. Associations for nonexudative AMD were robust across washout periods, follow-up intervals, mortality exclusion, and stepwise matching. Associations for exudative AMD were consistently positive but less stable. Control outcomes supported the specificity and internal validity of the findings.<br><br>CONCLUSIONS: Higher HDL-C levels were associated with increased risk of incident nonexudative AMD and a weaker, less consistent association with exudative AMD. These findings suggest that sustained HDL-C levels may be relevant to AMD risk assessment and warrant further investigation.}, }
@article {pmid42053222, year = {2026}, author = {Kuchernig, L and Reiter, GS and Schrittwieser, J and Eidenberger, A and Jeremic, N and Gumpinger, M and Bogunovic, H and Schmidt-Erfurth, U and Sacu, S}, title = {Choriocapillaris Flow Deficits Are Spatially Linked to Retinal Pigment Epithelium and Photoreceptor Integrity in Geographic Atrophy.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {68}, doi = {10.1167/iovs.67.4.68}, pmid = {42053222}, issn = {1552-5783}, mesh = {Humans ; Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/pathology ; *Geographic Atrophy/physiopathology/diagnosis ; Male ; Female ; Aged ; *Choroid/blood supply ; Fluorescein Angiography/methods ; Middle Aged ; Aged, 80 and over ; Regional Blood Flow/physiology ; Fundus Oculi ; *Photoreceptor Cells, Vertebrate/pathology ; }, abstract = {PURPOSE: To assess the correlation between choriocapillaris (CC) flow deficits and structural biomarkers of outer retinal degeneration in eyes with geographic atrophy (GA) secondary to nonexudative age-related macular degeneration, using a novel histology-informed binarization method and multimodal image registration.<br><br>METHODS: Patients with GA underwent spectral-domain optical coherence tomography (SD-OCT; Spectralis HRA + OCT) and swept-source optical coherence tomography angiography (SS-OCT-A; PLEX Elite 9000) imaging. Flow deficit percentage (FD%) was quantified via a novel histology-informed binarization approach. Retinal pigment epithelium loss (RPEL), ellipsoid zone loss (EZL), and ellipsoid zone (EZ) thickness were derived from SD-OCT using previously validated segmentation algorithms. Exact interdevice registration enabled spatial mapping. Linear mixed-effects models assessed global and local FD% associations with structural biomarkers.<br><br>RESULTS: We analyzed 115 eyes of 64 patients. Global FD% predicted RPEL (&#x3b2;, estimated effect = 0.16 mm/%FD; 95% confidence interval [CI], 0.10-0.22; P < 0.001) and EZL (&#x3b2; = 0.11 mm/%FD; 95% CI, 0.07-0.15; P < 0.001). Local FD% was elevated in RPEL (&#x3b2; = 22.95%FD; 95% CI, 20.86-25.04; P < 0.001) and EZL (&#x3b2; = 12.03%FD; 95% CI, 9.94-14.12; P < 0.001) regions. FD% negatively correlated with EZ thickness independent of drusen (&#x3b2; = -0.05&#xa0;&#xb5;m/%FD; 95% CI, -0.05 to -0.05; P < 0.001).<br><br>CONCLUSIONS: Using a novel multimodal pipeline combining structural SD-OCT, SS-OCT-A, and histology-informed choriocapillaris binarization, we demonstrate that CC flow deficits are spatially correlated with outer retinal degeneration and independently associated with photoreceptor integrity, supporting their potential as predictive biomarkers for GA severity. These findings support a model in which choriocapillaris hypoperfusion contributes to metabolic stress in the retinal pigment epithelium and compromises photoreceptor outer segment integrity in geographic atrophy.}, }
@article {pmid42053269, year = {2026}, author = {Monteiro, A and Mugisho, OO and de Souza, A and Liu, L and Agban, Y and Agarwal, P and Shome, A and Rupenthal, ID and Sheardown, H}, title = {A Cationic Block Co-Polymer for Gene Delivery in the Posterior Segment of the Eye.}, journal = {Journal of biomedical materials research. Part A}, volume = {114}, number = {5}, pages = {e70078}, doi = {10.1002/jbm.a.70078}, pmid = {42053269}, issn = {1552-4965}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Humans ; *Gene Transfer Techniques ; *Polymers/chemistry ; Animals ; Cell Line ; Cations/chemistry ; *Oligonucleotides, Antisense/pharmacology/administration &amp; dosage ; Retinal Pigment Epithelium/metabolism/cytology ; *Posterior Eye Segment/metabolism ; Cell Survival/drug effects ; }, abstract = {Diseases of the back of the eye such as neovascular age-related macular degeneration (nAMD) are vision threatening and treatment is burdensome for patients, often requiring ocular injections every other month. Injection risks and logistics lower patient compliance; however, even patients receiving optimal treatment can deteriorate. Gene silencing has shown great potential as a therapeutic alternative but is often limited by instability of the genetic payload, reducing efficacy. In the current work, a cationic block co-polymer was developed and investigated as a delivery system for an antisense oligonucleotide (ASO) to the posterior segment of the eye. This work details the synthesis, characterization, in vitro, and ex vivo testing of the polymer and the subsequent polyplexes formed between the polymer and ASO. pH-dependent polyplexes were formed which fully complexed the ASO at 1:1 and 10:1 ratios of polymer amine groups to ASO phosphate groups (N/P ratio). Neither formulation displayed a significant reduction in the viability of human retinal pigment epithelial (ARPE-19) cells. The polyplexes were under 150 nm in diameter, with a slightly negative zeta potential. In comparison to the naked ASO, the 10:1 polyplexes achieved superior transfection into ARPE-19 cells. After 24 h, the ASO delivered by the 10:1 polyplexes displayed significant knockdown of the target protein. Polyplexes were well distributed throughout the vitreous humor, retina, and choroid within 4 h of intravitreal administration in an ex vivo porcine eye. These materials show potential for gene delivery in the treatment of various posterior segment conditions including nAMD.}, }
@article {pmid42054085, year = {2026}, author = {Ayachit, A and Rao, S and Eqbal, S and Vibhute, G and Fatima, F and Joshi, S and Ayachit, G and Chhablani, J}, title = {Neovascular age-related macular degeneration management - Beyond anti-VEGF.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {5}, pages = {653-660}, doi = {10.4103/IJO.IJO_3274_25}, pmid = {42054085}, issn = {1998-3689}, mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Disease Management ; *Wet Macular Degeneration/drug therapy/diagnosis ; Intravitreal Injections ; }, abstract = {Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has transformed neovascular age-related macular degeneration (nAMD) into a chronic, treatable condition. However, real-world outcomes remain limited by treatment burden, limited durability, variable response, and progression of atrophy or fibrosis, highlighting the need for strategies beyond VEGF-A suppression. This narrative review summarizes emerging therapeutic approaches aimed at addressing these unmet needs. Adjunctive pharmacologic targets, including angiopoietin/Tie2 signaling, VEGF-C/D, integrins, hypoxia-inducible pathways, and intracellular tyrosine kinase inhibition, are discussed. Gene-based therapies offering the potential for prolonged intraocular VEGF suppression are discussed, though challenges related to inflammation, irreversibility, and patient selection persist. Finally, surgical and regenerative strategies such as retinal pigment epithelium monolayer transplantation are reviewed as investigational options for highly selected patients. Collectively, these developments signal a shift toward individualized, multipronged nAMD management, with anti-VEGF therapy remaining foundational, while biomarkers, intraocular biochemical milieu, and patient adherence may guide future care.}, }
@article {pmid42054086, year = {2026}, author = {Giridhar, A and Lekha, T and Chandran, K}, title = {Anti-vascular endothelial growth factor therapy in polypoidal choroidal vasculopathy.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {5}, pages = {669-680}, doi = {10.4103/IJO.IJO_3237_25}, pmid = {42054086}, issn = {1998-3689}, mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Polyps/drug therapy/diagnosis ; Fluorescein Angiography ; Tomography, Optical Coherence ; *Choroid/blood supply ; Intravitreal Injections ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Recombinant Fusion Proteins/administration &amp; dosage ; Fundus Oculi ; *Choroidal Neovascularization/drug therapy/diagnosis ; *Choroid Diseases/drug therapy/diagnosis ; Polypoidal Choroidal Vasculopathy ; }, abstract = {The diagnosis and management of polypoidal choroidal vasculopathy (PCV), a complex chorioretinal disease which constitutes 60% of neovascular age-related macular degeneration cases among Asians, have evolved significantly in the last decade. SD-OCT biomarkers can reliably diagnose and monitor PCV, restricting the role of invasive indocyanine green angiography to situations like suboptimal responders to therapy where it helps to clarify the diagnosis and explore other treatment options like laser. The introduction of Aflibercept resulted in a paradigm shift in the treatment from combination therapy (photodynamic therapy plus injection of anti-VEGF drugs) to anti-VEGF monotherapy after it was proven noninferior to the former in the PLANET trial. The limited availability of PDT also favored this shift. The longer half-life of Aflibercept led to adoption of proactive treatment regimens like treat and extend guided by fluid markers on OCT, reducing the treatment burden. Newer molecules with more potency and durability like Brolucizumab and Faricimab demonstrated superior drying effects and achieved a longer treatment interval of up to 16 weeks, offering additional options for anti-VEGF monotherapy. HAWK and HARRIER trials proved the noninferiority of Brolucizumab to Aflibercept, though there were safety concerns of inflammation. Interim analysis of the on-going SALWEEN trial for Faricimab in PCV has also shown favorable outcomes. Characterizing the different phenotypes of PCV based on OCT and choosing the appropriate drug and treatment regimen are important to maximize visual outcome while reducing the treatment burden. This article reviews the evolution of anti-VEGF therapy in PCV and provides recommendations for optimal management in the real world.}, }
@article {pmid42054089, year = {2026}, author = {Chakraborty, D and Sinha, TK and Boral, S and Das, A}, title = {Biosimilar anti-vascular endothelial growth factor agents: Clinical outcomes, safety, and cost-effectiveness in India.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {5}, pages = {760-766}, doi = {10.4103/IJO.IJO_3222_25}, pmid = {42054089}, issn = {1998-3689}, mesh = {Humans ; India/epidemiology ; Cost-Benefit Analysis ; *Biosimilar Pharmaceuticals/economics/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/economics/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Ranibizumab/therapeutic use/economics ; *Retinal Diseases/drug therapy/economics/epidemiology ; Treatment Outcome ; }, abstract = {Retinal vascular diseases, including neovascular age-related macular degeneration, diabetic macular edema, retinal vein occlusion, myopic choroidal neovascularization, and retinopathy of prematurity, are a major cause of visual morbidity in India. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed the management of these conditions, long-term outcomes in real-world Indian practice are frequently limited by affordability-related undertreatment. The introduction of biosimilar anti-VEGF agents, particularly ranibizumab biosimilars, has therefore assumed critical importance in improving access to sustained retinal care. This narrative review synthesizes the available Indian evidence on the clinical efficacy, safety, immunogenicity, and cost-effectiveness of biosimilar anti-VEGF agents. A comprehensive literature search was conducted in PubMed, MEDLINE, EMBASE, and Scopus from inception through September 2025 using predefined keywords related to biosimilar ranibizumab, retinal vascular diseases, safety, immunogenicity, real-world evidence, and cost-effectiveness. Additional studies were identified through manual screening of reference lists. Peer-reviewed English-language randomized trials, phase 3 studies, post-marketing surveillance reports, and large real-world cohorts from India were included. Across major retinal indications, phase 3 trials consistently demonstrated equivalence or noninferiority of biosimilars to the reference molecule in visual and anatomical outcomes, with comparable safety and low immunogenicity. Large real-world datasets further corroborate these findings and provide reassurance regarding ophthalmic use of biosimilar anti-VEGF. Importantly, reduced treatment costs have translated into improved treatment initiation and adherence. Overall, current evidence supports biosimilar ranibizumab as a safe, effective, and cost-effective alternative for retinal diseases in resource-limited settings.}, }
@article {pmid42054256, year = {2026}, author = {Gruszka-Goh, MH and Donachie, PHJ and Chhabra, RR and McKibbin, M}, title = {The Royal College of Ophthalmologists National Ophthalmology Database Age-related Macular Degeneration (AMD) Audit, Report 2: Baseline characteristics, the care pathway and 12-month visual acuity and safety outcomes for 54,882 eyes starting treatment for neovascular AMD.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {}, number = {}, pages = {1-16}, doi = {10.1159/000552289}, pmid = {42054256}, issn = {1423-0267}, abstract = {AIMS: To report aggregate data from the United Kingdom AMD (age-related macular degeneration) Audit, focussing on baseline characteristics, treatment and one year acuity and safety outcomes for eyes starting treatment for neovascular AMD between April 2021 and March 2023.<br><br>METHODS: Anonymised demographic and clinical data, collected as part of routine clinical care, were extracted from electronic medical records at participating centres providing NHS-funded treatment. Analyses were restricted to eyes with baseline visual acuity recorded at treatment initiation.<br><br>RESULTS: Analysis included 54,882 eyes of 48,371 patients from 78 participating treatment centres. Just over 60% were female and the median age at the start of treatment was 79.9 years for first treated eyes and 82.2 years for second treated eyes. Median baseline acuity was 60 ETDRS letters (interquartile range (IQR)= 44-70) and 28.1% of eyes had "good" acuity, defined as &#x2265; 70 ETDRS letters. The initial three injections, during the loading phase of monthly treatment, were given within 10 weeks in 64% of eyes and the median number of injections in the first 12 months was 6 (IQR 4-8). The median interval between injections at the end of the first year of treatment was 8 weeks (IQR 6-12 weeks). Trained non-medical healthcare professionals administered at least 72% of injections. Median acuity after 12 months was 65 ETDRS letters (IQR 48-75) and 43.1% had "good" visual acuity. The incidence of intra-ocular inflammation and presumed infectious endophthalmitis after each injection were 0.03% (1 in 3,176) and 0.014% (1 in 7,013) respectively. There was no difference in the incidence of either complication by profession of the injector.<br><br>CONCLUSIONS: Aggregate data from the UK AMD Audit provides real-world evidence and a benchmark against which other countries and centres can compare local performance and outcomes. Almost 91% of eyes retained stable acuity and avoided moderate visual loss after 12 months of treatment. The best acuity outcomes were obtained in younger patients and in eyes treated second, with good baseline acuity, prompt completion of the loading phase of treatment and receiving more injections during the first 12 months of treatment.}, }
@article {pmid42054488, year = {2026}, author = {Zhou, Y and Xu, M and Xu, Y and Shao, A and Cui, W and Shen, W and He, Y and Chen, Z and Zhang, Y and Miao, Q and Han, H and Ye, J}, title = {Iron Homeostasis Restoration via Triple-Pool-Targeted Nanotherapy for Enhanced Amelioration of Age-Related Macular Degeneration.}, journal = {ACS nano}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsnano.6c00302}, pmid = {42054488}, issn = {1936-086X}, abstract = {Oxidative stress-induced retinal pigment epithelium (RPE) damage and ferroptosis are critical in retinal degenerative diseases, particularly in age-related macular degeneration (AMD)─a major cause of irreversible blindness. Current clinical AMD treatment is predominantly dependent on intravitreal anti-VEGF administration targeting only late-stage choroidal neovascularization (CNV), with limitations of incomplete response and adverse effects. Herein, a facile synthesis of Nuci@PAM-BR, which was designed by modification of antioxidant bilirubin to the surface and encapsulation of antiferroptosis nuciferine in the hydrophobic cavity of polyamidoamine dendrimers, was reported, thus achieving iron homeostasis restoration via triple-pool-targeted scavenging properties for eradicating CNV in AMD management. Our results demonstrated that Nuci@PAM-BR could significantly attenuate CNV by targeting the detrimental "triple pool" in damaged RPE cells, exhibiting excellent antioxidant and anti-inflammatory properties that contributed to its excellent antiangiogenic effect, achieving an over 80% reduction in leakage area and an over 85% decline in neovascular lesion. Such triple-pool-targeted nanotherapy offers a promising alternative and holds significant potential for the future clinical treatment of diverse fundus neovascularization diseases, including AMD.}, }
@article {pmid42054989, year = {2026}, author = {Wang, T and Xu, Y}, title = {RetinalFRNet: retinal vessel segmentation in OCTA images using the feature reconstruction network.}, journal = {Biomedizinische Technik. Biomedical engineering}, volume = {}, number = {}, pages = {}, pmid = {42054989}, issn = {1862-278X}, abstract = {OBJECTIVES: Automated segmentation of retinal blood vessels in optical coherence tomography angiography (OCTA) images is essential for early diagnosis of ocular diseases such as diabetic retinopathy, myopia, and macular degeneration. This study evaluates the performance of the Retinal Feature Reconstruction Network (RetinalFRNet), a full-resolution deep learning architecture designed for OCTA retinal vessel segmentation.<br><br>METHODS: RetinalFRNet integrates recurrent neural network modules within a ConvNeXt backbone while preserving full spatial resolution without downsampling. Its performance was compared with five algorithms&#xa0;-&#xa0;fuzzy C-means (FCM), U-Net, ResUnet, Vision Transformer (ViT), and VM-Unet&#xa0;-&#xa0;using three publicly available datasets (OCTA-3&#xa0;mm, OCTA-6&#xa0;mm, and ROSSA). All models were trained using the Adam optimizer for 100 epochs and evaluated using seven standard metrics including Accuracy, Dice coefficient, Sensitivity, and mean Intersection over Union (IoU).<br><br>RESULTS: RetinalFRNet achieved the highest overall performance across all datasets, reaching a Dice coefficient of 91.72&#x202f;% and mean IoU of 84.93&#x202f;% on the ROSSA dataset, improving performance by up to 30.66&#x202f;% over the FCM baseline.<br><br>CONCLUSIONS: RetinalFRNet demonstrates superior accuracy and robustness for OCTA retinal vessel segmentation. Its downsampling-free architecture enables improved detection of fine vascular structures critical for ophthalmic diagnosis. Further multi-center validation is recommended prior to clinical deployment.}, }
@article {pmid42055007, year = {2026}, author = {Arduini, BL and Blenkinsop, TA and Naimark, M and Borden, S and Charniga, C and Campbell, M and Rugenstein, N and Davis, RJ and Alam, N and Prusky, G and Frye, AM and Mazzoni, F and Finnemann, SC and Zhao, C and Lederman, P and Saini, JS and Kiehl, TR and Renga, N and Kozak, JA and Rocchio, PA and Salero, E and Boles, NC and Goderie, SK and Lotz, S and Adamo, JE and Zaccaglino, S and Onanuga, K and Fiske, M and Capela, A and Temple, S and Stern, JH}, title = {IND-enabling safety and efficacy of RPESC-RPE-4W, an adult RPE progenitor cell therapy for dry age-related macular degeneration.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {102779}, doi = {10.1016/j.xcrm.2026.102779}, pmid = {42055007}, issn = {2666-3791}, abstract = {Dry age-related macular degeneration (AMD) is a prevalent blinding disorder characterized by loss of retinal pigment epithelium (RPE) cells and resulting central vision impairment. Here, we describe preclinical studies supporting an investigational new drug (IND) application for adult RPE stem cell-derived RPE (RPESC-RPE) cell replacement therapy. We establish donor-to-donor reproducibility and Good Manufacturing Practice (GMP) processes and evaluate the GMP cell product in preclinical studies conducted in accordance with Good Laboratory Practice principles. Efficacy experiments in Royal College of Surgeons rats show that subretinal implantation of the 4-week, postmitotic, progenitor-stage product (RPESC-RPE-4W) produces significant and durable vision rescue compared to vehicle control. Biodistribution and safety studies in immunocompromised Rowett Nude rats demonstrate a favorable safety profile, with no adverse effects related to the cell product. These studies underpin allowance of an ongoing phase 1/2a clinical trial.}, }
@article {pmid41851876, year = {2026}, author = {Zhang, J and Zhang, F and Wang, P and Lin, B and Yang, M and Chen, Q}, title = {Fellow-eye effect of intravitreal aflibercept 8mg in a patient with bilateral refractory nAMD: a case report and literature review.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {}, pmid = {41851876}, issn = {1471-2415}, support = {No. 82171062//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Intravitreal anti–vascular endothelial growth factor (anti-VEGF) therapy remains first-line therapy for the treatment of neovascular age-related macular degeneration (nAMD), but the high frequency of injections imposes a substantial burden on elderly patients. High-dose aflibercept 8 mg has been shown to extend dosing intervals while maintaining anatomical control. Fellow-eye effects have been reported with other anti-VEGF agents but not with aflibercept 8 mg.<br><br>CASE PRESENTATION: An 89-year-old woman with bilateral refractory nAMD had received 23 prior anti-VEGF injections in the right eye. Owing to financial constraints, she underwent unilateral aflibercept 8&#xa0;mg injection in the right eye only. Baseline best-corrected visual acuity (BCVA) was 0.82 the logarithm of the minimum angle of resolution (logMAR) in the right eye and 1.0 logMAR in the left eye. One week after intravitreal injection, optical coherence tomography (OCT) showed marked bilateral improvement: central subfield thickness (CST) decreased from 629 to 327&#xa0;&#x3bc;m in the treated eye and from 357 to 308&#xa0;&#x3bc;m in the untreated fellow eye. BCVA remained stable in the treated eye, while improved to 0.70 logMAR in the fellow eye.<br><br>CONCLUSION: This is the first reported case of a fellow-eye effect associated with aflibercept 8&#xa0;mg. The findings suggest a potential systemic effect of high-dose aflibercept, but it should be noted that, for patients with bilateral nAMD, bilateral treatment is still necessary to avoid insufficient treatment of the contralateral eye.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12886-026-04751-7.}, }
@article {pmid42046820, year = {2026}, author = {Karpecki, P and Ayres, B and Donnenfeld, E and Farid, M and Gaddie, IB and Gupta, PK and Koetting, C and Lindstrom, R and McGee, S and Nichols, KK and Periman, LM and Pflugfelder, S and Starr, C and Venkateswaran, N and Yeu, E}, title = {Lotilaner ophthalmic solution 0.25% in the treatment of Demodex blepharitis: A case report.}, journal = {SAGE open medical case reports}, volume = {14}, number = {}, pages = {2050313X261443128}, pmid = {42046820}, issn = {2050-313X}, abstract = {Demodex blepharitis is a chronic inflammatory ocular condition caused by Demodex mite infestation of the eyelid that can negatively impact quality of life. Currently, lotilaner ophthalmic solution 0.25% is the only FDA-approved treatment for Demodex blepharitis. The Demodex Expert Panel on Treatment and Eyelid Health has established consensus that lotilaner ophthalmic solution 0.25% should be considered the preferred first-line treatment for Demodex blepharitis. We report a patient who presented with collarettes, the pathognomonic sign of Demodex blepharitis, meibomian gland dysfunction, and poor visual acuity. The patient also had a history of neovascular age-related macular degeneration. Consistent with the Demodex Expert Panel on Treatment and Eyelid Health consensus recommendations, the patient was treated with lotilaner ophthalmic solution 0.25%, lid scrubs, and warm compresses. At the 2-month follow-up, collarettes had resolved, and signs of meibomian gland dysfunction had improved. This case supports the Demodex Expert Panel on Treatment and Eyelid Health recommendation that lotilaner ophthalmic solution 0.25% should be considered the preferred first-line treatment for Demodex blepharitis.}, }
@article {pmid42046926, year = {2026}, author = {Çalışkan, B and Demir, Y}, title = {Serum Cholinesterases as Indicators of Cholinergic Dysfunction in Exudative Age-Related Macular Degeneration.}, journal = {Current eye research}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/02713683.2026.2664597}, pmid = {42046926}, issn = {1460-2202}, abstract = {PURPOSE: The aim of this study was to measure serum acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities in order to evaluate the potential role of the cholinergic system in exudative type age-related macular degeneration (AMD).<br><br>METHODS: This case-control study involved 38 individuals diagnosed with exudative AMD and 41 healthy individuals with similar characteristics in terms of age and gender. The Ellman method was used to evaluate serum AChE and BChE activity after each subject underwent an ophthalmological examination. Multivariate logistic regression, ROC curve analysis, t-tests, and Mann-Whitney U tests were used in the statistical studies.<br><br>RESULTS: Serum AChE activity levels were higher in the AMD-diagnosed group compared to the control group (1.155&#x2009;&#xb1;&#x2009;0.178&#x2009;&#xb5;mol/mL vs. 1.029&#x2009;&#xb1;&#x2009;0.150&#x2009;&#xb5;mol/mL; p&#x2009;=&#x2009;0.002). There was no statistically significant difference in BChE activity levels (p&#x2009;=&#x2009;0.24). AChE activity showed moderate diagnostic performance according to ROC analysis (AUC = 0.697; 95% CI: 0.580-0.814; optimal threshold &#x2265;1.106&#x2009;&#xb5;mol/mL; sensitivity 63.2%; specificity 70.7%). According to logistic regression analysis, AChE activity levels were considered an independent predictor of AMD (OR = 89.34; p&#x2009;=&#x2009;0.005).<br><br>CONCLUSIONS: The increased serum AChE activity observed in exudative AMD suggests that the cholinergic system plays a role in retinal degeneration. AChE levels could be considered as potential AMD pathogenesis biomarkers and as a potential treatment target.}, }
@article {pmid42047667, year = {2026}, author = {Sun, N and Li, J and Wang, J and Wang, J and Chen, T and Wang, Y and Liu, C and Yang, S and Yao, T and Feng, H and Wang, Z}, title = {Endothelial TRPV1 Drives Choroidal Neovascularization in Wet Age-Related Macular Degeneration via NF-κB Signaling.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {64}, doi = {10.1167/iovs.67.4.64}, pmid = {42047667}, issn = {1552-5783}, mesh = {Animals ; *TRPV Cation Channels/genetics/metabolism/biosynthesis ; *Choroidal Neovascularization/metabolism/etiology/genetics/pathology ; *NF-kappa B/metabolism ; Mice ; Humans ; *Wet Macular Degeneration/metabolism/complications/genetics ; Signal Transduction/physiology ; Mice, Knockout ; Mice, Inbred C57BL ; Disease Models, Animal ; Tomography, Optical Coherence ; Fluorescein Angiography ; Male ; Real-Time Polymerase Chain Reaction ; Blotting, Western ; Human Umbilical Vein Endothelial Cells/metabolism ; Cells, Cultured ; Female ; Aged ; Endothelial Cells/metabolism ; Retinal Pigment Epithelium/metabolism/pathology ; }, abstract = {PURPOSE: We investigated the effects of endothelial cell transient receptor potential vanilloid 1 (TRPV1) activation on neovascularization and endothelial cell-microglial crosstalk, aiming to clarify the mechanisms underlying choroidal neovascularization (CNV) in wet age-related macular degeneration (wAMD).<br><br>METHODS: We performed bioinformatics analysis on transcriptomes of retinal pigment epithelium-choroidal tissues from wAMD patients. Vascular leakage was assessed in laser-induced CNV and TRPV1 knockout (TRPV1-/-) mice using fundus fluorescein angiography, optical coherence tomography, hematoxylin and eosin staining, and isolectin B4 staining. TRPV1 expression in CNV mice was determined via immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction analyses. Angiogenesis and microglial activation were examined via pharmacological intervention, siRNA silencing, and co-culture assays. Physiological TRPV1 agonists were analyzed by public metabolomics datasets.<br><br>RESULTS: TRPV1 was upregulated in patients with wAMD and mice with laser-induced CNV. TRPV1 activation exacerbated vascular leakage in CNV mice, whereas inhibition or knockout had the opposite effects. In human umbilical vein and retinal microvascular endothelial cells, TRPV1 activation promoted tube formation, with no measurable effects on proliferation or migration. TRPV1 promoted the release of inflammatory factors from endothelial cells by regulating the nuclear factor kappa B (NF-&#x3ba;B) pathway, which in turn induced pro-inflammatory polarization of microglia and the secretion of angiogenic factors from microglia, further facilitating angiogenesis. Moreover, linoleic acid, a physiological ligand of TRPV1, activated the endothelial TRPV1/NF-&#x3ba;B pathway to promote angiogenesis.<br><br>CONCLUSIONS: Endothelial TRPV1 mediated endothelial dysfunction and microglial activation via NF-&#x3ba;B, thereby promoting CNV, with linoleic acid serving as a key activator. TRPV1 can be considered a potential therapeutic target for treating wAMD.}, }
@article {pmid42048095, year = {2026}, author = {Shadrichev, FE and Strunina, YV}, title = {[Cost analysis of aflibercept 8 mg versus other anti-VEGF agents].}, journal = {Vestnik oftalmologii}, volume = {142}, number = {2}, pages = {40-48}, doi = {10.17116/oftalma202614202140}, pmid = {42048095}, issn = {0042-465X}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage/economics ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Intravitreal Injections/economics/methods ; Russia ; Angiogenesis Inhibitors/economics/administration &amp; dosage ; *Macular Edema/drug therapy/economics/etiology/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Ranibizumab/economics/administration &amp; dosage ; Male ; Cost-Benefit Analysis ; Female ; Treatment Outcome ; Costs and Cost Analysis ; *Diabetic Retinopathy/drug therapy/economics/diagnosis/complications ; Aged ; Antibodies, Monoclonal, Humanized ; }, abstract = {PURPOSE: This study aimed to assess the economic impact of aflibercept 8 mg (114.3 mg/ml, 0.263 ml; hereinafter aflibercept 8 mg) compared with alternative anti-VEGF agents in adult patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) over a 2-year treatment period.<br><br>MATERIAL AND METHODS: The study compared different anti-VEGF therapies (aflibercept 8 mg; aflibercept 2 mg - 40 mg/ml, 0.278 ml; brolucizumab 6 mg - 120 mg/ml, 0.23 ml; ranibizumab 0.5 mg - 10 mg/ml, 0.23 ml) from the perspective of the healthcare system of the Russian Federation over a 2-year horizon. The number of intravitreal injections was determined based on an indirect comparative analysis; the number of administrations was reconstructed using an anchor value for aflibercept 8 mg and published differences in injection frequencies. Costs were calculated using the weighted average procurement price per package. The burden on the compulsory health insurance (CHI) system was estimated based on the average cost per insurance case (Diagnosis-Related Group, DRG, for "Intravitreal drug administration") of 47 459.63 RUB.<br><br>RESULTS: The costs over 2 years were lower with aflibercept 8 mg, resulting in savings of 99 713-140 434 RUB per patient with nAMD and 98 305-173 196 RUB with DME, depending on the comparator drug. When assessing the burden on the CHI system, savings amounted to 142 378-489 783 RUB per patient with nAMD and 119 598-541 039 RUB per patient with DME.<br><br>CONCLUSION: The use of aflibercept 8 mg in nAMD and DME reduces both direct treatment costs and expenditures of the CHI system in the first and second years of therapy, as well as cumulatively over 2 years. The results remain robust under price reductions and support the economic feasibility of the use of aflibercept 8 mg.}, }
@article {pmid42048097, year = {2026}, author = {Litvina, EA and Illarionova, AR and Potapova, OM}, title = {[Antiangiogenic therapy after cataract surgery in neovascular age-related macular degeneration (clinical observation)].}, journal = {Vestnik oftalmologii}, volume = {142}, number = {2}, pages = {57-62}, doi = {10.17116/oftalma202614202157}, pmid = {42048097}, issn = {0042-465X}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; Female ; Male ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Visual Acuity ; Tomography, Optical Coherence/methods ; Treatment Outcome ; *Phacoemulsification/methods/adverse effects ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/adverse effects ; Retrospective Studies ; *Cataract/complications/diagnosis ; *Wet Macular Degeneration/diagnosis/drug therapy/complications ; Intravitreal Injections ; Aged, 80 and over ; }, abstract = {UNLABELLED: The combination of age-related cataract and neovascular age-related macular degeneration (nAMD) presents a clinically challenging scenario, as it requires continuation of anti-angiogenic therapy during the perioperative period. The impact of cataract phacoemulsification (PE) on nAMD activity and the need for continued anti-VEGF treatment remains a subject of debate.<br><br>PURPOSE: This study assessed the safety profile and progression of nAMD over 12 months following phacoemulsification in patients undergoing treatment with aflibercept and brolucizumab.<br><br>MATERIAL AND METHODS: This retrospective-prospective study included 24 patients (24 eyes) with nAMD and age-related cataract. Two groups were formed: the brolucizumab group (n=12) and the aflibercept group (n=12). All patients underwent PE with intraocular lens (IOL) implantation. The examination protocol included best-corrected visual acuity (BCVA) assessment, biomicroscopy, fundus photography, optical coherence tomography (OCT), and OCT angiography. Outcomes were evaluated over 12 months preoperatively and 12 months postoperatively. The analysis included BCVA, central retinal thickness (CRT), presence of intra-, subretinal, and subpigment epithelial fluid, and the number of anti-VEGF injections.<br><br>RESULTS: The number of injections did not increase during the 12 months after surgery amounting to 3.1&#xb1;1.1 in the brolucizumab group and 3.8&#xb1;1.4 in the aflibercept group (p=0.22). BCVA improved by 0.10 in the brolucizumab group and by 0.05 in the aflibercept group. CRT decreased by 46 &#xb5;m and 29 &#xb5;m, respectively. Patients treated with brolucizumab demonstrated more pronounced positive structural dynamics, including a reduction in the frequency of subretinal and intraretinal fluid occurrence. No postoperative adverse events were recorded.<br><br>CONCLUSION: Phacoemulsification does not negatively affect the course of nAMD and does not require increased frequency of anti-VEGF therapy. The data confirm the safety of continuing treatment after cataract surgery. Brolucizumab demonstrated more pronounced functional and morphological improvements compared with aflibercept.}, }
@article {pmid42048983, year = {2026}, author = {Trinquet, L and Matonti, F and Chavane, F and Lorenceau, J and David, T}, title = {[Functional assessment of maculopathies and diabetic retinopathy by chromatic multifocal pupillometry].}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {6}, pages = {104878}, doi = {10.1016/j.jfo.2026.104878}, pmid = {42048983}, issn = {1773-0597}, abstract = {PURPOSE: To evaluate the performance of an innovative, noninvasive, rapid chromatic multifocal dynamic pupillometry protocol (mPFTCo) in detecting functional retinal changes in three chronic diseases: age-related maculopathy (ARM), age-related macular degeneration (AMD), and diabetic retinopathy (DR).<br><br>METHODS: A cohort of 222 participants (68 controls, 18 ARM, 79 AMD, 57 DR) was tested with mPFTCo. This one-minute test per eye used a multifocal stimulus covering 40&#xb0; of the visual field, divided into nine regions, each periodically modulated in luminance, with chromatic alternation (blue, red, green, gray) every 15s. Regional and spectral pupillary responses were analyzed to characterize functional deficits. Group comparisons were performed using Student's t-tests and ROC curve analyses.<br><br>RESULTS: Compared with controls, significant regional alterations were observed in all three diseases. In AMD, pupillary responses were reduced in central and paracentral regions, particularly under red stimulation (P<0.001). In ARM, a moderate paracentral deficit was observed with blue and green stimulation (P<0.005). In DR, a diffuse deficit affected the entire visual field across all colors (P<0.001). This brief, objective, well-tolerated test showed excellent diagnostic performance (AUC=1).<br><br>CONCLUSION: mPFTCo enables rapid, noninvasive topographic assessment of retinal function. It effectively discriminates between pathological profiles and identifies subclinical alterations not detected by conventional visual tests, representing a promising tool for screening, monitoring, and functional evaluation of treatments in routine clinical practice.}, }
@article {pmid42049512, year = {2026}, author = {Wienbar, SR and Bryman, GS and Do, MTH}, title = {HIGH-FIDELITY backpropagation through primate foveal cones.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1523/JNEUROSCI.0085-26.2026}, pmid = {42049512}, issn = {1529-2401}, abstract = {Primate vision has exceptionally high spatial acuity and contrast sensitivity. This performance originates in specialized photoreceptors of the fovea. These cones transduce light into electrical signals in the outer segment, and convey these signals to the presynaptic terminal for transmission. Backpropagating signals are also possible, as the terminal receives inputs. Such signals could influence phototransduction itself. To test this idea, we recorded electrophysiologically from both ends of single cones dissociated from the macaque fovea (either sex). We found that backpropagation was effective despite the extreme slenderness and length of these cells. Backpropagation was also effective in a passive compartmental model, indicating that amplification by voltage-gated channels is not required. We then modeled foveal cones receiving terminal inputs from retinal networks. Despite faithful backpropagation of these inputs, they appear unlikely to influence phototransduction. Thus, even though foveal cones exhibit effective backpropagation, their encoding of visual information may remain compartmentalized.Significance Statement Humans, like other primates, see a fineness of detail that eludes other mammals. This capability is used for tasks like reading and recognizing faces. It is lost in leading forms of vision impairment, such as age-related macular degeneration. Investigating it therefore provides insight into the origin of exceptional sensory performance while strengthening the foundation for preserving and restoring sight. This study examines cells that initiate high-acuity vision, the foveal cones, which produce electrical signals from light and send them forward. It reveals that electrical signals also travel effectively in reverse, from the site of transmission to that of production, and how the production of light responses may be independent nonetheless.}, }
@article {pmid42038919, year = {2025}, author = {Bokhary, KA}, title = {Narrative Review of Artificial Intelligence in Ophthalmic Disease Detection : Artificial Intelligence in Ophthalmic Diseases Detection.}, journal = {Galen medical journal}, volume = {14}, number = {}, pages = {e3979}, pmid = {42038919}, issn = {2322-2379}, abstract = {BACKGROUND: Artificial intelligence (AI) is revolutionizing ophthalmology and optometry by utilizing high-resolution imaging modalities such as optical coherence tomography (OCT), fundus photography, and corneal topography. These modalities generate quantifiable data suitable for machine learning (ML), facilitating automated diagnosis of ocular conditions like diabetic retinopathy, glaucoma, and age-related macular degeneration (AMD), which are leading causes of visual impairment worldwide. This narrative review evaluates the role of ML in improving diagnostic accuracy and accessibility in eye care, focusing on methodological complexities, supervised and unsupervised learning approaches, and challenges in clinical integration.<br><br>MATERIALS AND METHODS: A comprehensive narrative literature review was conducted, analyzing ML applications in ophthalmology.<br><br>RESULTS: AI systems exhibit high sensitivity and specificity, often outperforming human graders in diabetic retinopathy screening and early detection of glaucoma and AMD using OCT and fundus imaging. Anterior segment diseases benefit from AI-driven corneal topography analysis. Challenges include image quality, dataset imbalances, and variability in imaging protocols, necessitating fine-tuning for diverse clinical environments. Unsupervised learning shows potential for identifying novel biomarkers but requires further validation.<br><br>CONCLUSION: AI-driven ML models significantly enhance eye disease diagnostics, improving accuracy and accessibility, particularly in resource-limited settings. However, challenges like data standardization and model generalizability must be addressed to ensure robust clinical adoption.}, }
@article {pmid42038949, year = {2026}, author = {Almusib, RBA and Awad, AH and Ghandorah, AM and AnbarSerry, AOM and Aljumah, HK and Albarrak, AI and Alghanmi, RM and Alshami, FME and Alhejaili, BFR and Alboqami, AFF and Mohayya, EMH and Almatrafi, AM and Alzuwayr, MA}, title = {Relationship of Atropine in Controlling Myopia Progression Among Pediatric Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {590501}, pmid = {42038949}, issn = {1177-5467}, abstract = {PURPOSE: Myopia is a refractive error where light focuses in front of the retina, causing blurred distance vision. It is linked to complications such as macular degeneration, retinal detachment, glaucoma, and cataracts, potentially resulting in irreversible vision loss. Controlling myopia progression is critical to reduce long-term impairment. This systematic review evaluate and compare different atropine concentrations for slowing myopia progression in pediatric patients.<br><br>PATIENTS AND METHODS: A comprehensive electronic search was conducted in PubMed, Google Scholar, Embase, and the Cochrane Central Register of Controlled Trials for studies published between June 1, 2006, and September 1, 2024. Included studies enrolled participants aged <18 years, used a randomized placebo-controlled design, and evaluated atropine effects on myopia progression in individuals with spherical equivalent &#x2264; 0.25 D. Primary outcomes, spherical equivalent refractive error (SER) and axial length (AL), were analyzed via meta-analysis using mean differences (MDs) with 95% confidence intervals (CIs).<br><br>RESULTS: This meta-analysis included 10 studies (2006-2024) evaluating atropine effects on myopia progression. Atropine significantly slowed progression versus placebo. At 6 and 12 months, MD in SER was 0.26 (95% CI, 0.17-0.34) and 0.54 (95% CI, 0.26-0.82), respectively, (p < 0.001). Atropine also significantly reduced AL growth at 6 months (MD -0.09, 95% CI, -0.14 to -0.04).<br><br>CONCLUSION: Atropine effectively reduced AL growth and myopia progression. Heterogeneity across studies suggests variability. Further research is essential to clarify its mechanism.}, }
@article {pmid42039586, year = {2026}, author = {Ghosh, S and Koontz, V and Xin, Y and Bammidi, S and Meyer, D and Wang, H and Babu, VS and Dutta, P and Cherukaraveedu, D and Mohanakrishnan, SA and Mondal, AK and Das, J and Nguyen, J and Soundararajan, A and Adekale, IA and Bhaumik, D and Hose, S and Rowan, S and Pattabiraman, PP and Kannan, RM and Handa, JT and Yi, J and Sripathi, SR and Qian, J and Sinha, D}, title = {Gut-derived metabolic reprogramming drives immune aging and tissue degeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.04.14.718497}, pmid = {42039586}, issn = {2692-8205}, abstract = {Aging is characterized by changes in gut microbiome, metabolic imbalance and chronic inflammation, yet how these processes integrate to drive tissue degeneration remains poorly defined. Using age-related macular degeneration (AMD) as a model of tissue aging, we identify a diet-induced metabolic-immune axis that promotes systemic and retinal degeneration. In mice, a high-fat, cholesterol-enriched (HFC) diet induced perturbations in the gut structural integrity and microbiome repertoire, as well as systemic metabolic aging signatures, prominently marked by reduced circulating histidine. Plasma histidine levels were similarly decreased in AMD patients and inversely correlated with body mass index (BMI) in control donors. These diet-induced gut microbiome changes and subsequent metabolic alterations promoted peripheral innate immune reprogramming, with expansion of inflammatory neutrophils and monocytes that infiltrated the outer retina in a mouse model. Mechanistically, the gut-derived IGF1R/AKT2 signaling acts as a central regulator of global epigenetic remodeling and systemic immune aging under high-fat conditions in C. elegans . In a mouse model with an age-dependent dry AMD-like pathology, distinct retinal pigment epithelium (RPE) subpopulations exhibited downregulation of the histidine transporter SLC7A5, linking metabolic stress to activation of MIF/CD74-dependent inflammatory signaling between RPE and infiltrating immune cells. Histidine supplementation or AKT2 phospho-state modulation attenuated systemic immune activation and rescued retinal degeneration. These findings identify histidine-axis dysregulation as a mechanistic bridge between diet-induced microbiome changes, metabolic stress, immune aging, and retinal degeneration.}, }
@article {pmid42040622, year = {2026}, author = {Zhang, X and Cui, B and Liu, Y and Ji, X and Tian, X and Hou, S and Yang, L and Yang, J}, title = {Psychosocial determinants of anti-VEGF treatment adherence in AMD patients: optimization of one-stop intravitreal injection service model.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1745453}, pmid = {42040622}, issn = {2296-858X}, abstract = {OBJECTIVE: To investigate modifiable psychosocial determinants of anti-VEGF treatment adherence in patients with neovascular age-related macular degeneration (nAMD) and evaluate the optimization effects of a one-stop intravitreal injection service model.<br><br>METHODS: This historical control mixed-methods study included patients receiving anti-VEGF treatment at Cangzhou Regional Ophthalmology Center from August 2022 to October 2024. Patients were divided into three groups based on service models: traditional multiple-visit group (historical control, n = 165), one-stop standard group (n = 161), and one-stop AI-enhanced group (n = 162). The Hospital Anxiety and Depression Scale (HADS) was used to assess psychological status, and geographic information systems analyzed spatial accessibility impacts. Primary outcome measures included 12-month retention rate, early discontinuation rate (within 6 months), and appointment adherence rate. In-depth semi-structured interviews were conducted with patients from the one-stop standard and AI-enhanced groups, using thematic analysis to identify key influencing factors. Logistic regression analysis was used to analyze adherence predictors.<br><br>RESULTS: Compared to the historical control group, the one-stop standard and AI-enhanced groups showed significantly reduced clinic-to-injection time (23.87 vs. 6.47 vs. 6.01 h, P < 0.05), significantly improved 12-month retention rates (52.12 vs. 73.29 vs. 85.80%, P < 0.05), and significantly reduced early discontinuation rates (29.09 vs. 17.39 vs. 9.88%, P < 0.05). Regarding clinical outcomes, patients in the AI-enhanced group showed more significant best-corrected visual acuity (BCVA) improvement (logMAR change: -0.08 vs. -0.12 vs. -0.17, P < 0.05) and more pronounced central retinal thickness reduction (57.83 vs. 86.92 vs. 111.75 &#x3bc;m, P < 0.05). Multifactorial analysis showed that residential distance >38 km, baseline high anxiety levels, and baseline depressive symptoms were independent risk factors for treatment discontinuation. AI-enhanced intervention significantly reduced early discontinuation risk (P < 0.05). Qualitative analysis identified five main themes: treatment anxiety, service experience, expectation management, social support, and service improvement needs. Safety event incidence rates showed no significant differences between groups (P > 0.05).<br><br>CONCLUSION: The one-stop intravitreal injection service model significantly improved treatment adherence in nAMD patients, with AI-enhanced intervention further optimizing outcomes. Baseline anxiety and depression levels, along with geographic distance, are important modifiable determinants of treatment adherence. Personalized service models integrating psychosocial interventions provide new insights for precision management of chronic eye diseases.}, }
@article {pmid42040936, year = {2026}, author = {Azargui, S and Lisker-Cervantes, A and Patnaik, JL and Gnanaraj, R and Mehta, N and Gange, B and Lynch, AM and Palestine, AG and Mathias, MT and Manoharan, N and Mandava, N and Forest, TEC}, title = {Imaging Biomarkers To Predict Progression of Intermediate AMD with Avascular Pigment Epithelial Detachment in the University of Colorado AMD Registry.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-9193520/v1}, pmid = {42040936}, issn = {2693-5015}, abstract = {Purpose: To investigate whether specific imaging biomarkers predict progression to neovascular AMD (nAMD) or geographic atrophy (GA) in eyes with high-risk intermediate age-related macular degeneration (iAMD) and avascular pigment epithelial detachment (PED). Methods: Prospective longitudinal cohort study of eyes with iAMD and avascular PED from the University of Colorado AMD registry (August 2014 - August 2023) with ≥1 month of follow-up through February 2024. Multimodal imaging, including color fundus photos (CFP), fundus autofluorescence (FAF), and optical coherence tomography (OCT), was graded by two reviewers for presence of specific imaging biomarkers. Time-to-progression survival analysis was conducted with hazard ratios calculated. Results: Over a median follow-up period of 35 months, 224 eyes (142 patients) were included. 31 (13.8%) eyes progressed to nAMD, and 63 (28.1%) to GA. Progression to nAMD was significantly predicted by pigmentary changes on CFP (HR=4.43 (95%CI: 1.77, 11.1), p=0.001) and intraretinal hyperreflective foci (iHRF) on OCT (HR=4.90 (95%CI: 2.02, 11.9), p=0.0005). Progression to GA was significantly predicted by pigmentary changes on CFP (HR=3.60 (95%CI: 1.94, 6.67), p<0.0001), iHRF (HR=4.13 (95%CI: 2.14, 7.94), p<0.0001), acquired vitelliform lesions (AVL; (HR=2.97 (95%CI: 1.55, 5.68), p=0.001)) and incomplete retinal pigment epithelium and outer retina atrophy (iRORA; (HR=4.18 (95%CI: 1.52, 11.4), p=0.006)). No other biomarkers demonstrated significance. Conclusion: In eyes with avascular PED, pigmentary changes and iHRF were significantly associated with progression to nAMD and GA, while AVL and iRORA were specifically to GA. We highlight in this study important imaging biomarkers that help identify high-risk eyes that may warrant closer monitoring to ensure timely therapeutic intervention.}, }
@article {pmid42041185, year = {2026}, author = {Ju, H and Jin, L and Qin, X and Tian, Y and Peng, H and Wang, X}, title = {Associations of Frailty Index and Composite Dietary Antioxidant Index With Major Ocular Diseases and Analysis of Component Contributions: A Cross-Sectional Study.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {4}, pages = {25}, doi = {10.1167/tvst.15.4.25}, pmid = {42041185}, issn = {2164-2591}, mesh = {Humans ; Cross-Sectional Studies ; Male ; *Antioxidants/metabolism ; Middle Aged ; Female ; *Frailty/epidemiology ; *Eye Diseases/epidemiology ; Aged ; Nutrition Surveys ; *Diet ; Adult ; United States/epidemiology ; }, abstract = {PURPOSE: To evaluate the independent and joint effects of the frailty index (FI) and composite dietary antioxidant index (CDAI) with major ocular diseases and quantify contributions of their components.<br><br>METHODS: We analyzed 4455 U.S. adults aged &#x2265;40 years from NHANES 2005-2008. Frailty was defined using a 49-item deficit accumulation FI (FI > 0.21 considered frail), and CDAI was derived from six antioxidants (carotenoids, vitamins A, C, E, selenium, zinc). Weighted multivariable logistic regression, variable importance, restricted cubic spline analyses, and sensitivity analyses assessed associations with retinopathy, cataract, diabetic retinopathy (DR), glaucoma, and age-related macular degeneration.<br><br>RESULTS: Higher FI was associated with higher odds of all major ocular diseases (any ocular disease: odds ratio [OR] = 1.35; DR: OR = 2.21; glaucoma: OR = 1.34), whereas higher CDAI was associated with lower odds (any ocular disease: OR = 0.97; glaucoma: OR = 0.91). Participants with high FI and low CDAI had the highest odds, based on predefined cutoff categories (any ocular disease: OR = 2.22; DR: OR = 4.92; cataract: OR = 2.50; glaucoma: OR = 3.18; all P < 0.05). Exploratory analyses showed that CDAI contributions varied by disease, whereas chronic disease burden dominated among FI domains.<br><br>CONCLUSIONS: Higher FI and lower CDAI were independently and in combination associated with major ocular diseases, highlighting the relevance of considering frailty status and dietary antioxidant profiles together in ocular health.<br><br>TRANSLATIONAL RELEVANCE: Higher FI and lower CDAI show combined associations with major ocular diseases, emphasizing their relevance to vision-related health.}, }
@article {pmid42041592, year = {2026}, author = {Yang, Y and Liu, P and Li, J and Deng, Y and Xiao, L and Peng, Q and Peng, J}, title = {Retinal Pigment Epithelium Ageing: Cellular and Molecular Mechanisms of Long-Term Homeostasis and Age-Related Dysfunction.}, journal = {Cells}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/cells15080725}, pmid = {42041592}, issn = {2073-4409}, support = {82274341, 82405487//National Natural Science Foundation of China/ ; 2024JJ5304, 2025JJ60633//Natural Science Foundation of Hunan Province/ ; 2024JK2122//Key Research and Development Program of Hunan Province/ ; 23A0278, 23B0346//Scientific research project of Hunan Provincial Department of Education/ ; }, mesh = {Humans ; *Retinal Pigment Epithelium/pathology/metabolism ; *Homeostasis ; *Aging/pathology/metabolism ; Animals ; Macular Degeneration/pathology/metabolism ; Mitochondria/metabolism ; *Cellular Senescence ; }, abstract = {The retinal pigment epithelium (RPE) is a long-lived, highly polarised epithelial monolayer that performs essential functions in retinal homeostasis, including outer blood-retina barrier maintenance, visual cycle activity, metabolic exchange, phagocytic clearance of photoreceptor outer segments, and regulation of oxidative and immune balance. Because RPE cells persist for decades under conditions of sustained oxidative, metabolic, and phagocytic stress, this tissue provides a valuable model for examining how long-lived post-mitotic cells preserve function over time and how age-related dysfunction emerges when that balance weakens. Although much of the current literature on RPE ageing has been shaped by age-related macular degeneration (AMD), age-dependent change in the RPE should not be understood solely as a preclinical stage of disease. Rather, the ageing RPE offers a broader framework for studying cellular maintenance under chronic physiological load. In this review, we synthesise current evidence on RPE ageing across four interrelated domains: structural remodelling, mitochondrial and metabolic imbalance, proteostatic and lysosomal burden, and chronic inflammatory dysregulation. Across these processes, ageing in the RPE is expressed less as widespread cell loss than as progressive decline in cellular organisation, buffering capacity, and functional precision. Structural irregularity, altered mitochondrial regulation, incomplete degradative clearance, and persistent low-grade inflammatory signalling together reduce the ability of the RPE to maintain long-term homeostasis and increase vulnerability to age-related retinal dysfunction. We further argue that ageing in the RPE is best understood not as abrupt failure of isolated pathways, but as gradual loss of system coherence among interacting homeostatic systems that remain active while operating under increasing constraint. This view helps integrate diverse cellular and molecular findings and highlights the RPE as an informative model for understanding ageing in long-lived post-mitotic tissues.}, }
@article {pmid41840594, year = {2026}, author = {Liu, Y and Zhao, J and Huang, J and Qin, Y and Huang, Y and Fan, H and Zhou, W and Han, H and You, C and Cui, Z and Belfort Junior, R and Fernandes, RAB and Yan, H}, title = {Real-world cost evaluation of conbercept vs. ranibizumab for retinal and choroidal vascular diseases from 2021 to 2024: evidence from societal and medical insurance perspectives.}, journal = {BMC public health}, volume = {26}, number = {1}, pages = {}, pmid = {41840594}, issn = {1471-2458}, support = {22ZYYYQ05//Tianjin Medical University General Hospital Excellent Youth Science Fund/ ; 23JCQNJC01180//Tianjin Natural Science Foundation Youth Project/ ; 23JCZXJC00140//Beijing-Tianjin-Hebei Special Project/ ; 82530032&#xff0c;82330031//National Natural Science Foundation of China/ ; 25JCZDJC00390//Natural Science Foundation of Tianjin/ ; NO. TJYXZDXK-3-004A//The Tianjin Key Medical Discipline Construction Project/ ; }, abstract = {BACKGROUND: Retinal and choroidal vascular diseases including age-related macular degeneration (AMD), branch and central retinal vein occlusion (BRVO, CRVO), diabetic macular edema (DME), and choroidal neovascularization secondary to pathologic myopia (PM) are important causes of blindness. Their treatments by anti-VEGF agents imply heavy economic impact.<br><br>METHODS: The Markov model was constructed based on best-corrected visual acuity, real-world injection frequencies and medical costs of 15,266 patients in Tianjin (2021&#x2013;2024), utility values, and transition probabilities derived from clinical trials. Costs and outcomes were calculated separately under societal and medical insurance perspectives. Incremental cost-effectiveness ratios (ICERs) were computed, and sensitivity analyses (one-way, two-way and probabilistic) were conducted to assess result robustness.<br><br>RESULTS: From both the societal and medical insurance perspectives, conbercept was more cost-effective than ranibizumab in BRVO, CRVO, DME, and PM with ICERs as -442,423.176, -2,429,628.701, -69,339.384, -410,661.276 as Chinese Yuan/quality-adjusted life year (RMB/QALY) under the societal perspective, and&#x2009;-370,506.503, -2,491,085.315, -66,253.162, -432,736.475 RMB/QALY under the medical insurance perspective in 2023, respectively. In contrast, ranibizumab consistently showed greater effectiveness for AMD, with conbercept&#x2019;s ICER reaching 53,927.073 RMB/QALY in 2024 under the medical insurance perspective. Sensitivity analyses confirmed the robustness of these findings.<br><br>CONCLUSION: Conbercept is a cost-effective alternative to ranibizumab in RVO, DME, and PM from societal and medical insurance perspectives. In AMD, ranibizumab remains more clinically effective option. These findings provide economic evidence to support value-based decision-making anti-VEGF therapy in China.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-026-26994-1.}, }
@article {pmid42033410, year = {2026}, author = {Gu, X and Terebuh, P and Xu, R and Kaelber, DC and Davis, PB}, title = {Age-related macular degeneration and dementia: Association through pathogenesis or visual impairment?.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {}, number = {}, pages = {13872877261438849}, doi = {10.1177/13872877261438849}, pmid = {42033410}, issn = {1875-8908}, abstract = {BackgroundStudies suggest a link between blindness, age-related macular degeneration (AMD), and dementia risk, but whether this stems from AMD pathology or blindness remains unclear. This study examines the relationship between AMD and dementia.ObjectiveTo evaluate the association between AMD and 5-year dementia risk in non-blind patients.MethodsThis retrospective cohort study used TriNetX to compare non-blind patients with exudative AMD (n = 35,021) and non-exudative AMD (n = 96,809) to those without AMD (n = 1,801,879) for five-year dementia risk. Blind (n = 90,615) and non-blind (n = 800,737) patients were compared. Cohorts were propensity-matched for confounding factors.ResultsNon-blind AMD patients had decreased Alzheimer's disease risk, while blindness showed a strong positive association. Exudative AMD had HR of 0.84 (95% CI = [0.72, 0.97]), non-exudative AMD had HR of 0.95 (95% CI = [0.87, 1.04]), but blindness increased Alzheimer's disease risk (95% HR = 1.29, CI = [1.17, 1.41]).ConclusionsThese findings suggest that previously reported associations between AMD and dementia may be partially mediated by visual impairment. The modest reduction in dementia risk in non-blind AMD patients may reflect differences in healthcare utilization or treatment exposure among AMD patients.}, }
@article {pmid42033485, year = {2026}, author = {Desmettre, T and Ledesma-Gil, G and Paques, M}, title = {Bidirectional Retro mode differential imaging improves drusen boundary depiction in early and intermediate AMD: a pilot study.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42033485}, issn = {1435-702X}, }
@article {pmid42033607, year = {2026}, author = {Zhang, R and Tunon-Robinson, I and Nguyen, AK}, title = {Visual Outcomes Following Infectious Endophthalmitis from Intravitreal Injections of Biologic Drugs: An Intelligent Research in Sight Registry Retrospective Analysis.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42033607}, issn = {2193-8245}, abstract = {INTRODUCTION: Intravitreal (IVT) injections are now among the most frequently performed intraocular procedures globally. Evidence regarding post-IVT-injection infectious endophthalmitis is primarily derived from a limited number of randomized controlled trials and retrospective case series. This study assesses visual acuity outcomes after IVT biologic therapy utilizing data from a large-scale ophthalmic registry, with the objective of elucidating the real-world effects of post-IVT-injection infectious endophthalmitis on patient visual function.<br><br>METHODS: Data were obtained from the Intelligent Research in Sight[&#xae;] (IRIS[&#xae;]) Registry, focusing on subjects who received commercially available IVT anti-VEGF and anti-complement biologic drugs.<br><br>RESULTS: As of 31 December 2024, 1,998,399 individuals received at least one IVT injection in one or both eyes, and 13,074 subjects (affecting 13,317 eyes) were diagnosed with infectious endophthalmitis. Incidence of infectious endophthalmitis per IVT injection was 0.052%. The cumulative rate of infectious endophthalmitis per subject rose from 0.31% after 10 IVT injections to 0.58% after 60 injections. The proportion of subjects who were legally blind (defined as&#x2009;&#x2264;&#x2009;35 letters or&#x2009;&#x2264;&#x2009;20/200) increased from 19.4% before the infectious endophthalmitis event to 46.1% afterward. In total, 94 eyes affected by infectious endophthalmitis underwent evisceration or enucleation. Subjects with retinal vein occlusion and myopic choroidal neovascularization had the highest incidence rates of infectious endophthalmitis compared with those with neovascular (wet) age-related macular degeneration and diabetic macular edema/diabetic retinopathy.<br><br>CONCLUSIONS: In the real world, the cumulative incidence of infectious endophthalmitis per subject is positively correlated with the total number of IVT injections administered. While the incidence of post-IVT-injection infectious endophthalmitis was comparable to literature values reported after cataract surgery, visual acuity outcomes were worse in the post-IVT injection group. Implementing strategies aimed at reducing IVT injection frequency may have the potential to lower the incidence of infectious endophthalmitis and the consequent risk of significant vision loss.}, }
@article {pmid42033608, year = {2026}, author = {Haase, M and Wittenborn, E}, title = {Rapid Effects on Anatomical and Functional Outcomes following Upload with Faricimab in Treatment-Naïve nAMD: German Single-Center Study 45DRY.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42033608}, issn = {2193-8245}, abstract = {INTRODUCTION: The bispecific antibody faricimab inhibits vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2), two key mediators in the pathophysiology of neovascular age-related macular degeneration (nAMD), which is characterized by choroidal neovascularization, vascular instability, leakage, and intra/subretinal fluid with consequent vision loss. The aim of our study was to assess the effectiveness of faricimab at week 16 versus baseline in patients with treatment-naïve nAMD managed under real-world conditions in Germany.<br><br>METHODS: 45DRY was a retrospective, single-center analysis of consecutive patients with treatment-na&#xef;ve nAMD initiating faricimab (four monthly injections at weeks 0, 4, 8, and 12). Outcomes were evaluated at baseline and week 16 (&#xb1;&#x2009;14&#xa0;days). The&#xa0;primary endpoint was change from baseline in central retinal thickness (CRT); secondary endpoints were change in best-corrected visual acuity (BCVA) and presence/absence of intraretinal fluid (IRF), subretinal fluid (SRF), combined IRF&#x2009;+&#x2009;SRF, and subretinal pigment epithelium (sub-RPE) fluid. Analyses were descriptive.<br><br>RESULTS: A total of 45 eyes from 45 patients were included (mean age 82.1&#xa0;years; 51.1% female). Mean CRT decreased by&#x2009;-140.8&#xa0;&#x3bc;m from 343.1&#xa0;&#xb5;m at baseline to 202.4&#xa0;&#xb5;m at week 16 [95% confidence interval (CI)&#x2009;-178.2 to&#x2009;-103.3]. Mean BCVA improved by -0.15 logMAR at week 16. Among eyes with retinal fluid at baseline, IRF resolved in 100% (24/24), SRF in 94.1% (32/34), combined IRF&#x2009;+&#x2009;SRF in 100% (17/17), and sub-RPE fluid in 90% (9/10). Maintenance of fluid-free status was universal in eyes negative at baseline for IRF (21/21), SRF (11/11), and combined IRF&#x2009;+&#x2009;SRF (28/28); sub-RPE fluid remained absent in 100% (35/35).<br><br>CONCLUSIONS: In routine clinical practice, a four-dose faricimab upload per label at the time of study conduct led to a rapid and substantial anatomical drying effect at week 16 with improvement in BCVA and marked CRT reduction. These real-world findings confirm that faricimab rapidly and effectively reduces retinal fluid, in line with post hoc analyses of the pivotal TENAYA and LUCERNE trials.}, }
@article {pmid42036126, year = {2026}, author = {Turnbull, PRK and Acosta, ML and Lee, A and Solanki, B}, title = {Optometrist attitudes towards delivering intravitreal injections in Aotearoa New Zealand.}, journal = {Clinical &amp; experimental optometry}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/08164622.2026.2652580}, pmid = {42036126}, issn = {1444-0938}, }
@article {pmid42027463, year = {2026}, author = {Drago, L and De La Motte, LR}, title = {The eye's coral reef: toward a planetary-health agenda for ocular-microbiome stewardship.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1816460}, pmid = {42027463}, issn = {1664-302X}, abstract = {Coral reefs and the human ocular surface represent ecologically distinct yet structurally comparable microbial ecosystems in which resilience depends on finely regulated host-microbe interactions. In coral reef science, microbial shifts precede visible bleaching and ecosystem collapse, enabling the development of predictive stress indices such as Degree Heating Weeks (DHW). Comparable principles are emerging in host-associated, low-biomass microbiomes, where subtle perturbations may trigger disproportionate functional consequences. Here, we propose a systems-level conceptual framework linking coral reef holobionts and the ocular surface as sentinel ecosystems governed by cumulative stress, threshold dynamics, and microbial instability. We introduce two heuristic constructs-the Cumulative Desiccating Load (CDL) and the Ocular Dysbiosis Sentinel Index (ODSI)-to frame dysbiosis as a trajectory of resilience loss driven by cumulative perturbations. Aging-related conditions such as age-related macular degeneration are discussed as examples of microbial and metabolic senescence within the human holobiont, conceptually paralleling coral reef decline under chronic sublethal stress. By integrating environmental and host-associated microbiome research within a planetary-health perspective, this article advances a resilience-oriented systems framework applicable across biological scales.}, }
@article {pmid42027954, year = {2026}, author = {Li, J and Yan, Z and Mao, D and Liu, X and Lee, P and Lyu, Y and Feng, N}, title = {Microneedle technology in the treatment of ocular diseases: Advances and applications.}, journal = {Asian journal of pharmaceutical sciences}, volume = {21}, number = {2}, pages = {101129}, pmid = {42027954}, issn = {2221-285X}, abstract = {Microneedle (MN) technology has emerged as a transformative approach for treating ocular diseases, addressing the limitations of conventional drug delivery methods such as low bioavailability and poor patient compliance. This review highlights the advancements and applications of MNs in managing both anterior and posterior segment ocular diseases. MNs overcome physiological barriers, enabling precise, minimally invasive drug delivery with enhanced efficacy. Various MN designs, such as solid, coated, soluble, hollow, hydrogel and cryo-MNs, are tailored for specific therapeutic needs, offering rapid or sustained drug release. Applications include treating keratitis, glaucoma, age-related macular degeneration and diabetic retinopathy, demonstrating improved drug penetration and reduced side effects. Despite challenges in manufacturing and clinical translation, MN technology holds promise for revolutionizing ocular therapeutics through innovations in materials, design, and personalized medicine.}, }
@article {pmid42028099, year = {2026}, author = {Shah, SH and Zhu, Y and Bennett, C and Tracy, J and Ploumi, I and Barton, KM and Gumustop, S and Nodecker, K and Wagner, S and Chen, C and Ding, X and Stevanovic, M and Lains, I and Miller, JB}, title = {Standardized Ultra-Widefield Swept-Source OCT Imaging: A Reproducible Protocol for Peripheral Retinal Assessment.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {581561}, pmid = {42028099}, issn = {1177-5467}, abstract = {BACKGROUND: The utilization of ultra-widefield (UWF) photography and, more recently, UWF-OCT has increased greatly in retina clinic. The most widely available UWF-OCT uses navigated swept-source OCT (SS-OCT), which lacks a standardized protocol, consequently limiting comparisons across patient visits or larger population-based studies. We present a structured imaging protocol to address this limitation.<br><br>TECHNIQUE: A universal template standardizes the number, type, and anatomical positioning of seven scans per patient, including three 21 mm line scans and four UWF volume scans. Scans are automatically positioned per protocol and ultimately stitched into a composite image, which is optimized for longitudinal and inter-patient comparisons.<br><br>DISCUSSION: This protocol enhances efficiency and ensures reproducible assessment of peripheral retinal findings. It may be adapted for other UWF systems and is currently being evaluated for clinical applications.}, }
@article {pmid42028334, year = {2026}, author = {Wang, WX and Wang, CC and Hsu, WC and Peng, YJ}, title = {From Supplements to Sight: Quantifying the Impact of Lutein and Carotenoid on Age-Related Macular Degeneration-A Systematic Review and Meta-Analysis of Randomized Controlled Trials.}, journal = {Journal of ophthalmology}, volume = {2026}, number = {}, pages = {2155378}, pmid = {42028334}, issn = {2090-004X}, abstract = {PURPOSE: To quantify the effects of lutein-containing supplementation on structural and functional visual outcomes in patients with age-related macular degeneration (AMD), with particular focus on disease stage and treatment exposure.<br><br>METHODS: A meta-analysis of randomized, placebo-controlled trials was conducted. Nine RCTs involving 860 participants were included. Eligible studies evaluated oral lutein alone or in combination with zeaxanthin or epilutein and reported pre- and post-treatment measurements of macular pigment optical density (MPOD) and best-corrected visual acuity (BCVA). Random-effects models were applied to calculate pooled effect sizes using Hedges' g. Subgroup and meta-regression analyses were performed to explore stage-specific responses and dose-duration associations.<br><br>RESULTS: Across the 9 RCTs, lutein-containing supplementation significantly improved MPOD (Hedges' g&#x2009;=&#x2009;-0.589, p < 0.001) and BCVA (Hedges' g&#x2009;=&#x2009;-0.827, p = 0.001). Improvements were predominantly observed in early-stage AMD, whereas no statistically significant benefit was detected in late-stage disease. Lutein monotherapy demonstrated greater visual benefit than combination regimens. Meta-regression analyses revealed significant positive associations between treatment effect and both supplementation duration and total lutein exposure. Contrast sensitivity and serum lutein concentrations also improved significantly.<br><br>CONCLUSION: Lutein-based supplementation is associated with measurable structural and functional visual benefits in early-stage AMD. Treatment effects appear dose- and duration-dependent, while evidence in late-stage AMD remains limited. These findings support early intervention strategies and warrant further investigation into long-term therapeutic impact.}, }
@article {pmid42029948, year = {2026}, author = {Labishetty, SC and Kumar, N and Kumari, S}, title = {Comment on "Conjunctival microbiota in retinal diseases requiring anti-VEGF therapy: Age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion".}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261445275}, doi = {10.1177/11206721261445275}, pmid = {42029948}, issn = {1724-6016}, }
@article {pmid42030193, year = {2026}, author = {Molins, B and Nabaes Jodar, MS and de Oliveira, E and Estanyol, JM and Peña, E and Bezunartea, J and Hernández, M and Figueras-Roca, M and Adan, A}, title = {Decellularized Aged Bruch's Membrane Confers Unique Biochemical Cues to Retinal Pigment Epithelium for In Vitro Modeling of Age-Related Macular Degeneration.}, journal = {Aging cell}, volume = {25}, number = {5}, pages = {e70501}, doi = {10.1111/acel.70501}, pmid = {42030193}, issn = {1474-9726}, support = {PI22/00782//Instituto de Salud Carlos III/ ; //Novartis Farmac&#xe9;utica/ ; }, mesh = {Humans ; *Bruch Membrane/metabolism/pathology ; *Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/pathology/metabolism ; Aged ; *Models, Biological ; Male ; Female ; Proteomics ; }, abstract = {Age-related macular degeneration (AMD), a chronic inflammatory disease, is a major cause of irreversible blindness worldwide. It involves the degeneration of the retinal pigment epithelium (RPE) and the accumulation of deposits between the RPE and the Bruch's membrane (BrM), ultimately leading to photoreceptor death. The multifactorial and chronic nature of AMD makes it challenging to model in vitro. We developed a biomaterial based on decellularized BrM (dECM-BrM) from aged donors to evaluate its ability to induce an AMD-like phenotype in RPE monolayers. BrM from 5 young and 5 aged human donors was decellularized and the protein profile analyzed by LC-MS/MS. dECM-BrM was then used as a coating substrate for RPE culture. A total of 281 proteins were identified and proteomic analysis screened 49 differentially expressed proteins in aged dECM-BrM. Gene Ontology analysis showed that they were associated with extracellular region, antioxidant activity, lipid metabolism and transport. Moreover, the KEGG pathway related to complement and coagulation cascade was significantly enriched. RPE culture on aged dECM-BrM allowed RPE polarization and after 60 days, transepithelial electrical resistance significantly decreased compared to RPE grown on young dECM-BrM, accompanied by increased IL-33 secretion and marked expression of drusen components such as vitronectin and apolipoprotein E, lipid deposition and complement factors C3 and C9. We showed a successful approach to obtain a BrM mimic based on decellularized BrM that ensured cellular removal while preserving ECM structure and identified differentially expressed proteins in aged dECM-BrM that may provide specific biochemical cues fundamental to model AMD in vitro.}, }
@article {pmid42030962, year = {2026}, author = {Beiner, D and Zhu, H and Bosholm, CC and Wang, HC and Criswell, T and Atala, A and Ma, JX and Zhang, Y}, title = {Derivation and characterization of retinal pigment epithelium from urine-derived iPSCs.}, journal = {FEBS open bio}, volume = {}, number = {}, pages = {}, doi = {10.1002/2211-5463.70246}, pmid = {42030962}, issn = {2211-5463}, support = {NIH/HIAID R21 AI152832//National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID, NIH)/ ; NIH/NEI R21 EY0358332024//National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID, NIH)/ ; R03 AI165170/AI/NIAID NIH HHS/United States ; 2024 Pilot Research Grant//Eye Bank Association of America (EBAA)/ ; HT94252510856//Department of Defense/ ; 2025 Ignition Fund Pilot Award//Wake Forest School of Medicine (WFSM)/ ; 2025 Translational Team Science Pilot Award//Translational Eye and Vision Research Center (TrEVR), Wake Forest School of Medicine (WFSM)/ ; }, abstract = {Age-related macular degeneration (AMD), particularly its dry form, is a leading cause of irreversible vision loss due to retinal pigment epithelium (RPE) dysfunction and loss. Addressing this unmet therapeutic need requires non-invasive strategies for generating patient-specific RPE cells. This study reports the successful generation and initial characterization of RPE cells derived from urine-derived induced pluripotent stem cells (u-iPSC-RPE). Urine-derived stem cells (USCs) were isolated from healthy individuals and comprehensively characterized, confirming strong expression of renal progenitor makers and mesenchymal stem cell markers, while lacking standard hematopoietic markers. USCs were reprogrammed into iPSCs using the integration-free Sendai virus expressing the Yamanaka factors. The reprogrammed u-iPSC clones displayed characteristic pluripotency marker expression and demonstrated clearance of the Sendai virus by later passages. Subsequently, these u-iPSCs were efficiently differentiated into RPE cells, exhibiting characteristic hexagonal morphology and pigmentation which was confirmed by the expression of key RPE-specific proteins. Our findings demonstrate the feasibility and reliability of generating patient-specific u-iPSC-RPE cells from readily accessible USCs providing a foundation for future studies to investigate their functional potential for retinal disease modeling and therapeutic applications for AMD.}, }
@article {pmid42031005, year = {2026}, author = {Palakkan, AA and Shankar, G and Vignesh, TP and Kim, R}, title = {A tunable, biofabricated light-delivery platform for in vitro modelling of age-related macular degeneration using iPSC-derived RPE cells.}, journal = {Biomedical materials (Bristol, England)}, volume = {}, number = {}, pages = {}, doi = {10.1088/1748-605X/ae6498}, pmid = {42031005}, issn = {1748-605X}, abstract = {The lack of physiologically relevant and controllable experimental systems has limited mechanistic understanding of age-related macular degeneration (AMD) and the development of effective therapeutic strategies. Here, we present a tunable in vitro retinal pigment epithelium (RPE) stress model that integrates engineered light delivery with lipid modulation to reproduce early AMD-like cellular pathology under standard culture conditions. Human RPE cells (ARPE-19 and iPSC-derived RPE) were exposed to precisely controlled, low-intensity light-induced oxidative stress in the presence of docosahexaenoic acid (DHA), a highly unsaturated retinal lipid, or palmitic acid (PA) as a saturated lipid control. Cellular responses were assessed using functional and structural readouts including lysosomal and mitochondrial activity, membrane integrity, epithelial morphology, tight junction organization, and lipid peroxidation. A programmable LED-based exposure system enabled fine control over light intensity, duration, and cycling, allowing delivery of sub-lethal, chronic oxidative stress. Combined light and DHA exposure selectively induced lipid peroxidation, disruption of ZO-1-defined tight junctions, and progressive loss of RPE viability, while PA-treated cells and non-retinal HuH7 hepatocytes showed minimal sensitivity. ARPE-19 cells responded rapidly, whereas iPSC-derived RPE cells exhibited delayed but comparable pathological changes, reflecting differences in cellular maturity and stress resilience. Pharmacological inhibition of ferroptosis using ferrostatin-1 significantly reduced lipid peroxidation and rescued epithelial integrity and cell viability, identifying ferroptosis as a key mechanism underlying RPE vulnerability in this system. By enabling programmable and reproducible delivery of oxidative lipid stress, this modular light-based platform provides a biofabrication-compatible framework for modeling early AMD, with potential for integration into more complex retinal constructs, co-culture systems, and high-throughput therapeutic screening pipelines.}, }
@article {pmid42031134, year = {2026}, author = {Anegondi, N and Lam, D and Guymer, RH and Steffen, V and Cukras, CA and Ferrara, D and Wu, Z}, title = {Vision-Related Quality of Life in Geographic Atrophy: Association with Topographic Lesion Distribution.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.04.019}, pmid = {42031134}, issn = {1549-4713}, abstract = {PURPOSE: To understand the associations between the topographic lesion distribution and vision-related quality of life (VR-QoL) in individuals with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).<br><br>DESIGN: Analysis of data from Chroma (NCT02247479) and Spectri (NCT02247531), which are two identically designed Phase III clinical trials of lampalizumab.<br><br>PARTICIPANTS: Eight-hundred and fifty-six participants that were &#x2265;50 years old with bilateral GA who completed the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) at baseline.<br><br>METHODS: The NEI VFQ-25 was used to determine estimates of VR-QoL in the visual functioning (NEI VFQ-VF) domain, using calibrated item measures and rating category thresholds from Rasch analysis. GA were automatically segmented on combined fundus autofluorescence and near-infrared reflectance images, and its extent in central regions across varying diameters (from 0.25- to 6.00-mm, in 0.25-mm intervals) relative to the fovea were then derived.<br><br>MAIN OUTCOME MEASURES: Association between NEI VFQ-VF person measures and the minimum eye-level GA extent in the region evaluated within an individual (referred to as the minimum GA extent).<br><br>RESULTS: Minimum GA extent within the central region across varying diameters between 0.25- to 6.00-mm were all significantly associated with the NEI VFQ-VF person measures (P &#x2264; 0.001 for all), but the highest proportion of variance explained was seen when evaluating the central 2.50-mm diameter region (R[2] = 0.11). A multivariable analysis showed that only the minimum GA extent within the central 2.50-mm region (P < 0.001), but not the 2.50- to 6.00-mm annulus (P = 0.541), was independently associated with NEI VFQ-VF person measures.<br><br>CONCLUSIONS: In this cohort, VR-QoL is most strongly associated with minimum eye-level GA extent within the central 2.50-mm region within an individual. These findings underscore the importance of evaluating GA extent in this region, beyond simply considering foveal GA involvement, when seeking to evaluate structural changes most closely associated with self-reported impairments in visual functioning.}, }
@article {pmid42031505, year = {2026}, author = {Jonas, JB and Panda-Jonas, S and Pan, Z and Xu, J and Jonas, RA and Wang, YX}, title = {Prevalence and associations of intraretinal hyperreflective foci in age-related macular degeneration: the Beijing Eye Study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328004}, pmid = {42031505}, issn = {1468-2079}, abstract = {BACKGROUND: To assess prevalence and associations of intraretinal hyperreflective foci (HRFs) in a general population.<br><br>METHODS: Participants of the population-based Beijing Eye Study underwent optical coherence tomography and macula photography.<br><br>RESULTS: The study cohort included 1641 eyes (mean age: 62.8&#xb1;9.1 years; range: 50-93 years). Prevalence of any HRF or HRFs located only above the ellipsoid zone (EZ) increased from 33/590 (5.6%; 95%&#x2009;CI 4.0 to 7.0) and 22/590 (3.7%; 95%&#x2009;CI 2.2 to 5.2), respectively, in normal eyes to 371/725 (51.2%; 95%&#x2009;CI 47.7 to 54.7) and 246/725 (33.9%; 95%&#x2009;CI 30.4 to 37.4), respectively, in eyes with early age-related macular degeneration (AMD), to 283/314 (90.1%; 95%&#x2009;CI 87.1 to 93.1) and 260/314 (82.8%; 95%&#x2009;CI 78.8 to 86.8), respectively, in eyes with intermediate AMD, and to 12/12 (100%) and 12/12 (100%), respectively, in late AMD. HRFs above the EZ were spatially associated with EZ defects in 298/540 (55.2%) eyes and external limiting membrane (ELM) defects in 203/540 (37.6%) eyes. 52 (96%) of 54 eyes with macular hyperpigmentations showed HRFs above the EZ, and 52 (9.6%) of 540 eyes with HRFs above the EZ had corresponding macular hyperpigmentations. Higher HRF prevalence was associated (multivariable analysis) with higher AMD stage (OR: 1.75; 95%&#x2009;CI 1.36 to 2.26; p<0.001), and higher prevalences of EZ defects (OR: 36.6; 95%&#x2009;CI 8.56 to 157; p<0.001), reticular pseudodrusen (OR: 1.91; 95%&#x2009;CI 1.29 to 2.82; p<0.001), retinal pigment epithelium (RPE) elevations (OR: 34.5; 95%&#x2009;CI 10.4 to 111; p<0.001) and interdigitation zone thinnings (OR: 4.22; 95%&#x2009;CI 1.90 to 9.35; p<0.001).<br><br>CONCLUSIONS: The HRF prevalence was relatively high in early AMD and increased to late AMD. HRF location and shape suggested intraretinally migrated RPE cells as their equivalent. The majority of HRFs were not associated with an ophthalmoscopically detected macular hyperpigmentation. HRFs can also be found in locations with a localised interdigitation zone thinning with spatially corresponding EZ defects and ELM defects.}, }
@article {pmid41933583, year = {2026}, author = {Zhou, Y and Liu, Y and Chen, H and Yu, Y and Li, Y and Sun, Z and Han, X and Li, H and Zou, X and Sui, R}, title = {Expanding the Clinical and Genetic Spectrum of TTLL5-Associated Retinal Dystrophy: A Single-Center Cohort Study.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.03.017}, pmid = {41933583}, issn = {2468-6530}, abstract = {PURPOSE: To characterize the clinical and genetic spectrum of TTLL5-related retinal dystrophy.<br><br>DESIGN: Retrospective observational study.<br><br>SUBJECTS: Twenty-one affected individuals from 19 unrelated families carrying biallelic TTLL5 variants.<br><br>METHODS: Patients with inherited retinal dystrophy and confirmed biallelic TTLL5 variants were retrospectively reviewed. Genetic diagnosis was established using whole-exome sequencing followed by Sanger confirmation and cosegregation analysis. Clinical assessments included best-corrected visual acuity, multimodal retinal imaging, visual field testing, and full-field electroretinography.<br><br>MAIN OUTCOME MEASURES: Visual function, retinal structural and functional characteristics, and genotype-phenotype correlation.<br><br>RESULTS: The cohort included 10 males and 11 females, aged 6 to 66 years. Based on phenotypic classification, 2 patients were diagnosed with cone dystrophy (CD), 12 with cone-rod dystrophy (CRD), and 7 with rod-cone dystrophy (RCD). Best-corrected visual acuity ranged from 0 to 2.70 logarithm of the minimum angle of resolution (LogMAR) (median, 0.6 LogMAR; interquartile range, 1.55) and was significantly correlated with age (Spearman R = 0.704; P < 0.001). All patients were myopic, with spherical equivalent values ranging from -1.13 to -18.00 diopters, and 14 of 21 (66.67%) had bilateral high myopia (&#x2264;-6.0 diopters). Retinal involvement was characterized by macular degeneration with progressive extension beyond the posterior pole. Fundus autofluorescence demonstrated parafoveal or macular hyperautofluorescent rings followed by expanding hypoautofluorescent areas, whereas OCT revealed parafoveal-to-diffuse disruption or loss of the ellipsoid zone with outer nuclear layer thinning. Genetic analysis identified 24 pathogenic variants, of which 19 (79.17%) were novel. The recurrent missense variant c.437G>A (p.Gly146Glu) was the most frequent allele in this cohort and was consistently associated with a CRD phenotype. Extraocular manifestations were uncommon, with sensorineural hearing loss observed in 1 patient.<br><br>CONCLUSIONS: TTLL5-associated retinal dystrophy exhibits a broad clinical spectrum encompassing CD, CRD, and RCD, with a high prevalence of myopia as a shared feature. The recurrent p.Gly146Glu variant showed a consistent association with the CRD phenotype, suggesting specific allele-phenotype correlations. These findings expand the recognized phenotypic and genetic spectrum of TTLL5-related disease and provide an important clinical framework for diagnosis, counseling, natural history, and future therapeutic studies.<br><br>FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid42021400, year = {2026}, author = {Kniggendorf, V and Silveira, TC and Costa, VDM and Soriano, DS and Regatieri, CV and Sugai, RF and Bordon, A and Nutels, GS and Peixoto, AL and Moreira-Neto, CA and Miranda, JVC and Nehemy, MB and Damico, FM and Zacharias, LC and Lavinsky, D and Machado, CG and Veloso, CED and Cyrino, FV and Cella, W and Roisman, L and Brasil, OF and Andrade, GC and Stefanini, F and Malerbi, FK and Penha, FM and , }, title = {Real-world performance of faricimab for neovascular age-related macular degeneration and diabetic macular edema: experience from the BrazilRetNet multicenter study. Report 1.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00860-z}, pmid = {42021400}, issn = {2056-9920}, }
@article {pmid42021792, year = {2025}, author = {Iztleuov, M and Abugaliyeva, N and Ryzhkin, S and Iztleuov, Y and Saparbaev, S and Smagulova, G}, title = {Current Insights into Plausible Mechanisms of Chromium (VI) Neurotoxicity in the Brain and Future Perspectives.}, journal = {Medical journal of the Islamic Republic of Iran}, volume = {39}, number = {}, pages = {157}, pmid = {42021792}, issn = {1016-1430}, abstract = {BACKGROUND: Hexavalent chromium (Cr (VI)) is a known neurotoxin and environmental contaminant. Despite its recognition, the underlying mechanisms by which Cr (VI) induces neurological damage remain insufficiently explored. The complexities of the Central Nervous System (CNS), including the Blood Brain Barrier (BBB) and supporting brain cells, contribute to regions-specific susceptibility within the brain. Understanding Cr (VI) neurotoxicity is crucial for its potential role in neurodegenerative diseases.<br><br>METHODS: A Systematic Review was conducted using international databases (PubMed, Medline, Scopus, and Web of Science) and Google Scholar. Only open-access, free full-text articles published in English between 2010 and 2025 were included. Following PRISMA 2020 guidelines, a total of 19 relevant studies were selected, comprising 12 animal-based and 7 human cohort studies.<br><br>RESULTS: Animal studies investigated the effects of Cr (VI) via various administration methods and doses, revealed evidence of oxidative stress, inflammatory markers, and apoptotic changes in the brain. Interventional studies showed delayed toxicity when antioxidant agents were used prior to Cr (VI) exposure, including PDC (Potassium Dichromate), SA (Sodium Alginate), and TNG (Tangeretin). Human studies, including autopsies and cell culture analyses, demonstrated neurotoxic effects in conditions such as ALS (Amyotrophic Lateral Sclerosis), nAMD (Neovascular Age-Related Macular Degeneration).<br><br>CONCLUSION: Animal studies have clarified the role of oxidative stress in Cr (VI)-induced neurotoxicity. Human cohort studies have identified Cr (VI) as an environmental risk factor for both neurodegenerative and neurobehavioral disorders. Future research should focus on defining harmful levels of Cr (VI) and exploring potential antioxidant therapies.}, }
@article {pmid42022797, year = {2026}, author = {Sannan, NS and Ramadan, M and Malli, I and Ishgi, L and Al Johani, R and Abualjamal, R}, title = {Frequency and comorbidities of age-related macular degeneration in KSA: A retrospective multiregional study.}, journal = {Journal of Taibah University Medical Sciences}, volume = {21}, number = {3}, pages = {411-419}, pmid = {42022797}, issn = {1658-3612}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. In this study, we characterized the frequency of AMD and its comorbidities in understudied regions.<br><br>METHODS: A retrospective cohort study was conducted using medical records from tertiary care hospitals in KSA (2016-2022). Patients aged &#x2265;40 years with a confirmed AMD diagnosis were included. Demographic and clinical data were analyzed, including comorbidities. Logistic regression analyses were performed.<br><br>RESULTS: Among the 335 patients diagnosed, 66.9% had the exudative form and 33.1% had the non-exudative form. The cohort had a mean age of 71.17 &#xb1; 10.12 years, and there was no significant difference in age between AMD subtypes (p = 0.29). High prevalences of diabetes (66.3%) and hypertension (65.1%) were observed. Estimation of annual case counts revealed a significant temporal variation in diagnosed AMD cases, peaking in 2019 and increasing again by 2021-2022. Logistic regression identified female gender (Exp(B) = 1.03; p = 0.009) and age at diagnosis of diabetes mellitus (Exp(B) = 0.93; p < 0.001) as significant predictors of age at AMD onset. Diabetes mellitus was independently associated with later AMD diagnosis (Exp(B) = 1.03; p = 0.02). Conversely, stroke history was linked to earlier AMD onset (Exp(B) = 0.94; p = 0.002). Other comorbidities, including hypertension, dyslipidemia, and heart failure, had no significant associations.<br><br>CONCLUSION: Our findings highlight the burden of AMD and its comorbidities in KSA. Diabetes and stroke are key predictors, demonstrating the need for integrated chronic disease management strategies.}, }
@article {pmid42023256, year = {2026}, author = {Sun, RS and Huo, SX and Zhang, TL and Ying, HJ and Wang, JH and Xu, LN and Luo, XL and Yang, Y and Hu, YD}, title = {Development of a predictive model for depressive symptoms in type 2 diabetes mellitus patients under community management: Based on visual function index.}, journal = {Ibrain}, volume = {12}, number = {1}, pages = {123-136}, pmid = {42023256}, issn = {2769-2795}, abstract = {Visual impairment has been recognized as a potential risk factor for depressive symptoms (DS) in diabetes patients, yet the role of visual function in predicting DS remains unexplored. This study aims to develop and validate a predictive model for DS risk in type 2 diabetes mellitus (T2DM) patients in community health settings, incorporating a visual function index (VF14). We conducted a cross-sectional study involving 542 T2DM patients from four community health centers in Guiyang. Univariate and multivariate logistic regressions identified significant predictors, while 10 machine learning algorithms were employed to construct the predictive model. Model performance was assessed using such metrics as receiver operating characteristic curves, accuracy, sensitivity, specificity, F1 score, Brier score, C-index, calibration curves, and decision curve analysis. A restricted cubic spline (RCS) analysis evaluated the score-dependent risk profiles between the VF14 and DS. Key predictors included body mass index (BMI), self-reported glycemic status, age-related macular degeneration, glycated hemoglobin (HbA1c), and VF14. Among the models, the gradient boosting machine exhibited the robust predictive performance, with an area under the curve of 0.73 and sensitivity of 0.72. The Shapley additive explanations analysis identified VF14, BMI, and HbA1c as the top risk factors. RCS analysis revealed a score-dependent risk profile between VF14 and DS risk. This study introduces a clinically interpretable tool for early DS risk stratification in T2DM patients, offering potential for improved risk assessment and timely intervention in community health settings.}, }
@article {pmid42024166, year = {2026}, author = {Gregori, G and Sahoo, NK and Lall, SR and Sadeghi, E and Schulman, A and Hasan, N and Chhablani, J}, title = {High choroidal vascularity index zones favor the distribution of drusenoid pigment epithelial detachment in intermediate age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42024166}, issn = {1435-702X}, }
@article {pmid42025255, year = {2026}, author = {Sagnard, M and Valero, B and D'aiello, A and Agard, E and El Chehab, H}, title = {Ocular risks related to light overexposure in maritime professionals in the Provence-Alpes-Côte d'Azur Region, France: The PHOTOPPA study.}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {5}, pages = {104885}, doi = {10.1016/j.jfo.2026.104885}, pmid = {42025255}, issn = {1773-0597}, abstract = {PURPOSE: To assess the prevalence of light-induced toxic effects on the ocular and palpebral regions in maritime professionals chronically exposed to light radiation in the Provence-Alpes-Côte d'Azur region and to compare the results to a non-overexposed population. The study also investigates risk factors for and protective factors against ocular phototoxicity in exposed individuals.<br><br>DESIGN: Single-center, cross-sectional comparative analysis.<br><br>PARTICIPANTS: The study included 77 maritime professionals (overexposed group) and 70 non-overexposed individuals (control group). Participants were examined between July 2023 and June 2024 at the ophthalmology department of Sainte-Anne Military Hospital.<br><br>METHODS: Cross-sectional comparative analysis was performed between the two groups. Participants underwent a clinical examination, including ocular imaging, focused on ocular conditions such as conjunctival lesions, cataracts, and macular changes linked to light overexposure, and completed questionnaires on sun exposure.<br><br>RESULTS: The study found no connection between age-related macular degeneration (AMD) and solar overexposure but highlighted the significant role of light reflection from water in other ocular conditions. Four basal cell carcinomas were found in the exposed group, consistent with the pathogenesis of these skin cancers. A higher risk of conjunctival lesions (pinguecula and/or pterygium) and cortical cataracts was noted. Macular epithelial damage was linked to increased light exposure. Protective solar equipment reduced the risk of ocular damage in certain conditions.<br><br>CONCLUSIONS: The PHOTOPPA study is the first to compare ocular pathologies related to light overexposure in maritime professionals. It confirms the increased risk of ocular conditions, emphasizing the importance of comprehensive sun protection to reduce light-induced ocular damage and possibly prevent AMD development.}, }
@article {pmid42025869, year = {2026}, author = {Abdouh, M and Sebag, W and Abdouh, N and Goyeneche, A and Burnier, MN}, title = {Differential protective effects of blue light (BL)-exposed retinal pigment epithelial cells by selective BL-filtering lenses.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111034}, doi = {10.1016/j.exer.2026.111034}, pmid = {42025869}, issn = {1096-0007}, abstract = {Blue light (BL) is harmful to eye posterior segment structures. It induces accelerated retina aging and the progression of retinal diseases. We reported that BL is cytotoxic to retinal pigment epithelial (RPE) cell through oxidative damage. Herein, we investigated the potential of selective BL-filtering intraocular lenses (BL-IOL) to mitigate these deleterious effects. Human RPE cells were exposed to BL in the absence or presence of a panel of BL-IOLs having different pigment compositions and BL-filtering potentials. Cells were analyzed for their oxidative status (levels of reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨM)), and growth (proliferation, metabolic activity and viability). Exposure of RPE cells to BL significantly increased the levels of cellular ROS and mitochondrial superoxide anion. While these effects did not affect cell proliferation, they triggered a collapse of the ΔΨM, a decrease in cell metabolic activity and an increase of cell death. Independent of the BL-IOL used in the BL beam, there was a drop in oxidative stress and ensuing protection of cells from the BL-mediated cytotoxic effects. Notably, BL-IOL with higher filtration potential of high-energy BL provided better photoprotection to exposed cells. This study highlights the need to selectively filter BL radiation wavelengths from light reaching the eye. It will help to define the best filtering devices to prevent RPE cell damage and eye posterior segment structure-related disease progression, such as during age-related macular degeneration.}, }
@article {pmid42026508, year = {2026}, author = {Chi, SC and Hwang, DK and Chen, SJ and Weng, CC and Huang, YM and Chou, YB and Lin, TC}, title = {Short-term efficacy of aflibercept 8 mg in refractory neovascular age-related macular degeneration: a retrospective case series from Taiwan.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04848-z}, pmid = {42026508}, issn = {1471-2415}, support = {(CI-113-26)//Yen Tjing Ling Medical Foundation/ ; V114C-191//Taipei Veterans General Hospital/ ; }, }
@article {pmid42015048, year = {2026}, author = {Ma, Q and Liu, X and Li, J and Bai, Y and Mu, W and Li, N and Yan, B and Wang, Z}, title = {AMD-UPerNet: a tool for retinal layer and fluid assessment in age-related macular degeneration.}, journal = {BMC medical imaging}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12880-026-02349-5}, pmid = {42015048}, issn = {1471-2342}, }
@article {pmid42017182, year = {2026}, author = {Sivachandran, N and Ji, PX and Khan, H and Pickel, L and Mojumder, O and Aziz, AA and Khan, H and Sulahria, H and Gahn, GM and Khanani, AM}, title = {Visual and Anatomic Outcomes of Faricimab in Naïve Neovascular Age-Related Macular Degeneration with Subretinal Hemorrhage: A Multi-Centre Retrospective Analysis.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {589703}, pmid = {42017182}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate functional and anatomical outcomes of faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) presenting with subretinal hemorrhage (SRH).<br><br>SUBJECTS AND METHODS: A multicenter retrospective chart review was completed in retina practices in Canada and the United States from June 2022 to September 2025. Treatment-na&#xef;ve nAMD patients with SRH receiving faricimab were evaluated. Standardized imaging protocols and treat-and-extend guidelines were employed. Primary outcome was visual acuity (VA) change; secondary outcomes included central subfield thickness (CST), pigment epithelial detachment (PED) height, and qualitative assessment of subretinal hyperreflective material (SHRM) and subretinal fibrosis. Outcomes were analyzed following three consecutive loading doses using Friedman statistics for repeated measures. Paired analysis was performed using Wilcoxon signed rank test. Detailed characterization of SRH included measurements of hemorrhage size in disc diameters (DD), location in terms of subfoveal versus extrafoveal, and duration from symptom onset to treatment initiation. Univariate regression analysis was performed to identify predictors of SRH resolution (effect ratio and 95% CI) and visual acuity improvement (odds ratio and 95% CI).<br><br>RESULTS: This study included 63 treatment-na&#xef;ve patients with nAMD and SRH (mean age was 81.6 &#xb1; 8.2 years; 58.2% females; n = 28 from Canada and n = 35 from United States; mean total follow-up duration was 17.5 &#xb1; 6.0 months). Significant VA improvement was observed (Friedman statistic: 26.3, p < 0.00001), with 42.6% of patients gaining &#x2265;3 lines of vision after loading doses. CST decreased substantially from 391.8&#xa0;&#xb5;m to 249.4&#xa0;&#xb5;m (p < 0.00001, z = -5.48) and mean PED height reduced from 309.6&#xa0;&#xb5;m to 110.7&#xa0;&#xb5;m (p < 0.00001, z = -3.51). SHRM and subretinal fibrosis were noted in 81.6% and 25.4% of cases, respectively, at baseline. Of this, 70% had resolution of SHRM and 50% had improvement in fibrosis, at last follow up visit. Univariate analysis of predictors of faricimab injection account to achieve SRH resolution in n = 33 patients identified three significant predictors: SHRM-presence at baseline (effect ratio = 0.531, 95% CI 0.399-0.707, p < 0.0001), combined intraretinal fluid (IRF) and subretinal fluid (SRF) (effect ratio = 1.43, 95% CI 1.09-1.87, p = 0.011), and non-Caucasian ethnicity (effect ratio = 1.45, 95% CI 1.03-2.04, p = 0.031). Analysis of predictors of VA improvement >3 lines did not reveal any clinically meaningful associations.<br><br>CONCLUSION: This study demonstrates faricimab's efficacy in nAMD with SRH, a challenging phenotype traditionally associated with poor visual prognosis. The dual-pathway inhibition of VEGF-A and Ang-2 achieved rapid hemorrhage clearance and meaningful vision gains, offering clinical hope for this high-risk population.}, }
@article {pmid42017838, year = {2026}, author = {Cui, X and Yuan, J and Zhao, Q and Yu-Wai-Man, P and Zheng, T}, title = {Sleep Regularity and Age-Related Eye Diseases: Prospective Analyses with Retinal Imaging and Multimorbidity Assessment in the UK Biobank.}, journal = {Sleep}, volume = {}, number = {}, pages = {}, doi = {10.1093/sleep/zsag111}, pmid = {42017838}, issn = {1550-9109}, abstract = {STUDY OBJECTIVES: Sleep regularity, a key circadian dimension of sleep health, has been linked to cardiometabolic and neurodegenerative outcomes, yet its relevance to ocular ageing remains unclear. The retina is a metabolically active, circadian-regulated neural tissue, suggesting that irregular sleep may contribute to the development of age-related eye diseases.<br><br>METHODS: We studied 78,839 adults in the UK Biobank. Sleep regularity was quantified using the Sleep Regularity Index (SRI). Associations with age-related macular degeneration (AMD), cataract, glaucoma, retinal vein occlusion (RVO), and diabetic retinopathy (DR) were examined using Cox models, restricted cubic splines, subgroup analyses, and propensity-score matching. Retinal structural and vascular metrics were additionally evaluated. Nomogram models integrating SRI with clinical risk factors were developed.<br><br>RESULTS: Lower SRI was consistently associated with higher risks of AMD (HR=0.87), cataract (HR=0.95), and glaucoma (HR=0.89), with clear dose-response patterns; no robust associations were found for RVO or DR. Higher SRI correlated with greater macular, retinal ganglion cell (RGC), and retinal nerve fiber layer (RNFL) thicknesses, and with more favourable retinal vascular geometry. Incorporating SRI improved prediction performance for AMD, cataract, and glaucoma (AUC 0.72-0.74). SRI also declined markedly with increasing ocular multimorbidity.<br><br>CONCLUSIONS: Sleep regularity was consistently associated with major age-related eye diseases, ocular multimorbidity, and retinal structural and vascular characteristics. These findings highlight sleep regularity as a clinically relevant behavioural correlate of ocular ageing and a potential adjunctive marker for prevention-oriented risk stratification.}, }
@article {pmid42018151, year = {2026}, author = {Nielsen, MA and Bjerager, J and Citirak, G and Subhi, Y and Holm, LM and Singh, A}, title = {Charles Bonnet syndrome in patients referred for cataract surgery.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42018151}, issn = {1435-702X}, abstract = {PURPOSE: To investigate the prevalence and clinical characteristics of Charles Bonnet Syndrome (CBS) in patients referred for bilateral cataract surgery.<br><br>METHODS: This prospective, cross-sectional clinical trial included 391 patients attending cataract assessment at a single-center tertiary cataract clinic. After clinical examination, participants were screened for presence of visual hallucinations (VHs). Participants experiencing complex VHs were further questioned regarding characteristics of their hallucinatory experiences to properly determine if they were attributable to CBS. CBS was defined as complex visual hallucinations with retained insight, no medical history or medication known to cause hallucinations and not limited to hypnagogic or hypnopompic states (hallucinations happening shortly before falling asleep and/or shortly after waking up).<br><br>RESULTS: Nineteen (4.9%) patients experienced complex VHs. Of these, 11 (2.8%) were diagnosed with CBS while 8 (2.1%) had complex hypnagogic and/or hypnopompic VHs. Multivariable logistic regression analysis identified lower best-corrected visual acuity (BCVA) in the better seeing eye as&#xa0;a significant predictor of CBS. When excluding participants with a BCVA>0.3, prevalence of complex VHs rose to 10.0%. Three of the patients with CBS (27.3%) had ocular comorbidities: two had exudative age-related macular degeneration (AMD), and one had drusenoid AMD. In the overall cohort, twenty-four patients (6.1%) reported prior knowledge of CBS.&#xa0; CONCLUSION: CBS was observed in a clinically relevant minority of cataract patients requiring bilateral surgical intervention. Given the high prevalence of cataract among the elderly, this study highlights the importance of healthcare personnel being aware of CBS and other complex VHs and their potential consequences for cataract patients.}, }
@article {pmid42018574, year = {2026}, author = {Vavvas, DG}, title = {Photobiomodulation in Dry Age-Related Macular Degeneration: Promising Signal, Familiar Questions.}, journal = {Retina (Philadelphia, Pa.)}, volume = {46}, number = {5}, pages = {765-767}, doi = {10.1097/IAE.0000000000004823}, pmid = {42018574}, issn = {1539-2864}, }
@article {pmid42019353, year = {2026}, author = {Deng, Q and Kishimoto, K and Sugiyama, O and Miyake, M and Tamura, H}, title = {Automatic selection of optical coherence tomography images for prognostic prediction models in age-related macular degeneration.}, journal = {Computer methods and programs in biomedicine}, volume = {282}, number = {}, pages = {109384}, doi = {10.1016/j.cmpb.2026.109384}, pmid = {42019353}, issn = {1872-7565}, abstract = {BACKGROUND AND OBJECTIVE: Age-related macular degeneration (AMD) is a leading cause of blindness. Current standard treatments require frequent intravitreal injections and entail high costs, placing a heavy burden on patients and healthcare providers. These challenges often lead to treatment discontinuation or overtreatment, highlighting the need for personalized AMD management. Accurate early prediction of long-term treatment outcomes is critical for optimizing these strategies. However, most existing prognostic models rely heavily on manual image selection by ophthalmologists. This labor-intensive process, which requires carefully selecting suitable images from large volumes of electronic medical record (EMR) data, significantly hinders real-world implementation. This study proposes an automated deep learning framework to select appropriate images from extensive EMR-stored optical coherence tomography (OCT) reports, thereby reducing the reliance on manual curation.<br><br>METHODS: We developed a vision transformer (ViT)-based architecture to perform automated image selection. The model integrates features from the fundus infrared reflectance (IR) images and the corresponding OCT images presented in the clinical reports.<br><br>RESULTS: Compared to related works using a single OCT image input, the proposed method outperformed to the baseline. At training the pretrained ViT framework achieved an overall accuracy of 89% in identifying suitable images. Furthermore, using the images selected by our method improved the downstream prognostic prediction accuracy by an average of 3.1 percentage points. Confidence scores showed a statistically significant difference between the proposed method and the baseline (p = 0.026). The 95% confidence interval (CI) of the performance difference was [0.002, 0.066].<br><br>CONCLUSIONS: These results demonstrate the feasibility of an automated module capable of reliably identifying suitable images for AMD prognosis. By streamlining image selection workflows, this approach can enhance clinical efficiency, support the accurate estimation of long-term treatment effects, and facilitate treatment planning.}, }
@article {pmid42019593, year = {2026}, author = {Goncalves, L and Hashimoto, Y and Barthelmes, D and Barry, R and Pollreisz, A and Wolff, B and Toole, LO and Ponsioen, TL and Morros, HB and Creuzot-Garcher, C and Gillies, M and Gabrielle, PH}, title = {Real-World Outcomes in Neovascular AMD with Visit Gaps under Anti-VEGF Therapy: Data from the FRB! Registry.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.04.007}, pmid = {42019593}, issn = {2468-6530}, abstract = {PURPOSE: To evaluate visual outcomes observed across visit gaps in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) therapy in routine clinical practice.<br><br>DESIGN: Retrospective data analysis from a prospectively designed observational outcomes registry: the Fight Retinal Blindness! (FRB!).<br><br>PARTICIPANTS: Treatment-na&#xef;ve nAMD eyes receiving intravitreal anti-VEGF therapy (&#x2265;1 injection), monitored at least quarterly during the first treatment year, and experiencing a visit gap of &#x2265;6 to 12 months, with subsequent follow-up over the next 9 months (&#x2265;3 visits).<br><br>METHODS: Visual outcomes were assessed using a segmented linear mixed-effect model. Cumulative incidence and risk factors for visit gaps were evaluated using Aalen-Johansen estimators and Cox regression models.<br><br>MAIN OUTCOME MEASURES: The main outcome was the mean estimated change in VA immediately after the visit gap. Secondary outcomes included the cumulative incidence and associated risk factors of visit gaps.<br><br>RESULTS: From 3694 eligible eyes for the survival analysis, we tracked 262 (7.1%) eligible eyes experiencing a visit gap for the visual outcome analysis. nAMD-treated eyes experiencing a 6-12 month visit gap had a significant drop in vision immediately after the visit gap, with a mean (95% confidence interval [CI]) estimated change in VA of -4.9 letters (-6.0 to -3.7; P < 0.001). Eyes with active choroidal neovascularization (CNV) lesions (difference -3.9 [-7.1 to -0.3] letters vs. inactive CNV) and without subfoveal macular atrophy (MA) (difference 3.4 [-0.3 to 7.0] letters vs. subfoveal MA) at the last visit before the gap experienced a greater decline in VA after the visit gap. A quarter of the eyes experienced a 6-12 month visit gap at 6.5 years. nAMD eyes with a longer time interval since last injection were more likely to experience a visit gap, while eyes with better VA and that had active CNV with subretinal fluid only at follow-up visits were less likely.<br><br>CONCLUSIONS: Visit gaps were common and associated with a significant visual decline across the visit gap in nAMD eyes treated with anti-VEGF therapy in routine clinical practice.}, }
@article {pmid42020899, year = {2026}, author = {Kumar, S and Zhao, D and Wong, VHY and Bui, BV and Liu, GS}, title = {Evaluation of CRISPR/CasRx-Mediated VEGF mRNA Knockdown in Mouse Retina.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {3023}, number = {}, pages = {25-37}, pmid = {42020899}, issn = {1940-6029}, abstract = {Neovascular eye diseases (NEDs) are a group of diseases caused by the abnormal overgrowth of blood vessels in the eye. Normal vasculature is maintained through a dynamic balance of the vascular endothelial growth factor (VEGF). In diseases such as advanced diabetic retinopathy (DR) and neovascular age-related macular degeneration (AMD), an overexpression of VEGF leads to the formation of structurally weak and leaky blood vessels, resulting in vision impairment and, without intervention, legal blindness. In the clinic, NEDs are presently managed through anti-VEGF agents that specifically bind and neutralize VEGF signaling. While effective, this approach requires invasive intravitreal injections monthly and places a heavy burden on patients and healthcare providers. A flexible, long-lasting therapeutic that can reduce or eliminate frequent anti-VEGF treatment will significantly advance NED management.RNA editing with clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (Cas) is an emerging strategy to achieve reversible gene editing. The CRISPR-Cas13 system exclusively targets single-stranded RNA and allows gene silencing in a safe manner through RNA knockdown, as the genome is left intact. In addition, the compact CasRx enzyme (930aa) allows RNA silencing to be achieved through the delivery of a single adeno-associated virus (AAV), ideal for gene therapy applications. Herein, we outline methods to target VEGFA mRNA using CRISPR/CasRx in a mammalian cell line and humanized VEGFA transgenic mice.}, }
@article {pmid42020902, year = {2026}, author = {Hall, J and Cheung, S and Shobhana, K and Cho, E and Lidgerwood, GE and Paull, D and Pébay, A}, title = {Quantification of Drusen-Like Deposits in Human Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cells Using Confocal Microscopy.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {3023}, number = {}, pages = {59-80}, pmid = {42020902}, issn = {1940-6029}, abstract = {Accessing pathologically relevant models of human retinal degeneration is crucial for understanding, screening, and developing accurate treatment strategies that prevent or slow progression of blinding diseases. Human pluripotent stem cells (hPSCs) are a powerful tool to investigate retinal disease, as cells from selected individuals or specific genetic background can be differentiated into cell types of interest. hPSC-derived retinal pigment epithelium (RPE) cells can produce drusen-like deposits that accumulate between the RPE and the underlying Bruch's membrane. These key pathological markers of specific retinal disorders are detectable using simple microscopy techniques. However, quantification of these deposits often requires slow, low-throughput manual counting of images. This further lends itself to issues including sampling biases while ignoring critical data parameters such as deposit volume and precise localization. To overcome these issues, we developed two methods for quantifying the presence of drusen-like deposits in vitro, using hPSC-derived RPE cultures. Both methods accurately quantify drusen-like deposit numbers, and the mid-throughput pipeline allows for quantification of drusen-like deposit volume, as well as discerns their apical or basal localization on RPE cells. The platform's ability to track changes in drusen-like deposits supports screening experimentation and personalized medicine initiatives, including for gene therapy optimization.}, }
@article {pmid42020908, year = {2026}, author = {Miller, AL and Bhatt, Y and Carvalho, LS}, title = {Intravitreal Injections in Mouse Models of Eye Disease.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {3023}, number = {}, pages = {167-176}, pmid = {42020908}, issn = {1940-6029}, abstract = {Intravitreal injections are a commonly used technique in the treatment of some vitreoretinal diseases. In clinical situations, intravitreal injections are often used to deliver drugs that treat diseases such as age-related macular degeneration, retinal vein occlusion, and uveitis. Many preclinical studies in animals such as mice utilize intravitreal injections to test neuroprotective treatments and gene therapies before clinical use can be indicated. Herein, we describe our method and favorable practices for intravitreal injection into the eye of both preweaned and adult mice.}, }
@article {pmid42008990, year = {2026}, author = {Said, S and Knecht-Bösch, M and Knecht-Bosch, P}, title = {Switching to the Biosimilar Ranibizumab-nuna for the Intravitreal Treatment of Retinal Diseases - a Real-World Study.}, journal = {Klinische Monatsblatter fur Augenheilkunde}, volume = {243}, number = {4}, pages = {434-439}, doi = {10.1055/a-2803-9757}, pmid = {42008990}, issn = {1439-3999}, mesh = {Humans ; *Ranibizumab/administration &amp; dosage/adverse effects/therapeutic use ; Female ; Male ; Retrospective Studies ; Aged ; Middle Aged ; Intravitreal Injections ; Aged, 80 and over ; *Biosimilar Pharmaceuticals/administration &amp; dosage/adverse effects/therapeutic use ; *Drug Substitution ; Tomography, Optical Coherence ; *Retinal Diseases/drug therapy ; Visual Acuity/drug effects ; Treatment Outcome ; Angiogenesis Inhibitors/administration &amp; dosage ; }, abstract = {ABSTRACT: INTRODUCTION: Following the expiration of ranibizumab's (Lucentis) patent, the biosimilar ranibizumab-nuna (Byooviz) offers an alternative intravitreal medication with identical indications. However, real-world data on its efficacy remain limited. This study aimed to investigate the efficacy and safety of retinal disorders in patients who were switched from Lucentis to Byooviz.<br><br>ABSTRACT: METHODS: This retrospective, single-center study assessed adult patients previously treated with intravitreal Lucentis and switched to Byooviz. We evaluated structural and functional outcomes based on Snellen visual acuity (VA), fundoscopy, and optical coherence tomography (OCT) parameters, and treatment safety. Disease activity was classified as active or inactive, with neovascular activity defined as retinal pigment epithelial detachments, intra- or subretinal fluid, subretinal hyperreflective material, or macular hemorrhage on OCT or fundoscopy.<br><br>ABSTRACT: RESULTS: Between June 2021 and December 2024, we identified 31 patients, 21 (67.7%) of whom were female. Median (IQR, range) age was 82 (76.5 to 85.5, 49 to 91) years. The most common indication was neovascular age-related macular degeneration (61.3%), followed by macular edema (ME) due to retinal vein occlusion (22.6%), diabetic ME (9.7%), and secondary choroidal neovascularization (6.5%). Right and left eyes were nearly equally represented (48.4% vs. 51.6%). The median (IQR) injection numbers were 15 (10 to 40) for Lucentis and 8 (5 to 10.5) for Byooviz. After the switch, VA improved in 8 eyes (25.8%), was unchanged in 10 (32.3%), and worsened in 13 (41.9%). Disease activity decreased in 6 eyes (20%), increased in 3 (10%), and remained stable in 22 (70%). Treatment intervals shortened in 8 (25.8%) patients and extended in 14 (45.2%). No cases of endophthalmitis or other complications occurred.<br><br>ABSTRACT: DISCUSSION: Switching from Lucentis to Byooviz was generally well tolerated, with anatomical disease stability maintained in most patients. Certain decline in VA is also be observed in real-world outcomes for Lucentis and may reflect underlying disease progression rather than reduced efficacy of the biosimilar. Overall, Byooviz seems to be a viable alternative for patients previously treated with Lucentis.}, }
@article {pmid42008992, year = {2026}, author = {Gabathuler, F and Cozzi, M and Fasler, K and Maloca, PM and Blaser, F and Zweifel, S}, title = {Real-World Case Series of Intravitreal Pegcetacoplan for Geographic Atrophy Secondary to Age-related Macular Degeneration in Switzerland.}, journal = {Klinische Monatsblatter fur Augenheilkunde}, volume = {243}, number = {4}, pages = {461-464}, doi = {10.1055/a-2825-0926}, pmid = {42008992}, issn = {1439-3999}, mesh = {Humans ; *Geographic Atrophy/drug therapy/etiology/diagnosis ; Male ; Female ; Switzerland ; Intravitreal Injections ; Aged ; Retrospective Studies ; *Macular Degeneration/complications/drug therapy ; Aged, 80 and over ; Treatment Outcome ; Visual Acuity/drug effects ; Tomography, Optical Coherence/methods ; }, abstract = {ABSTRACT: PURPOSE: To report early real-world experience with intravitreal pegcetacoplan for geographic atrophy secondary to age-related macular degeneration in Switzerland.<br><br>ABSTRACT: METHODS: This retrospective case series included patients with geographic atrophy secondary to age-related macular degeneration treated with intravitreal pegcetacoplan. Treatment exposure, best-corrected visual acuity, adverse events, and follow-up were assessed. Geographic atrophy was quantified on macula-centred OCT scans using the RetinAI Discovery platform, based on automated segmentation of total photoreceptor and RPE atrophy.<br><br>ABSTRACT: RESULTS: Seven eyes from six patients were included, receiving a total of 37 intravitreal pegcetacoplan injections. The median number of injections per eye was five (range 3&#x200a;-&#x200a;8), with a mean injection interval of 9.5&#x2009;&#xb1;&#x2009;2.4 weeks. Follow-up duration ranged from 4.4 to 14.0 months. Median best-corrected visual acuity declined by 7 ETDRS letters over the observation period. Mean geographic atrophy area increased from 7.6&#x2009;mm[2] at baseline to 8.7&#x2009;mm[2] at last follow-up. No severe adverse events were recorded.<br><br>ABSTRACT: CONCLUSIONS: In this real-world case series, intravitreal pegcetacoplan was well tolerated without severe adverse events during short-term follow-up, while visual acuity decline and continued geographic atrophy progression were observed.}, }
@article {pmid42009153, year = {2026}, author = {Ge, Z and Jia, Z and Liu, Y and Zhang, H}, title = {Injectable hyaluronic acid hydrogels for the treatment of ocular diseases: A review.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {152112}, doi = {10.1016/j.ijbiomac.2026.152112}, pmid = {42009153}, issn = {1879-0003}, abstract = {Globally, an increasing number of individuals suffer from ocular diseases, including dry eye syndrome, corneal injuries, and age-related macular degeneration (AMD), ultimately leading to visual impairment or complete blindness. The complex anatomy and physiological barriers of the eye limit the efficacy of conventional therapies such as eye drops and intraocular injections, while also posing challenges including frequent dosing requirements and inflammatory risks. Injectable hyaluronic acid (HA) hydrogels present a promising strategy to address the limitations of current ocular therapies, owing to their excellent biocompatibility, tunable physicochemical properties (including optical transparency and mechanical modulus), and sustained drug release capabilities. Recent research continues to explore the potential of functionalized injectable HA hydrogels to advance ophthalmic treatment paradigms. This review summarizes recent advances in the chemical modification and crosslinking strategies of HA, as well as innovative design concepts for functionalized injectable HA hydrogels in treating ocular disorders such as corneal injuries and age-related macular degeneration (AMD). Injectable HA hydrogels show considerable promise for improving therapeutic outcomes, reducing treatment frequency and side effects, lowering healthcare costs, and enhancing patient compliance. This review aims to provide theoretical support for the future development of emerging HA hydrogel-based platforms for ocular care.}, }
@article {pmid42009803, year = {2026}, author = {Zeng, Q and Hua, X and Liu, Y and Wang, S}, title = {Oxidative stress promotes the progression of age-related macular degeneration by up-regulating Spp1 to activate the JAK/STAT signaling pathway.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-48556-6}, pmid = {42009803}, issn = {2045-2322}, }
@article {pmid42011167, year = {2026}, author = {Ching, K and Meng, J and Wang, L and Cheng, K and He, W and Zhang, K and Lu, Y and Zhu, X}, title = {Swept-source OCTA assessment of iris vasculature as a biomarker for myopic macular degeneration severity.}, journal = {Advances in ophthalmology practice and research}, volume = {6}, number = {2}, pages = {139-145}, pmid = {42011167}, issn = {2667-3762}, abstract = {BACKGROUND: To investigate the vessel area density (VAD) and morphological features of the iris in patients at different stages of myopic macular degeneration (MMD) using swept-source optical coherence tomography angiography (SS-OCTA).<br><br>METHODS: In this retrospective case-control study, 106 eyes of 106 high myopia patients (axial length (AL) &#x2265;26 mm) were included and classified into different MMD categories according to the International META-PM Classification. The VAD of iris, iris volume (IV), area of anterior iris surface (IS), area of posterior IS, and average iris thickness (IT) were evaluated using SS-OCTA. Associations among iris vasculature, iris morphology, and MMD categories were investigated.<br><br>RESULTS: Full-range, inner-region, and intermediate-region VAD of the iris decreased significantly with increasing MMD severity (all P-trend <0.001), whereas outer-region VAD did not show a significant linear trend. The area of IS was larger in eyes with MMD 2 and MMD 4 compared to the other two groups (all P <0.05). The full-range and outer-region VAD of iris was negatively correlated with AL, while the inner-region VAD of iris was positively correlated with the area of anterior and posterior IS, especially in eyes with MMD 2 (all P <0.05). Multivariate linear regression revealed that greater full-range, inner-region and intermediate-region VAD were all significantly associated with milder MMD, whereas greater outer-region VAD was significantly associated with shorter AL.<br><br>CONCLUSIONS: Iris blood flow, quantified by VAD, decreased with increasing MMD severity. Iris VAD may represent a promising candidate biomarker for non-invasive monitoring of MMD severity. Additionally, the association between VAD and AL or iris morphology varied across MMD categories.}, }
@article {pmid42011205, year = {2026}, author = {Chen, ZJ and Yu, J and Ng, DSC and Ho, M and Zhu, X and Brelen, ME and Young, AL and Yam, JC and Tham, CC and Pang, CP and Chen, LJ}, title = {Associations of TNFRSF10A with Central Serous Chorioretinopathy, Polypoidal Choroidal Vasculopathy, and Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {5}, pages = {101161}, pmid = {42011205}, issn = {2666-9145}, abstract = {PURPOSE: To investigate the role of tumour necrosis factor receptor superfamily member 10A (TNFRSF10A) in chronic central serous chorioretinopathy (cCSCR), polypoidal choroidal vasculopathy (PCV), and neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Case-control genetic association study.<br><br>PARTICIPANTS: A total of 1478 Chinese participants were recruited, including 217 patients with cCSCR (174 without and 43 with macular neovascularization [MNV]), 288 patients with PCV, 341 patients with nAMD, and 632 healthy controls.<br><br>METHODS: Thirteen single-nucleotide polymorphisms (SNPs) in TNFRSF10A that covered both the promoter and coding regions were genotyped, including 12 haplotype-tagging SNPs and a manually selected reference SNP, rs13278062. Two variants showing significant deviation from Hardy-Weinberg equilibrium were excluded, leaving 11 SNPs for the final analysis. Logistic regression, adjusted for age and sex, was applied to assess both allelic and haplotype associations. Conditional analyses were conducted to evaluate independent effects. Single-nucleotide polymorphisms were annotated based on TNFRSF10A domains defined by UniProtKB.<br><br>MAIN OUTCOME MEASURES: Associations between individual SNPs and haplotypes in the TNFRSF10A with nAMD, PCV, and cCSCR (with or without MNV), respectively.<br><br>RESULTS: For cCSCR without MNV, 4 tagging SNPs showed significant associations: rs59693001 (odds ratio [OR] = 1.65, 95% confidence interval [CI]: 1.12 - 2.33; P = 0.0043), rs3808530 (OR = 1.91, 95% CI: 1.22 - 2.83; P = 0.0013), rs2235126 (OR = 1.74, 95% CI: 1.22 - 2.41; P = 7.50 &#xd7; 10[-4]), and rs7814465 (OR = 1.66, 95% CI: 1.22 - 2.28; P = 0.0016). The reference SNP, rs13278062, also showed a significant association (OR = 1.81, 95% CI: 1.31 - 2.51; P = 3.64 &#xd7; 10[-4]). In addition, 4 haplotypes within 2 blocks from a continuous region also showed significant associations. For PCV, only rs36005462 in an independent domain showed a marginally significant association (OR = 0.58; P = 0.0050). No significant association was identified for nAMD or cCSCR with MNV.<br><br>CONCLUSIONS: This study identified multiple TNFRSF10A variants associated with cCSCR without MNV, while a distinct protective SNP was linked to PCV. These findings provide preliminary evidence for varying TNFRSF10A association patterns across the pachychoroid disease spectrum.<br><br>FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid42011963, year = {2026}, author = {Posnic, A and Yagoub, S and Lebastard, C and Vaast, M and Poinas, A and Pabic, EL and Bellamy, JP and Delhay, C and Faure, S and Rouic, JL and Henry, A and Lebreton, O and Masse, H and Susini, F and Guillaumie, T and Fournier, I and Mainguy, A and Lez, ML and Khanna, RK and Mortemousque, G and George, A and Pipelart, V and Bernard, Y and Grimbert, P and Mazhar, D and Benzerroug, M and Briend, B and Clement, M and Jammes-Veaux, HP and Posnic, MP and Bonissent, A and Guyot, C and Rousseau, N and Dam, BTV and Bellot, L and Ferron, R and Meur, GL and Mouriaux, F and Weber, M and Maucourant, Y and Ducloyer, JB}, title = {Predictive factors for injection interval extension after switching to faricimab in neovascular AMD: The FAR WEST multicentre study.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70134}, pmid = {42011963}, issn = {1755-3768}, support = {//Centre Hospitalier Universitaire de Nantes/ ; }, abstract = {PURPOSE: To assess whether switching to faricimab allowed extending injection intervals after 12 months (M12) in patients with neovascular age-related macular degeneration (nAMD) and to identify predictive factors for interval extension.<br><br>DESIGN: FAR WEST was a multicentre, observational, retrospective cohort study.<br><br>PARTICIPANTS: Patients with nAMD treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections for at least 1&#x2009;year before switching to faricimab.<br><br>METHODS: The reason for switching (clinician's intent to extend the interval in the absence or presence of a recurrence or refractory status), and the switch strategy (whether an induction phase comprising 2, 3 or 4 injections was performed using the same or a shorter interval, or whether the interval was immediately extended from the second injection without induction) were left to the physician's discretion.<br><br>MAIN OUTCOME MEASURES: The following data were collected from the medical records at the time of the decision to switch to faricimab (M0) and at the M12 follow-up visit: recurrence-free interval, last injection interval, best-corrected visual acuity (BCVA), central macular thickness (CMT), exudation status and intraocular inflammation events.<br><br>RESULTS: A total of 845 eyes of 718 patients were included in 23 centres. The recurrence-free injection interval increased significantly from 5.7&#x2009;weeks at M0 to 8.6&#x2009;weeks at M12 (difference: +2.9&#x2009;weeks, p&#x2009;<&#x2009;0.001). The proportion of exudative patients decreased from 571 (68%) to 337 (42%) (- 41%, p&#x2009;<&#x2009;0.001). BCVA decreased from 0.33 (20/40) to 0.35 logMAR (20/40) (p&#x2009;=&#x2009;0.0038). Among 238 refractory cases at M0, 84 (35%) achieved a dry macula at M12. In multivariable analysis, absence of an induction phase was associated with greater injection interval gain. (p&#x2009;<&#x2009;0.001). There were no differences according to time since the first injection, type of neovascularization. The number of injections per year decreased from 8.7 at M0 to 6.1 at M12 (-2.6, p&#x2009;<&#x2009;0.001), and the number of consultations decreased from 6.1 at M0 to 5.2 at M12 (-0.9, p&#x2009;<&#x2009;0.001). The intraocular inflammation rate was 1.6% (n&#x2009;=&#x2009;14).<br><br>CONCLUSION: Switching to faricimab allowed significantly extending the recurrence-free injection interval, decreasing the proportion of exudative patients and reducing the therapeutic burden in nAMD patients. Further studies are needed to determine the most appropriate switching modalities and which patients actually require an induction phase.}, }
@article {pmid42012273, year = {2026}, author = {Shi, J and Xu, H and Zhao, H and Zhao, J and Chen, L and Xu, P and Jia, D and Jiang, C}, title = {Safety and Efficacy of cceAAV-aflibercept-Fc-YTE (F-CRG-B191): A Gene Therapy for Neovascular Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {47}, doi = {10.1167/iovs.67.4.47}, pmid = {42012273}, issn = {1552-5783}, mesh = {Animals ; *Genetic Therapy/methods ; *Recombinant Fusion Proteins/therapeutic use/genetics ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/genetics ; Mice ; Disease Models, Animal ; Humans ; Dependovirus/genetics ; *Choroidal Neovascularization/therapy ; Genetic Vectors ; Female ; Male ; *Wet Macular Degeneration/therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Treatment Outcome ; Visual Acuity ; Mice, Inbred C57BL ; Tomography, Optical Coherence ; }, abstract = {PURPOSE: To evaluate the safety and efficacy of a novel gene therapy vector, covalently closed-end double-stranded adeno-associated virus-aflibercept-Fc-YTE (cceAAV-aflibercept-Fc-YTE; clinical trial name F-CRG-B191), designed for sustained anti-vascular endothelial growth factor (VEGF) expression in the treatment of neovascular age-related macular degeneration (nAMD).<br><br>METHODS: We developed cceAAV-aflibercept-Fc-YTE. The therapeutic efficacy of cceAAV-aflibercept-Fc-YTE was evaluated in both mice and non-human primate (NHP) models with laser-induced choroidal neovascularization (CNV). The incidence of grade IV CNV lesions was quantified. A first-in-human administration of F-CRG-B191 was conducted to assess anatomical and functional outcomes, as well as safety. Immune responses and retinal toxicity were monitored in NHPs and the patient post-injection.<br><br>RESULTS: Compared to conventional AAV vectors expressing aflibercept, cceAAV-aflibercept-Fc-YTE significantly reduced the incidence of grade IV CNV lesions in both mice and NHP models. In the human subject, F-CRG-B191 administration led to a sustained reduction in CNV area and improvement in visual acuity. No significant immune response or retinal toxicity was observed in either preclinical models or the treated patient.<br><br>CONCLUSIONS: cceAAV-aflibercept-Fc-YTE (F-CRG-B191) is a promising gene therapy candidate for nAMD, demonstrating potent anti-VEGF efficacy, durable therapeutic effects, and favorable safety profiles in both preclinical and early clinical settings.}, }
@article {pmid42012371, year = {2026}, author = {Cha, E and Youn, J and Yun, C and Kim, SW and Choi, M}, title = {Impact of Phacoemulsification on Neovascular Age-Related Macular Degeneration Activity: Predictive Role of Choroidal Vascularity and MNV Subtypes.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004864}, pmid = {42012371}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate the impact of cataract surgery on disease activity in neovascular age-related macular degeneration (nAMD) and determine whether choroidal biomarkers and macular neovascularization (MNV) subtypes predict increased postoperative treatment requirements.<br><br>METHODS: This retrospective study included 84 eyes from 84 patients with nAMD who underwent phacoemulsification while receiving intravitreal anti-VEGF therapy. Increased treatment need was defined as a shortened injection interval or occurrence of submacular hemorrhage. Pre-and postoperative choroidal vascularity index (CVI), subfoveal choroidal thickness (SFCT), and central subfield thickness (CST) were analyzed using EDI-OCT within 1 month before and after surgery. MNV subtypes were classified as type 1, type 2, retinal angiomatous proliferation (RAP), and polypoidal choroidal vasculopathy (PCV).<br><br>RESULTS: Best-corrected visual acuity remained stable after cataract surgery (from 0.39 &#xb1; 0.27 [20/50] to 0.38 &#xb1; 0.28 logMAR [20/50]; p = 0.907), with no significant differences among MNV subtypes. Increased treatment need occurred in 45.2% of eyes. Both CVI and SFCT increased significantly postoperatively (p < 0.001). Eyes with increased treatment need showed significantly higher preoperative and postoperative CVI (p = 0.003 and p = 0.032, respectively). The PCV subtype demonstrated the highest rates of increased treatment need and the shortest injection intervals. Higher preoperative CVI independently predicted increased postoperative treatment need (OR = 1.13; p = 0.019).<br><br>CONCLUSIONS: Cataract surgery may affect disease activity in a subset of patients with nAMD, particularly those with PCV and increased CVI. Preoperative choroidal characteristics such as CVI and SFCT may provide valuable insights for risk stratification and postoperative management.}, }
@article {pmid42012698, year = {2026}, author = {Herold, TR and Finger, RP and Bauer-Steinhusen, U and Lommatzsch, A and Ziemssen, F}, title = {Opportunities to Improve Management of Neovascular Age-related Macular Degeneration: Communication at Diagnosis and Beyond : Insights from the German nAMD Barometer Survey.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42012698}, issn = {1435-702X}, }
@article {pmid42013734, year = {2026}, author = {Casablanca-Piñera, A and Alforja-Castiella, MS and Casaroli-Marano, RP}, title = {Changes on imaging after 10years of follow-up for concurrent melanocytoma and congenital hypertrophy of the retinal pigment epithelium in a patient treated with anti-VEGF intravitreal therapy for neovascular age-related macular degeneration.}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {6}, pages = {104876}, doi = {10.1016/j.jfo.2026.104876}, pmid = {42013734}, issn = {1773-0597}, }
@article {pmid42014412, year = {2026}, author = {Raul, P and Lee, T and Barry, R and Sabeti, F and van Boxtel, JJA}, title = {Visual noise in augmented reality improves vision in age-related macular degeneration.}, journal = {npj aging}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41514-026-00389-3}, pmid = {42014412}, issn = {2731-6068}, support = {DP220100406//Australian Research Council/ ; }, abstract = {Exudative age-related macular degeneration (eAMD) is a degenerative eye disease of the central retina that results in central vision loss, significantly affecting the daily functioning and quality of life of affected individuals. Although first-line treatments are quite effective in improving vision in eAMD, they are invasive and not suitable or efficacious for everyone. The non-invasive methods to enhance visual acuity (VA) in eAMD, are often limited in scope and burdensome for patients. Stochastic resonance (SR), a phenomenon in which optimal noise improves sensory perception, offers a promising non-invasive strategy with broad clinical potential. In this study, we tested whether visual noise delivered via an augmented reality (AR) headset enhanced binocular VA in binocular eAMD (N = 12) and in healthy individuals (N = 17) via the SR effect. Using a standard clinical letter chart, we observed an immediate improvement in vision, without the need for any training. Improvements were 2.5 letters and 2 letters at optimal noise levels for eAMD and healthy individuals, respectively. These findings demonstrate the potential of noise-based AR as a practical, wearable visual aid for individuals with eAMD or other visual disorders, offering enhancements that may complement or extend the benefits of current first-line treatments.}, }
@article {pmid42002030, year = {2026}, author = {Fernández-Vigo, JI and Gallego-Pinazo, R and Montero Hernández, J and Arias-Barquet, L and Arévalo, FJ and García-Layana, A}, title = {Photodynamic therapy in neovascular age-related macular degeneration: Past or present in the era of second-generation anti-VEGF agents?.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502558}, doi = {10.1016/j.oftale.2026.502558}, pmid = {42002030}, issn = {2173-5794}, }
@article {pmid42002032, year = {2026}, author = {Benedictus, B and Tsania, S and Ronik, HK and Dwinastiti, YA and Priscilla, B and Nova, E}, title = {Associations of Dose Adjustment with Efficacy and Safety of Faricimab for Age-related Macular Degeneration Disorders: A Systematic Review and Meta-analysis.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502562}, doi = {10.1016/j.oftale.2026.502562}, pmid = {42002032}, issn = {2173-5794}, abstract = {This paper reviews the efficacy and safety of various dosing regimens and treatment cycles of intravitreal faricimab as therapy for Age-related macular degeneration (ARMD). The included studies were randomized controlled trials (RCTs) or post-hoc analyses of RCTs involving a population of ARMD or macular related disorder patients receiving faricimab therapy. Study outcomes were assessed by best-corrected visual acuity (BCVA) or central macular subfield thickness (CST). Data extracted from the journals included characteristics of the patient population, subgroup population, treatment used, therapeutic dose, treatment cycle, BCVA, CVA, number of populations with severe adverse events, and severe ocular adverse events. Study heterogeneity was assessed using the I[2] statistic, with values ≤40% considered homogeneous. A random effects model was applied when effect estimates crossed the line of no effect. Effect sizes were reported as mean differences with 95% confidence intervals. We included eight studies with a total of 8458 study populations. There are several doses that can be given (1.5 mg and 6 mg) and several cycles of administration (every 4, 8, 12, 16 weeks and personalized treatment interval). Faricimab 6 mg every sixteen weeks has shown a better effect than aflibercept and ranibizumab. These findings suggest that faricimab 6 mg administered every sixteen weeks demonstrated superior outcomes in improving best-corrected visual acuity (BCVA) and greater reductions in central subfield thickness (CST) compared to aflibercept 2 mg every eight weeks. However, a more frequent regimens were associated with significantly higher severe adverse events, especially ocular severe adverse events.}, }
@article {pmid42003716, year = {2026}, author = {Airody, A and Hanson, RLW and Bunola-Hadfield, I and Sivaprasad, S and Morland, AB and Chakravarthy, U and Gale, RP and , }, title = {The long-term impact of neovascular age-related macular degeneration undergoing routine treatment in first and second eyes on vision-related quality-of-life: FASBAT Report 3.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70150}, pmid = {42003716}, issn = {1755-3768}, support = {OAP030A2401T//Novartis Pharmaceuticals Corporation/ ; }, abstract = {PURPOSE: The study evaluated the long-term effect on vision-related quality-of-life (VRQoL) of routinely treated neovascular age-related macular degeneration (nAMD) in first and second eyes.<br><br>METHODS: The FASBAT (Observing Fibrosis, macular Atrophy and Subretinal highly reflective material Before and After Treatment with anti-VEGF treatment) study followed individuals with new unilateral nAMD (first eye) undergoing routine treatment for up to 4.5&#x2009;years. Visual acuity (VA) was measured as part of routine care and VRQoL was assessed using the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25).<br><br>RESULTS: Of the 424 participants, 307 had only the first eye affected by nAMD (mean age&#x2009;=&#x2009;76.5, SD&#x2009;=&#x2009;8.4&#x2009;years). The mean VA was 58.1 (SD&#x2009;=&#x2009;15.5) and 79.4 (SD&#x2009;=&#x2009;5.6) letters at baseline, and 58.4 (SD&#x2009;=&#x2009;20.9)/78.5 (SD&#x2009;=&#x2009;7.8) letters at 36-months in the affected and unaffected eyes, respectively. The mean composite NEI-VFQ-25 score was 87.1 (SD&#x2009;=&#x2009;11.9) at baseline and 85.2 (SD&#x2009;=&#x2009;13.5) at 36-months. One hundred and seventeen participants (mean age&#x2009;=&#x2009;77.6, SD&#x2009;=&#x2009;7.3&#x2009;years) developed second eye nAMD, with a mean of 18.9 (SD&#x2009;=&#x2009;10.2) months following the first eye. Mean VA in first and second eye was 56.3 (SD&#x2009;=&#x2009;19.3)/74.1 (SD&#x2009;=&#x2009;9.9) letters at the time of second eye development, and 51.1 (SD&#x2009;=&#x2009;22.5)/73.6 (SD&#x2009;=&#x2009;8.9) letters after 24-months. Mean composite NEI-VFQ-25 score was 81.4 (SD&#x2009;=&#x2009;14.6) and 79.1 (SD&#x2009;=&#x2009;17.2) at these time points.<br><br>CONCLUSIONS: Long-term VRQoL remains stable in unilateral treated nAMD. However, a clinically meaningful reduction in VRQoL occurs following development and treatment in the second eye which does not recover. It is important to offer appropriate support when the first and then second eye develop nAMD.}, }
@article {pmid42005206, year = {2026}, author = {Faustine, G and Bastion, MC}, title = {A Case Series of Familial Macular Drusen: Clinical, Imaging, and Diagnostic Considerations in the Spectrum Between Age-Related Macular Degeneration (AMD) and Other Macular Disorders.}, journal = {Cureus}, volume = {18}, number = {3}, pages = {e105478}, pmid = {42005206}, issn = {2168-8184}, abstract = {Familial clustering of macular drusen in younger adults can mimic age-related macular degeneration (AMD) but may reflect an underlying inherited macular disorder. We describe a 72-year-old Chinese woman with high myopia and advanced neovascular AMD in one eye, who presented with progressive visual decline. Despite anti-vascular endothelial growth factor therapy, vision remained poor. Concerned about familial risk, her three adult children were examined. All three adult children (aged 46, 38, and 36 years) were asymptomatic despite drusen being detected on examination. This multigenerational clustering of drusen at relatively young ages raises suspicion for a possible hereditary macular disorder. This case highlights the need for family screening and genetic evaluation in atypical AMD presentations.}, }
@article {pmid42005909, year = {2026}, author = {Lim, JI and Ambresin, A and Avery, RL and Chaikitmongkol, V and Eter, N and Gomi, F and Khanani, AM and London, NJS and Harrell, E and Margaron, P and Patel, S and Souverain, A and Yang, M and Lai, TYY}, title = {Reduction in Pigment Epithelial Detachment Thickness with Faricimab versus Aflibercept 2 mg during Head-to-Head Dosing in TENAYA/LUCERNE.}, journal = {Ophthalmology science}, volume = {6}, number = {5}, pages = {101148}, pmid = {42005909}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the effects of dual angiopoietin-2 (Ang-2)/VEGF-A pathway inhibition with faricimab versus VEGF pathway inhibition with aflibercept 2 mg on pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: TENAYA/LUCERNE (NCT03823287/NCT03823300) post hoc analysis.<br><br>PARTICIPANTS: Patients with treatment-na&#xef;ve nAMD.<br><br>METHODS: Patients were randomized 1:1 to faricimab 6 mg up to every 16 weeks (n = 665) after 4 initial every-4-week (Q4W) doses or aflibercept 2 mg every 8 weeks (n = 664) after 3 Q4W doses. Pigment epithelial detachment was defined as retinal pigment epithelium (RPE) elevation width &#x2265;350 &#x3bc;m and graded as predominantly/purely serous (serous PED) or predominantly/only fibrovascular (fibrovascular PED). Large PED definition: thickness &#x2265;125 &#x3bc;m.<br><br>MAIN OUTCOME MEASURES: Pigment epithelial detachment thickness change from baseline during initial 12-week head-to-head dosing, proportion of patients with serous PED at the end of head-to-head dosing, and time to first reduction of maximum PED thickness by 50%.<br><br>RESULTS: Baseline PED characteristics were similar between arms. At week 12, the adjusted mean decrease from baseline in maximum PED thickness was greater with faricimab than aflibercept 2 mg in eyes with large (-119.1 [n = 500] vs. -101.4 &#x3bc;m [n = 496]; nominal P = 0.0028), serous (-136.1 [n = 128] vs. -108.2 &#x3bc;m [n = 114]; nominal P = 0.0147), and any type (-87.9 [n = 644] vs. -74.5 &#x3bc;m [n = 638]; nominal P = 0.0067) PED at baseline. The proportion of eyes with serous PED at baseline remaining serous at week 12 was lower with faricimab than aflibercept 2 mg (4.7% vs. 13.4%; nominal P = 0.0258). In eyes with large PED at baseline, the cumulative incidence of PEDs achieving time to first reduction of maximum PED thickness by 50% at week 12 was 35.3% with faricimab versus 25.7% with aflibercept 2 mg. The corresponding incidence in eyes with serous PED at baseline was 61.1% with faricimab versus 51.8% with aflibercept 2 mg. The incidence of RPE tears was low (faricimab, 2.9%; aflibercept 2 mg, 1.5%).<br><br>CONCLUSIONS: In TENAYA/LUCERNE, dual Ang-2/VEGF-A inhibition with faricimab elicited greater improvements in PED outcomes versus aflibercept 2 mg during head-to-head dosing. These findings are consistent with the greater drying of retinal fluid with faricimab during head-to-head dosing, which may allow for rapid treatment interval extension.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42005954, year = {2026}, author = {Seddon, JM and De, D}, title = {The Macular Degeneration Preventive Diet and Lifestyle for Providers and Patients: From Evidence to Action.}, journal = {American journal of lifestyle medicine}, volume = {}, number = {}, pages = {15598276261438371}, pmid = {42005954}, issn = {1559-8284}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among older adults, with both genetic and modifiable risk factors contributing to disease progression. Robust prospective evidence demonstrates that dietary patterns rich in lutein, zeaxanthin, and omega-3 fatty acids-particularly through green leafy vegetables, fatty fish, and Mediterranean diet adherence-reduce AMD progression risk by 20-56% across disease stages. Lifestyle factors including smoking cessation, weight management, and regular physical activity also confer protective benefits. Despite ample evidence, counseling about the benefits of these dietary and lifestyle behaviors remains underutilized in ophthalmic practice, largely due to inadequate medical education in preventive medicine and perceived barriers to implementation of such recommendations. This perspective examines the current evidence, highlights the gap between scientific evidence and clinical implementation, and proposes a framework for systematic reform. Recommendations include embedding nutrition education into medical school and residency training, establishing ocular nutrition as a continuing education requirement, and equipping clinicians with tools for incorporating these guidelines into routine AMD clinical care. Aligning ophthalmic practice with the recommended nutritional guidelines and other behavioral changes through the Macular Degeneration Preventive Diet and Lifestyle, represents a timely opportunity to translate evidence into interventions that preserve vision.}, }
@article {pmid42007660, year = {2026}, author = {Le, VH and El-Mulki, OS and Zhang, Y and Pan, H and Kumar, S and Shen, M and Beqiri, S and Badla, O and Berni, A and Kastner, J and Gregori, G and Rosenfeld, PJ and Wang, RK}, title = {Hyporeflective Core Drusen Cause an Artifactual Bending of Bruch's Membrane on OCT Images: Optical Mechanism and Proposed Quantitative Metrics.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {43}, doi = {10.1167/iovs.67.4.43}, pmid = {42007660}, issn = {1552-5783}, abstract = {PURPOSE: To investigate the optical mechanism and impact of the artifactual bending of Bruch's membrane (BM) beneath hyporeflective core drusen (hypoRCD) on optical coherence tomography (OCT).<br><br>METHODS: This observational and experimental laboratory study analyzed volumetric OCT scans with hypoRCD from an age-related macular degeneration (AMD) cohort. The optical mechanism underlying BM bending was examined using tissue phantoms with different oil droplets to model different refractive indices (RIs) of hyporeflective cores (hypoRCs). Three metrics were proposed to quantify hypoRCD: (1) hypocore bending index (CoreBI), (2) drusen bending index (DruBI), and (3) maximum bending index (Bmax). The impact of BM bending on choriocapillaris flow deficit (CCFD) analysis was assessed by comparing CCFD measurements before and after correcting BM segmentation under hypoRCD.<br><br>RESULTS: BM bending was consistently observed beneath the core region of hypoRCD in both structural OCT and optical attenuation coefficient (OAC) B-scans. Phantom experiments demonstrated that the bending was associated with differences in the RIs of the hypoRCs. The degree of bending, quantified by the CoreBI, increased with the RI of the core material (P < 0.001). The CCFD percentage beneath hypoRCD was significantly reduced by 25.9% &#xb1; 7.7% (P = 0.005) after correcting the BM segmentation. Morphological changes associated with the bending could be quantified using the three proposed metrics.<br><br>CONCLUSIONS: BM bending induced by hypoRCD is an artifactual OCT feature that reflects the optical properties of the hypoRCs. This morphological characteristic may improve our understanding of hypoRCD, raise cautions in quantitation of CCFDs under hypoRCD, and provide additional insights into their role in AMD.}, }
@article {pmid41999267, year = {2026}, author = {Delcourt, C and Hucteau, E and Gattoussi, S and Pérès, K and Delyfer, MN and Helmer, C and Korobelnik, JF}, title = {Association of treated neovascular AMD with disability and mood disorders: A longitudinal nationwide study.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70130}, pmid = {41999267}, issn = {1755-3768}, support = {//Bayer Healthcare (Lille, France)/ ; }, abstract = {PURPOSE: To describe the associations of treated neovascular AMD with the risk of disability, falls, fractures and mood disorders in a large sample representative of the French population.<br><br>METHODS: Analyses were based on 77&#x2009;582 individuals belonging to the 'Echantillon G&#xe9;n&#xe9;raliste des B&#xe9;n&#xe9;ficiaires', a 1/97 random sample of the French population, aged 65&#x2009;years or more on 1 April 2009 and followed until 31 December 2019. Treated neovascular AMD (nAMD) was identified through the reimbursement of anti-VEGF drugs, intravitreal injections and after exclusion of other pathologies requiring the use of intravitreal anti-VEGFs. Activities of daily living (ADL) disability was identified using a previously developed algorithm, while falls, fractures, head trauma and mood disorders were identified using relevant ICD codes and medications. Associations of nAMD with outcomes were assessed using Cox models with nAMD as a time-dependent variable and adjustment for confounders.<br><br>RESULTS: During the study period, 1662 cases of incident nAMD were identified. After adjustment for age, sex, Charlson comorbidity index and number of drugs, nAMD was significantly associated with the occurrence of ADL disability (Hazard ratio (HR): 1.19, 95% confidence interval (CI): 1.08-1.30; p&#x2009;=&#x2009;0.0002) and of mood disorders (HR: 1.19, 95%CI: 1.07-1.32; p&#x2009;=&#x2009;0.002). Associations with falls, fractures and head trauma were not statistically significant.<br><br>CONCLUSION: Treated neovascular AMD remains associated with a 19% increased risk of disability and mood disorders, while no association was detected with falls, fractures and head trauma. These results are consistent with a major improvement in functional outcomes, with respect to the pre-anti-VEGF era.}, }
@article {pmid41999355, year = {2026}, author = {Thomsen, AK and Villarruel Hinnerskov, JM and Maung, M and Mutschler, A and Sadda, S and Sørensen, TL}, title = {Junctional sensitivity and atrophy progression rate of geographic atrophy secondary to age-related macular degeneration.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70151}, pmid = {41999355}, issn = {1755-3768}, support = {00024226//Velux Fonden/ ; R29-A1337//Region Sj&#xe6;lland/ ; //Fight for Sight Denmark/ ; //Synoptik-Fonden/ ; //Dagmar Marshalls Fond/ ; //Grosserer L. F. Foghts Fond/ ; }, abstract = {PURPOSE: To determine the relationship between the baseline junctional retinal sensitivity measured with microperimetry and the atrophy progression rate in eyes with geographic atrophy (GA) secondary to age-related macular degeneration.<br><br>METHODS: In this prospective cohort study, patients with GA were examined with fundus autofluorescence (FAF) to determine the atrophy area at baseline and at follow-up of 13.1&#x2009;&#xb1;&#x2009;2.5&#x2009;months in order to determine the atrophy progression rate. Microperimetry and optical coherence tomography (OCT) were evaluated at baseline. Microperimetry was superimposed on the baseline FAF image to determine mean junctional sensitivity. Multivariable linear regression was performed adjusting for age, presence of junctional intraretinal hyperreflective foci (HRF), subretinal drusenoid deposits (SDD) and FAF pattern.<br><br>RESULTS: Fifty-six eyes with GA of 56 patients were included. There was a significant association between baseline junctional sensitivity and the atrophy progression rate in GA eyes (&#x3b2;, -8.84&#x2009;&#x3bc;m/year/dB; 95% CI, -16.56 to -1.11; p&#x2009;=&#x2009;0.026) tested with simple linear regression. However, when adjusting for age, structural factors and junctional FAF patterns in a multivariable linear regression model, the association between junctional sensitivity and atrophy progression rate was no longer statistically significant (&#x3b2;, -6.40&#x2009;&#x3bc;m/year/dB; 95% CI, -16.04 to 3.25; p&#x2009;=&#x2009;0.18). The diffuse trickling FAF pattern was independently and significantly associated with progression rate (p&#x2009;=&#x2009;0.019).<br><br>CONCLUSIONS: Microperimetric junctional sensitivity may have relevance in predicting atrophy progression rate in eyes with GA, although the FAF pattern may be of greater importance. Larger, longitudinal studies are necessary to further elucidate this relationship.}, }
@article {pmid41999445, year = {2026}, author = {Pearce, I and Dinah, C and Downey, L and Patwardhan, A and Vardarinos, A and Williams, G}, title = {Faricimab in Treatment-Naïve nAMD: Regional UK Real-World Experience.}, journal = {Advances in therapy}, volume = {}, number = {}, pages = {}, pmid = {41999445}, issn = {1865-8652}, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease leading to significant vision loss. Previous standard of care, anti-vascular endothelial growth factor (anti-VEGF) monotherapy, requires frequent injections to maintain efficacy. Faricimab, which targets angiopoietin-2 and VEGF-A, has shown efficacy in patients with nAMD with extended dosing intervals in randomised controlled trials (RCTs). However, results from RCTs are often challenging to replicate in real-world practice. This study aimed to explore outcomes in patients with nAMD treated with faricimab in real-world settings in the UK.<br><br>METHODS: Newly diagnosed patients with nAMD receiving first-line faricimab between 2022 and 2024 were examined across six UK sites in England and Wales. Patients were generally treated per the National Institute of Health and Care Excellence (NICE)-recommended protocol for approximately 1&#xa0;year, with some deviations at individual sites. Outcomes reported included best-corrected visual acuity (BCVA), optical coherence tomography (OCT) fluid, retinal thickness, treatment intervals and safety. Data were analysed separately for each site; adverse event incidence was pooled.<br><br>RESULTS: The total number of eyes treated was 505 from 473 patients. Baseline characteristics were similar across sites, with a mean age of 77.0-82.0&#xa0;years. BCVA, OCT fluid and retinal thickness improvements from baseline were observed across all sites, irrespective of timepoint or treatment protocol. BCVA improvements from baseline ranged from&#x2009;+&#x2009;5.1 to&#x2009;+&#x2009;7.7 letters at the first post-loading visit and from&#x2009;+&#x2009;5.0 to&#x2009;+&#x2009;8.2 letters at 12&#xa0;months. Mean change in retinal thickness from baseline ranged from&#x2009;-&#x2009;92.3 to&#x2009;-&#x2009;127.7&#xa0;&#x3bc;m at 12&#xa0;months. Most patients received faricimab at intervals of&#x2009;&#x2265;&#x2009;8&#xa0;weeks following the loading phase. The pooled incidence of adverse events was low.<br><br>CONCLUSION: Faricimab demonstrated consistent visual and anatomical improvements in real-world UK settings across a heterogeneous group of patients with nAMD. Further real-world studies will be essential to confirm long-term safety and effectiveness in clinical practice.}, }
@article {pmid41999903, year = {2026}, author = {Domalpally, A and Chew, EY and Eydelman, MB and Keenan, TDL and Keane, PA and Lee, AY and Lee, CS and Lad, EM and Lim, JI and Lowenstein, A and Schmidt-Erfurth, U and Abramoff, MD and , }, title = {Reference Standard for Validation of Age-Related Macular Degeneration Screening Algorithms.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.04.013}, pmid = {41999903}, issn = {1549-4713}, abstract = {PURPOSE: Artificial intelligence (AI)-based screening models hold promise for identifying individuals with undiagnosed age-related macular degeneration (AMD) in non-specialist settings. A standardized reference framework for image labeling is needed to enable consistent training, validation, and deployment of AI based screening algorithms.The goal of the present study is to establish expert consensus on image -based reference standard for labeling AMD DESIGN: Modified Delphi consensus study Subjects/ Participants: fellowship-trained retina specialists, ophthalmologists, AI specialists, and imaging specialists METHODS: A prespecified Delphi process was conducted using structured surveys . Over two rounds, panelists assessed opinions on existing reference standards, including the AREDS scale and Beckman scale, as well as imaging modalities such as color, optical coherence tomography (OCT), and autofluorescence. The surveys also evaluated imaging features of AMD, including drusen, pseudodrusen, and pigment changes, as well as referral criteria. Consensus was defined using a 9-point Likert scale, with predefined statistical thresholds for agreement.<br><br>MAIN OUTCOME MEASURES: Agreement on key elements of a reference standard RESULTS: Consensus was reached on adopting the Beckman Classification as the level 1 reference standard (median score 8; agreement). OCT use for identifying key AMD features, including drusen, GA, and CNV, also reached consensus (median scores 8.5-9; agreement). Pigment change detection did not reach consensus (median 7.5; uncertain), and screening age thresholds showed non-consensus (median 8; uncertain). Referral thresholds reached consensus, including urgent referral for neovascular AMD and non-urgent referral for GA and intermediate AMD (median 9; agreement).<br><br>CONCLUSIONS: This study defines a consensus-based reference standard for labeling AMD from images for AI based screening. These recommendations are intended to support consistent AI model development and evaluation, while remaining distinct from clinical practice guidelines.}, }
@article {pmid41814412, year = {2026}, author = {Yin, W and Xu, M and Niu, Z and Gao, Y and Su, N and Song, Y and Liu, Q}, title = {Targeting CDH13 as a therapeutic strategy to mitigate pathological ocular angiogenesis.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41814412}, issn = {1479-5876}, support = {82471096//National Natural Science Foundation of China/ ; 82271100//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Anti-angiogenic therapies, which suppress pathological vessel growth in neovascular diseases such as diabetic retinopathy and neovascular age-related macular degeneration (nAMD), have transformed the clinical landscape. However, a critical unmet challenge is to shift the therapeutic paradigm from broad inhibition towards achieving vascular normalization, as non-selective angiogenic blockade can result in detrimental off-target effects. Consequently, the identification of novel molecular targets is imperative for developing more precise and effective treatment strategies.<br><br>METHODS: We evaluated CDH13 expression in fibrovascular membranes (FVMs) and nAMD derived from human using bioinformatics analysis and confirmed its presence in mouse models of oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) via western blot, RT-PCR, and immunostaining. We then investigated CDH13 function through in vitro transwell, wound healing, and EdU assays following its knockdown, and extended our analysis in vivo using isolectin B4 staining, fundus fluorescein angiography, and immunofluorescent staining in mice subjected to CDH13 knockdown or treated with the oral inhibitor GW3965. Finally, we employed dual-luciferase reporter assays, RT-PCR, and western blot to elucidate the underlying molecular mechanisms.<br><br>RESULTS: We observed substantial CDH13 expression in endothelial cells of human nAMD fibrovascular membranes and mouse models of OIR and CNV. CDH13 knockdown inhibited pathological vessel growth, promoted vascular normalization, and induced a pro-regenerative environment. Mechanistically, hypoxia inhibits NR2F2, thereby de-repressing CDH13 transcription and activating the NF-&#x3ba;B pathway to drive vascular dysfunction. Additionally, oral GW3965 treatment reduced LDL deposition and alleviated pathological neovascularization through LXR activation, countering CDH13-mediated effects.<br><br>CONCLUSION: Together, these findings establish CDH13 as a promising therapeutic target for driving vascular normalization in neovascular retinal diseases.<br><br>GRAPHICAL ABSTRACT: [Image: see text]<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-026-07972-y.}, }
@article {pmid41992419, year = {2026}, author = {Chen, YS and Chang, HC and Chi, SC and Tanaka, K and Chen, SJ and Lin, TC}, title = {Different aflibercept regimens for wet age-related macular degeneration: A systematic review and network meta-analysis.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {}, number = {}, pages = {}, doi = {10.1097/JCMA.0000000000001379}, pmid = {41992419}, issn = {1728-7731}, abstract = {BACKGROUND: Intravitreal aflibercept injection for wet age-related macular degeneration (AMD) was initially approved with a regimen consisting of three monthly loading doses followed by maintenance doses every 8 weeks. Alternative regimens with a reduced treatment burden have been explored. The treat-and-extend (TAE) regimen involves gradually extending the treatment interval in accordance with disease activity, and the pro re nata (PRN) regimen involves administering injections only when signs of disease activity are observed during follow-up visits. This study evaluated these alternative regimens aimed at reducing treatment burden in real-world clinical practice.<br><br>METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases for relevant randomized controlled trials (RCTs). A random-effects model was adopted for network meta-analysis. Results are presented as standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs). Methodological quality of the included RCTs was assessed using the Cochrane risk-of-bias 2.0 tool.<br><br>RESULTS: Seven RCTs (1,683 patients with wet AMD) were included in the network meta-analysis. No significant interregimen differences were observed in visual acuity or central retinal thickness. The TAE and PRN regimens required significantly fewer injections than did bimonthly and monthly regimens, respectively (TAE vs. bimonthly: SMD -1.091, 95% CI -2.030 to -0.153; TAE vs. monthly: SMD -3.024, 95% CI -4.584 to -1.465; PRN vs. Bimonthly: SMD -1.919, 95% CI -3.307 to -0.532; PRN vs. Monthly: SMD -3.852, 95% CI -5.717 to -1.988). However, injection count did not differ significantly between the TAE and PRN regimens (TAE vs. PRN: SMD 0.828, 95% CI -0.847 to 2.503). Nonetheless, the TAE regimen was associated with fewer clinic visits than the PRN regimen.<br><br>CONCLUSION: The TAE regimen maintains efficacy while reducing treatment burden in patients with wet AMD receiving intravitreal aflibercept.}, }
@article {pmid41993457, year = {2026}, author = {Cakir, B and Yeh, TC and Lin, CH and Wu, MR and Boilard, &#xc9; and Pelletier, M and Singh, AM and Breton, Y and Patel, S and Benson, T and Almeida, DR and Wang, S and Mahajan, VB}, title = {Mitochondrial Transplantation in the Eye: A Review and Evaluation of Surgical Approaches.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.04.06.716722}, pmid = {41993457}, issn = {2692-8205}, abstract = {PURPOSE: Mitochondrial dysfunction contributes to major blinding diseases, including age-related macular degeneration and glaucoma. Although mitochondrial transplantation has shown therapeutic potential in multiple organ systems, translation to the eye remains limited, partly due to uncertainty regarding optimal delivery. We summarize the biologic rationale and preclinical evidence supporting ocular mitochondrial transplantation and present feasibility data evaluating clinically relevant delivery routes.<br><br>METHODS: We conducted a focused narrative review of ocular mitochondrial transplantation. For feasibility experiments, mitochondria with an endogenous fluorescent dye were isolated from liver donor mice. Postnatal day 7 pups received subretinal injections, and adult CD1 mice received intravitreal injections, including optic nerve head directed delivery. Eyes were analyzed using fluorescence microscopy and immunohistochemistry. Mitochondrial uptake was assessed in cultured retinal pigmental epithelial (RPE) cells using co-incubation assays. Suprachoroidal delivery feasibility was evaluated in cadaveric human near-real surgical specimens using a novel dedicated suprachoroidal injector.<br><br>RESULTS: The literature on ocular mitochondrial transplantation remains limited and consists primarily of small preclinical studies using intravitreal delivery and imaging-based detection. In our experiments, intravitreal delivery produced donor signals predominantly within inner retinal layers, with enrichment along retinal nerve fiber bundles when directed toward the optic nerve head. Cultured RPE cells demonstrated dose-dependent uptake of exogenous mitochondria. Subretinal delivery localized donors signal to the RPE and adjacent outer retina. Suprachoroidal injections demonstrated procedural feasibility with reliable access to the suprachoroidal space and visible injectate distribution.<br><br>CONCLUSIONS: Ocular mitochondrial transplantation is in an early stage of investigation. Our feasibility data indicate that established posterior-segment delivery routes expose distinct retinal compartments and that route selection strongly influences anatomic distribution. Further studies are needed to verify intracellular uptake, define dosing and durability, and evaluate safety in disease-relevant models.}, }
@article {pmid41993761, year = {2026}, author = {Bousamri, A and Al-Shehri, M and Mestarihi, M and Almutairi, TB and Alaredhi, M and Mahanna, B and Alharbi, F}, title = {Clinical Outcomes of High-Dose Aflibercept 8 mg in Polypoidal Choroidal Vasculopathy: A Systematic Review and Meta-Analysis.}, journal = {Cureus}, volume = {18}, number = {4}, pages = {e106769}, pmid = {41993761}, issn = {2168-8184}, abstract = {Polypoidal choroidal vasculopathy (PCV) is a distinct subtype of neovascular macular disease with variable responses to anti-vascular endothelial growth factor (anti-VEGF) therapy. This systematic review and meta-analysis evaluated the visual, anatomical, and lesion-regression outcomes of intravitreal aflibercept 8 mg, a formulation developed to extend dosing intervals while maintaining efficacy, in patients with PCV. PubMed, Embase, Scopus, Web of Science, and Google Scholar were searched from inception to March 12, 2026 (PROSPERO: CRD420261339679). Eligible studies enrolled adults with indocyanine green angiography (ICGA)-confirmed PCV treated with aflibercept 8 mg and reported at least one co-primary outcome: change in best-corrected visual acuity (BCVA), central retinal or subfield thickness (CRT/CST), or complete polyp regression. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2), Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I), and Joanna Briggs Institute (JBI) appraisal tools. Complete polyp regression was analyzed using a generalized linear mixed model with a logit link; continuous outcomes were pooled using restricted maximum likelihood estimation with the Hartung-Knapp-Sidik-Jonkman correction. Certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Five studies encompassing 362 eyes (245 treated with aflibercept 8 mg) were included. The pooled complete polyp regression rate was 57% (95% confidence interval (CI), 39%-73%; I[2]=55.9%; k=3). The pooled mean CRT/CST change was -157.8 µm (95% CI, -176.9 to -138.7 µm; I[2]=0%; k=2), though the estimate was predominantly driven by a single study contributing 95.5% of the inverse-variance weight. BCVA outcomes were not pooled due to metric incompatibility and clinical heterogeneity; however, individual study results were directionally favorable, with Early Treatment Diabetic Retinopathy Study (ETDRS) gains of +8.4 to +9.5 letters at 48 weeks in the largest contributing study. Extended dosing intervals were maintained in 80.5% (q12) and 86.5% (q16) of treated eyes at 48 weeks. One study reported intraocular inflammation in 10.8% of the overall neovascular age-related macular degeneration (AMD) cohort in that study, a safety signal not observed in the remaining studies. The certainty of evidence was low for CRT/CST change and very low for polyp regression and BCVA. Available evidence suggests that aflibercept 8 mg may produce clinically relevant polyp regression and substantial anatomical improvement in PCV, with a potential reduction in injection frequency. However, given the low to very low certainty of the current evidence base across all co-primary outcomes, definitive efficacy and safety conclusions cannot yet be drawn. Prospective, PCV-specific trials with standardized outcome reporting are needed.}, }
@article {pmid41994559, year = {2026}, author = {Cheng, CK and Tsai, CJ and Bai, CH}, title = {Reassessing high-dose ranibizumab in the era of durable anti-VEGF therapy.}, journal = {Frontiers in ophthalmology}, volume = {6}, number = {}, pages = {1802903}, pmid = {41994559}, issn = {2674-0826}, }
@article {pmid41995082, year = {2026}, author = {Patel, MK and Piedade, WP and Famulski, JK}, title = {Cdhr1a and pcdh15b may link photoreceptor outer segments with calyceal processes revealing a potential mechanism for cone-rod dystrophy.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, doi = {10.7554/eLife.102258}, pmid = {41995082}, issn = {2050-084X}, support = {P20GM103436//KYINBRE core facility voucher/ ; }, mesh = {Animals ; *Cadherins/metabolism/genetics ; Zebrafish ; Humans ; *Cone-Rod Dystrophies/pathology/genetics/metabolism ; Cadherin Related Proteins ; *Zebrafish Proteins/metabolism/genetics ; Mice ; *Retinal Photoreceptor Cell Outer Segment/metabolism ; }, abstract = {Cone-rod dystrophy (CRD) is a macular degeneration disorder characterized by initial cone cell degeneration. Mutations in CDHR1, a photoreceptor-specific cadherin, have been found to be associated with the incidence of CRD. While studying the function of CDHR1, we observed that the localization of the zebrafish homologue, cdhr1a, resembles that of calyceal process (CPs). When co-labeling CPs using pcdh15b, we observed that cdhr1a, in the outer segment (OS), juxtaposes with pcdh15b, found in the CP. Similar localization patterns were detected in human, macaque, xenopus, ducks, gerbil, and mouse. Using immunoprecipitation and K652 cell aggregation assays, we demonstrate that pcdh15b and cdhr1a can interact and thus potentially link the OS and CP. To analyze the consequences of OS-CP interactions in CRD, we established a cdhr1a mutant line (cdhr1a[fs*146]). Homozygous cdhr1a[fs*146] mutants exhibit minor cone OS defects starting at 15 dpf and severe OS disruption and cell loss by 3 months. Shortening of CPs coincided with cone OS defects which were significantly exacerbated when combined with the loss of pcdh15b. Rod OS defects were mild and delayed until 3-6 months. In conclusion, we propose that cdhr1a and pcdh15b function to link cone OSs with CPs and maintain OS integrity.}, }
@article {pmid41995436, year = {2026}, author = {Pu, J and Zhuang, X and Hao, X and Li, M and Su, Y and He, G and He, Y and Zhang, G and Wen, F}, title = {Longitudinal Tracking of Photoreceptor Integrity in Neovascular AMD: Early Restoration Predicts 24-Month Structural and Visual Outcomes.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {41}, doi = {10.1167/iovs.67.4.41}, pmid = {41995436}, issn = {1552-5783}, mesh = {Humans ; Female ; Male ; Aged ; Prospective Studies ; *Visual Acuity/physiology ; Tomography, Optical Coherence/methods ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Follow-Up Studies ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Fluorescein Angiography ; *Photoreceptor Cells, Vertebrate/pathology ; Ranibizumab/therapeutic use/administration &amp; dosage ; Time Factors ; }, abstract = {PURPOSE: The purpose of this study was to longitudinally characterize photoreceptor band changes over 24 months and determine whether early restoration predicts long-term outcomes in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective study enrolled treatment-na&#xef;ve patients with nAMD receiving anti-vascular endothelial growth factor therapy following 3 + pro re nata (PRN) regimen. Impaired areas of outer nuclear layer (ONL), ellipsoid zone (EZ), external limiting membrane (ELM), and interdigitation zone (IZ) were quantified at baseline, 1 week, 1, 2, 3, 12, and 24 months, and associations between early restoration and long-term structural and visual outcomes were assessed.<br><br>RESULTS: Eighty-two eyes from 82 patients (mean age = 65.15 &#xb1; 7.47 years) completed a 24-month follow-up. All bands showed significant changes over 2 years (P < 0.05 for all). Only EZ demonstrated significant early restoration at 1 week and 1 month (P = 0.041 and 0.004, respectively). Month 3 restoration of all bands predicted corresponding 1- and 2-year structural changes (Std&#x3b2; = 0.432-0.912, P < 0.05, except for 2-year ONL and IZ: P = 0.201 and 0.304, respectively). Moreover, month 2 ONL changes also independently predicted long-term ONL changes (P = 0.011 and P < 0.001 for 1 and 2 years, respectively). For visual outcomes, month 3 IZ restoration predicted 1-year BCVA improvement (Std&#x3b2; = -0.334, P = 0.032), whereas month 2 ONL restoration predicted 2-year BCVA improvement (Std&#x3b2; = -0.378, P = 0.003).<br><br>CONCLUSIONS: Photoreceptor bands showed layer-specific restoration patterns, with EZ responding earliest. Early restoration at months 2 to 3 predicted long-term outcomes, with ONL and IZ as independent visual predictors.}, }
@article {pmid41998200, year = {2026}, author = {Cheah, IK and Fong, ZW and Chen, L and Tang, RMY and Zhou, L and Yanagi, Y and Cheng, CY and Su, X and Li, X and Teo, KYC and Cheung, CMG and Tan, TE and Halliwell, B}, title = {Ergothioneine as a potential protective agent against macular degeneration and other eye disorders.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-48438-x}, pmid = {41998200}, issn = {2045-2322}, support = {OFYIRG22jul-0027//National Medical Research Council/ ; R1752/75/2020//SERI Lee Foundation Grant/ ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in ageing populations, with oxidative stress recognised as a key pathogenic driver. The dietary antioxidant and cytoprotectant, L-ergothioneine (ET), is avidly accumulated in many tissues, especially the eye. However its relationship to AMD is unclear. Here, we examined ET's distribution in human ocular tissues and measured serum and intraocular ET levels in patients with neovascular AMD. Compared with ocularly-normal age-matched individuals, AMD patients exhibited significantly lower serum ET; elevated levels of ET metabolites, hercynine and ETSO3, which may be generated by oxidative stress; and elevated levels of serum allantoin, a biomarker of oxidative damage to urate in humans. Levels of ET in aqueous humour in AMD patients were marginally lower than cataractous patients, who are already known to have significantly lower ET levels than healthy eyes. High ET levels were seen in human ocular tissues, concentrating in regions vulnerable to oxidative damage, including the lens, retina, retinal pigment epithelium, and choroid, supporting a physiological protective role of ET in the eye. These findings identify a strong association between low ET levels and AMD, warranting further studies to determine whether ET supplementation can modify AMD risk or progression.}, }
@article {pmid41998289, year = {2026}, author = {Küçükerdönmez, C and Tedford, SE}, title = {Response to "Letter to the Editor Regarding 'Multiwavelength Photobiomodulation Improves Multiple Aspects of Visual Function in Early-Stage Dry Age-Related Macular Degeneration'".}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s40123-026-01383-4}, pmid = {41998289}, issn = {2193-8245}, }
@article {pmid41998290, year = {2026}, author = {Karakosta, C and MacLaren, RE}, title = {Letter to the Editor Regarding "Multiwavelength Photobiomodulation Improves Multiple Aspects of Visual Function in Early-Stage Dry Age-Related Macular Degeneration".}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41998290}, issn = {2193-8245}, }
@article {pmid41987023, year = {2026}, author = {Horita, S and Saki, M and Takigawa, S and Kanai, Y and Murotani, K and Gomi, F}, title = {Ocular pharmacokinetics of tivozanib eye drops in patients with neovascular age-related macular degeneration: comparison with phase 1 trials of oral tivozanib in solid tumors.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {}, pmid = {41987023}, issn = {2056-9920}, abstract = {Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the standard treatment for neovascular age-related macular degeneration (nAMD) but is invasive and burdensome for patients. To overcome these obstacles, tivozanib, a pan-VEGF receptor inhibitor approved for renal cell carcinoma, is in development as eye drops. The phase 1 study of a 3-week administration of tivozanib eye drops showed a preferable safety profile and exploratory efficacy signs in Japanese patients with nAMD. During eye drop administration, two drug delivery pathways affect ocular pharmacokinetics, either directly through the ocular tissues or through systemic circulation. To assess the ocular pharmacokinetics of tivozanib eye drops, we conducted an integrated analysis of systemic adverse event occurrence and systemic exposure in patients with nAMD treated with tivozanib eye drops and in patients with cancer treated with oral tivozanib, using previous phase 1 study results. Systemic exposure was significantly lower with tivozanib eye drops versus oral tivozanib, with no drug-related hypertension due to the systemic pan-VEGF receptor inhibition observed, suggesting systemic VEGF receptors are not fully inhibited by tivozanib. Exploratory efficacy signs in patients with nAMD after short-term use of tivozanib eye drops also suggest tivozanib might reach the retina and inhibit VEGF receptors, although further long-term efficacy studies are warranted. Given the integrated analysis, we hypothesize that tivozanib eye drops could predominantly be delivered to the posterior eye segment through the ocular tissues, with limited contribution by the systemic drug delivery pathway. This hypothesis provides meaningful insights into the ocular pharmacokinetics of tivozanib eye drops.}, }
@article {pmid41987034, year = {2026}, author = {Mohamed, MI and Halwag, MI and Mahmoud, NH and Salib, M and Nada, MA}, title = {Migraine as a risk factor for retinal vascular events and maculopathies: a systematic review and meta-analysis of 47 million individuals.}, journal = {The journal of headache and pain}, volume = {}, number = {}, pages = {}, doi = {10.1186/s10194-026-02353-8}, pmid = {41987034}, issn = {1129-2377}, }
@article {pmid41987176, year = {2026}, author = {Zhang, Y and He, W and Wang, C and Liu, B and Wen, J and Zhao, Y and Zhang, Y and Liu, L and Yang, Q and Li, J and Dong, Y and Zhang, X and Xu, Q and Zhai, G and Ye, L and Qu, Y}, title = {A sequential dual-drug delivery system for multi-target inhibition of subretinal fibrosis.}, journal = {Journal of nanobiotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12951-026-04390-6}, pmid = {41987176}, issn = {1477-3155}, abstract = {BACKGROUND: Subretinal fibrosis (SRF), a severe vision-threatening complication secondary to neovascular age-related macular degeneration (nAMD), remains a major clinical challenge due to its complex pathogenesis and prolonged disease course. The fibrotic process is driven by multiple synergistic factors, including chronic inflammation, hypoxia, epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, and pathological neovascularization, which collectively lead to the ineffectiveness of conventional anti-vascular endothelial growth factor (VEGF) monotherapies in halting disease progression.<br><br>RESULTS: This study developed a sequential dual-drug delivery system based on the terpolymer P(NIPAM-co-AA-co-HEMA) hydrogel (NAHGel), designed to achieve multi-targeted regulation from the pathological microenvironment to downstream fibrotic processes. NAHGel exhibits excellent thermal responsiveness, biomechanical stability, and biodegradability, and is co-loaded with matrine (MT) and cRGD-modified sorafenib liposomes (SF/cLP). The hydrogel undergoes thermal contraction to enable the rapid release of hydrophilic MT, exerting anti-inflammatory and anti-hypoxic effects. As the hydrogel progressively degrades, SF/cLP is released in a delayed manner and, under cRGD mediation, is targeted to RPE cells and vascular endothelial cells. This enables modulation of key pathways including TGF-&#x3b2;2/MEK1/2/ERK1/2 and HIF-&#x3b1;/VEGF/PDGF, thereby inhibiting EMT and endothelial proliferation. In a laser-induced SRF mouse model, MT&#x2009;+&#x2009;SF/cLP@NAHGel formed a stable in situ gel within 24&#xa0;h after intravitreal injection and remained structurally intact in the dynamic vitreous environment, enabling sustained retention for up to 8 months. Imaging and histological analyses demonstrated that, compared with aflibercept and other group, this system significantly reduced choroidal neovascularization and fibrotic lesion areas. Transcriptomic analysis further confirmed its broad inhibition of signaling pathways related to inflammation, angiogenesis, and fibrosis, with marked downregulation of key mediators including VEGFA, TGF-&#x3b2;2, TNF-&#x3b1;, and HIF-1&#x3b1;.<br><br>CONCLUSION: MT&#x2009;+&#x2009;SF/cLP@NAHGel achieves sequential drug release and multi-targeted synergy to intervene in key pathological processes such as inflammation, hypoxia, EMT, and pathological neovascularization, thereby effectively halting SRF progression. Combining sustained therapeutic efficacy with excellent biosafety, this system holds strong translational potential as a long-acting treatment strategy for SRF and other multifactorial retinal diseases.}, }
@article {pmid41987778, year = {2026}, author = {Li, M and Gu, A and Li, H and Li, Y and Liang, R and Su, T and Wu, Y}, title = {Machine-learning for age-related macular degeneration using multimodal fundus data.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1756787}, pmid = {41987778}, issn = {2296-858X}, abstract = {OBJECTIVE: To develop an integrated model that combines multimodal fundus image features for accurately predicting the individualized risk of progression from early to late stages of age-related macular degeneration (AMD).<br><br>METHODS: A retrospective analysis was conducted on the data of 324 patients with AMD. The patients were randomly divided into a training set (n = 227) and a validation set (n = 97) at a ratio of 7:3. The follow-up period was 3 years, and patients with disease progression were defined as the progression group. In the training set, indicators related to prognosis were screened through univariate analysis. After variable compression by LASSO regression, independent influencing factors for poor prognosis were determined using multivariate logistic regression. Random Forest, Support Vector Machine, XG BOOST, and K-Nearest Neighbor algorithm prediction models were constructed using Python software. The performance of the models was evaluated by the area under the receiver operating characteristic curve (AUC), and the optimal model was selected.<br><br>RESULTS: There were no significant differences in the baseline characteristics between the training set and the validation set patients (P > 0.05), indicating comparability. In the training set, multivariate logistic regression analysis showed that pigmentary abnormalities, the total area of drusen in the macular area, and the ellipsoid zone were independent risk factors for disease progression (P < 0.05), while subfoveal choroidal thickness and choroidal capillary blood flow density were independent protective factors (P < 0.05). The AUC values of the Random Forest model (0.779 in the training set and 0.700 in the validation set) were significantly higher than those of the K-Nearest Neighbor algorithm (0.717 in the training set and 0.596 in the validation set), the Support Vector Machine model (0.768 in the training set and 0.646 in the validation set), and XG BOOST (0.702 in the training set and 0.762 in the validation set), making it the optimal prediction model.<br><br>CONCLUSION: In this study, an AMD progression prediction model based on multimodal fundus images was successfully developed, which can effectively identify patients at high risk of progression and provide a new paradigm for clinical individualized precision medicine.}, }
@article {pmid41987800, year = {2026}, author = {Garcia-Atutxa, I and Martinez-Baliu, L and Villanueva-Flores, F}, title = {Robust benchmarking of DeepLabv3 hybrid models for multiclass fundus screening and referable-disease triage on the FIVES dataset.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1771083}, pmid = {41987800}, issn = {2296-858X}, abstract = {BACKGROUND: Automated analysis of color fundus photographs can support scalable screening for diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma, but single-run reporting and accuracy-only summaries can mask clinically relevant instabilities and failure modes.<br><br>METHODS: Using the public FIVES dataset, we benchmarked six deep learning configurations for four-class fundus screening (AMD, DR, glaucoma, normal): three DeepLabv3-backbone hybrids (ResNet50, DenseNet121, EfficientNet-B0) and three backbone-only classifiers. All experiments were evaluated using five independent stratified splits generated with different random seeds (n = 5 runs), each defining a distinct 20% held-out test set. Models were trained on the remaining 80% (training/validation), and all reported metrics are computed on the 20% test set of each run and summarized as mean &#xb1; SD across runs. Performance was summarized with accuracy, sensitivity, specificity, and one-vs.-rest AUC; we further characterized clinical behavior via row-normalized confusion matrices, per-class precision/recall/F1, and a screening-style binary triage setting (referable = AMD &#x222a; DR &#x222a; glaucoma vs. normal).<br><br>RESULTS: Hybrid models consistently achieved higher discrimination than simple classifiers (AUC 0.969-0.979 vs. 0.908-0.920), despite similar accuracies (0.924-0.941). The selected model, DeepLabv3-DenseNet121, reached the highest AUC (0.979 &#xb1; 0.009). Class-wise analysis revealed strong performance for Normal (F1 0.970 &#xb1; 0.014) and Glaucoma (F1 0.896 &#xb1; 0.048), while DR was the main bottleneck (sensitivity 0.738 &#xb1; 0.117), with most DR errors redistributed to AMD (13.6%) and Glaucoma (12.0%) and minimal confusion with Normal (0.5%). In binary triage, the model achieved sensitivity 0.993 &#xb1; 0.011 and specificity 0.963 &#xb1; 0.034, with PPV 0.987 &#xb1; 0.013 and NPV 0.980 &#xb1; 0.032, and a stable referral rate (&#x223c;0.73-0.77) across runs.<br><br>CONCLUSION: DeepLabv3-based hybrids provide a robust advantage in AUC for multiclass fundus screening on FIVES. The residual risk concentrates in the DR-AMD-Glaucoma decision boundary, suggesting that deployment-oriented policies should prioritize conservative handling of DR-adjacent cases while leveraging the stability of Normal predictions for screening workflows.}, }
@article {pmid41988431, year = {2026}, author = {Auer, EA and Gnanaraj, R and Lynch, AM and Mandava, N and Palestine, AG and Mathias, MT and Manoharan, N and Lisker-Cervantes, A and de Carlo Forest, TE and Kohrt, WM and Patnaik, JL}, title = {Menopausal Hormone Therapy and Conversion from Intermediate to Advanced Age-Related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261428770}, pmid = {41988431}, issn = {2474-1272}, abstract = {Purpose: To evaluate the relationship between self-reported menopausal hormone replacement therapy use and conversion to an advanced form of AMD among female patients with intermediate AMD (iAMD). Methods: Female patients with iAMD enrolled in the University of Colorado AMD Registry between July 2014 and July 2024 were included in this prospective cohort study, with follow-up through November 2024. Conversion to an advanced form of AMD, either advanced non-neovascular AMD or neovascular AMD, was assessed by review of patients' multimodal imaging. Kaplan-Meier curves and Cox proportional hazards modeling were used to assess time to conversion. Hazard ratios (HRs) with 95% CIs are presented for multivariable models. Results: Among 285 female patients with iAMD, the mean (±SD) follow-up time was 36.3 ± 26.7 months. In a total of 82 patients (28.8%), conversion to advanced AMD occurred during follow-up. In univariate analysis, a history of ever having used hormone replacement therapy (55.4%), compared with never having used hormone replacement therapy (44.6%), was not associated with conversion to either of the advanced forms of AMD. In multivariable analysis, patients who had ever used hormone replacement therapy did not have significantly elevated risks of conversion to advanced non-neovascular AMD (HR, 1.03, 95% CI, 0.54-1.96; P = .94) or neovascular AMD (HR, 2.10, 95% CI, 0.86-5.02; P = .10). Conclusions: Among female patients with iAMD, self-reported use of hormone replacement therapy was not associated with an increased risk of conversion to either of the advanced forms of AMD.}, }
@article {pmid41988735, year = {2026}, author = {Sun, H and Gao, E and Li, Y and Xiang, D and Lu, F and Zhou, Y and Zhu, W and Shi, F and Nie, B and Chen, X and Zhang, L and Cai, J and Peng, D and Peng, T}, title = {Refining feature representation for accurate fundus lesion segmentation.}, journal = {Medical physics}, volume = {53}, number = {4}, pages = {e70441}, doi = {10.1002/mp.70441}, pmid = {41988735}, issn = {2473-4209}, support = {62371328//National Nature Science Foundation of China/ ; 61971298//National Nature Science Foundation of China/ ; 62371326//National Nature Science Foundation of China/ ; 62271337//National Nature Science Foundation of China/ ; 62471326//National Nature Science Foundation of China/ ; BK20231310//Natural Science Foundation of Jiangsu Province/ ; 24KJB510042//Natural Science Foundation of the Jiangsu Higher Education Institutions of China/ ; JSTJ-2024-434//Technology Young Science and Technology Talent Support Project/ ; PRJ2022008//DKU Education Development Fund/ ; }, mesh = {*Image Processing, Computer-Assisted/methods ; Humans ; *Fundus Oculi ; Deep Learning ; Choroidal Neovascularization/diagnostic imaging ; Macular Degeneration/diagnostic imaging ; Retina/diagnostic imaging ; }, abstract = {BACKGROUND: Accurate segmentation of retinal lesions is essential for early detection of age-related macular degeneration (AMD), particularly its key indicators, choroidal neovascularization (CNV) and choroidal non-perfusion (CNP). However, the highly variable shapes and appearances of lesions pose substantial challenges for automated segmentation.<br><br>PURPOSE: To tackle these challenges, we propose a deep-learning model, the Retinal Feature Enhancement Network (RFENet), designed to improve the accuracy and robustness of retinal lesion segmentation under challenging imaging&#xa0;conditions.<br><br>METHODS: RFENet builds upon the UNeXt backbone and introduces two modules tailored for retinal lesion segmentation: an Adaptive Feature Refinement Unit (AFRU), which selectively emphasizes informative features, and an Optimized Channel-Wise Convolution Unit (OCCU), which captures fine structural details in irregular lesions. Two expert-annotated datasets were used: 1070 OCT B-scans from 83 CNV patients and 184 FFA images from 107 CNP patients. Images were split at the patient level into training (70%), validation (10%), and test (20%) sets. Performance was compared against state-of-the-art segmentation models, including UNet++, Swin-UNet, SelfReg-UNet, DAEFormer, and Mamba-UNet. Evaluation metrics included Dice coefficient and Intersection over Union (IoU). Statistical significance was assessed using paired two-tailed t-tests (&#x3b1; = 0.05 $\alpha = 0.05$), and effect sizes were reported with Cohen's d $d$ .<br><br>RESULTS: On the CNV dataset, RFENet achieved a Dice of 82.50% and an IoU of 71.66%, with clear improvements over competing models. On the CNP dataset, RFENet achieved a Dice of 74.43% and an IoU of 60.80%, slightly surpassing the best benchmark. Most pairwise comparisons were statistically significant, including CNV compared with Swin-UNet and SelfReg-UNet (p < $<$ 0.001) and CNP compared with DAEFormer (p = $=$ 0.035). Statistical analyses, including effect size evaluation, further confirmed the robustness of these improvements, with the most notable gains observed in the CNV&#xa0;dataset.<br><br>CONCLUSIONS: RFENet demonstrated consistent improvements over strong benchmarks on both CNV and CNP tasks, with statistical evidence supporting the reliability of these gains. These results indicate that RFENet provides a reliable technical advance for automated segmentation of CNV and CNP lesions associated with AMD. To facilitate reproducibility and further research, the source code is publicly available at https://github.com/HaoSun223/RFENet.}, }
@article {pmid41989239, year = {2026}, author = {Jonas, JB and Panda-Jonas, S and Jonas, RA and Wang, YX}, title = {Prevalence and associations of hyper-reflective bodies in the posterior vitreous: The Beijing eye study.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70139}, pmid = {41989239}, issn = {1755-3768}, support = {82271086//National Natural Science Foundation of China/ ; }, abstract = {PURPOSE: To assess prevalence and associations of intra-vitreal hyper-reflective bodies (vHRBs) in the posterior vitreous in a general population.<br><br>METHODS: Participants of the population-based Beijing Eye Study underwent systemic and ophthalmological examinations. We included into this study a randomly selected group of normal eyes without retinal diseases and a randomly selected group of eyes with age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PVC) or central serous choroidopathy (CSC). Using serial optical coherence tomography scans of the posterior fundus region, we searched for vHRBs in the posterior vitreous compartment.<br><br>RESULTS: The study consisted of 1347 eyes (age: 64.3&#x2009;&#xb1;&#x2009;9.8&#x2009;years, range: 50-91&#x2009;years; axial length: 23.04&#x2009;&#xb1;&#x2009;1.00&#x2009;mm, range: 19.39-28.93&#x2009;mm). vHRB were detected in 314/1347 eyes (23.3%; 95% confidence interval [CI]: 21.1, 25.6), that is, in 137 out of 447 normal eyes (28.9%; 95% CI: 24.8, 33.0), 110/458 eyes with early AMD (24.0%; 95% CI: 20.1, 27.9), 45/278 eyes with intermediate AMD (16.2%; 95% CI: 11.8, 20.5), 3/35 eyes with PCV (8.6%; 95% CI: 0.00, 18.3), and in 19/94 eyes with CSC (20.2%; 95% CI: 11.9, 28.5). In multivariable analysis, higher vHRB prevalence was associated with younger age (OR: 0.93; 95% CI: 0.91, 0.95; p&#x2009;<&#x2009;0.001), shorter axial length (OR: 0.69; 95% CI:0.56, 0.84; p&#x2009;<&#x2009;0.001), and lower stage of posterior vitreous detachment (OR: 0.53; 95% CI: 0.44, 0.64; p&#x2009;<&#x2009;0.001). It was independent of AMD stage (p&#x2009;=&#x2009;0.87), and prevalence of PCV (p&#x2009;=&#x2009;0.67) and CSC (p&#x2009;=&#x2009;0.40). Higher amount of vHRBs (multivariable linear regression analysis) correlated with younger age (beta: -0.21; B: -0.02; 95% CI: -0.03, -0.02; p&#x2009;<&#x2009;0.001), shorter axial length (beta: -0.07; B: -0.09; 95% CI: -0.16, -0.02; p&#x2009;=&#x2009;0.009) and lower stage of posterior vitreous detachment (beta: -0.15; B: -0.13; 95% CI: -0.19, -0.08; p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: vHRBs were detected in one out of four normal eyes of individuals aged 50+ years, in dependence on younger age, shorter axial length and lower degree of posterior vitreous detachment. They were independent of a concurrence of AMD, PCV and CSC.}, }
@article {pmid41989896, year = {2026}, author = {Wen, Y and Zeng, Y and Bi, L and Zhao, X and Shi, W and Fu, H and Sheng, B}, title = {M2Net: Multimodal Multitask Mutual Learning for Anti-VEGF Efficacy Prediction.}, journal = {IEEE transactions on medical imaging}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TMI.2026.3684331}, pmid = {41989896}, issn = {1558-254X}, abstract = {Age-related macular degeneration with abnormal blood vessel growth (neovascular AMD) is the leading cause of vision loss in elderly populations. While anti-VEGF injections are the standard treatment, they present financial burdens for patients and vary in effectiveness. Predicting treatment efficacy is therefore crucial for patient care. Current prediction methods fail to fully integrate information from different imaging techniques, typically focusing on either forecasting vision improvements or generating post-treatment images-but not both simultaneously. This approach overlooks the important relationship between these tasks. We present M2Net, a novel joint generation and classification network based on Multimodal Multitask Mutual learning, to simultaneously predict changes in visual acuity and generate post-treatment retinal images. M2Net employs a dual-branch structure that processes both fundus photographs and Optical Coherence Tomography (OCT) scans to improve prediction accuracy. Our framework includes two key innovations: the Multimodal Collaborative Treatment Efficacy Prediction module, which interacts the features between the two modalities and provides initial visual acuity change classification to guide the generation of post-treatment images; and the Pre-Post Treatment Image Joint Analysis module, which identifies both common and changing features between pre-treatment and post-treatment images to enhance prediction accuracy. To validate our approach, we created the dataset (MMPD) containing paired multimodal retinal images with corresponding visual acuity measurements. Experiments on the dataset demonstrate that M2Net achieves superior performance compared to existing methods, with a classification accuracy of 96.03%, an SSIM of 0.6377 on the OCT modality, and an SSIM of 0.8347 on the fundus modality. Our code will be available at https://github.com/zengying123/M2Net.}, }
@article {pmid41990324, year = {2026}, author = {Rhodes, EY and Xia, JL and de Carlo Forest, TE and Manoharan, N and Palestine, AG and Reddy, AK}, title = {Hypertensive Anterior Uveitis Following Intravitreal Faricimab.}, journal = {Ocular immunology and inflammation}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/09273948.2026.2658753}, pmid = {41990324}, issn = {1744-5078}, abstract = {PURPOSE: Describe findings of three cases of culture and PCR negative hypertensive anterior uveitis following intravitreal faricimab.<br><br>METHODS: This is a case series of three patients undergoing treatment for diabetic macular edema (DME) or neovascular age-related macular degeneration (nAMD). Data collected included visual acuity, intraocular pressure (IOP), slit lamp examination (SLE), anterior chamber (AC) tap, vitreous tap with culture, and fluorescein angiography (FA).<br><br>RESULTS: Three patients developed hypertensive uveitis following repeated intravitreal faricimab injections for DME or nAMD. All presented within 2-5&#x2009;weeks of injection with ocular pain and redness. Exam revealed elevated intraocular pressure (22-52&#x2009;mmHg), and keratic precipitates with anterior chamber inflammation. Infectious and inflammatory workups, including aqueous and/or vitreous PCR for HSV, VZV, and CMV, were negative in all cases. Faricimab was discontinued and topical and/or local corticosteroids initiated, with adjunctive IOP-lowering therapy as indicated. Inflammation resolved in all patients within 3&#x2009;months without recurrence after switching intravitreal anti-VEGF agents. Final visual acuity ranged from 20/25 to count fingers, limited by glaucomatous optic neuropathy in one case.<br><br>CONCLUSIONS: Hypertensive anterior uveitis with diffuse KPs is a potential rare complication of intravitreal faricimab and must be considered in patients presenting with new ocular inflammation or IOP elevation while undergoing treatment with faricimab. The intraocular inflammation appears to respond well to discontinuation of faricimab and treatment with local corticosteroids.}, }
@article {pmid41990841, year = {2026}, author = {Grün, M and Faatz, H}, title = {[Optical coherence tomography angiography].}, journal = {Klinische Monatsblatter fur Augenheilkunde}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2729-1450}, pmid = {41990841}, issn = {1439-3999}, abstract = {Optical coherence tomography angiography (OCTA) has become increasingly established as a diagnostic procedure in clinical practice in recent years. In the field of medical retina in particular, it serves as a useful aid to the morphological assessment of vascular diseases such as neovascular age-related macular degeneration and diabetic retinopathy. Technically speaking, it is a further development of optical coherence tomography (OCT) and therefore offers the advantage of being non-invasive. Even though other imaging modalities still need to be used for certain clinical matters, OCTA offers a suitable alternative to invasive procedures in some situations or can be a helpful supplement in cases of unclear findings. In addition, OCTA has led to a better understanding of the pathophysiology and course of vascular diseases in a scientific context. Recent developments have already reduced or eliminated some of the limitations of OCTA and further improvements for use in clinical practice can be expected in the future.}, }
@article {pmid41990981, year = {2026}, author = {Keenan, TDL and Hébert, M and Chew, EY and Johnson, MW}, title = {What Should Patients with Age-Related Macular Degeneration Eat?.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.04.003}, pmid = {41990981}, issn = {1879-1891}, abstract = {PURPOSE: To summarize relevant data on what individuals with age-related macular degeneration (AMD) should eat and to propose simple, evidence-based, dietary and micronutrient supplement guidelines that can be shared with patients and physicians.<br><br>DESIGN: Focused literature review with interpretation and clinical perspective METHODS: We selectively reviewed literature on the associations between diet, oral micronutrient supplementation, and AMD progression, synthesizing evidence by disease stage. Sources included the Age-Related Eye Disease Studies (AREDS/AREDS2) in the United States, and major epidemiologic and cohort studies in Europe and North America.<br><br>RESULTS: Across disease stages, closer adherence to a Mediterranean diet is consistently associated with substantially slower AMD progression. In AREDS, individuals with early AMD who adhered more closely to a Mediterranean diet were significantly less likely to develop intermediate AMD. In AREDS/AREDS2 participants with intermediate AMD, higher Mediterranean diet adherence was strongly associated with decreased risk of progression to late AMD, especially for geographic atrophy (GA). Specific dietary components were particularly influential: higher fish intake was most protective, followed by higher vegetable and lower red meat intake. For individuals with geographic atrophy (GA), a Mediterranean diet was associated with markedly slower GA enlargement, including slower expansion towards the fovea. Higher intake of fruit and vegetables, lower intake of red meat, and avoidance of heavy alcohol consumption were most important in the modulation of GA expansion. Oral micronutrient supplementation with the AREDS2 formulation decreased progression to late AMD for individuals with intermediate AMD (or advanced disease in one eye) and slowed expansion of extrafoveal GA towards the fovea. Notably, the benefits of healthy diet and AREDS2 supplementation were found to be complementary and non-redundant.<br><br>CONCLUSION: Individuals with AMD should adopt a Mediterranean diet (or similar pattern), which appears beneficial at all disease stages. Dietary emphasis may vary by stage. A predominantly plant-based diet appears preferable to an animal-based diet, particularly for late AMD with GA. The AREDS2 formulation is recommended for individuals with intermediate or advanced AMD, and may be especially helpful for those with extrafoveal GA. A Mediterranean diet and micronutrient supplementation have complementary actions, so should be used together for maximal benefit.}, }
@article {pmid41787550, year = {2026}, author = {Spero, V and Escher, P and Braga-Lagache, S and Enzmann, V and Zinkernagel, M}, title = {Systemic inflammation triggers local complement production in the mouse retina and RPE.}, journal = {Journal of neuroinflammation}, volume = {23}, number = {1}, pages = {}, pmid = {41787550}, issn = {1742-2094}, abstract = {UNLABELLED: Systemic inflammation is increasingly recognized as a potential contributor in sight threatening retinal diseases such as Age-related Macular Degeneration (AMD). Yet, its impact on local eye immune responses and further pathological processes remains poorly understood. This study aims to elucidate the effect of peripheral immune activation on the local complement system, a central component of innate immunity with a dual role in maintaining ocular homeostasis and mediating inflammation, in the mouse retina and retinal pigment epithelium (RPE). Using a systemic lipopolysaccharide (LPS) challenge and a high-resolution proteomic approach, we observed a significant increase in complement factor 3 (C3) production in the RPE and retina 24 h post-injection. Further analysis confirmed the local source of complement signaling in resident cells such as astrocytes and RPE, independently from blood-retina barrier disruption. These findings reveal a direct cross-talk between systemic immune activation and ocular complement activation, and highlight the potential implications of systemic inflammation in the pathogenesis of ocular diseases, underlining the importance of future research into targeted therapies for inflammation-driven conditions.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-026-03737-y.}, }
@article {pmid41982839, year = {2025}, author = {Agarwal, K and Sadeghi, E and Mehrotra, K and Bollepalli, SC and Vupparaboina, KK and Chhablani, J}, title = {Uncomplicated Cataract Surgery and Neovascular Conversion of Age-Related Macular Degeneration: Fifteen-Year Follow-Up Study.}, journal = {Journal of current ophthalmology}, volume = {37}, number = {3}, pages = {346-351}, pmid = {41982839}, issn = {2452-2325}, abstract = {PURPOSE: To evaluate the impact of cataract surgery on neovascular age-related macular degeneration (nAMD) conversion over a 15-year follow-up period.<br><br>METHODS: This 15-year retrospective study on dry AMD patients compared Group A (cataract surgery) and Group B (no surgery). It assessed nAMD conversion rates, mean logMAR best-corrected visual acuity (BCVA), and final central macular thickness (CMT) changes. Kaplan-Meier survival curves and log-rank tests evaluated the impact of cataract surgery on time to conversion.<br><br>RESULTS: This study included 73 eyes from 46 patients, with a mean baseline age of 68.78 &#xb1; 8.62 years. Among them, 31 (67.39%) were female. Final analyses comprised 43 eyes in Group A and 30 eyes in Group B. Group A had a higher baseline age (70.3 &#xb1; 8.58 vs. 65.6 &#xb1; 7.24; P = 0.01), but baseline BCVA was similar (0.26 &#xb1; 0.33 vs. 0.29 &#xb1; 0.40; P = 0.61). The nAMD conversion rate showed no difference (32.55% vs. 36.66%; P = 0.491), as well as mean age at conversion (77.5 &#xb1; 8.10 vs. 77 &#xb1; 3.66; P = 0.80). The mean interval of conversion from cataract surgery was 5.24 &#xb1; 3.22 years. Final logMAR BCVA (0.78 &#xb1; 0.73 vs. 0.8 &#xb1; 0.76; P = 0.61) and mean CMT at final follow-up (167.6 &#xb1; 77.26 vs. 187 &#xb1; 85.19; P = 0.90) were also similar. The log-rank test showed no association between cataract surgery and conversion rate (P = 0.789).<br><br>CONCLUSIONS: The present study did not find a significant difference in conversion from dry to wet AMD between patients who underwent cataract surgery and who did not. No significant difference was noted in the age at the time of conversion between the two groups.}, }
@article {pmid41984164, year = {2026}, author = {Mauschitz, MM and Goerdt, L and Helbig, H and Holz, FG and Finger, RP and Brandl, C}, title = {Nutrition and dietary supplements in age-related macular degeneration.}, journal = {Die Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41984164}, issn = {2731-7218}, abstract = {BACKGROUND: Nutrition has an influence on the condition of our retina and appears to play a role in the complex, multifactorial pathogenesis of age-related macular degeneration (AMD).<br><br>OBJECTIVES: This article summarizes the current epidemiological evidence on nutrition and AMD and discusses the intake of specific nutrients as well as nutritional supplements and their potential role in prevention and disease modification.<br><br>MATERIAL AND METHODS: A&#xa0;narrative literature review of epidemiological studies, clinical trials and experimental work on the role of individual micronutrients, supplements and dietary patterns in AMD was carried out.<br><br>RESULTS: There is evidence of a&#xa0;protective effect for individual nutrients such as lutein, zeaxanthin, zinc and omega&#x2011;3 fatty acids. The AREDS studies in particular show a&#xa0;reduction in the progression of intermediate AMD to late stages through defined supplements. In addition, a&#xa0;Mediterranean diet correlates with a&#xa0;reduced risk of AMD. Nevertheless, the study results remain contradictory in some cases, which is due to methodological limitations and the complex pathogenesis of AMD.<br><br>DISCUSSION: Nutrition can potentially influence and reduce the risk for and progression of AMD. The existing literature underlines the potential of nutrition-based approaches, which must be further investigated in the future.}, }
@article {pmid41984830, year = {2026}, author = {Brillante, S and Volpe, M and Diana, A and Negueruela, S and Molinari, M and Saurino, R and Cipollaro, E and Polishchuk, E and Tenderini, E and Damiano, C and Tornabene, P and Polishchuk, R and Parenti, G and Tarallo, A and Banfi, S and Trapani, I and Carrella, S and Indrieri, A}, title = {Uncovering mitochondrial defects in photoreceptors opens therapeutic opportunities for Stargardt disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {16}, pages = {e2504764123}, doi = {10.1073/pnas.2504764123}, pmid = {41984830}, issn = {1091-6490}, support = {M2020184//BrightFocus Foundation (BFF)/ ; PRIN2020 grant 2020XBCMHJ//Ministero dell'Universit&#xe0; e della Ricerca (MUR)/ ; TGM22MT01//Fondazione Telethon (FT)/ ; }, mesh = {Animals ; *Stargardt Disease/genetics/therapy/pathology/metabolism ; MicroRNAs/genetics/metabolism ; *Mitochondria/metabolism/pathology/genetics ; Mice ; Humans ; Retinal Pigment Epithelium/metabolism/pathology ; ATP-Binding Cassette Transporters/genetics/metabolism ; *Macular Degeneration/congenital/genetics/pathology/therapy/metabolism ; GTP Phosphohydrolases/metabolism/genetics ; Mice, Knockout ; Disease Models, Animal ; Organoids/metabolism/pathology ; *Photoreceptor Cells, Vertebrate/metabolism/pathology ; }, abstract = {Stargardt disease type 1 (STGD1) is the most common hereditary macular degeneration. It is caused by mutations in ABCA4, which result in the progressive degeneration of the retinal pigment epithelium (RPE), ultimately leading to photoreceptor loss. Despite extensive efforts, STGD1 currently lacks effective treatments. Here, we first identified mitochondrial defects in the photoreceptors of Abca4[-/-] mice and STGD1 patient-derived retinal organoids. Specifically, we found reduced mitochondrial content, defective cristae morphology, and downregulation of OPA1, a critical regulator of mitochondrial integrity, demonstrating that photoreceptor defects in STGD1 also have a cell-autonomous origin, besides the RPE dysfunction. Importantly, we also demonstrated that correcting this pathological phenotype through the modulation of microRNAs 181a and b (miR-181a/b), key regulators of mitochondrial function, ameliorates the STGD1 phenotype. Indeed, genetic inactivation and adeno-associated viral vector-mediated silencing of miR-181a/b in STGD1 models restored OPA1 levels, improved mitochondrial phenotype, and reduced lipofuscin accumulation in the RPE. Our study demonstrates that mitochondrial dysfunction in photoreceptors is an important contributor to STGD1 pathology, opening promising therapeutic avenues for this disorder.}, }
@article {pmid41985834, year = {2026}, author = {Chen, KY and Chan, HC and Hwang, YS and Lin, WW and Chan, CM}, title = {Are Müller Glial Cells Gatekeepers of Neuroprotection and Regeneration in Age-Related Macular Degeneration? Unraveling Their Roles in Pathophysiology and Therapeutic Innovation.}, journal = {Progress in retinal and eye research}, volume = {}, number = {}, pages = {101471}, doi = {10.1016/j.preteyeres.2026.101471}, pmid = {41985834}, issn = {1873-1635}, abstract = {Age-related macular degeneration (AMD) is traditionally conceptualized as a disorder of the retinal pigment epithelium (RPE)-photoreceptor axis; however, this paradigm incompletely explains early disease dynamics and therapeutic failure in geographic atrophy (GA). This review aims to redefine AMD progression through a Müller glial cell-centered framework that integrates cellular homeostasis, structural transitions, and stage-dependent therapeutic implications. Emerging transcriptomic, histologic, and functional evidence demonstrates that Müller glial cells actively participate in AMD pathobiology, including complement regulation, metabolic coupling, redox control, and inflammatory signaling. In early AMD, Müller glial cells exhibit adaptive responses that preserve retinal integrity despite increasing metabolic and extracellular stress. Progressive accumulation of basal laminar deposits and extracellular remodeling imposes diffusion constraints and inflammatory burden, promoting glial reprogramming. A critical transition occurs at external limiting membrane (ELM) descent, which corresponds to loss of photoreceptor support, disruption of retinal compartmentalization, and onset of irreversible degeneration. Beyond this threshold, Müller glial cells undergo structural remodeling and contribute to formation of subretinal glial membranes, reflecting a shift from homeostatic support to containment. This framework proposes a biologically testable staging axis from preserved Müller glial cell function to progressive dysfunction, aligning disease progression with therapeutic windows. Pre-ELM stages are characterized by retained plasticity and suitability for neuroprotective and metabolic interventions, whereas post-ELM stages require strategies focused on stabilization and limiting degeneration. Importantly, current clinical trials do not incorporate Müller glial cell state or ELM integrity as stratification variables, contributing to outcome insensitivity. In conclusion, Müller glial cells function as central regulators of retinal homeostasis and disease progression in AMD. Integrating glial biology with structural biomarkers may enable stage-specific precision therapies and improve clinical trial design.}, }
@article {pmid41986091, year = {2026}, author = {Lee, JH and Bae, K and Lee, EK and Yoon, CK and Park, KH and Park, UC}, title = {Effect of intraocular pressure-lowering agents in highly myopic eyes.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-327484}, pmid = {41986091}, issn = {1468-2079}, abstract = {BACKGROUND/AIMS: To evaluate the effects of intraocular pressure (IOP)-lowering agents in highly myopic eyes.<br><br>METHODS: Highly myopic patients with axial length (AL) data for longer than 5 years were included. The changes in IOP, AL and myopic macular complications during the study period were compared between the eyes treated with IOP-lowering agents (treatment group) and those never treated (control group).<br><br>RESULTS: The treatment (30 eyes of 30 patients) and control (90 eyes of 90 patients) groups had comparable baseline characteristics except for IOP, which was significantly higher in the treatment group (p=0.020). During the study period, the treatment group showed a greater mean percentage decrease in IOP per year compared with the control group (-2.13&#xb1;2.51%&#x2009;/year vs+0.30 &#xb1; 2.31%&#x2009;/year; p<0.001). The mean change in AL per year was +0.032 &#xb1; 0.050&#x2009;mm/year in the treatment group and +0.058 &#xb1; 0.054&#x2009;mm/year in the control group (p=0.022), and the difference was more pronounced in eyes with posterior staphyloma or without dome-shaped macula. The progression of myopic macular degeneration (MMD), myopic retinoschisis and myopic choroidal neovascularisation during the study period was comparable between groups, but the increase in MMD category was significantly less frequent in the treatment group (3.3% vs 20.0%; p=0.040). In the multivariate analysis, use of IOP-lowering agents was associated with both decreased axial elongation and lower likelihood of MMD category increase.<br><br>CONCLUSION: IOP-lowering agents may be effective in alleviating axial elongation and progression of myopic maculopathy in highly myopic eyes.}, }
@article {pmid41975624, year = {2026}, author = {Miranda, M and Gupta, P and Sukkar, B and Cantó Catalá, A and Hosseinzadeh, Z}, title = {Müller glial cells for regeneration, retinal organoids, cell transplantation, and neuroprotection.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-01256}, pmid = {41975624}, issn = {1673-5374}, abstract = {Müller glial cells are essential for retinal structure and homeostasis and increasingly recognized as dual regulators of retinal degeneration and regeneration. Beyond providing metabolic and structural support, Müller glial cells actively shape disease progression while retaining latent regenerative potential. Growing evidence highlights their roles in retinal degeneration, development, and neuroprotection, particularly in age-related macular degeneration, diabetic retinopathy, and inherited retinal disorders. This review integrates recent advances across five key areas: (1) Müller glial cell dysfunction in retinal disease pathology, including gliosis, inflammatory signaling, and vascular dysregulation; (2) their regenerative capacity, with a critical appraisal of efforts to reprogram Müller glial cells into retinal progenitors in mammalian models and the ongoing controversy surrounding functional neuronal replacement; (3) their contribution to the maturation of induced pluripotent stem cells-derived retinal organoids; (4) their neuroprotective roles through antioxidant, immunomodulatory, and trophic mechanisms; and (5) their emerging applications in cell-based therapies. By highlighting unresolved knowledge gaps-particularly the molecular barriers limiting Müller glial cell reprogramming and the signals governing their switch between protective and pathogenic states, this review positions Müller glial cells as central targets for future retinal regenerative and therapeutic strategies.}, }
@article {pmid41976951, year = {2026}, author = {Ciszewska, K and Winiarczyk, M and Winiarczyk, D and Mackiewicz, J}, title = {Microperimetry-Based Fixation Training in Patients with Age-Related Macular Degeneration (AMD).}, journal = {Journal of clinical medicine}, volume = {15}, number = {7}, pages = {}, pmid = {41976951}, issn = {2077-0383}, abstract = {Background: Age-related macular degeneration (AMD) is the primary cause of severe visual acuity loss in individuals over 60 with increasing prevalence. Currently, no effective treatments exist for geographic atrophy and macular scarring, highlighting the need for visual rehabilitation in these patients. Microperimetry offers functional assessment at any AMD stage and employs fixation training to help patients utilize the most effective retinal areas for vision. Methods: A prospective study involving 25 patients (50 eyes) aged 67 to 90. The MAIA II microperimeter assessed scotoma size and location, retinal sensitivity, macular integrity, fixation parameters (P1, P2, 63%BCEA, 95%BCEA), fixation stability, and preferred retinal locus. Quality of life was evaluated using the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). A subgroup with inactive AMD-related macular changes, either bilateral geographic atrophy (13 patients, 26 eyes) or bilateral scarring (12 patients, 24 eyes), was identified, all exhibiting bilateral absolute central scotomas of at least 2 degrees. Each patient completed 10 fixation training sessions with a microperimeter, training the eye with better acuity weekly. One-week post-training, a functional assessment was performed on both trained and untrained eyes. Results: Fixation training significantly improved best corrected visual acuity (BCVA) in trained eyes (mean change -0.14 logMAR, p < 0.001, large effect size) and also in fellow untrained eyes (-0.16 logMAR, p < 0.001). BNVA improved from 2.25 to 1.86 in trained eyes (p < 0.001) and from 2.96 to 2.76 in untrained eyes (p = 0.004). Fixation stability parameters improved significantly, including increases in P1 and P2 and reductions in Bivariate Contour Ellipse Area (BCEA). Quality of life measured using the NEI-VFQ-25 questionnaire improved significantly in 9 of 11 domains. Conclusions: Microperimetry may be a valuable tool for assessing visual function in AMD patients. Fixation training with the MAIA II microperimeter is both safe and effective for vision rehabilitation in those with geographic atrophy and macular scarring.}, }
@article {pmid41977310, year = {2026}, author = {Yang, JY and Choi, JS and Park, TK}, title = {AAV2.7m8-Mediated MicroRNA Expression Suppresses VEGF-Induced Angiogenic Responses in HUVEC.}, journal = {International journal of molecular sciences}, volume = {27}, number = {7}, pages = {}, doi = {10.3390/ijms27073123}, pmid = {41977310}, issn = {1422-0067}, support = {RS-2025-02217948//National Research Foundation of Korea/ ; RS-2024-00452984//National Research Foundation of Korea/ ; }, mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Human Umbilical Vein Endothelial Cells/metabolism ; *Vascular Endothelial Growth Factor A/metabolism/pharmacology/genetics ; *Dependovirus/genetics ; Cell Proliferation ; Cell Movement/genetics ; Genetic Vectors/genetics ; *Neovascularization, Physiologic/genetics ; *Neovascularization, Pathologic/genetics/metabolism ; Signal Transduction ; }, abstract = {Vascular endothelial growth factor (VEGF)-driven pathological angiogenesis constitutes a primary driver of neovascular diseases, including neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR). Although anti-VEGF agents demonstrate clinical efficacy, their limited intraocular half-life mandates repeated intravitreal injections, thereby highlighting the imperative for long-term therapeutic strategies. In the present study, we assessed the anti-angiogenic potential of retinal organoid-derived microRNAs (miRNA) delivered via an engineered adeno-associated virus vector. Human umbilical vein endothelial cells (HUVEC) were transduced with AAV2.7m8 vectors to overexpress three candidate miRNA (miR-26a, miR-122, and let-7a), followed by VEGF stimulation to evaluate downstream signaling pathways and angiogenic responses. AAV2.7m8-mediated transduction of HUVEC demonstrated high efficiency without inducing detectable cytotoxicity. Overexpression of these miRNA markedly attenuated VEGF-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. Functional assays demonstrated suppression of endothelial cell proliferation and cell cycle progression, with miR-122-5p additionally inhibiting migration. All three miRNA substantially inhibited capillary-like tube formation. In aggregate, these results affirm that AAV2.7m8-mediated delivery of retinal organoid-derived miRNA -namely miR-26a-5p, miR-122-5p, and let-7a-5p-markedly suppresses VEGF-induced angiogenic signaling cascades and endothelial cell activation in vitro, thereby establishing their viability as a sustained therapeutic approach for pathological retinal neovascularization.}, }
@article {pmid41977482, year = {2026}, author = {Phillips, R}, title = {Nutrition, Cell Signalling, Mitochondrial Function, and Chronic Non-Communicable Disease.}, journal = {International journal of molecular sciences}, volume = {27}, number = {7}, pages = {}, doi = {10.3390/ijms27073303}, pmid = {41977482}, issn = {1422-0067}, mesh = {Humans ; *Mitochondria/metabolism ; *Signal Transduction ; Animals ; *Noncommunicable Diseases ; Chronic Disease ; Homeostasis ; Energy Metabolism ; }, abstract = {Cellular homeostasis is a dynamic process which balances anabolic processes with catabolic and recycling processes. These processes require nutrients, which are converted to energy to fuel the complex interactions of intracellular signalling. Cellular health requires that, on average, energy input and energy requirements are matched. Cells contain a nutrient-sensing mechanism which controls the balance between anabolism and catabolism. Normal intracellular functions generate products which regulate signalling pathways, and health at a cellular level requires a fluctuation between relative nutrient abundance and relative nutrient scarcity. This allows clearance of damaged intracellular molecules and organelles. When nutrient supply exceeds cellular requirements, adaptations to intracellular signalling occur, resulting in energy being stored as glycogen in muscle and the liver and fatty acids in adipose tissue. Overfuelling and aberrant fuelling of mitochondria result in oxidative stress, which not only disrupts cellular homeostasis but can alter epigenetic expression, with intergenerational effects. If the recycling mechanisms of the cell are insufficient to clear metabolic products, apoptosis may result or expression of Damage-Associated Molecular Patterns (DAMPs) on the cell surface may occur, activating immunity and inflammation at a systemic level. Disrupted cellular signalling affects cells with different "professional" functions in different organs, and it is the mechanism which underlies the associations between chronic non-communicable diseases such as cancer, type 2 diabetes, cardiovascular disease, neurodegenerative disease, autoimmune diseases, and macular degeneration. Mitochondria are the controllers of energy production and are pivotal in cell signalling. Mitochondrial function governs health at cellular and organismal levels. This paper reviews the influence of nutrition on mitochondrial function, nutrient sensing, autophagy, insulin signalling, and apoptosis-the key pathways in cellular homeostasis.}, }
@article {pmid41979251, year = {2026}, author = {Zhao, Z and Ou, Q and Zhu, J and He, Z and Yang, Y and Jiang, J and Wang, Q and Zhou, Y and Liu, Y and Zhu, X and Cui, T and Liu, Y and Xu, J and Gao, F and Jin, C and Wang, J and Lu, L and Bi, Y and Xu, GT and Xu, JY and Tian, H}, title = {Modulation of Iron-Induced Glucose Metabolic Reprogramming Alleviates Retinal Pigment Epithelial Cell Senescence.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {30}, doi = {10.1167/iovs.67.4.30}, pmid = {41979251}, issn = {1552-5783}, mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Cellular Senescence/drug effects/physiology ; Mice ; *Glucose/metabolism ; Reactive Oxygen Species/metabolism ; Humans ; Blotting, Western ; Mitochondria/metabolism ; Mice, Inbred C57BL ; Ferric Compounds/toxicity/pharmacology ; Cells, Cultured ; Induced Pluripotent Stem Cells/metabolism ; Electroretinography ; Disease Models, Animal ; Quaternary Ammonium Compounds/toxicity ; Metabolic Reprogramming ; }, abstract = {PURPOSE: This study aimed to investigate whether iron overload induces retinal pigment epithelial (RPE) cell senescence through glucose metabolic reprogramming and to evaluate the therapeutic potential of targeting this metabolic pathway.<br><br>METHODS: We utilized human-induced pluripotent stem cell-derived RPE cells and induced RPE cells, along with mouse models with intravitreal or intraperitoneal injection of ferric ammonium citrate (FAC), to evaluate the effect of iron overload on RPE senescence. Proteomics, targeted metabolomics, reactive oxygen species (ROS) assay kits, JC-1 assay kit, reverse-transcription polymerase chain reaction, SA-&#x3b2;-gal staining, and western blot were used to assess mitochondrial function, ROS, and senescence markers. 2-Deoxy-d-glucose (2-DG), pyruvate kinase M2 inhibitor-1 (PKM2-IN-1), and sodium oxamate (SO) were used to modulate glucose metabolism flux. Flash electroretinography recording was used to assess visual function.<br><br>RESULTS: Iron overload triggered significant glucose metabolic reprogramming in RPE cells, characterized by a time-dependent metabolic shift. Early exposure to FAC induced a transient surge in glucose metabolic flux, which elevated mitochondrial ROS production and disrupted mitochondrial homeostasis, ultimately leading to cellular senescence. Importantly, early inhibition of this metabolic surge with 2-DG or PKM2-IN-1 effectively attenuated senescence by reducing ROS levels and preserving mitochondrial function. Conversely, enhancing pyruvate flux with SO exacerbated senescence. The protective effect of 2-DG against iron-induced RPE senescence was further confirmed in a mouse model, where it preserved visual function and reduced senescence markers.<br><br>CONCLUSIONS: Glucose metabolic reprogramming mediates iron-induced RPE senescence, with transient glucose flux surge driving pathology via ROS-related mitochondrial damage. Targeting glucose metabolism may preserve mitochondria homeostasis and prevent RPE degeneration in age-related macular degeneration.}, }
@article {pmid41979253, year = {2026}, author = {Foshe, S and Anderson, BD and Song, Y and Shi, S and Lee, S and Bell, BA and Park, HG and Brenna, JT and Shchepinov, M and Dunaief, JL}, title = {Oral Deuterated Docosahexaenoic Acid Protects Against Onset and Progression of RPE Degeneration in a Mouse Model of Chronic Oxidative Stress.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {28}, doi = {10.1167/iovs.67.4.28}, pmid = {41979253}, issn = {1552-5783}, mesh = {Animals ; *Oxidative Stress/drug effects ; *Docosahexaenoic Acids/administration &amp; dosage ; *Retinal Pigment Epithelium/pathology/drug effects/metabolism/ultrastructure ; Mice ; Disease Models, Animal ; Mice, Knockout ; Tomography, Optical Coherence ; Disease Progression ; Mice, Inbred C57BL ; Administration, Oral ; Electroretinography ; Female ; *Macular Degeneration/prevention &amp; control ; Ophthalmoscopy ; Hepcidins/genetics ; }, abstract = {PURPOSE: Oxidative stress is associated with many retinal diseases, including age-related macular degeneration (AMD). The purpose of this study is to investigate the efficacy of oral deuterated docosahexaenoic acid (D-DHA), an oxidation-resistant lipid, in a mouse model with features of dry AMD. We also evaluated whether long-term D-DHA dosing affects normal retinal structure or function.<br><br>METHODS: Liver-specific hepcidin (Hepc) and ceruloplasmin/hepcidin (Cp/Hepc) knock-out (KO) mice were fed experimental diet containing 0.25% D-DHA or control containing normal H-DHA during various stages of disease progression. Retinal pigment epithelium (RPE) damage was assessed with in vivo scanning laser ophthalmoscopy (SLO) imaging and histology. For the safety study, wild-type mice were fed the diets beginning in utero or at 3 months of age, continuing for 12 months. These mice were analyzed to assess retinal structure (SLO, optical coherence tomography [OCT], and transmission electron microscopy [TEM]), function (ERG), and gene expression (qPCR).<br><br>RESULTS: KO mice fed control diet developed expanding autofluorescent patches of hypertrophic RPE cells. This damage was markedly prevented or halted by diet with D-DHA, depending on age at diet onset. Wild-type mice administered diet with D-DHA from age 3 to 15 months had no retinal abnormalities. Mice administered D-DHA beginning in utero had normal retinal development and structure but minor deficits in ERG amplitudes and Rpe65 expression by age 12 months.<br><br>CONCLUSIONS: Oral D-DHA was strongly protective against RPE ferroptosis, with minimal side effects. This study suggests that DHA oxidation is a key mechanism of retinal iron toxicity and supports the potential clinical application of D-DHA for diseases involving retinal oxidative stress.}, }
@article {pmid41979423, year = {2026}, author = {Jiang, H and Wang, X and Wang, L and Fan, Y and Li, Z and Ma, M and Liu, S and Li, B and Shi, J and Li, C and Ma, L and Li, J and Zhang, W}, title = {Association of dietary calcium and its food sources with age-related macular degeneration in China: a population-based case-control study.}, journal = {Food &amp; function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5fo04327a}, pmid = {41979423}, issn = {2042-650X}, abstract = {Background &amp; aims: Recent studies, primarily in developed countries, suggest that higher dietary calcium intake is associated with lower odds of age-related macular degeneration (AMD). However, evidence on this association is lacking in China, where the population has unique dietary patterns and relatively low calcium intake. The aim of this study was to investigate the association of dietary calcium and its major sources with the likelihood of AMD in a Chinese population. Methods: A case-control study was performed within the frame of the Xi'an Eye Study. A total of 284 AMD cases and 284 matched controls who completed the eye examination and a detailed semi-quantitative food frequency questionnaire were included in the present analysis. Multivariable-adjusted conditional logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of dietary calcium and its main sources. Results: In the multivariable adjusted model, an increasing amount of dietary calcium intake was associated with significantly lower odds of AMD, especially among participants with a dietary calcium intake of less than 800 mg per 2000 kcal per day. The OR for the comparison of the top with the bottom tertile of dietary calcium intake was 0.46 (95%CI: 0.23, 0.90; P-trend = 0.02). Regarding major sources of calcium, a significant inverse association was only observed for dairy-based calcium intake, with an OR of 0.45 (95%CI: 0.23, 0.89; P-trend = 0.02). Consumption of dairy products, particularly milk (OR: 0.45 from a comparison of ≥4 servings per week with never/rarely; 95%CI: 0.22, 0.90; P-trend = 0.05) and yogurt (OR: 0.38 from a comparison of ≥2 servings per week with never/rarely; 95%CI: 0.19, 0.78; P-trend = 0.01), was also associated with lower odds of AMD. No significant associations were found for milk powder or dietary intake of calcium from vegetables or legumes. Conclusions: Higher intake of calcium and its major food sources, such as milk and yogurt, was associated with a significantly decreased likelihood of AMD in a Chinese population with relatively low dietary calcium intake. These findings align with current public health recommendations for maintaining adequate calcium status and emphasize that the health implications of calcium may depend on its dietary sources.}, }
@article {pmid41979761, year = {2026}, author = {Brandl, C and Heid, IM and Helbig, H and Holz, FG and Finger, RP and Mauschitz, MM}, title = {Risk factors for age-related macular degeneration.}, journal = {Die Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41979761}, issn = {2731-7218}, }
@article {pmid41981257, year = {2026}, author = {Janmohamed, IK and Harahn, H and Carr, B and Sahbi, S and Ahmed, H and Farahat, A and Hannan, S and Membrey, L}, title = {Early real-world outcomes of aflibercept 8 mg in previously treated neovascular age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41981257}, issn = {1476-5454}, abstract = {BACKGROUND: Real-world evidence of aflibercept 8 mg in treatment-experienced patients remains limited. This study evaluated early outcomes of switching treatment-refractory patients with neovascular age-related macular degeneration (nAMD) to aflibercept 8 mg.<br><br>METHODS: This retrospective cohort study analysed previously-treated patients who switched to aflibercept 8&#x2009;mg between January and June 2025. Best-corrected visual acuity (BCVA), central macular thickness (CMT), pigment epithelial detachment (PED) height, macular fluid status and treatment intervals were evaluated at baseline, 3 months, 6 months and final visit.<br><br>RESULTS: 58 patients (66 eyes) were included. Patients received a mean 24.98&#x2009;&#xb1;&#x2009;18.04 anti-VEGF injections per eye over 49.41&#x2009;&#xb1;&#x2009;35.74 months pre-switch. Mean 5.15&#x2009;&#xb1;&#x2009;1.51 aflibercept 8&#x2009;mg injections were administered per eye over a mean follow-up period of 25.86&#x2009;&#xb1;&#x2009;8.34 weeks. Median treatment intervals increased significantly from baseline to final visit (4&#xa0;to 6 weeks, p&#x2009;<&#x2009;0.001). 23 eyes (34.8%) achieved &#x2265;8-week intervals by final follow-up. Median BCVA remained stable (70 ETDRS letters, interquartile range [IQR] 62-76 baseline and final follow-up, p&#x2009;=&#x2009;0.571), as did median CMT (230.5&#x2009;&#x3bc;m (IQR 189.5-281.2) at baseline to 226.5&#x2009;&#x3bc;m (IQR 195-257) at final follow-up, p&#x2009;=&#x2009;0.494). Median PED height showed a significant reduction (175&#x2009;&#x3bc;m (IQR 106-287) at baseline to 173&#x2009;&#x3bc;m (IQR 105-251) at final follow-up, p&#x2009;=&#x2009;0.045). Complete macular fluid resolution occurred in 23.9% of eyes with baseline fluid at the final visit. No serious ocular adverse events occurred in this cohort.<br><br>DISCUSSION: Aflibercept 8&#x2009;mg demonstrated modest interval extension with stable functional and anatomical outcomes in heavily pre-treated nAMD patients. Long-term studies are needed to establish durability.}, }
@article {pmid41971199, year = {2025}, author = {Shakeel, A and Bhatt, D and Sripriya, S and Ratra, D}, title = {Early-onset drusen in Malattia Leventinese with EFEMP1 mutation differ from drusen in age-related macular degeneration.}, journal = {Romanian journal of ophthalmology}, volume = {69}, number = {4}, pages = {598-605}, pmid = {41971199}, issn = {2501-2533}, mesh = {Humans ; Male ; Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnosis/genetics ; *Extracellular Matrix Proteins/genetics/metabolism ; *Macular Degeneration/diagnosis/genetics ; Fluorescein Angiography/methods ; *Mutation ; Female ; Pedigree ; Middle Aged ; Fundus Oculi ; Age of Onset ; DNA Mutational Analysis ; Diagnosis, Differential ; Adult ; Phenotype ; *DNA/genetics ; Visual Acuity ; Optic Disk Drusen/congenital ; }, abstract = {PURPOSE: To study the clinical, genetic, and phenotypic aspects of Malattia Leventinese (ML)/Doyne honeycomb retinal dystrophy (DHRD) and to differentiate it from age-related macular degeneration (AMD).<br><br>METHODS: Three cases of ML/DHRD from the Indian population were evaluated, including fundus examination, fundus autofluorescence (FAF), and swept-source optical coherence tomography (SSOCT). Genetic investigations involved screening for an inherited retinal gene panel using the Illumina MiSeq platform for one case. Pedigree charting, blood collection, DNA extraction, and variant annotation were performed, followed by pathogenicity assessment of the identified variants using multiple bioinformatics tools.<br><br>RESULTS: All cases exhibited early-onset central vision loss and small, radially distributed drusen, consistent with ML/DHRD. Genetic analysis done in patient one revealed a heterozygous, autosomal dominant, pathogenic mutation (c.1033C>T p.ARG345Trp) in the EFEMP1 gene, confirming the ML diagnosis. Patient 1 had no late-stage complications, whereas patients 2 and 3 developed macular neovascularization (MNV). OCT showed gross thickening of the retinal pigment epithelium with hyperreflectivity, along with outer retinal tubulations (ORT) and interlaminar bridges, indicating outer retinal degeneration.<br><br>DISCUSSION: Malattia Leventinese is a rare autosomal dominant macular dystrophy caused by a single EFEMP1 missense mutation (R345W), leading to early-onset radial or honeycomb drusen and central vision loss in the third decade. In this series, all patients showed typical radial drusen, with macular neovascularization in two cases, and demonstrated interlaminar bridges and ORTs on OCT. The mutant EFEMP1 protein misfolds and accumulates abnormally between the RPE and Bruch's membrane, accelerating drusen formation. Some phenotypic variability, including intrafamilial differences, likely reflects additional genetic or environmental modifiers. The presence of the R345W mutation, age at onset, and drusen distribution pattern are crucial for differentiating ML/DHRD from AMD.<br><br>CONCLUSION: The identified pathogenic EFEMP1 mutation (R345W) established a molecular link to ML/DHRD. Typical phenotypic patterns and drusen characteristics can differentiate ML/DHRD from AMD.}, }
@article {pmid41971250, year = {2026}, author = {Rowe, LW and Macha, NN and Aggarwal, N and Singh, RP and Maturi, RK}, title = {Visual Acuity and Durability Outcomes of Faricimab Compared With Other Antivascular Endothelial Growth Factor Agents Within Routine Clinical Practice for Neovascular Age-Related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261428749}, pmid = {41971250}, issn = {2474-1272}, abstract = {Purpose: To compare the visual acuity (VA) outcomes and dosing intervals of faricimab with those of other antivascular endothelial growth factor agents in treatment-naïve and treatment-experienced eyes with neovascular age-related macular degeneration (nAMD). Methods: De-identified electronic medical records (Vestrum Health treatment and outcomes database) of patients with nAMD treated with bevacizumab, ranibizumab, aflibercept, or faricimab between January 2021 and December 2023 were included. Mean VA change and mean number of days between injections were collected through 6 injections for treatment-naïve eyes and through 2 injections for treatment-switched eyes. Results: A total of 736 treatment-naïve eyes receiving faricimab experienced nonsignificantly lower VA gains than all other drugs; 5467 eyes switched to faricimab demonstrated lower VA gains relative to other drugs. This includes significantly lower gains than aflibercept or bevacizumab when switched from ranibizumab (P < .01). Bevacizumab achieved the highest VA gains-significantly more than aflibercept (P < .01) in the treatment-naïve cohort and significantly more than faricimab and aflibercept when switched from ranibizumab (P < .01). After adjusting for significant VA differences at baseline and at the switch date, all drugs displayed similar VA gains in both cohorts. Compared with all other drugs, faricimab provided up to 4 additional days on average between injections and had the highest proportion of eyes extended over 50 days between the final 2 injections for both cohorts. Relative to aflibercept and ranibizumab, these injection frequencies for faricimab were significantly longer (P < .01). Conclusions: Treatment-naïve and treatment-experienced nAMD eyes receiving faricimab demonstrated VA gains and minimally longer injection intervals, comparable to other antivascular endothelial growth factor agents.}, }
@article {pmid41972930, year = {2026}, author = {Fasler, K and Multone, E and Stahel, M and Gabathuler, F and Blaser, F and Zweifel, SA}, title = {Misfolded Proteins in the Eye - Vitreous Amyloidosis.}, journal = {Retinal cases &amp; brief reports}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICB.0000000000001927}, pmid = {41972930}, issn = {1937-1578}, abstract = {PURPOSE: The aim of this study was to describe a case of vitreous amyloidosis as a rare aetiology of vitreous opacities and to show diagnostic value of vitreous biopsy in the diagnostic process as well as show a potiential new non-invasive diagnostic for vitreous amyloidosis.<br><br>METHODS: Retrospective case report with presentation of medical record data, clinical imaging, and pathological work-up.<br><br>RESULTS: A 82-year-old man underwent diagnostic vitrectomy due to dense vitreous opacities in the right eye. While visual acuity did not improve much due to an underlying advanced fibrotic age related macular degeneration, pathology confirmed amyloid material in the vitreous. The patient was diagnosed with hereditary amyloid transthyretin amyloidosis (ATTRv) and offered a transthyretin stabilising therapy (tafamidis, vindaqel&#xae;).<br><br>DISCUSSION: While vitreous opacities are a common usually benign phenomenon, it is important to recognise atypical presentation. Diagnostic work-up may include diagnostic vitrectomy, which can aid in diagnosing relevant underlying systemic disease such as ATTRv amyloidosis. While pathologic work-up of vitreous material is the current gold standard, there may be novel non-invasive imaging techniques to aid in diagnosis of vitreous amyloidosis.}, }
@article {pmid41973161, year = {2026}, author = {Chang, CW and Liu, PK and Cheng, KC and Lai, HC and Wu, HJ and Lee, DY and Lo, MW and Chen, KJ and Lin, HC and Chang, YC}, title = {Anatomic and functional outcomes of intravitreal faricimab for polypoidal choroidal vasculopathy: a review.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {41973161}, issn = {1573-2630}, mesh = {Humans ; Intravitreal Injections ; *Choroid/blood supply/pathology ; *Visual Acuity ; *Antibodies, Bispecific/administration &amp; dosage ; *Polyps/drug therapy/diagnosis/physiopathology ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence ; Fluorescein Angiography ; Treatment Outcome ; *Choroidal Neovascularization/drug therapy/physiopathology/diagnosis ; Fundus Oculi ; Polypoidal Choroidal Vasculopathy ; }, abstract = {PURPOSE: This review examines anatomic and functional outcomes of intravitreal faricimab for treating polypoidal choroidal vasculopathy (PCV), a neovascular age-related macular degeneration subtype common in Asian populations. Faricimab is a bispecific antibody targeting both VEGF-A and Ang-2, potentially offering more durable effects than standard anti-VEGF monotherapy.<br><br>METHODS: A narrative review was conducted by searching PubMed, Embase, and Web of Science through July 2024. Keywords included faricimab, polypoidal choroidal vasculopathy, and anti-VEGF. Eligible studies comprised English-language, peer-reviewed human trials (prospective, retrospective, case series, and reports). Conference abstracts and non-peer-reviewed sources were excluded.<br><br>RESULTS: In treatment-na&#xef;ve patients, preliminary data suggest that faricimab may yield favorable results, though findings are largely derived from small retrospective studies. Functionally, a one-year study reported significant improvement in mean best-corrected visual acuity (BCVA), from 0.30&#xb1;0.33 logMAR at baseline to 0.16&#xb1;0.26 logMAR at final visit. However, some studies note visual gains may not be statistically significant during initial loading phase. Anatomically, high polyp regression rates are key findings, with one study reporting 61.1% rate after three monthly injections. High rates of dry macula (60-80%) and significant reductions in central foveal thickness (CFT) and central choroidal thickness (CCT) are consistently observed. For patients with suboptimal response to prior anti-VEGF therapies, switching to faricimab presents mixed picture. While a prospective cohort study found no significant average improvement in visual acuity for switched PCV eyes, a case report showed dramatic improvement from 20/100 to 20/60 after two injections in a ranibizumab-refractory case. Anatomically, switched patients show significant reduction in choroidal thickness and serous pigment epithelial detachments (PEDs). However, the presence of polypoidal lesions was identified as a negative predictive factor for successfully extending the treatment interval.<br><br>CONCLUSIONS: Based on limited retrospective evidence, faricimab may represent a promising therapeutic candidate for PCV, with several studies reporting anatomical improvements. The dual mechanism of action targeting both VEGF-A and Ang-2 may help address certain pathological features of the disease; however, confirmation from larger prospective studies is needed.}, }
@article {pmid41973601, year = {2026}, author = {Tse, DY and Ma, MM and Hon, Y and Ho, LM and Lam, WC and Shih, KC and Zhang, X and Lam, DMK and Kong, ACW and Lam, TC and Lam, CSY and Lian, TJ and Morgan, I and To, CH and Chun, RKM and Leung, CKS}, title = {Effectiveness of Low-Dose Atropine Combined With Bright Light Therapy for Controlling Myopic Eye Growth in Schoolchildren: Study Protocol for a Randomized Controlled Trial.}, journal = {JMIR research protocols}, volume = {15}, number = {}, pages = {e90893}, doi = {10.2196/90893}, pmid = {41973601}, issn = {1929-0748}, mesh = {Humans ; *Atropine/administration &amp; dosage/therapeutic use ; *Myopia/therapy/drug therapy ; Child ; Female ; Male ; *Phototherapy/methods ; Treatment Outcome ; Single-Blind Method ; Disease Progression ; Randomized Controlled Trials as Topic ; Hong Kong ; }, abstract = {BACKGROUND: Myopia is increasingly prevalent worldwide, with projections indicating that nearly 50% of the global population may have myopia by 2050. This surge poses significant concerns due to its impact on vision and quality of life and its link to a range of blinding diseases, including myopic macular degeneration, glaucoma, and retinal detachment. Current pharmacologic and optical interventions offer limited effectiveness in slowing myopia progression, highlighting the urgent need for more effective treatments.<br><br>OBJECTIVE: This study aims to examine the combined effect of bright light therapy and low-dose atropine on myopic progression.<br><br>METHODS: This is a single-site, 2-arm, single-masked (examiner-masked) randomized controlled trial to compare the effectiveness of low-dose atropine alone and its combination with bright light therapy in retarding myopia progression. The study protocol has been approved by the institutional review boards of Hong Kong Polytechnic University (HSEARS 20180829002-05) and the University of Hong Kong and Hospital Authority Hong Kong West Cluster (UW 20-362). Schoolchildren with myopia aged 7 to 12 years who have not undergone any previous myopic control intervention will be recruited and randomly allocated into 2 groups (n=67 per group) after baseline measurements. Both groups will receive 0.01% atropine twice daily for 24 months. The combination treatment group will also receive a high-intensity lamp for bright light therapy. The primary and secondary outcome measures will be the changes in cycloplegic autorefraction in spherical equivalent refraction and axial length, respectively, measured every 6 months over 2 years from baseline.<br><br>RESULTS: The project was funded in January 2019. The recruitment process started on March 21, 2023, and was completed on February 2, 2024. Data collection is expected to be completed in April 2026.<br><br>CONCLUSIONS: This study will provide new information on whether the combination of bright light therapy and low-dose atropine is more effective than atropine alone in slowing down myopia progression. It will also assess the effectiveness of low-dose atropine used twice daily. Combining bright light therapy and atropine could become a new treatment option if shown to be effective. New data on the effectiveness of using atropine twice daily might also expand available treatment options.}, }
@article {pmid41974662, year = {2026}, author = {Parween, S and Saviola, AJ and Howell, AC and Varghese, S and Galindo, DC and Vergara, MN}, title = {Human retinal organoid model of disease-relevant photoreceptor cell death amenable to drug screening.}, journal = {Cell death &amp; disease}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41419-026-08724-y}, pmid = {41974662}, issn = {2041-4889}, abstract = {Dry age-related macular degeneration (AMD) is characterized by the progressive loss of retinal pigment epithelium cells in the macula, leading to photoreceptor degeneration and loss of central vision. Current treatments only modestly delay disease progression, but once photoreceptors are damaged, vision loss becomes irreversible. Therefore, there is an urgent need to develop therapies that prevent photoreceptor cell death and that may complement current and emerging treatment strategies. A critical step toward this goal is establishing pathophysiologically relevant human disease models for therapeutic testing. In this study, we developed a human induced pluripotent stem cell-derived retinal organoid (RO) model that recapitulates key aspects of AMD-associated photoreceptor degeneration. To mimic environmental stressors relevant to AMD, we treated mature ROs with cigarette smoke extract (CSE), a known oxidative agent and major modifiable risk factor for the disease. CSE exposure induced oxidative stress, mitochondrial membrane depolarization, and cell death primarily in the outer nuclear layer. Photoreceptor degeneration in this model involves the activation of the intrinsic apoptotic pathway and ferroptosis, which is accompanied by lipid peroxidation and dysregulation of the glutathione system. Proteomic profiling confirmed alterations in metabolic, redox, and cell death pathways consistent with AMD pathophysiology, and offered further insight into the mechanistic interplay among these pathways. Furthermore, we integrated this model with robust, quantitative outcome measures in live ROs, offering a powerful platform for preclinical therapeutic screening in dry AMD.}, }
@article {pmid41963383, year = {2026}, author = {Zhang, F and Wang, C and Tang, Q and Ao, T and Li, J and Liu, Y}, title = {Integrated transcriptomic and metabolomic analyses reveal distinct energy metabolic signatures and functional properties of RPE cells under two culture conditions.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {41963383}, issn = {2045-2322}, support = {CSTB2024NSCQ-BSX0015//Chongqing Natural Science Foundation - Doctoral "Fast Track" Project/ ; JFLKYXM202203AZ-217//Jinfeng Lab Fundamental Research Funds/ ; CQERC-OIBM20241005//Open Project of Chongqing Engineering Research Center of Organ Intelligent Bio-Manufacturing/ ; }, abstract = {UNLABELLED: Retinal pigment epithelium (RPE) degeneration is a major cause of vision loss in multiple retinal diseases, including age-related macular degeneration, Bietti crystalline dystrophy and Stargardt disease. Induced pluripotent stem cell (iPSC)-derived RPE cells hold promise for regenerative therapies. B27- and KSR-based media are among the most commonly used for RPE culture; however, how these culture conditions shape RPE cell identity and features remain incompletely understood. Here, we performed comprehensive transcriptomic and metabolomic profiling of iPSC-derived RPE cells cultured in B27 or KSR media to systematically compare their gene expression and metabolic features. B27- and KSR-cultured RPE cells exhibited distinct morphologies and barrier properties. Integrated multi-omics analyses revealed that KSR-cultured RPE cells displayed a relative bias toward fatty acid oxidation and oxidative phosphorylation, whereas B27-cultured RPE cells showed a relative bias toward glycolytic metabolism. The glycolytic tendency observed in B27-RPE cells was accompanied by increased expression of extracellular matrix–related genes and higher transepithelial resistance. In contrast, KSR-RPE cells exhibited comparable tricarboxylic acid cycle activity but higher expression of oxidative phosphorylation–related genes compared with B27-RPE cells. Together, these results demonstrate that RPE cells cultured under different conditions adopt distinct but partially overlapping metabolic and transcriptional states, which are associated with differences in RPE-related features and barrier properties. Our findings highlight the importance of metabolic balance between glycolysis and fatty acid oxidation in shaping in vitro RPE phenotypes.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-39689-9.}, }
@article {pmid41967781, year = {2026}, author = {Sha, C and Wei, D and Xu, W and Sun, H and Yin, Y and Su, S and Zhao, M and Duan, JA}, title = {Zhujing Pill ameliorates age-related macular degeneration by regulating lipid metabolism, complement activation, and inflammatory responses: an integrated network pharmacology and metabolomics study.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {121674}, doi = {10.1016/j.jep.2026.121674}, pmid = {41967781}, issn = {1872-7573}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the elderly, with particularly limited therapeutic options for dry AMD. Zhujing Pill (ZJP), a traditional Chinese medicinal formula recorded in Taiping Sheng Hui Fang of the Northern Song Dynasty, has historically been prescribed for visual disorders attributed to age-related "liver and kidney deficiency", a traditional syndrome sharing core clinical features with AMD. However, the pharmacological basis and molecular mechanisms underlying its therapeutic effects remain largely unexplored.<br><br>AIM OF THE STUDY: To systematically elucidate the bioactive constituents and therapeutic mechanisms of ZJP in AMD using an integrated strategy combining network pharmacology, molecular docking, metabolomics, and experimental validation.<br><br>MATERIALS AND METHODS: The chemical profiles and principal constituents of ZJP and ZJP-medicated serum (ZJW) were characterized by UHPLC-MS analysis. Network pharmacology and molecular docking were applied to identify key compounds and potential molecular targets. Protective effects were evaluated using lysophosphatidylcholine (LPC)-induced ARPE-19 cell injury and sodium iodate-induced AMD mouse models. Retinal structure and function were assessed by behavioral testing, optical coherence tomography (OCT), and histopathology. Serum and intracellular metabolomics were performed using UPLC-QTOF-MS. The expression of inflammatory, complement-related, and lipid and cholesterol metabolism-associated genes were analyzed by RT-qPCR.<br><br>RESULTS: A total of 386 constituents were identified in ZJP, and 222 compounds were detected in ZJP-medicated serum, predominantly flavonoids, iridoids, phenylethanoid glycosides, and bile acid-related metabolites. Network pharmacology highlighted quercetin, kaempferol, isorhamnetin, and sophoranol as key active compounds targeting core proteins such as AKT3, HSP90AA1, and PIK3CA. In in vivo evaluations, compared with the AMD model group, high-dose ZJP treatment increased the time spent in the dark chamber by 90.51% (P < 0.001), significantly restored retinal thickness by 84.76% (P < 0.001), and improved the histopathological score by 52.88% (P < 0.001). In ARPE-19 cells, ZJP increased LPC-induced cell viability by 105.56% (P < 0.001), inhibited complement overactivation, and suppressed inflammatory cytokine. Metabolomic analyses demonstrated that ZJP markedly corrected lipid metabolism, bile acid biosynthesis, energy metabolism, and inflammatory eicosanoid pathways, and promote retinal cholesterol efflux via upregulation of LXR&#x3b1; and ABCA1, and modulate LDLR-mediated cholesterol uptake.<br><br>CONCLUSIONS: Rooted in the TCM theory of 'nourishing liver and kidney to benefit eyesight', ZJP (composed of Cuscutae Semen, Plantaginis Semen, and Rehmanniae Radix) ameliorates AMD by regulating LXR&#x3b1;/ABCA1-mediated cholesterol efflux, suppressing complement activation, and normalizing lipid and bile acid metabolism. These findings provide mechanistic support for the traditional use of ZJP in ocular disorders and highlight its potential as a therapeutic candidate for AMD.}, }
@article {pmid41958546, year = {2026}, author = {Bautista-Hernández, MA and Torres-Rosas, R and Argueta-Figueroa, L and Moreno-Rodríguez, A and Pérez-Cervera, Y and Acevedo-Mascarúa, AE and Martínez-Martínez, EA}, title = {Acupuncture in the treatment of inflammation-related ocular degenerations: a systematic review.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1749297}, pmid = {41958546}, issn = {2296-858X}, abstract = {BACKGROUND: Inflammation-related ocular degenerations include dry eye syndrome, diabetic retinopathy, age-related macular degeneration, and glaucoma. Until now, there are no efficient protocols for treating inflammation-related ocular degenerations. On the other hand, acupuncture therapy modulates the inflammatory and oxidative stress responses in several inflammatory diseases and has been proposed as an emerging therapy for the potential treatment of ocular pathologies.<br><br>OBJECTIVE: This work aimed to conduct a comprehensive systematic review to address the efficacy of acupuncture therapy for Inflammation-related ocular degenerations.<br><br>METHODS: The designs of the included studies were clinical trials and observational studies, whereas case series, in vivo, and in vitro studies were excluded. The search was performed in five databases. Relevant data from all included studies were recorded, the outcomes analyzed were intraocular pressure and visual acuity for glaucoma; score of symptoms, pain, tear-film breakup time, and mm of Schirmer test for dry eye syndrome; visual acuity, retinal structure or disease progression for diabetic retinopathy; and finally visual acuity and scores of symptoms for age-related macular degeneration. Risk of bias (using the RoB 2 tool) and quality (using the Grading of Recommendations Assessment, Development, and Evaluation [GRADE] tool) assessments were conducted.<br><br>RESULTS: The included studies showed heterogeneity, risk of bias, inconsistency, and very low certainty of evidence.<br><br>CONCLUSION: There is no conclusive evidence to support that acupuncture is an effective therapy in patients with inflammation-related ocular degeneration disease.<br><br>https://www.crd.york.ac.uk/PROSPERO/view/CRD42022368882, identifier PROSPERO (CRD42022368882).}, }
@article {pmid41959212, year = {2026}, author = {Voigt, AP and Mullin, NK and Mulfaul, K and Lozano, LP and Navratil, EM and Flamme-Wiese, MJ and Lavine, JA and Fingert, JH and Tucker, BA and Stone, EM and Scheetz, TE and Mullins, RF}, title = {Single-Cell Gene Expression and eQTL Analyses in the Human Retina, RPE, and Choroid in Macular Degeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.30.714946}, pmid = {41959212}, issn = {2692-8205}, abstract = {Age-related macular degeneration (AMD) is a common, complex disease affecting older individuals that can lead to severe vision loss. It is characterized by early anatomical changes in the retina, retinal pigment epithelium (RPE), and choroid, especially in the central (macular) region. AMD can progress to severe atrophy and/or pathologic angiogenesis that leads to visual decline. Over 30 genetic loci have been identified as contributing to AMD risk; however, the mechanisms by which genetic variants affect pathology has not been thoroughly explored. In this report we examined single-nucleus gene expression in the retina, RPE and choroid of 88 individuals categorized by AMD stage, as well as 37 previously published samples. Genotyping was performed on 1.8 million SNPs, with additional SNPs imputed, on each donor to identify expression quantitative trait loci (eQTLs). We found that two AMD-risk loci (PILRB and ARMS2/HTRA1) affected the expression of PILRB and HTRA1, respectively. The risk allele of PILRB was associated with increased PILRB RNA in cones, fibroblasts, choroidal macrophages, and RPE, whereas the HTRA1 risk locus was associated with decreased HTRA1 RNA in the RPE. We also identified an age-related decrease in complement inhibitors in the choriocapillaris, a tissue susceptible to complement mediated damage in AMD.}, }
@article {pmid41959804, year = {2026}, author = {Yeh, TC and Lin, JB and Mruthyunjaya, P and Leng, T and DeBoer, C and Sepah, YJ and Almeida, DR and Smith, S and Mahajan, VB}, title = {A Simplified Classification for Age-Related Macular Degeneration Based on Optical Coherence Tomography.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.29.26349635}, pmid = {41959804}, abstract = {BACKGROUND AND OBJECTIVE: As optical coherence tomography (OCT) has enabled the identification of an expanding set of age-related macular degeneration (AMD) risk biomarkers and become central to routine clinical practice, there remains a need for a simplified grading scheme that allows physicians to communicate and synchronize AMD grading directly from standard OCT imaging rather than relying on traditional color fundus imaging. This study aims to establish a standardized OCT-based AMD classification that balances diagnostic accuracy with practicality for use across clinical and research settings.<br><br>PATIENTS AND METHODS: Spectral-domain optical coherence tomography scans were independently graded by two retinal specialists following the newly proposed Stanford OCT-Based AMD Classification (SOAC). Discrepancies were adjudicated by a third independent retinal specialist. Intergrader agreement was assessed using weighted kappa coefficients.<br><br>RESULTS: Among the 109 eyes from 108 patients (mean age 79.61&#x25a1;&#xb1;&#x25a1;7.57 years; 41.7% male, 58.3% female), AMD staging based on SOAC was distributed as follows: normal aging in 9 patients (8.3%), early AMD in 16 (14.7%), intermediate AMD in 32 (29.4%), neovascular AMD (nAMD) in 18 (16.5%), geographic atrophy (GA) in 20 (18.3%), and combined nAMD and GA in 14 (12.8%). The overall intergrader agreement demonstrated robust consistency, with a weighted kappa value of 0.95 (95% CI: 0.92-0.98), signifying excellent intergrader reliability and reinforcing the validity of SOAC.<br><br>CONCLUSION: SOAC provides a standardized, OCT-based framework for AMD grading that demonstrates high intergrader agreement. By enabling consistent classification from commonly acquired OCT scans, SOAC supports reliable disease staging and facilitates integration across clinical studies and translational research. As imaging and molecular data continue to expand, SOAC can serve as a common OCT-based reference for phenotype refinement and longitudinal AMD studies.<br><br>KEY QUESTIONS: What is already known on this topic? Existing classifications of age-related macular degeneration (AMD) rely heavily on color fundus photography and inconsistently incorporate optical coherence tomography (OCT) biomarkers, despite OCT's superior resolution for detecting subclinical structural changes. What this study adds? This study introduces an OCT-based classification framework that consolidates key biomarkers with proven prognostic relevance into a simplified, tiered staging protocol. By prioritizing a curated set of evidence-supported, high-risk OCT biomarkers, the Stanford OCT-Based AMD Classification (SOAC) provides a common framework and shared language for OCT-based AMD staging, facilitates longitudinal monitoring, and reduces intergrader variability through standardized reporting guidelines. The framework deliberately balances clinical practicality with scientific rigor, excluding less significant or potentially confusing features to ensure scalability across diverse clinical and research settings. How this study might affect research, practice or policy? SOAC provides an OCT-based framework for AMD staging with high inter-physician agreement. This is particularly important in real-world clinical and translational research settings, where color fundus photography is not always available. By offering a common OCT-based reference, SOAC reduces diagnostic variability and supports more consistent AMD staging across clinicians and studies. The classification incorporates up-to-date, evidence-based, high-risk OCT features associated with disease progression and is designed to be scalable, allowing integration with emerging multimodal data, including AI-driven imaging analysis and molecular profiling. By bridging advances in retinal imaging with practical clinical application, SOAC lays the groundwork for improved risk stratification, longitudinal outcome studies, and more standardized reporting in AMD.}, }
@article {pmid41960189, year = {2026}, author = {Ryu, Y and Jeong, D and Kim, JH and Kim, YK}, title = {CircAFF3 modulation of p53-ID2 signaling in the retinal pigment epithelium links inflammation with cell death in dry age-related macular degeneration.}, journal = {Frontiers in cell and developmental biology}, volume = {14}, number = {}, pages = {1733888}, pmid = {41960189}, issn = {2296-634X}, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) represents a multifactorial disease that is influenced by age, genetic, and environmental factors. AMD is characterized by dysfunction of the retinal pigment epithelium (RPE) resulting from oxidative stress, inflammation, and complement activation. As the disease progresses, the loss of the RPE and photoreceptors leads to geographic atrophy, which is a hallmark of dry AMD. Although research is ongoing, there is currently no established effective treatment for dry AMD. Notably, circular RNAs (circRNAs) have been studied in various diseases; however, the role of circRNAs in eye diseases remains poorly understood. To fill this gap, this study aimed to investigate circRNAs as potential therapeutic targets for dry AMD.<br><br>METHODS: We identified candidate circRNAs using a laser-induced choroidal neovascularization (CNV) model. The function of circAFF3 was investigated through knockdown experiments in ARPE-19 cells, followed by transcriptomic analysis, pathway enrichment, and functional assays, including qPCR, western blotting, immunofluorescence, monocyte adhesion, and measurements of ROS, iron, lipid peroxidation, and apoptosis. Interaction between circAFF3 and p53 was explored using binding prediction, RNA-binding protein immunoprecipitation, and cycloheximide chase assay.<br><br>RESULTS: We found that circAff3 levels were downregulated in RPE samples at day 3 after laser injury. Moreover, silencing circAFF3 induced an inflammatory response in ARPE-19 cells. Based on these results, a subsequent transcriptomic analysis of circAFF3 knockdown in ARPE-19 cells was conducted to further elucidate its function. These analyses showed that genes downregulated by circAFF3 knockdown in ARPE-19 cells were significantly associated with retinal degeneration. Additionally, reduced circAFF3 expression promoted a decrease in ID2 levels, resulting in increased oxidative stress and cell death. Our study further demonstrated that circAFF3 directly interacts with p53, thereby regulating ID2 expression in ARPE-19 cells.<br><br>CONCLUSION: Collectively, our study reveals that circAFF3 plays a crucial role in RPE dysfunction by modulating a circAFF3/p53/ID2 pathway, suggesting that circAFF3 can serve as a key regulator with therapeutic potential in dry AMD.}, }
@article {pmid41960651, year = {2026}, author = {Zeender, G and Moulin, A and Rizzuto, P and Elbany, S and Gascon, P and Allaix, K and Feldman, A and De Bats, F and Wolff, B and Bassouamina-Kinanga, E and Dot, C and Kodjikian, L and Mathis, T}, title = {Recurrence after treat-and-extend suspension in neovascular age-related macular degeneration: A real-world analysis by macular neovascularization subtype.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70132}, pmid = {41960651}, issn = {1755-3768}, }
@article {pmid41960966, year = {2026}, author = {Akada, M and Ideyama, M and Kido, A and Miyata, M and Ueda-Arakawa, N and Tamura, H and Ooto, S and Miyake, M and Tsujikawa, A and Hata, M}, title = {Age-Specific Increases in the Prevalence and Treatment Burden of Neovascular Age-Related Macular Degeneration in a Super-Aged Society.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {19}, doi = {10.1167/iovs.67.4.19}, pmid = {41960966}, issn = {1552-5783}, mesh = {Humans ; Aged ; Male ; Female ; Prevalence ; Cross-Sectional Studies ; Japan/epidemiology ; Aged, 80 and over ; Middle Aged ; *Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/epidemiology/drug therapy ; Adult ; Databases, Factual ; *Cost of Illness ; Intravitreal Injections ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Comorbidity ; Age Distribution ; Recombinant Fusion Proteins/therapeutic use ; }, abstract = {PURPOSE: To characterize age-specific changes in the prevalence and treatment burden of neovascular AMD (nAMD) from 2014 to 2019 in a super-aged society and to assess whether comorbidities contribute to this increase.<br><br>METHODS: We performed a nationwide repeated cross-sectional study using Japan's national claims database (>95% population coverage). Adults aged &#x2265;40 years in 2014 and 2019 were included to estimate age-stratified nAMD prevalence. Treatment burden was evaluated as the total number of nAMD-related treatment claims and mean administrations among users of each agent. Diabetes, hypertension, and dyslipidemia were identified from claims. Multivariable logistic regression compared nAMD cases with controls and assessed whether comorbidity adjustment attenuated the odds of nAMD in 2019 versus 2014.<br><br>RESULTS: We identified 76,125 cases in 2014 and 125,190 in 2019; age-standardized prevalence increased from 101.3 to 152.4 per 100,000. Prevalence peaked at ages 80-84 in both years but increased most steeply among those &#x2265;75 years (62.9%). Total treatment claims increased markedly, driven primarily by aflibercept. Among users of each agent, mean administrations increased modestly. Comorbidities were associated with higher odds of nAMD, but adjusting for them did not change the higher odds of nAMD in 2019 compared with in 2014.<br><br>CONCLUSIONS: Between 2014 and 2019, the prevalence and treatment burden of nAMD increased substantially in Japan, with a disproportionate rise among older age groups in a super-aged population. Comorbidities did not account for the temporal increase, suggesting that factors beyond aging and comorbidity are contributing to the growing burden.}, }
@article {pmid41961694, year = {2026}, author = {Dugiełło, B and Bolek, B and Walasz, K and Kijonka, M and Wylęgała, E and Wylęgała, A}, title = {OCT angiography-derived biomarkers of retinal and choroidal microvascular changes in dry age-related macular degeneration.}, journal = {Medicine}, volume = {105}, number = {15}, pages = {e48033}, doi = {10.1097/MD.0000000000048033}, pmid = {41961694}, issn = {1536-5964}, mesh = {Humans ; Cross-Sectional Studies ; Female ; Male ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/diagnostic imaging ; Aged ; *Retinal Vessels/diagnostic imaging/pathology ; Biomarkers ; Middle Aged ; *Macular Degeneration/diagnostic imaging ; Fluorescein Angiography/methods ; *Microvessels/diagnostic imaging/pathology ; Aged, 80 and over ; }, abstract = {This study aimed to identify optical coherence tomography angiography (OCTA) biomarkers associated with disease severity in dry age-related macular degeneration (dAMD). This cross-sectional study included 142 eyes (104 patients) with dAMD, classified as early (n = 34), intermediate (n = 40), or late stage (n = 37) according to the Beckman Classification, and 30 control eyes without AMD. OCTA-images were obtained using the ZEISS PLEX Elite 9000, vascular metrics such as vessel density, total number of junctions, total and average vessel length, junction density, total number of endpoints, and lacunarity were assessed in the superficial capillary plexus, deep capillary plexus (DCP), and choriocapillaris (CC) using AngioTool software. The CC showed the most pronounced changes, with vessel percentage area reduced from 58.98 ± 4.86% in controls to 52.14 ± 10.30% in intermediate and 31.34 ± 11.27% in late AMD (P <.001). Total vessel length declined from 407.52 ± 16.33 mm to 367.09 ± 49.18 mm and 217.23 ± 86.88 mm, respectively (P <.001), while lacunarity increased nearly 50-fold in late AMD (0.56 ± 0.91 vs 0.01 ± 0.00; P <.001). In the DCP, vessel percentage area decreased from 45.68 ± 4.92% in controls to 41.95 ± 5.08% in intermediate and 38.24 ± 6.71% in late AMD (P <.001). Vessel length dropped from 275.21 ± 21.82 mm to 254.13 ± 28.78 mm and 224.68 ± 36.37 mm (P <.001), with increased lacunarity in intermediate and late stages (P <.01). The superficial capillary plexus showed early alterations, with vessel percentage area reduced from 41.46 ± 1.58% in controls to 39.42 ± 3.45% in early AMD (P = .017) and total vessel length decreased from 202.85 ± 10.65 mm to 191.42 ± 18.67 mm and 185.92 ± 18.09 mm in intermediate AMD (P <.001). Mean lacunarity was elevated in all AMD stages (P <.001). OCTA reveals distinct, layer-specific microvascular changes in AMD mainly within DCP and CC. Vessel percentage area, total vessel length, and lacunarity represent sensitive, noninvasive OCTA biomarkers of microvascular impairment in dry AMD, with potential applicability for longitudinal disease monitoring and as quantitative imaging endpoints in future interventional trials.}, }
@article {pmid41962145, year = {2026}, author = {Basyal, D and Bhandari, SK and Kim, HJ}, title = {Targeting retinal degeneration: zeaxanthin dipalmitate from Lycium barbarum L. prevents A2E photooxidation under blue light.}, journal = {Natural product research}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/14786419.2026.2654653}, pmid = {41962145}, issn = {1478-6427}, abstract = {The accumulation of the toxic byproduct A2E in retinal pigment epithelial cells, coupled with blue-light-induced photooxidation, is a key driver of oxidative damage in early age-related macular degeneration (AMD). Zeaxanthin dipalmitate (ZD), the esterified carotenoid abundant in goji berries, has higher lipophilicity and stability. In this study, ZD was isolated from the berries using its fat-soluble nature and purified using medium-pressure liquid chromatography. Isolated ZD and synthesised A2E were structurally characterised using HPLC, NMR, and positive mode LC-ESI-TQ-MS. An acellular photo-oxidation assay revealed that ZD significantly suppressed A2E degradation under blue light with higher efficacy than vitamin E, a standard antioxidant control. This indicates ZD's potent ability to filter blue light and scavenge reactive oxygen species, mitigating A2E photooxidation and phototoxicity. These findings highlight ZD's unique structural advantages for sustained retinal protection. The findings also support further in vivo and clinical studies of ZD as a natural photoprotective agent that targets early events in AMD.}, }
@article {pmid41962545, year = {2026}, author = {Copland, DA and Liu, J and Chan, YK and Dick, AD and Clare, AJ}, title = {Can NRF2 provide a gene-agnostic approach to treating age-related macular degeneration?.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2026.03.029}, pmid = {41962545}, issn = {1525-0024}, }
@article {pmid41952808, year = {2026}, author = {Gad El Sayed, M and Vu Pham, N and Bandaru, D and Abboud, I and Zakhary, MB and Zakhary, M and Bishay, RGE and Rezaei, K and Khaksar, P and Enciso, J and Tran, K and Martinez, SJ and Mikhail, K and Glendrange, RR and Fouad, Y}, title = {Smoking and Risk of Vision Threatening Complications: A Global Database Analysis.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {596936}, pmid = {41952808}, issn = {1177-5467}, abstract = {PURPOSE: To investigate the association between smoking and the incidence of vision-threatening conditions, including cataract, glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vascular occlusion, uveitis, and ischemic optic neuropathy (ION) in a large real-world database to provide quantitative risk estimates to inform smoking cessation counseling.<br><br>METHODS: A retrospective cohort study was conducted using the TriNetX electronic health records platform, analyzing 12,183,254 patients. Patients were categorized into smokers (n = 304,823) and non-smokers (n = 11,878,431), and then a propensity score matching was utilized to balance both groups for demographic features and vascular risk factors. The incidence rates of the studied ocular conditions were then compared over a ten-year period using risk ratios (RR).<br><br>RESULTS: Matched cohorts included 300,867 patients per group. Smokers exhibited a significantly higher 10-year risk for all studied ophthalmic outcomes (p < 0.0001). The strongest associations were observed for posterior subcapsular cataract (RR 2.60; 95% CI, 2.41-2.82), uveitis (RR 2.43 [2.25-2.63]), and retinal vascular occlusions (CRAO: RR 2.35; CRVO: RR 2.16). Increased risks were also consistent across glaucoma subtypes (RR 1.57-2.47), AMD (RR 1.85), and diabetic retinopathy (RR 1.21).<br><br>CONCLUSION: Smoking is significantly associated with an increased risk of multiple vision-threatening ocular diseases. These findings highlight the need for ophthalmologists and public health professionals to incorporate smoking history into risk stratification and screening programs and to emphasize ocular health during smoking cessation counseling.}, }
@article {pmid41952906, year = {2026}, author = {Chen, Q and Zhang, J and Xu, K and Liu, X and Liang, L}, title = {Qiju Granule alleviates retinal damage in a mouse model of age-related macular degeneration.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1781217}, pmid = {41952906}, issn = {2296-858X}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of visual loss in older people. Despite recent advances, the pathophysiology of AMD remains incompletely understood, and current therapies are limited. Qiju Granule is a traditional herbal formulation with therapeutic potential; however, its efficacy and mechanisms in AMD remain unclear.<br><br>OBJECTIVE: The aim of this study was to evaluate the protective effects of Qiju Granule in a mouse model of AMD and investigate potential underlying mechanisms.<br><br>METHODS: AMD-like retinal injury was induced in C57BL/6J mice by chronic light exposure combined with hydroquinone feeding. Retinal function and structure were assessed using electroretinography and histomorphological analyses. Retinal cell apoptosis and the expression of key angiogenic factors (VEGF and CD31) were assessed to explore underlying mechanisms.<br><br>RESULTS: Qiju Granule treatment significantly preserved retinal function, as reflected by improved electroretinographic responses, and maintained structural integrity of the retina and RPE layer. Mechanistically, Qiju Granule exerted potent anti-apoptotic effects, evidenced by a marked reduction in TUNEL-positive retinal cells. Furthermore, it downregulated VEGF and CD31 expression, indicating suppression of aberrant angiogenic signaling.<br><br>CONCLUSION: Our findings identified a protective role of Qiju Granule in mitigating AMD-related retinal damage and suggested its potential as a therapeutic candidate to prevent progression to advanced AMD.}, }
@article {pmid41953649, year = {2026}, author = {Armendariz, BG and Kent, D}, title = {Submacular tissue repair and fibrosis in neovascular macular degeneration: A predictable outcome secondary to a chronic age-related endotheliopathy.}, journal = {Molecular vision}, volume = {32}, number = {}, pages = {22-32}, pmid = {41953649}, issn = {1090-0535}, mesh = {Humans ; Fibrosis ; *Macular Degeneration/pathology/metabolism/drug therapy/physiopathology ; Animals ; Extracellular Matrix/metabolism/pathology ; Chronic Disease ; *Aging/pathology ; Endothelial Cells/pathology/metabolism ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Capillary Permeability ; }, abstract = {Fibrosis is strictly a histopathological term that refers to the replacement of functional tissue with permanent deposition of nonfunctional extracellular matrix (ECM), following an injury or disease, and can occur in any tissue in the body. In this histological setting, there is no overt difference between fibrosis and scarring. However, in the clinical context, fibrosis tends to be associated with chronic disease, as it ensures ongoing ECM deposition. This could be considered "excessive" when compared to ECM deposition in acute or end-stage chronic disease. This perspective highlights how fibrosis in neovascular age-related macular degeneration follows a stereotypical tissue repair process similar to that seen in other tissues and how salient biologic processes, such as aging and metabolic health, impact fibrosis development. In addition, we highlight the emerging and pivotal profibrogenic role played by progressive endothelial cell (EC) dysfunction, together with secondary blood flow impedance in the neovasculature. This results in abnormal vascular permeability, endothelial-to-mesenchymal transition, and EC senescence-associated secretory phenotype, processes that could potentially be targeted therapeutically. Finally, the dramatic impact of anti-vascular endothelial growth factor therapy, by primarily targeting permeability of the nascent microvasculature, on the natural history of fibrosis in neovascular age-related macular degeneration indirectly highlights the potentially significant role of ECs in fibrosis development and points toward how novel future targeting of these cells could further modulate the development of fibrosis.}, }
@article {pmid41954091, year = {2026}, author = {Lin, Y and Du, Y and Shu, Q and Su, W and Peng, H and Wang, X}, title = {Belzutifan Attenuates Choroidal Neovascularization by Suppressing the HIF-2α/PAI-1 Axis.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {7}, pages = {e71740}, doi = {10.1096/fj.202503954RR}, pmid = {41954091}, issn = {1530-6860}, support = {CSTB2024NSCQ-MSX0705//CSTC | Natural Science Foundation of Chongqing Municipality ()/ ; CSTB2024NSCQ-MSX1234//CSTC | Natural Science Foundation of Chongqing Municipality ()/ ; //Chongqing Medical University/ ; }, mesh = {Animals ; *Choroidal Neovascularization/drug therapy/metabolism/pathology ; Rats ; Humans ; *Basic Helix-Loop-Helix Proteins/metabolism/antagonists &amp; inhibitors/genetics ; *Plasminogen Activator Inhibitor 1/metabolism/genetics ; Rats, Sprague-Dawley ; Male ; Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Vascular Endothelial Growth Factor A/metabolism ; Indenes ; }, abstract = {Choroidal neovascularization (CNV) is the hallmark pathology of exudative age-related macular degeneration (AMD). Although anti-vascular endothelial growth factor (VEGF) therapy is widely used, its limitations, including drug resistance and treatment burden, necessitate alternative targets. This study aimed to investigate the role of hypoxia-inducible factor-2α (HIF-2α) in CNV pathogenesis and evaluate the therapeutic potential of its inhibitor Belzutifan, with a particular focus on validating the functional significance of the HIF-2α/plasminogen activator inhibitor-1 (PAI-1) axis. The efficacies of Belzutifan were assessed in a laser-induced CNV rat model using H&amp;E staining, OCT, fundus photography, and immunofluorescence. Network pharmacology identified potential therapeutic pathways. In vitro, CoCl2-injured HUVECs were used to evaluate the effects of drugs on proliferation, migration, and tube formation. The expression levels of HIF-2α, PAI-1, VEGF-A, Ve-cadherin, and inflammatory factors were assessed by ELISA, immunofluorescence, and Western blot analysis. This study demonstrated that Belzutifan inhibits CNV by targeting the HIF-2α/PAI-1 axis. It also showed that Belzutifan can markedly reduce the expression levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α). Both the HIF-2α inhibitor and the PAI-1 inhibitor suppressed the proliferation, migration, and tube formation of HUVECs. Intravitreal injection of both inhibitors effectively reduced neovascularization from Day 14 to Day 21 in the laser-induced CNV rat model. Collectively, these findings provide a novel therapeutic strategy for exudative AMD and highlight its significant clinical translational value.}, }
@article {pmid41954492, year = {2026}, author = {Spaide, RF and Lee, K and Kuo, JW and Akiba, M and Durbin, M and Naderi, A and Ko, TH and Tafreshi, A}, title = {Retinal Blood Velocity after Intravitreal Injection for Neovascular Age-Related Macular Degeneration with Optical Coherence Tomography Using Speckle Analysis.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004851}, pmid = {41954492}, issn = {1539-2864}, abstract = {PURPOSE: To quantify the effect of transient intraocular pressure (IOP) elevation after intravitreal injection on retinal blood flow using a validated speckle-based optical coherence tomography (OCT) method.<br><br>METHODS: Nineteen eyes of 19 patients with neovascular age-related macular degeneration underwent OCT imaging and IOP measurement before, immediately after, and for &#x223c;15 minutes after anti-VEGF injection. Retinal blood flow was quantified using a speckle-derived flow index proportional to the erythrocyte velocity. Flow changes were analyzed with linear mixed-effects models incorporating IOP, age, and vessel type.<br><br>RESULTS: Mean pre-injection IOP was 14.1 mm Hg, rising to 54.4 mm Hg immediately post-injection and decreasing to 24.1 mm Hg after 15.4 minutes. Flow remained stable for IOPs &#x2264; 40 mm Hg but declined by 3.6% per mm Hg above this threshold (P < 0.001). Older patients exhibited less arterial flow reduction at higher pressures, a modest effect observed only in arteries, not veins. In a limited comparison of the youngest and oldest participants, the arteriolar walls in older eyes appeared thicker and more reflective, consistent with arteriolosclerosis.<br><br>CONCLUSIONS: Speckle-based OCT enables direct, quantitative assessment of retinal blood flow in vivo. Retinal perfusion remains stable through transient IOP elevations up to about 40 mm Hg, likely reflecting autoregulatory reserve, but declines at higher pressures. The relative flow preservation in older eyes may result from increased vascular wall rigidity. Speckle-based OCT provides a practical, quantitative method to assess retinal blood flow dynamics in vivo.}, }
@article {pmid41954837, year = {2026}, author = {Eker, S and Erdem, A and Acar, U and Gönül, &#x15e;}, title = {Evaluation of the triglyceride-glucose index, serum inflammatory biomarkers and lipid profile in patients with neovascular age-related macular degeneration.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {41954837}, issn = {1573-2630}, mesh = {Humans ; Female ; Male ; Biomarkers/blood ; Retrospective Studies ; Aged ; *Triglycerides/blood ; *Blood Glucose/metabolism ; Case-Control Studies ; *Lipids/blood ; *Wet Macular Degeneration/blood/diagnosis ; Middle Aged ; Inflammation/blood ; Aged, 80 and over ; }, abstract = {PURPOSE: To evaluate the triglyceride-glucose index (TyG), novel systemic inflammatory biomarkers, and lipid profile in patients with neovascular age-related macular degeneration (nAMD), and to investigate their potential relationship with disease presence.<br><br>METHODS: This retrospective case-control study included 59 patients diagnosed with nAMD and 67 age- and sex-matched healthy controls. Demographic characteristics, fasting biochemical tests, lipid profile, complete blood count, and serum inflammatory indices were recorded. Triglyceride-glucose index, systemic inflammatory indices derived from various hematological parameters and lipid levels were calculated. Laboratory parameters and calculated indexes were compared between the two groups using Statistical Package for the Social Sciences (SPSS).<br><br>RESULTS: Triglyceride-glucose index was significantly higher in the nAMD group than in controls (4.84&#x2009;&#xb1;&#x2009;0.27 vs. 4.69&#x2009;&#xb1;&#x2009;0.17, p&#x2009;=&#x2009;0.0001). Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels were also elevated in the nAMD group (p&#x2009;=&#x2009;0.0001 for both). Among hematological markers, white blood count (WBC), neutrophil, and monocyte counts were significantly increased in nAMD patients (p&#x2009;=&#x2009;0.012, p&#x2009;=&#x2009;0.001, p&#x2009;=&#x2009;0.015, respectively). Inflammatory indices including neutrophil/lymphocyte ratio (NLR) (p&#x2009;=&#x2009;0.015), monocyte/HDL-C ratio (MHR) (p&#x2009;=&#x2009;0.003), systemic inflammation aggregate index (AISI) (p&#x2009;=&#x2009;0.025), and C reactive protein/albumine ratio (CAR) (p&#x2009;=&#x2009;0.006) were significantly higher in the nAMD group, whereas the systemic immune inflammation index (SII), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) showed no significant differences (p&#x2009;>&#x2009;0.05). Serum lipid levels and atherogenic lipid ratios did not differ between the groups.<br><br>DISCUSSION: Patients with nAMD exhibit increased systemic inflammatory activity and metabolic stress, reflected by elevated NLR, MHR, AISI, and CAR levels. In addition, TyG, a novel indicator of systemic insulin resistance, was found to be elevated in nAMD patients. These findings suggest that metabolic dysregulation and chronic low-grade systemic inflammation may contribute to nAMD pathogenesis independently of serum lipid levels. The TyG and inflammation-derived biomarkers may serve as potential systemic indicators for nAMD risk or disease activity.}, }
@article {pmid41954906, year = {2026}, author = {Thottarath, S and Gurudas, S and Kubravi, S and Kazantzis, D and Keskin, AM and Sivaprasad, S and , }, title = {Nonexudative Macular Neovascularization in Age-Related Macular Degeneration.}, journal = {JAMA ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1001/jamaophthalmol.2026.0459}, pmid = {41954906}, issn = {2168-6173}, abstract = {IMPORTANCE: Nonexudative macular neovascularization (neMNV) is a risk factor for exudation in fellow eyes of patients with unilateral exudative age-related macular degeneration (AMD). Accurate estimation of prevalence of neMNV is required for sample size calculations for clinical trials evaluating novel interventions to delay exudation from neMNV. Certain dimensions of double-layer sign (DLS) on optical coherence tomography (OCT) are often regarded as a surrogate for neMNV.<br><br>OBJECTIVE: To assess the prevalence of fellow-eye neMNV on OCT angiography (OCT-A) in eyes with AMD with DLS on OCT among patients with unilateral new-exudative AMD in the first eye.<br><br>This prospective observational cohort multicenter study took place in the United Kingdom from January 2021 through June 2025. The study included 862 participants with OCT and OCT-A within 3 months of initiation of anti-vascular endothelial growth factor (VEGF) therapy, of whom 550 (63.8%) had both OCT and OCT-A performed within 30 days of the date of the first anti-VEGF injection to the fellow eye. These data were analyzed from July 2025 through October 2025.<br><br>MAIN OUTCOMES AND MEASURES: Prevalence of DLS, neMNV, and assessment of univariable and adjusted associations with neMNV and DLS were assessed using logistic regression models.<br><br>RESULTS: Among 550 eyes (mean [SD] participant age, 78.0 [7.6] years; 315 female [57.3%] and 235 male [42.7%]), 112 (20.4%; 95% CI [Wilson score], 17.1%-24.0%) had DLS and 47 eyes (8.5%; 95% CI [Wilson score], 6.4%-11.3%) had neMNV at baseline, including 42 (89.36%) within DLS, 3 (6.4%) in fibrovascular irregular shallow-pigment epithelial detachment, and 2 (4.3%) below drusen. Prevalence of neMNV was higher among eyes with thick DLS (n&#x2009;=&#x2009;36 [48%]) compared with those with thin DLS (16.2%; n&#x2009;=&#x2009;6; difference&#x2009;=&#x2009;-31.8%; 95% CI [Wilson score], -46.9% to -11.7%; P&#x2009;=&#x2009;.002).<br><br>CONCLUSIONS AND RELEVANCE: While 1 in 5 fellow eyes had DLS on OCT among patients with unilateral new-onset exudative AMD in the first eye, the prevalence of neMNV on OCT-A was only 40% among these eyes with DLS. These results suggest DLS on OCT in fellow eyes of patients with new-onset exudative AMD in the first eye is not a good surrogate for neMNV.<br><br>TRIAL REGISTRATION: ISRCTN registry Identifier: ISRTCTN13798759.}, }
@article {pmid41955658, year = {2026}, author = {Desmettre, T and Paques, M}, title = {[Retro mode imaging and early-stage AMD].}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {5}, pages = {104859}, doi = {10.1016/j.jfo.2026.104859}, pmid = {41955658}, issn = {1773-0597}, abstract = {Age-related macular degeneration (AMD) is a chronic disease whose progression toward advanced stages is closely related to the phenotype observed at the early and intermediate stages. The detection and characterization of drusen and pigmentary abnormalities are central to the stratification of progression risk. Retro mode imaging, based on indirect infrared retro-illumination, enhances the visualization of retinal surface elevation, depth-related features, and variations in pigment density. This review examines the contribution of the various retro mode configurations (deviated left [DL]; deviated right [DR]; and ring aperture [RA]) in AMD, based on recent data in the literature as well as our clinical experience. When integrated into a multimodal imaging strategy, the combined use of DL and DR modes improves the detection and morphological assessment of drusen, while the ring aperture mode facilitates the identification of subtle pigment migration at the onset of the disease. A more precise characterization of these lesions allows refinement of AMD staging and provides clinically meaningful prognostic information.}, }
@article {pmid41955664, year = {2026}, author = {Mathis, T and Devin, F and Gabrielle, PH and Grenet, T and Gualino, V and El Khatib, N and Del Rio, M and Balez, S and Souied, E}, title = {PICCTURE: Survey of French ophthalmologists' practices for the treatment of neovascular age-related macular degeneration patients currently treated with anti-VEGF.}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {5}, pages = {104861}, doi = {10.1016/j.jfo.2026.104861}, pmid = {41955664}, issn = {1773-0597}, abstract = {PURPOSE: To evaluate the practices of French ophthalmologists in the management of neovascular age-related macular degeneration (nAMD) with regard to the identification of criteria influencing therapeutic decision-making and motivating the need for a new molecule.<br><br>METHODS: A survey of practices based on the validated case-vignette method was conducted from January to September 2023 and included 110 ophthalmologists throughout France. A total of 480 clinical cases were developed based on disease progression (worsening, stability, improvement), the presence or absence of exudative signs (intraretinal fluid, subretinal fluid, or subretinal hyperreflective material), and the volume of retinal fluid (obvious or subtle). For each case, ophthalmologists assessed whether to continue the current anti-VEGF treatment or change the injection interval and/or molecule, and they assessed the benefit of having a new molecule available.<br><br>RESULTS: In 76.9% of cases, clinical cases showed disease activity (56.5% worsening and 20.4% disease stability). The fluid present was mostly subtle in 55% of the cases and obvious in 38.8% of the cases. Among the responding physicians, 82.5% intended to change the treatment entirely, and 71.8% opted to change only one parameter (molecule or treatment interval). The common criterion for a change in treatment was disease worsening. For the same clinical case, 92% of those who opted for a single change and 87% of those who opted for a change in interval and molecule would consider it relevant to propose a new anti-VEGF. Among the physicians, 55.8% would maintain the treatment interval identical to that of the previous treatment. The most common criteria for the need for a new molecule was the obvious presence of exudative signs (P<0.001), treatment every&#x2264;6weeks (P<0.001), initial treatment for 3-6months (P<0.001), and visual acuity of 20/200 (P<0.001).<br><br>CONCLUSION: This survey provides an overview of current management strategies for patients with nAMD in France and identifies criteria influencing therapeutic decision-making based on different patient profiles. This highlights the interest of ophthalmologists in having new molecules to treat insufficiently controlled patients.}, }
@article {pmid41956945, year = {2026}, author = {Li, S and Gao, T and Wang, Y and He, Q and Ma, H and Ye, H and Shen, Y and Wang, Y and Wang, Y and Li, X and Fang, S and Chen, Q and Liu, Q and Sun, G and Xin, H and Xue, J and Liu, S and Zhu, M and Xu, W and Wang, Z and Shao, J and Xie, M}, title = {Rationally designed light-inducible RNA-releasing protein for translational regulation and optogenetic control of gene therapies.}, journal = {Trends in biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tibtech.2026.03.004}, pmid = {41956945}, issn = {1879-3096}, abstract = {In this study, we describe a rationally designed light-inducible RNA-releasing protein (LIRP) capable of inhibiting mRNA translation in the dark while permitting gene expression upon exposure to blue or ambient light. This LIRP-dependent gene switch is compatible with various delivery routes of gene- and cell-based therapy, such as subcutaneous implantation of microencapsulated light-sensitive cells or expression in various light-accessible body sites using single adeno-associated virus (AAV) vectors. To exemplify a gene therapy approach that directly harnesses ambient light as a natural illumination source to induce therapeutic action, we show how intradermal delivery of AAV2 vectors carrying a LIRP-regulated gene switch controlling murine thymic stromal lymphopoietin expression was effective in enabling light-dependent prevention and treatment of diet-induced obesity. To describe another therapeutic scenario, we engineered AAV2 vectors for LIRP-dependent expression of Vascular endothelial growth factor (VEGF) inhibitors for the treatment of retinal neovascular diseases. Upon intravitreal delivery into mice suffering from wet macular degeneration, VEGF inhibitors were constantly produced when animals were exposed to daylight, but therapeutic actions could be flexibly interrupted either by exposure to dark environments or by administration of a selective blue light filter at any point in time. When compared to conventional treatment strategies based on constitutive VEGF inhibition over the course of 3 months, we show that a regulated gene therapy approach through LIRP-dependent optogenetics was advantageous in maintaining a normal retina thickness. This work not only provides a valuable addition to the optogenetic toolbox but also offers a perspective to translate light-dependent gene switches toward therapeutic usage.}, }
@article {pmid41957251, year = {2026}, author = {Koh, A and Staurenghi, G and Chhablani, J and Panos, GD and Tan, CS and Yamaguchi, TCN and Empeslidis, T}, title = {Long-Term Management of Polypoidal Choroidal Vasculopathy: A Narrative Review.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41957251}, issn = {2193-8245}, abstract = {Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular age-related macular degeneration (nAMD), characterised by polypoidal lesions. Prevalence data indicate that PCV is more common in people of Asian ethnicity, although it also occurs in non-Asian individuals. However, because of a lack of globally agreed diagnostic criteria and routine screening programmes, PCV is likely to be under-diagnosed in some populations. Recent consensus suggests that PCV is a form of type 1 macular neovascularisation and should be classified as a subtype of nAMD. Anti-vascular endothelial growth factor (VEGF) monotherapy has demonstrated short-term efficacy in terms of visual acuity in PCV, and outcomes may be further improved by combining anti-VEGF therapy with photodynamic therapy. However, data on the long-term (≥ 5 years) efficacy of these treatments are limited and often conflicting. Although some people with PCV can achieve long-term remission following initial treatment (21.7-51.5%), eventual lesion reactivation is reported for approximately four-fifths of patients (81.3%). The socioeconomic impact of long-term PCV management could be reduced by identifying and characterising the subpopulations least likely to require chronic treatment. Large, global, randomised, placebo-controlled studies with long-term follow-up periods are needed in addition to real-world evidence to allow clinicians to reliably stratify people with PCV and support the stopping of anti-VEGF therapy in people at low risk of disease reactivation.}, }
@article {pmid41948241, year = {2026}, author = {Neupane, R and Rance, J and McKenna, T and Kesselman, MM}, title = {Effects of Metformin on Mitochondrial Health and Oxidative Stress in Age-Related Macular Degeneration: A Systematic Review.}, journal = {Cureus}, volume = {18}, number = {3}, pages = {e104820}, pmid = {41948241}, issn = {2168-8184}, abstract = {Age-related macular degeneration (AMD) is a chronic, progressive condition and a leading cause of irreversible central vision loss in older patients. It is driven by oxidative stress, mitochondrial dysfunction, chronic inflammation, and degeneration of retinal pigment epithelium (RPE) cells. Current AMD treatments include lifestyle modifications, nutritional supplements, and/or anti-vascular endothelial growth factor therapies and primarily aim to slow disease progression. As a result, interest has grown in repurposing established medications with potential cytoprotective properties. Metformin, a widely-used anti-diabetic agent, has been proposed as a candidate due to its anti-inflammatory and mitochondrial-modulating effects. We conducted a systematic review to identify studies published between January 2015 and November 2025 that evaluate metformin therapy in (1) adults with AMD and (2) experimental retinal models designed to replicate AMD-related degeneration or pathogenesis. Comparators included individuals with AMD who were not taking metformin therapy, were untreated, and/or were given standard treatment therapy. Outcomes of interest included in the review focused on clinical endpoints of AMD incidence and severity and mechanistic endpoints of mitochondrial function, oxidative stress markers, and cellular senescence. This systematic review includes evidence from epidemiologic, clinical, and experimental studies to link molecular mechanisms with observed disease progression. A total of 10 studies published met the inclusion criteria and demonstrated that metformin is associated with cytoprotective effects in RPE cells by reducing oxidative stress (ROS) and upregulating antioxidant enzymes through activation of the Nrf2 pathway. The drug was also shown to preserve mitochondrial function via activation of AMP-activated protein kinase by enhancing mitophagy, supporting DNA repair, and promoting mitochondrial biogenesis. Observational studies suggested that metformin use was associated with a lower risk of AMD development, particularly dry AMD, with stronger associations observed with a longer duration and higher cumulative exposure. However, findings were context-dependent. Under certain stress conditions, such as sodium iodate exposure, metformin-mediated inhibition of mitochondrial complex I appeared to increase oxidative stress, highlighting a potential "double-edged" effect. Overall, current preclinical and observational studies suggest a possible association between metformin use and mitochondrial modulation in AMD. Prospective studies are needed to clarify dosing, safety, and therapeutic relevance before clinical recommendations can be made.}, }
@article {pmid41948417, year = {2026}, author = {Takebayashi, K and Iemura, Y and Yamauchi, M and Hara, K and Tsuchiya, T and Machida, S and Hashimoto, K}, title = {Acute onset of neovascular age-related macular degeneration after initiation of tirzepatide.}, journal = {Diabetology international}, volume = {17}, number = {2}, pages = {37}, pmid = {41948417}, issn = {2190-1678}, abstract = {Recent retrospective cohort studies showed that use of glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) increased the incident risk of diabetic retinopathy and nonarteritic anterior ischemic optic neuropathy (NAION). Furthermore, it was recently reported that use of GLP-1RAs for more than 6 months increased the risk of neovascular age-related macular degeneration (nAMD) by about twofold, although the association between a gastric inhibitory polypeptide (GIP)/GLP-1 receptor dual agonist (GIP/GLP-1RA) and nAMD is not clearly established. We describe the case of a middle-aged male patient with type 2 diabetes without apparent diabetic retinopathy. Due to poor glycemic control, tirzepatide (a GIP/GLP-1RA) was started instead of sitagliptin (a dipeptidyl peptidase-4 inhibitor). After switching from sitagliptin to tirzepatide, glycemic control rapidly improved, but the patient felt haziness with distortion of the central part of the left eye. A diagnosis of neovascular age-related degeneration (nAMD) was made by ophthalmologists in our hospital. The basis for the possible association of tirzepatide administration with onset of nAMD is unknown. However, clinicians should pay attention to potential visual impairments after achieving acute glycemic control with incretin-related drugs, including tirzepatide.}, }
@article {pmid41943786, year = {2026}, author = {Aldaher, KE and Azmeh, A and Wehby, B and Alhalabi, N}, title = {Retinal Angiomatous Proliferation and Pachychoroid: A Case Report.}, journal = {Cureus}, volume = {18}, number = {3}, pages = {e104749}, pmid = {41943786}, issn = {2168-8184}, abstract = {Retinal angiomatous proliferation (RAP), also known as type 3 macular neovascularization (MNV), is a distinct and less common subtype of neovascular age-related macular degeneration (nAMD). This condition is typically associated with a thinner subfoveal choroid than in age-matched control eyes. However, the coexistence of RAP and pachychoroid, which is characterized by increased choroidal thickness and choriocapillaris attenuation, is rarely documented in the literature. In this report, we present the case of a 56-year-old male patient diagnosed with RAP in conjunction with pachychoroid. This case highlights the importance of multimodal imaging techniques, including optical coherence tomography (OCT), fluorescein angiography (FA), and optical coherence tomography angiography (OCT-A), to achieve a comprehensive assessment. Additionally, we emphasize the need for a thorough differential diagnosis to accurately identify and manage such overlapping retinal disorders. We hypothesize that choroidal ischemia secondary to compression of choriocapillaris by choroidal pachyvessels led to outer retinal ischemia and upregulation of vascular endothelial growth factor (VEGF), which caused RAP formation starting at the level of retinal superficial and deep capillary plexus and extended to the outer retina. Thus, our hypothesis supports that choriocapillaris atrophy is a common pathology between these two entities and may explain their coexistence.}, }
@article {pmid41944257, year = {2026}, author = {Alshaikhsalama, A and Thompson, K and Hashim, H and Patel, KG}, title = {Analyzing the association between age-related macular degeneration, retinal vascular occlusions, and dementia.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261438587}, doi = {10.1177/11206721261438587}, pmid = {41944257}, issn = {1724-6016}, abstract = {PurposeTo investigate the association between age-related macular degeneration (AMD), retinal artery occlusion (RAO), and retinal vein occlusion (RVO) and the future development of Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia (ACD).MethodsRetrospective propensity score-matched cohort study using TriNetX, a confederated healthcare network. The study population included 91,296 AMD, 15,372 RAO, 35,862 RVO, and 3,076,291 population control (PC) patients aged 65 and older. Propensity score matching was applied to control for baseline demographics and health characteristics. The primary outcome was the measured risk of developing AD, VaD, and ACD following incident diagnosis of AMD, RAO, or RVO.Major FindingsAMD was associated with a significantly elevated risk of AD (HR, 1.25; 95% CI, 1.17-1.34; P < 0.001), VaD (HR, 1.20; 95% CI, 1.11-1.31; P < 0.001), and ACD (HR, 1.12; 95% CI, 1.08-1.16; P < 0.001) following diagnosis with an average follow up of 45.0 ± 36.7 months. RVO patients also displayed higher risks across all dementia types (AD: HR, 1.46; 95% CI, 1.22-1.74; P < 0.001; VaD: HR, 1.51; 95% CI, 1.23-1.87; P < 0.001; ACD: HR, 1.34; 95% CI, 1.22-1.47; P < 0.001) with an average follow up of 46.6 ± 37.9 months.ConclusionsRetinal disease diagnoses may correlate with increased dementia risk. While AMD and RVO are associated with all dementias (AD, VaD, and ACD), RAO did not increase dementia risk.}, }
@article {pmid41944542, year = {2026}, author = {Francis, JH and Abramson, DH}, title = {Ocular Glymphatic System: Its Modulation and Role in Intraocular Tumors.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {11}, doi = {10.1167/iovs.67.4.11}, pmid = {41944542}, issn = {1552-5783}, mesh = {Humans ; *Glymphatic System/physiology/physiopathology ; *Eye Neoplasms/physiopathology ; Animals ; Glaucoma/physiopathology ; }, abstract = {The glymphatic system is a glial-based perivascular network that clears metabolic waste from the central nervous system (CNS), and its dysfunction is related to neurodegenerative disease. This review describes a correlate ocular glymphatic system in the eye and describes how this might relate to ophthalmic diseases. This review article summarizes the published literature on the CNS and ophthalmic glymphatic system and how its dysfunction relates to disease. There are associations in the pathogenesis among neurodegeneration, glaucoma, and age-related macular degeneration (AMD), which could be explained through glymphatic dysfunction in the CNS and eye, respectively. The protective effects of exercise and sleep further demonstrate associations among neurodegeneration, glaucoma, and AMD. We provide new insights on the role of the glymphatic system and intraocular tumors, proposing that tumors may hijack the glymphatic system as a bidirectional pathway of communication between the eye and the brain. New therapies for enhancing CNS glymphatic flow are discussed. Dysfunction of the glymphatic system may be a unifying pathogenesis among neurodegeneration, glaucoma, and AMD. Future research should analyze whether CNS-focused therapeutics may improve ocular disease. The role of the glymphatic system in the pathogenesis of intraocular tumors warrants further investigation.}, }
@article {pmid41944612, year = {2026}, author = {Jacob, N and Chhablani, J and Chandra Behera, U and Narayanan, R and Sahoo, NK}, title = {Large and medium choroidal vessel remodelling in progressive age-related macular degeneration and polypoidal choroidal vasculopathy.}, journal = {Retinal cases &amp; brief reports}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICB.0000000000001925}, pmid = {41944612}, issn = {1937-1578}, abstract = {PURPOSE: To describe the long-term follow-up of large and medium-sized choroidal vessels in eyes with age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV).<br><br>METHODS: This was a retrospective, observational analysis of eyes with AMD or PCV, with a minimum of five years of follow-up of indocyanine green angiography (ICGA). Qualitative analysis of the choroidal vessels was carried out at baseline until the final visit.<br><br>RESULTS: We analysed ten eyes of five patients diagnosed with either AMD or PCV with a follow-up duration ranging from seven to sixteen years. Eyes with active disease received various treatment modalities. On serial follow-up of ICGA images, remodelling of medium and large choroidal vessels was seen. The changes included large choroidal vessel attenuation, prominence/ dilatation of pre-existing choroidal vessels connecting the neovascular complex and formation of new anastomotic channels. These changes appeared adjacent to present or future neovascular complex locations. One uninvolved fellow eye showed minimal changes on follow-up.<br><br>CONCLUSION: We report the long-term changes in large and medium-sized choroidal vessels in eyes with AMD and PCV with serial ICGA images. These vascular alterations suggest the possible role played by these vessels in the pathogenesis of choroidal neovascular complexes.}, }
@article {pmid41937714, year = {2026}, author = {Samman, M and Khan, H and Aziz, AA and Patel, R and Khanani, AM}, title = {An update on the port delivery system with ranibizumab for retinal diseases.}, journal = {Expert opinion on drug delivery}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/17425247.2026.2652029}, pmid = {41937714}, issn = {1744-7593}, abstract = {INTRODUCTION: Age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME) are among the leading causes of irreversible vision loss globally. Anti-vascular endothelial growth factor (VEGF) therapeutics have revolutionized the treatment and management of retinal vascular diseases. Management of these retinal diseases is highly individualized, with treatment intervals ranging from 4 to 16 weeks. The port-delivery system (PDS) with ranibizumab is a refillable implant that has demonstrated safety and efficacy while also improving treatment burden by decreasing the need for frequent injections.<br><br>AREAS COVERED: Multiple FDA-approved therapeutics are available to physicians for treating and managing retinal diseases. The ultimate goal is to achieve optimal visual and anatomic outcomes while also ensuring individualized treatment. A literature search was conducted across PubMed, Google Scholar, and pharmaceutical companies' websites from 2005 to December 2025 to review clinical data, highlight the utility of the PDS, and detail the improved structure following the voluntary class III recall.<br><br>EXPERT OPINION: The PDS provides a medium to maintain treatment of retinal vascular disease over an extended period of time. Although physicians may feel hesitant to implant the device, refinements in surgical technique and the refill-exchange procedure, along with improvements to the device, may encourage more clinical uptake of PDS in appropriate patients.}, }
@article {pmid41939091, year = {2026}, author = {Hossain, B and Rahmatullah, S and Ahmed, T}, title = {Efficacy of brolucizumab and ranibizumab in diabetic macular edema and neovascular age-related macular degeneration: insights from a case series.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {4}, pages = {2477-2483}, pmid = {41939091}, issn = {2049-0801}, abstract = {BACKGROUND: The effectiveness of various anti-vascular endothelial growth factors in treating patients with diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) in Bangladesh lacks comprehensive information.<br><br>OBJECTIVE: We evaluated the efficacy of brolucizumab and ranibizumab and assessed the incidence of drug-related adverse events in nAMD and DME patients of Bangladesh.<br><br>METHODS: In this retrospective case series, 20 patients who had received either intravitreal brolucizumab (n&#xa0;=&#xa0;10) or ranibizumab (n&#xa0;=&#xa0;10) were included. Demographic and clinical characteristics, data on best-corrected visual acuity (BCVA), and optical coherence tomography (OCT) measurements, including macular volume (MV) and central subfield retinal thickness (CSRT), were recorded for each patient at baseline and follow-up visits. In addition, brolucizumab was compared with ranibizumab in terms of above mentioned parameters.<br><br>RESULTS: Both brolucizumab and ranibizumab induced changes in patient parameters, including BCVA, OCT measurements, and MV, relative to baseline values. At the 12-week follow-up, neither drug demonstrated statistically significant superiority over the other (P > 0.05 in all cases). However, over the course of treatment, the mean BCVA showed a significant improvement following the initiation of brolucizumab therapy (P =&#xa0;0.042). In terms of OCT findings, the mean CSRT significantly decreased from 508.5&#xa0;&#xb1;&#xa0;101.1&#xa0;&#xb5;m at baseline to 241&#xa0;&#xb1;&#xa0;40.4&#xa0;&#xb5;m at week 12, while the mean MV was significantly reduced from 10.3&#xa0;&#xb1;&#xa0;1.0 mm[3] to 8.2&#xa0;&#xb1;&#xa0;1.6 mm[3] (P < 0.05).<br><br>CONCLUSION: Intravitreal brolucizumab appeared to be an effective option for patients with nAMD and DME.}, }
@article {pmid41941161, year = {2026}, author = {Yuan, R and Zhang, Y and Liu, Z and Xu, P and Li, K}, title = {A Study of the Causal Association Between Autoimmune Diseases and Blinding Eye Diseases.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673409616260128140543}, pmid = {41941161}, issn = {1875-533X}, abstract = {INTRODUCTION: Autoimmune diseases (ADs) are known to affect multiple organs, including the eyes. This study aims to evaluate the causal associations of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) with cataracts, age-related macular degeneration (AMD), and glaucoma using Mendelian randomization (MR).<br><br>METHODS: Genome-wide association study (GWAS) data were utilized to identify single- nucleotide polymorphisms (SNPs) strongly associated with AS, SLE, RA, cataracts, AMD, and glaucoma, which served as instrumental variables (IVs). The basic analysis was performed via inverse variance weighting (IVW), complemented by weighted median (WM), MR-Egger regression, weighted mode, simple mode, and MR-Robust Adjusted contour scoring technique (RAPS). The Cochran Q test, MR-Egger intercept test, MR-Steiger test, leave-one-out analysis, funnel plot, and MR-PRESSO model were used to assess the robustness of doing sensitivity analysis.<br><br>RESULT: IVW estimated that primary angle-closure glaucoma (PACG) (OR=1.265), AMD (OR=1.063), DRY-AMD (OR=1.088), and cataracts were significantly related to RA. SLE is associated with drug-induced cataract (OR=1.113) and senile cataract (OR=1.012). AS is being linked with glaucoma (OR=1.265), PACG (OR=2.436), and primary open-angle glaucoma (POAG) (OR=1.400).<br><br>DISCUSSION: RA, SLE, and AS can directly contribute to the development of cataracts, AMD, and glaucoma. These results endorse the interdisciplinary interventions approach that can incorporate rheumatology and ophthalmology. All investigations were restricted to individuals of European descent. These findings should be verified and expanded by performing multi-ethnic studies.<br><br>CONCLUSION: The study is generally reliable in establishing the causal relationship between AS, SLE, RA, and selective blinding eye illnesses, with the rationale of applying clinical screening techniques and specific intervention strategies.}, }
@article {pmid41941273, year = {2026}, author = {Park, JH and Liu, RJY and Sun, X and Mahalingan, KK and Hiriyanna, S and Li, T and Roll-Mecak, A}, title = {Insights into retinal disease and non-tubulin glutamylation from a RPGR-TTLL5 complex structure.}, journal = {The Journal of cell biology}, volume = {225}, number = {6}, pages = {}, doi = {10.1083/jcb.202508020}, pmid = {41941273}, issn = {1540-8140}, support = {ZIAEY000490/NH/NIH HHS/United States ; 1ZIANS003163/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Animals ; *Eye Proteins/metabolism/chemistry/genetics ; Mice ; Crystallography, X-Ray ; Mutation ; *Retinitis Pigmentosa/genetics/metabolism ; *Peptide Synthases/metabolism/chemistry/genetics ; Protein Binding ; Models, Molecular ; Tubulin/metabolism ; }, abstract = {Mutations in retinitis pigmentosa GTPase regulator (RPGR) cause photoreceptor degeneration, vision loss, and eventual blindness. RPGR function requires glutamylation by tubulin tyrosine ligase-like 5 (TTLL5) whose mutation is also linked to severe forms of retinal degeneration. How TTLL5 targets RPGR and how mutations in either protein cause disease are unknown. Here we report the 2.8-Å X-ray crystal structure of the coactivator interacting domain (CID) of human TTLL5 in complex with the RPGR C terminus, both required for glutamylation. The RPGR C terminus forms a helix that intercalates through aromatic interactions into the CID helical bundle of novel fold. Interfacial residues are mutated in retinitis pigmentosa, as well as macular degeneration of unknown etiology. Key mutations at this interface abolish RPGR-TTLL5 interaction in vitro and RPGR glutamylation in mouse photoreceptors. Our work reveals mechanisms of non-tubulin substrate recognition by TTLL glutamylases, increasingly recognized as broad regulators of the proteome, and sheds light on mechanisms of disease associated with TTLL5 and RPGR mutations.}, }
@article {pmid41941952, year = {2026}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {Can Gene Therapy Revolutionize Treatment of Neovascular Age-Related Macular Degeneration.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.04.001}, pmid = {41941952}, issn = {1879-1891}, abstract = {TOPIC: This systematic review and meta-analysis (PROSPERO: CRD42024619992) evaluated whether gene therapy provides safe and clinically meaningful efficacy for patients with neovascular age-related macular degeneration (nAMD). The clinical question addressed outcomes in patients with nAMD receiving gene therapy (primarily adeno-associated virus-based anti-VEGF constructs) compared with baseline or standard care contexts, focusing on visual acuity, anatomical response, treatment burden, and safety. Anti-VEGF intravitreal injections remain the current standard of care but require frequent administration and long-term adherence.<br><br>CLINICAL RELEVANCE: nAMD is a major cause of irreversible vision loss in older adults and imposes substantial treatment burden due to repeated injections. Gene therapy aims to achieve sustained intraocular therapeutic protein expression after a single or infrequent administration, potentially reducing injection frequency while maintaining disease control. Establishing safety and functional efficacy is critical before translation into routine retinal practice.<br><br>METHODS: Following PRISMA guidelines, databases (PubMed, Embase, Scopus, Web of Science, Google Scholar, and Cochrane Library) were searched from inception to February 1, 2026. Eligible studies were prospective interventional clinical trials evaluating gene therapy in nAMD, including randomized and early-phase dose-escalation designs. Primary outcomes included best-corrected visual acuity (BCVA), central subfield thickness (CST), rescue anti-VEGF requirement, mortality, and adverse events. Risk of bias was assessed using RoB 2 and ROBINS-I tools. Multilevel random-effects meta-analyses using restricted maximum likelihood accounted for clustering of multi-arm cohorts.<br><br>RESULTS: Eight trials (7 randomized, 1 nonrandomized) comprising 203 treated participants were included. Multilevel REML analysis showed no significant pooled BCVA improvement (MD 0.54 letters; 95% CI -7.38 to 8.46) despite favorable fixed-effect estimates. CST demonstrated significant anatomical reduction (MD 37.13 &#xb5;m; 95% CI 26.63-47.62). Approximately 44% of eyes required rescue anti-VEGF injections. Safety outcomes demonstrated generally low-to-moderate event probabilities: mortality approximately 8%, serious adverse events approximately 21-38%, inflammation approximately 20%, and retinal hemorrhage approximately 12%, with negligible heterogeneity across most endpoints. Publication bias was detected for BCVA and CST but was minimal for safety outcomes.<br><br>CONCLUSION: Gene therapy for nAMD demonstrates encouraging safety and anatomical efficacy signals but lacks consistent functional visual improvement. Current evidence supports a treatment-burden-reducing adjunctive role rather than replacement of anti-VEGF therapy. Evidence strength is limited by early-phase designs, small sample sizes, and clinical heterogeneity; ongoing phase 3 trials are required to define long-term efficacy and clinical positioning.}, }
@article {pmid41943094, year = {2026}, author = {Jorge, R and Rego, MGB and Zupelli, AS and Calado, RT}, title = {Off-label intravitreal eculizumab for geographic atrophy: report of the first two cases.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {}, pmid = {41943094}, issn = {2056-9920}, }
@article {pmid41934603, year = {2026}, author = {Friedman, SM and Xu, Y and Sherman, S and Kuznik, A and Mojebi, A and Keeping, S and Chan, K and Leng, T and Patel, N}, title = {Correction: Aflibercept 8 mg versus Faricimab Treat-and-Extend for Diabetic Macular Edema or Neovascular Age-Related Macular Degeneration: A Bayesian Fixed-Effect Network Meta-analysis of Clinical Trials.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s40123-026-01377-2}, pmid = {41934603}, issn = {2193-8245}, }
@article {pmid41934654, year = {2026}, author = {Asanad, S and Boyer, DS}, title = {Gene therapy for wet AMD: a paradigm shift in the standard of care.}, journal = {Expert opinion on emerging drugs}, volume = {}, number = {}, pages = {}, doi = {10.1080/14728214.2026.2651330}, pmid = {41934654}, issn = {1744-7623}, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD), or wet AMD, remains a leading cause of vision loss in older adults. Current standard of care relies on repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, which create significant treatment burdens for patients and healthcare systems. Emerging gene therapies aim to address these challenges by delivering sustained therapeutic effects via single administration.<br><br>AREAS COVERED: Next-generation gene therapies are transforming AMD treatment by enabling sustained, autonomous production of therapeutic proteins within ocular tissues, enabling the eye to synthesize its own anti-VEGF agents. A comprehensive literature search was performed using both PubMed and ClinicalTrials.gov to identify pertinent manuscripts and clinical trials for this narrative review. Keywords utilized included: Gene therapy, wet AMD, neovascular AMD, Viral Vectors, Adeno-associated viral vectors, Subretinal, Suprachoroidal, and Retinal Pigment Epithelium.<br><br>EXPERT OPINION: Advances in gene therapy for wet AMD may revolutionize treatment by enabling sustained intraocular anti-VEGF protein, reducing frequent injections, improving patient adherence, and potentially lowering long-term healthcare costs. Although promising, challenges including long-term safety, complex delivery procedures, immune responses, regulatory hurdles, and the need for optimized vectors and clinical protocols must be addressed before widespread adoption and integration into standard care.}, }
@article {pmid41935142, year = {2026}, author = {Mehta, H}, title = {Social deprivation in neovascular age-related macular degeneration: when equal treatment does not deliver equal vision.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41935142}, issn = {1476-5454}, }
@article {pmid41935371, year = {2026}, author = {Moftakhar-Bazkiaei, A and Farzaneh, M}, title = {Network-based Transcriptomic Profiling of Fetal Astrocyte Differentiation Reveals Therapeutic Targets for Neurodegenerative Disease.}, journal = {Current molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115665240412373260224061022}, pmid = {41935371}, issn = {1875-5666}, abstract = {INTRODUCTION: Neurodegenerative disorders, including Alzheimer's Disease (AD), Parkinson's Disease (PD), and Age-related Macular Degeneration (AMD), are marked by the progressive loss of specific neuronal populations. Astrocytes, the glial cells surrounding neurons, play a critical role in maintaining neuronal health by providing neurotrophic support, producing antioxidants, and clearing waste. Dysfunctional astrocytes contribute to disease progression, yet their developmental trajectory and molecular regulation remain incompletely understood.<br><br>METHOD: This study aims to computationally characterize transcriptional differences between fetal astrocytes and neural stem cell lines to identify key regulatory genes, pathways, and therapeutic targets relevant to astrocyte-linked neurodegeneration. Using microarray data and bioinformatics pipelines, 359 Differentially Expressed Genes (DEGs) were identified, including 249 upregulated and 110 downregulated transcripts.<br><br>RESULTS: Protein-Protein Interaction (PPI) network analysis revealed ten hub genes- COL1A1, TIMP1, LOX, COL6A1, COL6A3, COL5A1, CD44, LTBP2, ACTA2, and PLAU-central to extracellular matrix remodeling and cell adhesion. Drug-gene interaction analysis linked these genes to compounds such as Estradiol valerate, Retinoic acid, and Calcitriol, suggesting therapeutic relevance.<br><br>DISCUSSION: Enrichment analysis highlighted transcriptional regulation, apoptosis, and ECM-receptor interaction as dominant biological themes. Key miRNA-mRNA interactions, including hsa-miR-877-5p and hsa-miR-767-5p targeting LOX and COL6A3 were also identified.<br><br>CONCLUSION: Overall, this study integrates transcriptomic profiling, network modeling, and drug-gene interaction analysis to uncover astrocyte-specific molecular targets, offering a computational framework for therapeutic exploration in neurodegenerative disease.}, }
@article {pmid41935442, year = {2025}, author = {Chen, KY and Chan, HC and Lin, WW and Chan, CM}, title = {Mitochondrial dynamics and their role in the pathogenesis of age-related macular degeneration: A comprehensive review.}, journal = {Redox biology}, volume = {93}, number = {}, pages = {103976}, doi = {10.1016/j.redox.2025.103976}, pmid = {41935442}, issn = {2213-2317}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly and has a multifactorial etiology involving advanced age, genetic susceptibility, and environmental risk factors. Accumulating evidence suggests that mitochondrial dysfunction is a central pathogenic mechanism in AMD, particularly in the retinal pigment epithelium (RPE). The RPE is critical for retinal homeostasis, and its high metabolic activity renders it vulnerable to age-related mitochondrial dysfunction. In AMD, the core processes of mitochondrial dynamics-fission, fusion, biogenesis, and mitophagy-are profoundly dysregulated, leading to a fragmented and dysfunctional mitochondrial network. This failure of quality control results in bioenergetic deficits, excessive oxidative stress, and the release of damage-associated molecular patterns that fuel chronic inflammation and complement-mediated damage. Experimental models and human tissue studies have strengthened the link between mitochondrial dysfunction and AMD pathology, revealing structural abnormalities, mitochondrial DNA (mtDNA) damage, and altered metabolic signatures. Therapeutic strategies targeting mitochondrial pathways, including mitochondria-targeted antioxidants, dynamic modulators, and enhancers of biogenesis and mitophagy, such as agents that restore defective mitophagosome formation, represent promising avenues for intervention. As the field advances, the integration of biomarker development and personalized approaches holds the potential to transform the clinical landscape of AMD by addressing the root causes of cellular dysfunction.}, }
@article {pmid41936183, year = {2026}, author = {Ju, Y and Lu, H and Liu, S and Chen, X and Ni, N and Su, Y and Liu, Y and Zhang, D and Chen, M and Huang, R and Zhang, J and Xiang, H and Chen, Y and Tang, Z and Gu, P}, title = {Molybdenum-based antioxidative nanomedicine fighting against retinal pigment epithelium degeneration.}, journal = {Biomaterials}, volume = {333}, number = {}, pages = {124192}, doi = {10.1016/j.biomaterials.2026.124192}, pmid = {41936183}, issn = {1878-5905}, abstract = {Oxidative stress-induced retinal pigment epithelium (RPE) degeneration is the pathologic basis of most retinal degenerative diseases, especially dry age-related macular degeneration (AMD), for which corresponding therapeutic strategies currently were still in their infancy and lack optimal efficacy. In the present study, cerium-doped molybdenum-based polyoxometalate (MoCe) nanoclusters (NCs) are designed as antioxidative nanocatalysts to inhibit oxidative stress-induced RPE degeneration and subsequent retinal damage. The synthesized MoCe NCs display prominent reactive oxygen species (ROS) scavenging efficacy with excellent in vivo biocompatibility. In RPE degeneration mice model, a single intravitreal administration of MoCe NCs effectively inhibit RPE oxidative degeneration and substantially protect retinal structure and visual function. Upon high-throughput sequencing combined with bioinformatics analysis, MoCe administration predominantly restores the expression of DNA repair-related genes and inhibits oxidative stress-induced apoptosis by suppressing the JNK/c-Jun signaling pathway. The ideal biocompatibility and remarkable protective effect render MoCe NCs as the promising nanomedicines combating RPE degeneration-associated retinal diseases especially AMD.}, }
@article {pmid41936993, year = {2026}, author = {Lizard, G and Sassi, K and Mackrill, JJ and Ghzaiel, I and Meziane, S and Hassen, E and Abdelkarim, M and Masmoudi-Kouki, O and Ghrairi, T and Brahmi, F and Gargouri, A and Rezig, L and Benkalifa, R and Khallouki, F and El Midaoui, A and Pincemail, J and Atanasov, AG and Vejux, A and Millot, N}, title = {7-ketocholesterol as a theranostic target: potential applications and future perspectives.}, journal = {Chemistry and physics of lipids}, volume = {}, number = {}, pages = {105588}, doi = {10.1016/j.chemphyslip.2026.105588}, pmid = {41936993}, issn = {1873-2941}, abstract = {7-Ketocholesterol (7KC) is mainly formed by cholesterol autoxidation and is a pro-oxidant and pro-inflammatory bioactive lipid that also induces different types of cell death, including oxiapoptophagy. It is frequently associated with major age-related diseases, such as cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease. 7KC can therefore be considered a biomarker for these diseases, offering the possibility of developing theranostic strategies combining diagnosis and treatment. Currently, all the elements are in place to develop tools for the design of theranostic therapies targeting 7KC in diseased organs: antibodies, nanoparticles used as nanoplatforms, molecules that neutralize 7KC such as enzymes which degrade it, as well as natural or synthetic compounds that inhibit the cytotoxic signaling pathways associated with oxidative stress, inflammation and cell death activated by 7KC. Identifying and neutralizing 7KC biological activities using a theranostic approach could also be of interest for growing medical fields such as space medicine widely concerned by oxidative stress, aging and age-related diseases, driven by microgravity. This review supports that most of key tools are now available to develop theranostic treatments targeting 7KC in age-related pathologies, especially in cardiovascular diseases associated with atheroma, but also in age-related macular degeneration and Alzheimer's disease. Discovery of effective treatments for these diseases is a major challenge and will answer an important need for both patients and caregivers.}, }
@article {pmid41937011, year = {2026}, author = {Bagewadi, S and Parameswaran, S and Sethuraman, S and Subramanian, A}, title = {Hyaluronic acid-poly (vinyl alcohol) composite hydrogels with self-assembled peptide nanofibers as Bruch's membrane mimics for age-related macular degeneration treatment.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {151748}, doi = {10.1016/j.ijbiomac.2026.151748}, pmid = {41937011}, issn = {1879-0003}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly, and effective curative therapies are not available. This study presents a tissue-engineering strategy for retinal regeneration using an injectable, in situ-forming hydrogel composed of thiol-functionalized hyaluronic acid (HA-SH) and polyvinyl alcohol (PVA), reinforced with peptide nanofibers. Decellularized Bruch's membrane derived from goat eyes was used as a control and exhibited a fiber diameter of 75.09 ± 12.99 nm, thickness of 6.26 ± 1.12 μm, and hydrophilic properties (contact angle: 39.46° ± 0.46). In comparison, the GAGA-YIGSR-based hydrogel membrane demonstrated comparable structural features with a fiber diameter of 92.38 ± 16.37 nm, a thickness of 13.43 ± 3.64 μm, and a contact angle of 72.13° ± 2.98. The HA-SH/PVA hydrogel incorporating peptide nanofibers significantly enhanced retinal pigment epithelium (RPE) cell viability, adhesion, proliferation, phagocytosis, and RPE-specific gene expression compared to the peptide-free hydrogel. In vivo functional evaluation using H&amp;E-stained retinal sections revealed that the HA-SH/PVA hydrogel containing the GAGA-YIGSR peptide markedly improved RPE cell organization, ONL nuclei density (1578.22 ± 187.03), ONL cell rows (9.02 ± 1.74), linear RPE cell count (10.6 ± 2.6), and ONL thickness (35.52 ± 4.44 μm) relative to saline controls. Furthermore, the hydrogel preserved retinal barrier integrity and ultrastructural parameters, including tight-junctions, subretinal pigment epithelium space (7.26 ± 4.92 μm), BM thickness (5.91 ± 1.07 μm), collagen area (21.74 ± 3.48%), collagen thickness (81.8 ± 24.17 μm), and collagen pore area (17.72 ± 9.19%), which were comparable to those of healthy controls. In conclusion, this study successfully developed and evaluated an injectable peptide-functionalized hydrogel as a promising therapeutic scaffold for retinal tissue regeneration in AMD.}, }
@article {pmid41933659, year = {2026}, author = {von der Emde, L and Reiter, GS and Mallwitz, M and Jauch, AS and Wall, K and Holz, FG and Pollreisz, A and Ach, T}, title = {Quantitative fundus autofluorescence in age-related macular degeneration.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.03.018}, pmid = {41933659}, issn = {1879-3304}, abstract = {Fundus autofluorescence captures the fluorescence of the retina, specifically the retinal pigment epithelium (RPE). Within the RPE, fluorophores, including lipofuscin, melanolipofuscin, and melanosomes, fluoresce when excited by light of varying wavelengths. Quantitative fundus autofluorescence (QAF), which has been implemented using blue excitation light, enables mapping and quantifying lipofuscin and melanolipofuscin fluorescence. This is achieved by using a reference bar to standardize measurements. The technical functionality of QAF relies on repeatability and high image quality. Multicenter studies, however, indicate variability. Age-related lens opacities also affect QAF, necessitating individualized correction formulas for accuracy. Accordingly, this review focuses on the development and application of QAF, addressing technical considerations and its relevance to structural and cellular changes in age-related macular degeneration (AMD), and highlighting how QAF can provide clinically meaningful information for AMD diagnosis and therapy monitoring. In AMD, numerous independent studies have found reduced autofluorescence at the posterior pole and as AMD progresses autofluorescence further decreases. Typical AMD lesions, such as subretinal drusenoid deposits, have been associated with significant QAF reduction. On a cellular level, granule aggregation and degranulation are identified as histological correlates. Subcellularly, technologies like serial block-face scanning electron and structured illumination microscopy have revealed a reduced lipofuscin volumetric density and RPE dysmorphia associated with AMD's reduced autofluorescence. New software tools enhance QAF's potential for detailed lesion analysis. Future advancements in QAF include integrating new excitation wavelengths and combining quantified emission spectra and fluorescence lifetimes to improve early detection of AMD-related changes. Despite challenges, QAF continues to evolve, promising better insights into retinal health and disease.}, }
@article {pmid41929012, year = {2026}, author = {Navratil, EM and Liu, X and Wiley, LA and Anderson, MG and Meyer, KJ and Brown, RF and Evans, IA and Taylor, EB and Stone, EM and Tucker, BA and Mullins, RF}, title = {Metabolic Analysis of Human Retinal Pigment Epithelium and Choroid Tissue in Aging and Macular Degeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.24.713982}, pmid = {41929012}, issn = {2692-8205}, abstract = {Age-related macular degeneration is a common ocular disease that causes vision loss in the elderly, with a complex set of risk factors and proposed mechanisms of pathogenesis. A powerful method for investigating changes in disease is metabolomics, by which small molecules can be identified and quantified simultaneously. We report here the metabolic analysis of human RPE-choroid tissue in aging and macular degeneration (AMD), as well as comparisons of human macular and extramacular RPE-choroid and neural retina. Levels of 215 metabolites were determined in young donors, AMD donors (early/intermediate, geographic atrophy, and neovascularization) and age-matched controls. The largest number of metabolite differences were observed between young and healthy aged controls, as opposed to between aged controls and any stage of AMD. Two notable metabolites found to be increased in aging choroids are trimethylamine N-oxide and uric acid, both of which were significant after Bonferroni correction. A mouse endothelial cell line treated with a high concentration of uric acid exhibited reduced migration in a wound closure assay. This study provides initial insights into the metabolome of human choroids in varying states of age and macular degeneration, as well as functional implications of these changes in the aging choroid.}, }
@article {pmid41929144, year = {2026}, author = {Mir, HA and Mahesh, G and Palanimuthu, A and Cioffi, CL and Petrukhin, K}, title = {Loss of Lamp2a-dependent chaperone-mediated autophagy drives dry AMD-like retinal pathology in mice and is rescued by BK channel activation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.19.712761}, pmid = {41929144}, issn = {2692-8205}, abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in elderly individuals for which no effective treatments are currently available. The photoreceptor loss in dry AMD is secondary to the demise of the retinal pigment epithelium (RPE) cells. The accumulation of extracellular deposits, known as drusen, resulting in part from deficient lysosomal and autophagosomal degradation, is a key feature of dry AMD pathogenesis. Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation pathway that maintains proteostasis by targeting specific cytosolic proteins for lysosomal translocation and degradation. LAMP2A (lysosome-associated membrane protein 2A) functions as the key lysosomal receptor required for CMA. Using Lamp2a knockout mouse, we show that selective CMA dysfunction recapitulates AMD-like pathologies, including sub-RPE lipid and protein deposits, RPE atrophy, Bruch's membrane thickening, and impaired autophagic activity. Furthermore, we identify large-conductance Ca[2+]-activated K[+] (BK) channels as a therapeutic target for restoring autophagic activity. Mechanistically, pharmacological activation of BK channels with the small-molecule agonist GLA-1-1 enhances macroautophagy and stimulates autophagic flux by promoting autophagosome-lysosome fusion. Importantly, oral administration of GLA-1-1 in markedly attenuates structural, functional, and molecular retinal abnormalities in Lamp2a -deficient mice, suggesting that pharmacological activation of macroautophagy through facilitating autophagosome-lysosome fusion can partially compensate for CMA deficiency. Together, these findings demonstrate that pharmacological activation of macroautophagy can ameliorate the retinal phenotype resulting from CMA dysfunction and support BK channel activation by GLA-1-1 as a promising therapeutic strategy for dry AMD.}, }
@article {pmid41929345, year = {2026}, author = {Chau, K and Allison, K and Braithwaite, T and Harley, ITW and Hassman, LM}, title = {Genomic network analysis links uveitis with systemic inflammatory diseases.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.24.26349228}, pmid = {41929345}, abstract = {OBJECTIVE: To determine whether uveitis shares genetic similarity with extraocular immune-mediated inflammatory diseases (IMIDs), we performed network analysis of putative causal genes associated with ocular inflammatory disease, IMIDs and eye-specific diseases, including age-related macular degeneration and monogenic disorders.<br><br>METHODS: We identified putative causal genes for genome-wide significance variants from uveitis, IMIDs and ocular diseases using OpenTargets and published studies. To assess the gene-level pleiotropy between disease groups, we quantified the causal gene overlap between groups, and the Jaccard Similarity Indices for individual disease pairs. We then used a network approach to assess the molecular genetic similarity between diseases at a biological pathway level and comparative statistics to identify diseases with greater network similarity to uveitis.<br><br>RESULTS: Seventy-five percent of the putative causal genes for uveitis are also causal for IMIDs, while no uveitis genes are shared with primary ocular disorders. Network analysis revealed that 1) uveitis genes are more closely networked with systemic IMIDs disease genes than with ocular-specific disease genes; and 2) significant network similarity links uveitis and specific IMIDs, such as ankylosing spondylitis and sarcoidosis.<br><br>CONCLUSIONS: Overlapping causal genes and network similarity indicate that uveitis is predominantly an inflammatory disease, sharing genetic architecture with other IMIDs. Future studies aimed at dissecting genetic heterogeneity within uveitis may determine whether subgroups share common immune pathways that could nominate endotype-specific therapeutic approaches.}, }
@article {pmid41931001, year = {2026}, author = {Easton, CA and Wilmarth, PA and Criss, M and Kim, K and Reddy, AP and Tanne, S and Boone, JQ and Tran, KD}, title = {Comparison of Transcript and Protein Abundance in Human Donor Retinas Support Extending Postmortem Interval From 12 to 18 Hours to Expand the Donor Pool for Biomedical Research.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {9}, doi = {10.1167/iovs.67.4.9}, pmid = {41931001}, issn = {1552-5783}, mesh = {Humans ; *Tissue Donors ; Proteomics/methods ; *Retina/metabolism ; Female ; *Eye Proteins/genetics/metabolism ; Middle Aged ; Male ; Aged ; *Biomedical Research ; *Postmortem Changes ; Adult ; Tandem Mass Spectrometry ; Time Factors ; Organ Preservation/methods ; *RNA, Messenger/genetics ; }, abstract = {PURPOSE: To evaluate whether extending the postmortem interval (PMI) from 12 to 18 hours affects transcript and protein abundances in the human retina.<br><br>METHODS: Donor eyes were recovered from postmortem donors (n = 7 pairs) and stored at 2&#xb0;C-8&#xb0;C. Only donor eyes with ocular cooling within eight hours of death were examined. The OD retina was preserved at 12 hours and the OS retina at 18 hours postmortem. Retinas were flash frozen with liquid nitrogen. The macular region superior to the fovea was used for RNA sequencing (RNA-seq), whereas the inferior region was processed for tandem mass tag (TMT) quantitative proteomics. RNA library preparations were performed simultaneously, and the sequencing of all samples were conducted on the same chip. Proteins were isolated and labeled with 16-plex TMTPro isobaric tags, and all samples were analyzed in a 20-fraction TMT-mass spectrometry experiment. RNA-seq data were processed using DESeq2 (Bioconductor) and proteomic data were analyzed using the previously published PAW pipeline.<br><br>RESULTS: RNA-seq identified 22,446 transcripts, with only five transcripts showing significant differential expression (adjusted P < 0.1 and a Log2FoldChange > 1) between 12 and 18 hours. No enriched pathways were associated with these changes. Proteomic analysis identified 6,109 proteins, with no significant differences in abundance (all adjusted P > 0.05). Retinal cell-type specific markers and markers relevant for disease research, such as age-related macular degeneration and glaucoma, remained stable across both time points.<br><br>CONCLUSIONS: Extending the PMI cutoff from 12 to 18 hours did not significantly impact transcriptomic or proteomic integrity in human donor retinas. This PMI extension greatly increases the availability of donor eyes for biomedical research.}, }
@article {pmid41932376, year = {2026}, author = {Cui, X and Hui, J and Han, Q}, title = {Traffic Noise, Air Pollution, and Greenness in Relation to Age-Related Macular Degeneration: Evidence from a Cross-National Cohort Study.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {}, number = {}, pages = {128042}, doi = {10.1016/j.envpol.2026.128042}, pmid = {41932376}, issn = {1873-6424}, abstract = {Age-related macular degeneration (AMD) is influenced not only by biological factors but also by the broader urban environment, yet evidence integrating multiple environmental exposures remains limited. We examined the associations of residential road traffic noise, fine particulate air pollution (PM2.5), and green space with AMD risk using data from the UK Biobank (207,859 controls and 5,571 incident AMD cases) and an independent hospital-based cohort from Tianjin, China (286 controls and 233 cases). Environmental exposures were assessed using harmonized metrics, and associations were estimated using Cox proportional hazards models in the UK Biobank and multivariable logistic regression in the Tianjin cohort. Restricted cubic splines were applied to evaluate non-linear exposure-response relationships, and joint exposure analyses assessed combined environmental effects. Higher levels of Lden, Lnight, and PM2.5 were consistently associated with increased AMD risk, whereas greater residential green space was associated with lower risk across both cohorts. Non-linear analyses revealed steep risk increases at moderate-to-high noise and PM2.5 levels and a J-shaped association for green space. Individuals exposed to both high noise and high PM2.5 exhibited the greatest risk. Feature selection using Boruta and LASSO identified environmental exposures alongside age, C-reactive protein, and HbA1c as key predictors. Machine-learning models integrating environmental exposures with inflammatory and metabolic biomarkers achieved good discrimination (XGBoost AUC = 0.81). Quantile g-computation further indicated that the combined burden of urban environmental exposures was strongly associated with AMD risk, with traffic noise contributing the largest share of the mixture effect. These findings suggest that traffic noise and air pollution are important, potentially modifiable environmental risk factors for AMD, while residential green space may help mitigate risk.}, }
@article {pmid41932381, year = {2026}, author = {Hjæresen, S and Gramkow, ET and Zhang, M and Svenningsen, &#xc5;F}, title = {HTRA1 and Brain Disorders: A Balancing Act Across Neurodegeneration and Repair.}, journal = {Progress in neurobiology}, volume = {}, number = {}, pages = {102914}, doi = {10.1016/j.pneurobio.2026.102914}, pmid = {41932381}, issn = {1873-5118}, abstract = {High temperature requirement protein A1 (HTRA1) is a trypsin-like serine protease increasingly recognized as a central regulator of brain homeostasis. HTRA1 is broadly expressed in the brain, where it regulates proteostasis, extracellular matrix (ECM) remodeling, and important signaling pathways such as: TGF-β, Wnt, and Notch. These functions are essential for maintaining blood-brain barrier integrity, supporting tissue repair, and restraining inflammation. HTRA1 is a double-edged sword, as both insufficient and excessive activity can lead to neurodegenerative and vascular pathology. Reduced HTRA1 levels are linked to ECM accumulation and vascular fibrosis, while elevated activity contributes to tissue breakdown, inflammation, and impaired repair. This dual role is implicated in a range of disorders, including cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, small vessel disease, age-related macular degeneration, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. We review recent insights into HTRA1's interactions with ApoE and tau, its roles in lipid and cytoskeletal regulation, and its modulation by inhibitors such as: Macrophage Migration Inhibitory Factor. Finally, we explore its biomarker potential and therapeutic targeting strategies. Understanding the mechanisms behind HTRA1's shift from protective to pathological is crucial for developing targeted therapies that preserve its beneficial roles.}, }
@article {pmid41736120, year = {2026}, author = {Xiang, Y and Zuo, G and He, X and Wang, K and Zhu, Y and Cheng, S}, title = {Therapeutic potential of mesenchymal stem cells in ocular degenerative disorders.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41736120}, issn = {1479-5876}, abstract = {BACKGROUND: Mesenchymal stem cells (MSCs), with their regenerative, anti‑inflammatory, and immunomodulatory properties, represent a promising therapeutic strategy for degenerative retinal diseases. Current treatments fail to address core pathologies-such as inflammation, oxidative stress, and apoptosis-in conditions including diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and glaucoma, underscoring the need for regenerative approaches.<br><br>METHODS: This review summarizes the signaling pathways through which MSCs and their exosomes promote tissue repair and neuroprotection in ocular disorders. It evaluates published preclinical and clinical data to outline the current therapeutic applications, efficacy, and safety profiles of MSC-based therapies in ophthalmology.<br><br>RESULTS: MSC-based interventions show potential in alleviating key pathogenic processes in retinal degeneration. Clinical trials indicate their ability to reduce inflammation, oxidative stress, and apoptotic cell death, thereby supporting retinal cell survival and function. These benefits are primarily mediated through paracrine signaling via extracellular vesicles such as exosomes.<br><br>CONCLUSION: MSCs constitute a significant advance toward retinal repair and functional restoration. However, translation of these findings is hindered by the lack of standardized and regulated treatment protocols. Future efforts should focus on establishing optimized delivery methods, safety standards, and a deeper understanding of molecular mechanisms to bridge the gap between promising experimental outcomes and reliable clinical application.}, }
@article {pmid41924198, year = {2026}, author = {Mizuma, R and Mizuki, Y and Kamata, A and Onishi, J and Sakono, T and Suzuki, M and Mizuki, N}, title = {One-Year Real-World Outcomes of Intravitreal Aflibercept 8 mg for Neovascular Age-Related Macular Degeneration in Japan: A Multicenter Retrospective Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {596218}, pmid = {41924198}, issn = {1177-5467}, abstract = {BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has improved outcomes in neovascular age-related macular degeneration (nAMD), but treatment burden remains substantial in real-world practice. High-dose aflibercept 8 mg was developed to extend dosing intervals; however, one-year real-world evidence in Japanese patients is limited.<br><br>OBJECTIVE: To evaluate one-year real-world efficacy, durability, and safety of aflibercept 8 mg for nAMD in Japan.<br><br>METHODS: This multicenter retrospective study was conducted across five institutions in Japan and included consecutive eyes with nAMD treated with aflibercept 8 mg between April and December 2024 and followed for at least 12 months. Visual acuity (VA; logMAR) and central subfield thickness (CST) were assessed at baseline and follow-up visits. Treatment followed an individualized treat-and-extend approach; 19, 1, and 20 eyes received 1, 2, and 3 loading injections, respectively. Durability was evaluated by comparing pre-switch and 12-month dosing intervals in eyes with paired data.<br><br>RESULTS: Forty eyes (36 patients) were analyzed: 35 previously treated eyes switched to aflibercept 8 mg and 5 treatment-na&#xef;ve eyes. Median baseline VA was 0.155 logMAR and CST was 284&#xa0;&#xb5;m. VA at 12 months did not differ significantly from baseline (Hodges-Lehmann -0.0395 logMAR; 95% CI, -0.111 to 0.0141; p = 0.148), whereas CST decreased significantly (-62.0&#xa0;&#xb5;m; 95% CI, -106 to -32.0; p = 0.000538). Among eyes with paired pre-switch interval data (n = 35), injection intervals increased from 8&#xa0;weeks (IQR, 7-12) to 12&#xa0;weeks (IQR, 8-14) at 12 months (median change +2&#xa0;weeks; p = 0.00471). No ocular or systemic adverse events potentially related to aflibercept 8 mg were observed.<br><br>CONCLUSION: In this Japanese real-world nAMD cohort, significant CST reduction was observed over 12 months, while visual acuity remained stable. Longer dosing intervals were also observed after switching.}, }
@article {pmid41925707, year = {2026}, author = {Allon, G and Sarrabia, G and Goren, L and Moisseiev, E and Segal, O}, title = {Assessing patients who are treated with intravitreal injections by ultra-wide field imaging versus slit lamp biomicroscopy.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261438854}, doi = {10.1177/11206721261438854}, pmid = {41925707}, issn = {1724-6016}, abstract = {PurposeTo evaluate the agreement between a virtual clinic model based on ultra-widefield imaging (UWFI) and spectral-domain optical coherence tomography (SD-OCT) and conventional face-to-face (F2F) slit-lamp fundus examination with SD-OCT for treatment decision-making in patients receiving intravitreal injections.MethodsIn this retrospective masked paired comparative study, consecutive patients receiving intravitreal injections underwent F2F evaluation by a retina specialist using slit-lamp biomicroscopy and SD-OCT. F2F examination was predefined as the reference standard. During the same clinical encounter, UWFI was obtained. A second retina specialist, masked to the clinical findings and decisions, independently reviewed the SD-OCT and UWFI images in a virtual setting and made management decisions.ResultsA total of 426 eyes from 304 patients were included. Of these, 217 eyes (50.94%) had neovascular age-related macular degeneration (NVAMD), 151 (35.45%) diabetic macular edema (DME), and 56 (13.15%) retinal vein occlusion (RVO; 36 branch RVO, 14 central RVO, and 6 hemi-retinal RVO). One eye (0.23%) had myopic choroidal neovascularization (CNV), and one (0.23%) had Sorsby macular dystrophy with CNV.The virtual assessment demonstrated 98.12% agreement with the F2F examination for treatment decisions (Cohen's κ = 0.90; 95% CI, 0.83-0.97). Recognition of NVAMD-associated macular hemorrhages was comparable between modalities. UWFI identified additional cases of neovascularization of the disc (NVD) and neovascularization elsewhere (NVE), all of which were subsequently confirmed on slit-lamp examination. The mean virtual review time was more than twofold shorter than the F2F evaluation (P < 0.001).ConclusionsVirtual assessment using ultra-widefield imaging demonstrated high agreement with F2F slit-lamp examination for treatment decision-making in patients receiving intravitreal injections. This approach may represent an efficient alternative for selected follow-up visits in which anterior segment evaluation is not required.}, }
@article {pmid41925898, year = {2026}, author = {Faiz Turan, M and Ozkaya, A}, title = {Imaging biomarkers associated with visual acuity in central serous chorioretinopathy: a multimodal analysis.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {41925898}, issn = {1573-2630}, mesh = {Humans ; *Central Serous Chorioretinopathy/physiopathology/diagnosis ; *Visual Acuity/physiology ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; *Fluorescein Angiography/methods ; *Multimodal Imaging/methods ; Middle Aged ; Adult ; Fundus Oculi ; Biomarkers ; Indocyanine Green/administration &amp; dosage ; Follow-Up Studies ; Aged ; Macula Lutea/pathology ; }, abstract = {OBJECTIVE: To assess the relationship between best-corrected visual acuity (BCVA) and multimodal imaging findings including optical coherence tomography (OCT), fluorescein angiography (FA), and indocyanine green angiography (ICGA) in patients diagnosed with central serous chorioretinopathy (CSC).<br><br>METHODS AND MATERIALS: We retrospectively analyzed 249 eyes of 164 patients with CSC. OCT parameters included central macular thickness (CMT), neurosensory and pigment epithelial detachments, outer retinal integrity, and degenerative changes. FA and ICGA findings were also evaluated. Associations between multimodal imaging features and BCVA were analyzed.<br><br>RESULTS: BCVA differed significantly among CSC subgroups (p&#x2009;<&#x2009;0.001), with the sequelae group showing the best visual acuity. CMT varied across subgroups (p&#x2009;<&#x2009;0.001) and was negatively correlated with BCVA in the overall cohort, driven primarily by acute cases. Outer retinal alterations on OCT and angiographic markers of disease activity were associated with worse BCVA. In multivariable analysis, intraretinal and/or subretinal hyperreflective dots, cystoid macular degeneration, FA leakage, and choroidal neovascularization remained independent predictors of poorer visual acuity.<br><br>CONCLUSION: Visual acuity in CSC varies across disease subtypes and is associated with distinct OCT, FA, and ICGA features. These findings highlight the value of multimodal imaging in the assessment of visual prognosis and in supporting individualized follow-up and treatment strategies in CSC.}, }
@article {pmid41927600, year = {2026}, author = {Kim, HM and Woo, SJ}, title = {Association between screening duration and treatment outcomes in the clinical trials of ranibizumab and aflibercept for neovascular age-related macular degeneration.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-41200-3}, pmid = {41927600}, issn = {2045-2322}, abstract = {The clinical implications of screening duration prior to treatment initiation in neovascular age-related macular degeneration (nAMD) are not well understood. This post hoc analysis investigated whether screening duration influences treatment outcomes in two multinational phase 3 randomized clinical trials, SB11 (ranibizumab biosimilar) and SB15 (aflibercept biosimilar), comprising a total of 1,152 participants (704 from the SB11 trial and 448 from the SB15 trial) with nAMD. Screening duration was assessed in relation to changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) at weeks 8 and 48. Multiple linear and logistic regression analyses, adjusted for age and baseline BCVA/CST, showed no significant associations between screening duration and either visual or anatomical outcomes at both time points. Linear regression coefficients for screening duration were not statistically significant for BCVA or CST at week 8 (BCVA: B = - 0.058, P = 0.242; CST: B = - 0.050, P = 0.908) or at week 48 (BCVA: B = - 0.015, P = 0.843; CST: B = 0.036, P = 0.930). These findings suggest that a screening period of up to 21 days does not adversely affect treatment efficacy in clinical trial settings and support the clinical feasibility of short pre-treatment delays.}, }
@article {pmid41918827, year = {2026}, author = {Stewart, C and Bhangu, JS and Swarnkar, PK and Rifat, M and Khalid, S and Al-Janabi, A and Awad, MH and Williams, GS}, title = {Real-World Outcomes of Switching to Faricimab in Treatment-Experienced and Resistant Neovascular Age-Related Macular Degeneration: A Single-Centre Retrospective Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {591029}, pmid = {41918827}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate anatomical, functional, and treatment burden outcomes of Faricimab in neovascular age-related macular degeneration (nAMD) patients with persistent disease activity despite prior anti-VEGF therapy.<br><br>PATIENTS AND METHODS: Single-centre retrospective study of 67 eyes switched to Faricimab (November 2022-December 2024). This cohort was unable to be extended beyond 4-6-week intervals on existing anti-VEGF therapy. All patients received three monthly loading doses followed by treat-and-extend regimen. Primary outcomes: central macular thickness (CMT), best-corrected visual acuity (BCVA), macular dryness over eight injections, and treatment interval extension.<br><br>RESULTS: The cohort had received mean 33 (range 10-78) prior anti-VEGF. Baseline mean BCVA was 0.42 logMAR (SD &#xb1; 0.28) and mean CMT was 244.5&#xa0;&#x3bc;m (SD &#xb1; 62.2). Statistically significant CMT reduction occurred by injection 8 (-16.9&#xa0;&#x3bc;m, p=0.0084). Complete macular dryness peaked by the time of third injection (43.3%) then declined to 32.8% at injection 8 (p=0.0089). Visual acuity remained unchanged (p=0.6043) with no correlation to CMT change (p=0.172). Treatment interval extension was achieved in 46.3% of patients (p=0.002). Dryness at injection 3 after switching to Faricimab did not predict treatment extension (p=0.217). Two patients (0.36% of total injections, 2/548) developed sterile intraocular inflammation requiring discontinuation.<br><br>CONCLUSION: Faricimab switching achieves statistically significant but modest anatomical improvement in heavily pretreated nAMD with meaningful treatment burden reduction in 46.3% of eyes. Our analysis revealed treatment burden did not indicate the potential for treatment interval extension.}, }
@article {pmid41918832, year = {2026}, author = {Wang, R and Durrani, AK}, title = {Severe Pancytopenia Secondary to Zinc Toxicity from Age-Related Eye Disease Study Vitamin Supplementation.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261436350}, pmid = {41918832}, issn = {2474-1272}, abstract = {Purpose: To report a case of zinc-induced hypocupremia associated with Age-Related Eye Disease Study 2 supplementation presenting with pancytopenia. Methods: A single case was retrospectively reviewed. Results: An 86-year-old woman taking Age-Related Eye Disease Study 2 supplementation presented to a hematology-oncology clinic with severe fatigue and pancytopenia. Laboratory evaluation demonstrated elevated zinc levels and low copper levels consistent with zinc-induced hypocupremia. Age-Related Eye Disease Study supplementation was discontinued, and the patient was started on copper supplementation. At the 4-month follow-up, the patient demonstrated near normalization of hematologic parameters and resolution of symptoms. Conclusions: Zinc-induced hypocupremia is a rare but potentially fatal complication of Age-Related Eye Disease Study 2 supplementation and may present with pancytopenia. Clinicians should consider this diagnosis in patients taking zinc-containing supplements who present with unexplained cytopenias.}, }
@article {pmid41919172, year = {2026}, author = {Ambrosio, L and Cammalleri, M and Panariello, S and Califano, G and Scala, A and Improta, G and Pisani, A and Rejdak, R and Ostrowski, I and Filippi, L and Bagnoli, P and Dal Monte, M and Toro, MD}, title = {Mirabegron in patients with age-related macular degeneration treated for overactive bladder: a study protocol for a prospective observational non-randomized trial.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1761473}, pmid = {41919172}, issn = {2296-858X}, abstract = {UNLABELLED: Although anti-vascular endothelial growth factor drugs have revolutionized the treatment of neovascular age-related macular degeneration (wet AMD), preventing eyes from converting from dry to wet AMD provides better long-term prognosis for sight and overall health. Mirabegron, an agonist at beta 3 adrenoceptors (β3-ARs), is licensed for the treatment of overactive bladder (OAB), but has potential effects on angiogenic proliferation in the retina, and therefore may reduce risk of conversion from dry to wet AMD. Both OAB and AMD are more common in older adults and share risk factors suggesting a potential link between these two conditions, thus highlighting the need for common therapy for the two diseases. Mirabegron use in AMD patients is supported by its rather safe profile at the eye level as macular and choriocapillary parameters do not seem to be affected in OAB patients. The purpose of this study will be to investigate the effects of mirabegron in patients concomitantly affected by OAB and dry AMD to evaluate its impact on slowing down AMD progression from the dry to the neovascular form.<br><br>CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT07305298, identifier NCT07305298.}, }
@article {pmid41922489, year = {2026}, author = {Morsy, MS and Dutta, NA and Eldessouky, EI and Kabil, MM and El-Koumy, HAEA and Mehta, NN and Ali, AL and Jena, S and Zhang, H and Bartsch, DU and Cheng, L and An, C and Nguyen, T and Freeman, WR}, title = {Artificial intelligence based assessment of treatment response in wet age related macular degeneration using paired OCT angiography.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-42999-7}, pmid = {41922489}, issn = {2045-2322}, support = {P30EY022589//UCSD Vision Research Center Core Grant/ ; R01EY033847,//NIH grant/ ; }, }
@article {pmid41913248, year = {2026}, author = {Hanhart, J and Celi, LA and Blumenthal, EZ and Almog, R and Behar, J}, title = {Artificial intelligence in retinal care: transforming the doctor-patient partnership.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00837-y}, pmid = {41913248}, issn = {2056-9920}, abstract = {BACKGROUND: The integration of artificial intelligence into retinal practice represents more than a technological advancement; it constitutes an anthropological shift fundamentally redefining the centuries-old therapeutic partnership between physician and patient.<br><br>OBJECTIVE: To examine how artificial intelligence integration into retinal care transforms the therapeutic partnership, revealing what this transformation illuminates about the nature of medical knowledge itself and identifying frameworks for conscious implementation.<br><br>METHODS: We conducted a structured narrative review examining AI-based diagnosis and monitoring of diabetic retinopathy and age-related macular degeneration (2018-2025), synthesizing clinical deployment evidence with qualitative implementation studies, adopting an anthropological interpretive stance to examine technology as a mediator of human relationships.<br><br>RESULTS: FDA-approved AI systems demonstrate robust diagnostic performance for diabetic retinopathy and age-related macular degeneration. AI integration shifts encounters from examination-based to screen-mediated, clinical reasoning from individual to algorithm-guided, and physicians from diagnosticians to interpreters. Three insights emerge. First, AI reveals that medical practice always combined mechanistic reasoning with pattern recognition, now separated algorithmically. Second, accountability operates asymmetrically: while all stakeholders derive benefits from algorithmic integration, authority over system selection and deployment remains concentrated among vendors and institutions rather than distributed to frontline clinicians or patients. Third, impact diverges along existing stratification: transformation may create access for excluded populations while potentially eroding relationships for those who had comprehensive care, raising fundamental questions about equitable distribution.<br><br>CONCLUSIONS: The AI transformation of retinal care offers a revealing mirror of medicine's algorithmic future. Success demands epistemological rigor, robust evaluation competencies and establishing frameworks for shared accountability among the various stakeholders. Our framework maps six fundamental dimensions where synthesis supersedes substitution: expanding algorithmic capabilities while preserving healing relationships, creating access while maintaining continuity. Medicine can embrace algorithmic intelligence while preserving its humanistic core through conscious choices about epistemology, equity, and the character of practice we create.}, }
@article {pmid41914966, year = {2026}, author = {Trinh, M and Nguyen, J and Lee, M and Wang, J and Tee, YG and Nivison-Smith, L}, title = {Eccentricity-Dependent Reflectivity Rates-of-Change Across the Retina in Intermediate Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {62}, doi = {10.1167/iovs.67.3.62}, pmid = {41914966}, issn = {1552-5783}, mesh = {Humans ; Tomography, Optical Coherence/methods ; Retrospective Studies ; Female ; Male ; Aged ; *Macular Degeneration/diagnosis ; *Retinal Ganglion Cells/pathology ; Bruch Membrane/pathology ; *Retinal Pigment Epithelium/pathology ; Aged, 80 and over ; Nerve Fibers/pathology ; Middle Aged ; *Retina/pathology ; Longitudinal Studies ; Disease Progression ; Visual Acuity ; Follow-Up Studies ; }, abstract = {PURPOSE: The purpose of this study was to characterize reflectivity rates-of-change and eccentricity patterns across all retinal layers and bands in intermediate age-related macular degeneration (iAMD), using topographical optical coherence tomography (OCT) analysis.<br><br>METHODS: This retrospective, longitudinal study included 58 consecutive individuals with iAMD and no progression to late AMD. Linear reflectivity was derived from manually segmented OCT macular cubes (25 &#xd7; 25 degrees) across 60 &#xd7; 60 grids and normalized to vitreous reflectivity, for each reflective retinal layer from the retinal nerve fiber layer (RNFL) to Bruch's membrane (BM). This included the outer retinal bands, that is, the external limiting membrane (ELM), ellipsoid zone (EZ), and retinal pigment epithelium (RPE), and the drusen layer (RPE-BM). Grids below large blood vessels, the optic nerve head, and above drusen were excluded. Reflectivity rates-of-change (median, interquartile range [IQR], %/year) and eccentricity patterns were evaluated, then compared with colocalized thickness using regression coefficient ratios.<br><br>RESULTS: RNFL and ganglion cell layer reflectivity decreased up to -10.2%/year, with para-foveal troughs at 1.5 to 1.6 mm eccentricity. Inner plexiform and outer plexiform layers showed more uniform decreases without eccentricity dependence. In the outer retina, EZ band reflectivity decreased with a parafoveal trough of -11.1%/year at 1.4 mm, whereas ELM band, RPE band, and drusen layer changes were smaller and spatially uniform (within &#xb1;3%/year). Reflectivity rates-of-change were up to 15 &#xd7; [IQR = 1.47-28.53] faster than thickness (P < 0.05), although relationships (R2) were weak.<br><br>CONCLUSIONS: In iAMD, reflectivity changes across all retinal layers, most prominently para-/centrally, and show minimal colocalization with thickness. Faster rates-of-change and distinct spatial profiles support reflectivity as a sensitive biomarker for early disease change over time.}, }
@article {pmid41915734, year = {2026}, author = {Bordon, AF and Kaiser, PK and Wolf, A and Cen, L and Heyn, J and Urosevic, D and Dodeller, F and Allmannsberger, L and Silva, R}, title = {Efficacy and Safety of the Proposed Biosimilar Aflibercept, SDZ-AFL, in Patients With Neovascular Age-Related Macular Degeneration: 52-Week Results From the Phase 3 Mylight Study: Erratum.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004832}, pmid = {41915734}, issn = {1539-2864}, }
@article {pmid41916277, year = {2026}, author = {Spirig, SE and Herrero-Navarro, &#xc1; and Utz, L and Arteaga-Moreta, VJ and Raics, Z and Posada-Céspedes, S and Chreng, S and Galuba, O and Galuba, I and Claerr, I and Renner, S and Boldogkoi, M and Moreno-Juan, V and Kleindienst, PT and Volak, A and Imbach, J and Malysheva, S and Siwicki, RA and Hahaut, V and Hou, Y and Rodrigues, TM and Picelli, S and Cattaneo, M and Jüttner, J and Cowan, CS and Duckely, M and Baeschlin, DK and Renner, M and Unterreiner, V and Roska, B}, title = {Cell-type-focused compound screen in human organoids reveals CK1 inhibition protects cone photoreceptors from death.}, journal = {Neuron}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuron.2026.02.024}, pmid = {41916277}, issn = {1097-4199}, abstract = {Human organoids that mirror their corresponding organs in cell-type diversity present an opportunity to perform large-scale screens for compounds that protect disease-affected or damaged healthy cell types. Here, we generated 20,000 human retinal organoids with green fluorescent protein (GFP)-labeled cone photoreceptors. Since degeneration of cones is a leading cause of blindness, we induced cone death and screened 2,707 compounds with known targets for those that saved cones or those that further damaged cones. We identified inhibitors of casein kinase 1 (CK1) that protected cones, heat shock protein 90 (HSP90) inhibitors that saved cones in the short term but damaged them in the longer term, and broad histone deacetylase (HDAC) inhibition by many compounds that significantly damaged cones. Finally, we confirmed the protective effects of identified compounds in a mouse model of photoreceptor degeneration. This work provides a database for cone-damaging compounds and describes compounds and targets that can be starting points to develop neuroprotection for cones in diseases such as macular degeneration.}, }
@article {pmid41916527, year = {2026}, author = {Chen, Y and Zhang, Z and Wu, J and Wang, Y and Lin, S}, title = {MiR-335-5p as a potential biomarker of wet age-related macular degeneration.}, journal = {Clinical &amp; experimental optometry}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/08164622.2026.2639834}, pmid = {41916527}, issn = {1444-0938}, abstract = {CLINICAL RELEVANCE: Early diagnosis and intervention are of vital importance in delaying the irreversible vision loss caused by wet age-related macular degeneration (wAMD).<br><br>BACKGROUND: wAMD can lead to blindness in severe cases. At present, the pathogenesis of wAMD is still unclear, so a new biomarker is needed to study wAMD.<br><br>METHODS: A total of 190 subjects were included in this study, including the control group (n&#x2009;=&#x2009;90) and the wAMD group (n&#x2009;=&#x2009;100). The expression of miR-335-5p and the diagnostic value of miR-335-5p in wAMD were analysed. ARPE-19 cells treated with 300&#x2009;&#xb5;M t-BHP for 24&#x2009;h or 600&#x2009;&#xb5;M H2O2 for 24&#x2009;h were selected as oxidative damage models. MiR-335-5p mimic and miR-335-5p inhibitor were transfected into oxidative damage models to up-regulate and down-regulate miR-335-5p, and then proliferation and apoptosis were measured. Targetscan was used to forecast the target of miR-335-5p and gain VEGFA, which was confirmed by the dual-luciferase reporter system. MiR-335-5p and VEGFA were overexpressed in oxidative damage models to detect the role of both in wAMD.<br><br>RESULTS: MiR-335-5p was reduced and may have high diagnostic value in wAMD. MiR-335-5p was a risk factor for wAMD. In the oxidative damage models, overexpressed miR-335-5p increased the cell viability and decreased the apoptosis, while the inhibition of miR-335-5p was reversed. VEGFA was the target of miR-335-5p and was negatively regulated by miR-335-5p in the oxidative damage models. VEGFA and miR-335-5p were negatively correlated in wAMD.<br><br>CONCLUSION: MiR-335-5p may have a high diagnostic value in wAMD, suggesting that miR-335-5p might be a biomarker of wAMD. VEGFA was the target of miR-335-5p, and the two were negative correlation in wAMD. MiR-335-5p regulates VEGFA secretion in RPE cells, thereby indirectly participating in the core pathological process of wAMD.}, }
@article {pmid41907382, year = {2026}, author = {Hwang, S and Kang, SW and Kim, SJ and Park, KH and Oh, J and Jo, YJ and Byeon, SH and Kim, JH and Son, KY and Choi, J and Sagong, M and Kim, K and Yu, SY and Hwang, DD and Park, YH and Lee, H and Choi, EJ and Lee, J and , }, title = {Design and Baseline Characteristics of the Korean Age-Related Maculopathy Study (KARMS): A Nationwide Multicenter Prospective Observational Study.}, journal = {Ophthalmology science}, volume = {6}, number = {4}, pages = {101121}, pmid = {41907382}, issn = {2666-9145}, abstract = {PURPOSE: To describe the design and baseline characteristics of the Korean Age-Related Maculopathy Study, a nationwide prospective cohort investigating age-related macular degeneration (AMD) in Koreans.<br><br>DESIGN: A 5-year prospective observational study conducted across 33 tertiary hospitals and ophthalmology clinics in Korea.<br><br>PARTICIPANTS: A total of 1159 Korean participants diagnosed with nonexudative or exudative AMD.<br><br>METHODS: Participants aged 50 to 80 years were assigned to the A Study for Intermediate AMD Natural Outcome (ASIANO) arm (nonexudative) or Korean Exudative AMD Treatment Study (KEATS) arm (newly diagnosed exudative AMD). A Study for Intermediate AMD Natural Outcome arm 1 included bilateral intermediate AMD with classic drusen (soft, reticular pseudodrusen, cuticular, or calcified drusen) without advanced AMD. A Study for Intermediate AMD Natural Outcome arm 2 included pachychoroid spectrum disease with unilateral or bilateral findings such as pachydrusen with retinal pigment epithelium undulation, focal attenuation of inner choroidal vessel, and dilated outer choroidal vessels or pigmentary abnormalities corresponding retinal pigment epithelium elevation or disruption in OCT, without significant classic drusen. The KEATS arm comprised active exudative AMD, including typical exudative macular neovascularization, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation. All underwent standardized multimodal imaging at baseline and are followed annually.<br><br>MAIN OUTCOME MEASURES: Baseline demographic, behavioral, and ocular characteristics across drusen-driven, pachychoroid-driven, and exudative AMD phenotypes.<br><br>RESULTS: Of the 1409 individuals screened, 1159 were enrolled (ASIANO 1: 551; ASIANO 2: 317; KEATS: 291). A Study for Intermediate AMD Natural Outcome arm 1 participants were older, predominantly female, and universally bilateral; arm 2 participants were younger, more often male, and frequently unilateral. Korean Exudative AMD Treatment Study showed a high proportion of patients with polypodal choroidal vasculopathy (39.5%, patient-based) and male predominance. Behavioral profiles also differed: the KEATS arm had lower eye-supplement use, higher smoking exposure, and less frequent sunglasses/sun-visor use. Exploratory follow-up analyses suggested differing rates of exudative conversion between ASIANO arm 1 and arm 2.<br><br>CONCLUSIONS: Korean Age-Related Maculopathy Study is the first large-scale, nationally representative prospective cohort in Koreans, distinguishing drusen-driven and pachychoroid-driven maculopathy phenotypes and detailing exudative subtypes. These baseline data provide a foundation for future phenotype-specific progression analyses and management strategies in Asian populations.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41910764, year = {2026}, author = {Savastano, MC and Fossataro, C and Hu, L and Mottola, F and D'Onofrio, NC and Cestrone, V and Giannuzzi, F and Rizzo, S}, title = {Non neovascular Age - related macular degeneration - Review on clinical and imaging advances.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41910764}, issn = {1435-702X}, }
@article {pmid41912546, year = {2026}, author = {Mani, P and Ramachandran, N and Sowmya, V and Ravi, V and Ramesh, PV and Alahmadi, TJ}, title = {Multi-scale adaptive fusion network for retinal layer and fluid segmentation in optical coherence tomography B-scans.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-44006-5}, pmid = {41912546}, issn = {2045-2322}, abstract = {Major treats to visual health includes diabetic macular edema (DME), age-related macular degeneration (AMD) and retinal vein occlusion (RVO), which require prompt and correct interpretation for effective treatment. Optical coherence tomography (OCT) is an imaging modality, providing intense cross-sectional views of the retina to aid in diagnosis. Diagnosis and localization of retinal diseases were complicated by the structure of retinal fluids. In order to cope with these challenges, a deep learning architecture, the Adaptive Multi-Domain Fusion Network (AMDF-Net), is initiated to improve the detection of retinal diseases. AMDF-Net assimilates state of the art modules like Hybrid Spectral-Spatial Transformer (HSST) to gain insight about global and local features effectively. Moreover, the Dynamic Attention Fusion (DAF) module enhances the work of the network by specifying the features unique to retinal fluids, and Disease-Inclusive Segmentation (DIS) module makes it easier to accurately diagnose primary fluids. Extensive analyses of publicly available and real-time data reveal that AMDF-Net shows notable results with Dice coefficient of 98. 87% and classification accuracy of 98. 12%. These remarks highlight the potential of AMDF-Net to elevate automated retinal disease analysis and provide valuable assistance in the development of decisions focused on treatment.}, }
@article {pmid41904432, year = {2026}, author = {Bulut, M and Reyhan, AH}, title = {A comparison of GPT-4V's capability in optical coherence tomography images of age-related macular degeneration with expert assessments.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04777-x}, pmid = {41904432}, issn = {1471-2415}, }
@article {pmid41896965, year = {2026}, author = {Kochnev Goldstein, A and Park, J and Zhou, Y and Jensen, N and Palanker, D}, title = {Simulation of prosthetic vision with the PRIMA system and enhancement of face representation.}, journal = {Journal of neuroengineering and rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12984-026-01958-z}, pmid = {41896965}, issn = {1743-0003}, support = {R01-EY-035227/NH/NIH HHS/United States ; W81XWH-22-1-0933//Department of Defense/ ; FA9550-19-1-0402//Air Force Office of Scientific Research/ ; }, abstract = {OBJECTIVE: Patients implanted with the PRIMA photovoltaic subretinal prosthesis in geographic atrophy report form vision with the average acuity matching the 100 μm pixel size. Although this remarkable outcome enables them to read and write, they report difficulty with perceiving faces. Despite the pixelated stimulation, patients report seeing smooth patterns rather than dots. This paper provides a novel, non-pixelated algorithm for simulating prosthetic vision the way it is experienced by PRIMA patients, compares the algorithm's predictions to clinical perceptual outcomes, and offers computer vision and machine learning (ML) methods to improve face representation.<br><br>APPROACH: Our simulation algorithm (ProViSim) integrates a grayscale filter, spatial resolution filter, and contrast filter. This accounts for the limited sampling density of the retinal implant (pixel pitch), as well as the reduced contrast sensitivity of prosthetic vision. Patterns of Landolt C and faces created using this simulator are compared to reports from actual PRIMA users. To recover the facial features lost in prosthetic vision due to limited resolution or contrast, we apply an ML facial landmarking model, as well as contrast-adjusting tone curves to the image prior to its projection onto the photovoltaic retinal implant.<br><br>MAIN RESULTS: Prosthetic vision simulated using the above algorithm matches the maximum letter acuity observed in clinical studies, as well as the patients' subjective descriptions of perceived facial features. Applying the inversed contrast filter to the image prior to its projection onto the implant and accentuating the facial features using an ML facial landmarking model helps preserve the contrast in prosthetic vision, improves emotion recognition and reduces the response time.<br><br>SIGNIFICANCE: Spatial and contrast constraints of prosthetic vision limit resolvable features and degrade natural images. ML based methods and contrast adjustments prior to image projection onto the implant mitigate some limitations and improve face representation. Even though higher spatial resolution can be expected with implants having smaller pixels, contrast enhancement still remains essential for face recognition.}, }
@article {pmid41897380, year = {2026}, author = {Kaštelan, S and Antunica, AG and Konjevoda, S and Tomić, Z and Sarić, A and Kulaš, M and Kulaš, L and Begović, EK and Čanović, S and Kovačević, P and Ivanković, M}, title = {Mitochondrial ROS in Retinal Neurodegeneration: Thresholds, Quality Control Failure, and Precision Therapeutic Windows.}, journal = {Biomolecules}, volume = {16}, number = {3}, pages = {}, doi = {10.3390/biom16030445}, pmid = {41897380}, issn = {2218-273X}, mesh = {Humans ; *Reactive Oxygen Species/metabolism ; *Mitochondria/metabolism/pathology ; Animals ; Oxidative Stress ; Oxidation-Reduction ; *Neurodegenerative Diseases/metabolism/pathology ; *Retina/metabolism/pathology ; }, abstract = {Mitochondrial reactive oxygen species (mtROS) play a dual role in retinal physiology, acting as essential redox signalling mediators under homeostatic conditions but driving oxidative damage and neurodegeneration once regulatory thresholds are exceeded. Owing to the exceptionally high energetic demands of retinal neurons and supporting cells, even subtle perturbations in mitochondrial redox balance can precipitate progressive retinal dysfunction. Increasing evidence indicates that retinal neurodegenerative diseases, including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), and inherited optic neuropathies, are characterised not by uniform oxidative stress, but by disease- and stage-specific mtROS signatures shaped by mitochondrial quality control capacity. This review synthesises current insights into the sources, regulation, and signalling functions of mtROS in the retina, with particular emphasis on threshold-dependent redox transitions, reverse electron transport, and the progressive failure of mitochondrial quality control mechanisms, including mitophagy, mitochondrial dynamics, and redox-responsive transcriptional networks. The limitations of non-selective antioxidant strategies are critically examined, highlighting why indiscriminate ROS suppression has yielded limited clinical benefit. In contrast, emerging therapeutic approaches aimed at recalibrating mitochondrial redox homeostasis, rather than abolishing physiological signalling, are discussed in the context of disease stage, metabolic state, and mitochondrial competence. By integrating redox biology with mitochondrial quality control and precision medicine concepts, this review proposes a unifying framework in which retinal neurodegeneration is governed by regulated mtROS signalling and the progressive exhaustion of mitochondrial resilience. This model defines critical therapeutic windows for mitochondria-targeted intervention and provides a framework for biomarker-guided patient stratification.}, }
@article {pmid41897428, year = {2026}, author = {Roberson, JK and Bauer, AN and Lopez-Ramirez, A and Jenness, DB and Cruz Zayas, S and Cooke Bailey, JN and Woodlief, TL}, title = {Environmental Exposures and Oxidative Stress in Retinal and Optic Nerve Diseases: Mechanisms, Consequences, and Therapeutic Opportunities.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {3}, pages = {}, doi = {10.3390/antiox15030281}, pmid = {41897428}, issn = {2076-3921}, support = {Institutional Startup Funds//East Carolina University Brody School of Medicine/ ; }, abstract = {Oxidative stress is a key contributing and convergent pathogenic mechanism linked to retinal and optic nerve diseases including age-related macular degeneration, diabetic retinopathy, and glaucoma. The retina is highly susceptible to redox imbalance due to intense mitochondrial activity, oxygen consumption, and light exposure. While endogenous drivers are well recognized, the contribution of environmental exposure to retinal oxidative injury remains incompletely defined. This review uniquely integrates emerging environmental contaminants with canonical oxidative stress pathways. We examine how cigarette smoke, ultraviolet radiation, heavy metals, microplastics, and per- and polyfluoroalkyl substances (PFASs) promote oxidative injury through mitochondrial dysfunction, inflammatory signaling, impaired antioxidant responses, and ferroptotic pathways. We also highlight therapeutic strategies targeting oxidative pathways and emphasize the importance of exposure-informed retinal and optic nerve disease research.}, }
@article {pmid41898716, year = {2026}, author = {Calbay, O and Hsieh, CL and Lu, C and Ghosh, S and Vijaykumar, V and Watts, I and Sweigard, H and Gandhi, J and den Hollander, AI}, title = {Mapping the Hypoxic Fitness Landscape of Retinal Pigment Epithelial Cells.}, journal = {International journal of molecular sciences}, volume = {27}, number = {6}, pages = {}, doi = {10.3390/ijms27062857}, pmid = {41898716}, issn = {1422-0067}, mesh = {*Retinal Pigment Epithelium/metabolism/cytology ; Humans ; Cell Hypoxia/genetics ; Gene Expression Profiling ; Cell Line ; Transcriptome ; Macular Degeneration/genetics/metabolism/pathology ; CRISPR-Cas Systems ; *Epithelial Cells/metabolism ; Mitochondria/metabolism ; *Hypoxia/genetics ; Oxygen/metabolism ; }, abstract = {Chronic hypoxia is a hallmark of aging and retinal diseases such as age-related macular degeneration (AMD), yet the molecular mechanisms that enable retinal pigment epithelium (RPE) cells to survive under sustained low-oxygen conditions remain poorly understood. To address this, we conducted transcriptomic profiling and a genome-wide CRISPR-Cas9 loss-of-function screen in ARPE-19 cells exposed to chronic hypoxia (1% and 5% O2), mimicking the retinal disease environment. The CRISPR screen identified genes whose loss compromises RPE viability or fitness under hypoxia, while transcriptomic profiling revealed oxygen-dependent shifts in key functional modules. These findings converged on pathways related to mitochondrial function, extracellular matrix remodeling, vascular signaling, and cell cycle regulation, identifying unique functional nodes specific to RPE cells. These core processes are also implicated in retinal diseases, such as AMD. Together, these complementary approaches provide an integrated view of the molecular networks driving RPE adaptation to hypoxic stress and highlight novel gene candidates that may serve as therapeutic targets in retinal disease.}, }
@article {pmid41901080, year = {2026}, author = {Baek, HI and Kim, I and Bae, J and Kwon, JE and Kang, SC}, title = {Effects of Long-Term Supplementation with Centella asiatica (L.) Urb. Extract (CA-HE50) on Macular Pigment Optical Density: A Randomized, Double-Blind, Placebo-Controlled Trial.}, journal = {Nutrients}, volume = {18}, number = {6}, pages = {}, doi = {10.3390/nu18060905}, pmid = {41901080}, issn = {2072-6643}, support = {117050-3//Ministry of Agriculture, Food and Rural Affairs/ ; }, mesh = {Humans ; Double-Blind Method ; Female ; Middle Aged ; Male ; *Plant Extracts/administration &amp; dosage/pharmacology ; *Dietary Supplements ; *Centella/chemistry ; Aged ; *Triterpenes/administration &amp; dosage/pharmacology ; *Macular Pigment/metabolism ; Antioxidants ; *Macula Lutea/drug effects/metabolism ; }, abstract = {Background/Objectives: Macular pigment optical density (MPOD) is a nutrition-responsive biomarker that indicates the antioxidant status of the macula. This study aimed to evaluate the effects of long-term supplementation with a standardized Centella asiatica (L.) Urb. extract (CA-HE50) on MPOD in a randomized, double-blind, placebo-controlled clinical trial. Methods: Eighty men and women aged 45-65 years, with baseline MPOD values between 0.2 and 0.4, were randomly assigned to receive either CA-HE50 (300 mg/day, n = 40) or a placebo (n = 40) for 6 months. Efficacy was assessed by measuring MPOD at baseline and on Days 60, 120, and 180. The primary efficacy endpoint was the change in MPOD from baseline to Day 180. Safety was evaluated through monitoring adverse events, vital signs, and clinical laboratory tests. Results: By Day 180, supplementation with CA-HE50 resulted in a statistically significant increase in MPOD compared to the placebo in the right eye, left eye, and the average of both eyes (all p < 0.001). Significant between-group differences were also observed at Day 120, indicating a time-dependent improvement in MPOD. Additionally, the proportion of responders was significantly higher in the CA-HE50 group compared to the placebo group (p < 0.001). CA-HE50 was well tolerated, with no serious adverse events or clinically relevant safety concerns identified during the intervention period. Conclusions: Long-term supplementation with C. asiatica extract significantly improved MPOD, supporting its potential role in enhancing macular nutritional status. These findings suggest that CA-HE50 may serve as a beneficial dietary intervention for maintaining macular health.}, }
@article {pmid41888298, year = {2026}, author = {Krasniakova, M and Pansell, T and Gustafsson, J}, title = {Impact of individualized colored spectacle filters on photophobia and visual comfort in central visual field defect patients: a one-year study.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-45302-w}, pmid = {41888298}, issn = {2045-2322}, abstract = {Visual comfort is a critical yet often overlooked aspect in managing patients with central visual field defects and photophobia. This study investigates the long-term effects of individualized colored spectacle filters on visual comfort and function in patients with Age-related Macular Degeneration and Leber Hereditary Optic Neuropathy. Patients were fitted with individualized precision tint spectacles tailored to improve vision comfort for one year. The study involved a comprehensive evaluation of visual acuity, contrast sensitivity, and photophobia symptoms alongside qualitative feedback from patient interviews. Results indicate significant improvements in subjective visual comfort and function, with a notable reduction in photophobia symptoms among patients with Leber Hereditary Optic Neuropathy. Colored filters, particularly those in the blue-green spectrum, were preferred by most patients and had a positive impact on comfort. Statistical analysis revealed trends in color preferences and subjective enhancements in visual function, underscoring the potential benefits of comfort-tint filters and the importance of personalized treatment approaches. The findings suggest that individualized colored spectacle filters can be valuable in enhancing visual comfort and function for patients with central visual field defects. This study shows the importance of integrating visual comfort considerations into clinical practice for a comprehensive approach to patient care.}, }
@article {pmid41888985, year = {2026}, author = {Helland-Hansen, BA and Sverstad, A and Petrovski, G and Larsen, SE}, title = {Eye-tracking-derived foveal biomarkers and functional alterations in dry AMD: findings from a controlled clinical study.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00838-x}, pmid = {41888985}, issn = {2056-9920}, support = {333925//Norges Forskningsr&#xe5;d/ ; 333925//Norges Forskningsr&#xe5;d/ ; 333925//Norges Forskningsr&#xe5;d/ ; 333925//Norges Forskningsr&#xe5;d/ ; }, }
@article {pmid41889981, year = {2026}, author = {Meng, R and Kenney, RC and Pan, M and Gupta, AK and Modi, YS and Chauhan, P and Curcio, CA and Srinivasan, VJ}, title = {Visible Light Optical Coherence Tomography Reveals Aging at the Retinal Pigment Epithelium-Bruch's Membrane Interface.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.18.712487}, pmid = {41889981}, issn = {2692-8205}, abstract = {UNLABELLED: Landmark histological studies have shown that as the retina ages, lipids and other debris accumulate within Bruch's membrane (BM) and in spaces introduced between BM and the retinal pigment epithelium (RPE). These deposits grow with age, increasing the risk of age-related macular degeneration (AMD), the leading cause of irreversible vision loss for older adults globally. Current in vivo imaging lacks specificity to study BM and the important spaces at the RPE/BM interface in living human eyes, while histological techniques suffer from processing artifacts that distort photoreceptors. Here we employ visible light Optical Coherence Tomography (OCT), with 1 micrometer depth resolution, to quantitatively analyze these tissues in living eyes. We identify age-related changes in a human cohort without retinal pathology: thickening and loss of contrast of the hyper-reflective BM band, and thickening of the RPE together with the sub-RPE basal laminar space (RPE+sBL). Both forms of thickening were locally coupled depending on eccentricity, suggesting related biosynthetic mechanisms. A thicker BM and RPE+sBL were locally associated with anomalies in the overlying photoreceptors. Thus, sub-clinical changes in aging eyes detected by visible light OCT resemble early versions of deposits found in AMD. Visible light OCT depicts the relationship between RPE+sBL, BM, and photoreceptors in aging, holding promise to precisely and non-invasively grade ocular phenotypes ranging from normal aging to early AMD.<br><br>SIGNIFICANCE STATEMENT: As humans age, lipids and other debris deposit in Bruch's membrane (BM) of the human eye (1) and spaces introduced between the retinal pigment epithelium (RPE) and BM. These deposition processes are linked to the eventual development of age-related macular degeneration (AMD), the leading blinding disease amongst older adults. Here we investigate these deposits with visible light OCT imaging in living human subjects without overt retinal pathology. Whereas early RPE/BM deposits were previously assessed only in donor eyes postmortem via preparations that distort photoreceptors, our results shed light on these AMD precursors and overlying photoreceptor changes in living human eyes.}, }
@article {pmid41890681, year = {2026}, author = {Agius, D and Mamo, J and Calleja, N and Cassar, D and Marku, X and Nappa, MC and Zammit, M and Pace, ME and Carbonaro, F}, title = {Prevalence of Refractive Errors, Myopic Macular Degeneration, and Associated Risk Factors in a Maltese Population-Based Study.}, journal = {Clinical optometry}, volume = {18}, number = {}, pages = {561426}, pmid = {41890681}, issn = {1179-2752}, abstract = {PURPOSE: To estimate the prevalence of refractive error and myopic macular degeneration in a nationally representative sample of older adults from Malta, evaluate associations with established risk factors.<br><br>PATIENTS AND METHODS: This population-based cross-sectional study included 1,794 participants aged 50-80 years from Malta, recruited as part of The Malta Eye Study (response rate 44.8%). Demographic, medical, behavioral, and ocular data were collected using structured questionnaires. Standardized ophthalmic examinations were performed, including autorefraction and retinal imaging with optical coherence tomography. Refractive error was classified by spherical equivalent as myopia (< -0.50 D) and hyperopia (> +0.50 D), while astigmatism was defined as &#x2264; -0.75 D. Myopic macular degeneration was graded using the meta-analysis for pathologic myopia classification. Associations were assessed using multivariable logistic regression.<br><br>RESULTS: Among right phakic, surgically untouched eyes, the prevalence of emmetropia, myopia, and hyperopia was 20.0% (95% CI 18.0-22.1%), 25.1% (95% CI 23.0-27.4%), and 54.8% (95% CI 52.3-57.3%), respectively. Vector-derived average astigmatism prevalence in both eyes was 44.3% (95% CI 41.6-46.9%), with against-the-rule astigmatism being the most common pattern. Effective refractive error coverage exceeded 90% for both distance and near vision. The prevalence of any myopic degeneration in either eye was 2.6% (95% CI 1.9-3.4%). Myopia prevalence among individuals aged 50-59 years was lower than that reported in other European populations, and use of long-acting anti-muscarinic agents was associated with myopic degeneration (OR 25.70, 95% CI 1.55-426.04, p=0.023).<br><br>CONCLUSION: This study reports refractive error and myopic macular degeneration prevalence broadly comparable to other European settings. Lower myopia prevalence among individuals aged 50-59 years may reflect complex gene-environment-behavior interactions. Further investigation of these interactions, as well as the potential impact of long-acting anti-muscarinic agents on myopic macular degeneration, is warranted, particularly in light of the wide confidence interval.}, }
@article {pmid41891014, year = {2026}, author = {Yeh, TC and Velez, G and Prasad, A and Lee, SH and Rasmussen, DK and Kumar, A and Chadha, M and Dabaja, MZ and Singh, AM and Sanislo, S and Smith, S and Mryuthyunjaya, P and Montague, A and Bassuk, AG and Almeida, D and Dufour, A and Mahajan, VB}, title = {Multi-omics liquid biopsy identifies mitochondrial dysfunction in geographic atrophy and supports the longevity-associated metabolite α-ketoglutarate as a therapeutic strategy.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.12.26347263}, pmid = {41891014}, abstract = {BACKGROUND: Mitochondrial dysfunction is an emerging metabolic hallmark of age-related diseases, yet tools to directly profile mitochondrial pathways and test metabolic interventions in the living human eye remain limited. Multi-omics ocular liquid biopsy enables real-time proteomic and metabolomic profiling of the intraocular microenvironment, complementing systemic biomarkers and imaging surrogates. Here, we used this approach to define mitochondrial and tricarboxylic acid (TCA) cycle dysregulation in geographic atrophy (GA) and to assess whether oral α-ketoglutarate (α-KG) supplementation can modulate mitochondrial metabolites within the eye.<br><br>METHODS: Mitochondrial and TCA cycle-related proteins were profiled in aqueous humor (AH) samples from patients with GA using DNA-aptamer-based proteomics. In a phase 0 study, a second cohort undergoing sequential cataract surgery provided paired AH samples collected at first-eye surgery and at second-eye surgery after interim &#x3b1;-KG supplementation. These samples underwent targeted metabolomic profiling using hydrophilic interaction liquid chromatography coupled with mass spectrometry.<br><br>RESULTS: In GA, 64 mitochondrial proteins were differentially expressed, including coordinated TCA-cycle deficiencies marked by reduced expression of enzymes regulating TCA entry and flux, including PDHB and DLST. In the phase 0 cohort, oral &#x3b1;-KG supplementation significantly increased intraocular &#x3b1;-KG levels and the &#x3b1;-KG-to-succinate ratio (P < 0.05), with coordinated shifts across TCA intermediates consistent with enhanced TCA cycle flux.<br><br>CONCLUSIONS: AH proteomics demonstrated mitochondrial pathway depletion in GA, consistent with reduced oxidative bioenergetic capacity. AH metabolomics provided first-in-human in vivo evidence that systemic &#x3b1;-KG supplementation can modify intraocular metabolites and may enhance intraocular energy metabolism. These findings support ocular liquid biopsy as a precision-health framework for per-patient biomarker-guided metabolic trials in GA.<br><br>PLAIN LANGUAGE SUMMARY: Geographic atrophy (GA) is an advanced form of age-related macular degeneration and a major cause of irreversible vision loss. To better understand the biology of GA, we studied proteins and small molecules in aqueous humor, the fluid inside the eye. We found that eyes with GA showed clear signs of mitochondrial dysfunction, including disruptions in the tricarboxylic acid (TCA) cycle, a key pathway for energy production. This suggests that impaired cellular metabolism is an important feature of the disease. We then tested whether oral &#x3b1;-ketoglutarate (&#x3b1;-KG), a metabolite involved in mitochondrial function and previously shown to have life-extending effects in preclinical studies, could alter these metabolic pathways in the human eye. We found that &#x3b1;-KG supplementation not only increased intraocular &#x3b1;-KG levels but changed metabolic markers linked to mitochondrial activity, providing the first direct evidence that oral supplementation can reach the eye and measurably modify metabolism inside the living human eye. Together, these findings show that liquid biopsy can provide a direct molecular snapshot of the living human eye and may help accelerate the development of biomarker-guided therapies for ocular diseases.<br><br>KEY POINTS: Questions: What specific mitochondrial and TCA-cycle dysfunctions occur in the aqueous humor (AH) of patients with geographic atrophy (GA), and can oral &#x3b1;-ketoglutarate (&#x3b1;-KG) supplementation measurably remodel these metabolic pathways in the living human eye?Findings: AH proteomics in GA patients revealed significant mitochondrial disruption and a coordinated depletion of TCA-cycle enzymes. In a paired-eye interventional metabolomics study, oral &#x3b1;-KG significantly increased intraocular &#x3b1;-KG levels and the &#x3b1;-KG-to-succinate ratio, proving that systemic therapy can drive measurable metabolic modulation within the human eye.Meaning: Multi-omics liquid biopsy provides a direct, eye-specific readout of mitochondrial metabolism in GA and offers early human proof-of-concept that a systemic metabolic therapy can successfully reach and modify intraocular pathways, paving the way for biomarker-guided clinical trials in AMD.}, }
@article {pmid41891097, year = {2026}, author = {Gallardo, MJ and Porter, M and Vincent, L and Sandrosyan, A and Koch, B and Kasuga, DT}, title = {Outcomes of Ab-Interno Canaloplasty and Gonioscopy-Assisted Transluminal Trabeculotomy in Eyes with Sustained Intraocular Pressure Elevation Following Intravitreal Injections.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {563035}, pmid = {41891097}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate the long-term efficacy and safety of combined ab-interno canaloplasty (ABiC) and gonioscopy-assisted transluminal trabeculotomy (GATT) with the iTrack microcatheter in patients with sustained intraocular pressure (IOP) elevation following intravitreal anti-VEGF or steroid injections.<br><br>PATIENTS AND METHODS: This was a retrospective, single-center study of patients who underwent ABiC and GATT with the iTrack microcatheter between 2017 and 2021 for secondary open-angle glaucoma or ocular hypertension following intravitreal injections. Eligible eyes had a preoperative IOP of &#x2265;18&#xa0;mmHg while on maximal tolerated medical therapy. Primary outcomes included IOP and glaucoma medication burden. Surgical success was defined using American Academy of Ophthalmology (AAO) criteria. Subgroup analyses were conducted by etiology (anti-VEGF vs steroid-induced). Kaplan-Meier analysis estimated cumulative success rates.<br><br>RESULTS: Thirty-four eyes from 30 patients were included, with a mean last follow-up of 15.3&#xb1;9.8 months. Mean IOP was reduced by 46%, from 28.1&#xb1;6.0&#xa0;mmHg at baseline to 14.3&#xb1;5.6&#xa0;mmHg (p<0.001) at the last follow-up, while the number of medications decreased from 2.79&#xb1;0.9 to 1.76&#xb1;1.5 (p=0.001). Surgical success was achieved in 71% of eyes. Medication-free status was reached in 29% of eyes, compared with none at baseline, and 26% achieved IOP &#x2264;15&#xa0;mmHg without medications. Additional glaucoma procedures were needed in 11.8% of eyes. Combined ABiC and GATT remained effective in eyes receiving post-procedure intravitreal reinjections or prolonged topical steroid use. Kaplan-Meier analysis showed a survival probability above 70% at 25 months.<br><br>CONCLUSION: Combined ab-interno canaloplasty and GATT using the iTrack microcatheter is a safe surgical option for selected eyes with sustained IOP elevation following intravitreal injections. The procedure achieved meaningful reductions in IOP and medication use, including in eyes requiring continued intravitreal therapy, supporting a primary surgical effect. Careful patient selection and long-term follow-up remain essential, as a subset of eyes may require additional intervention.}, }
@article {pmid41891889, year = {2026}, author = {Tabano, DC and Ali, FS and Borkar, DS and Leng, T and Ahmed, A and Ko, S and Myrick, A and Zwick, E and Downey, A and Barteselli, G and Singh, RP}, title = {One-year Real-world Outcomes With Faricimab in Neovascular Age-related Macular Degeneration.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {}, number = {}, pages = {1-9}, doi = {10.3928/23258160-20260302-02}, pmid = {41891889}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: This study evaluated real-world treatment patterns and 1-year outcomes in patients with neovascular age-related macular degeneration (nAMD) initiating faricimab.<br><br>PATIENTS AND METHODS: FARETINA-AMD was a retrospective study using data from the IRIS[&#xae;] Registry for patients diagnosed with nAMD initiating faricimab from February 2022 to March 2023.<br><br>RESULTS: Included in the study were 2,025 treatment-naive patients (2,184 eyes) and 22,253 patients (26,851 eyes) previously treated with anti-vascular endothelial growth factor (anti-VEGF) therapy. Visual acuity improved by 2.0 &#xb1; 15.0 (mean &#xb1; SD) letters in treatment-naive eyes (P < .001) and was maintained in previously treated eyes at injection 7. Central subfield thickness (CST) improved by -53.1 &#xb1; 64.8 &#x3bc;m in treatment-naive and -28.5 &#xb1; 79.7 &#x3bc;m in previously treated eyes (both P < .0001); 78.4% and 66.8%, respectively, had achieved/maintained CST &#x2264; 280 &#x3bc;m at injection 7. Dosing frequency was reduced in the second 6 months (mean 2.4-3.2 injections) versus the first 6 months (4.0-4.2) of treatment.<br><br>CONCLUSION: Outcomes among patients with nAMD receiving faricimab over 1-year follow-up support the real-world effectiveness and extended durability of treatment.}, }
@article {pmid41891912, year = {2026}, author = {Antonietti, M and Mercado, C and Fortun, JA and Albini, TA and Dubovy, SR and Smiddy, WE and Schwartz, SG and Kovach, JL}, title = {Real-world Safety Profile of Avacincaptad Pegol in the Management of Geographic Atrophy.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {}, number = {}, pages = {1-5}, doi = {10.3928/23258160-20260305-01}, pmid = {41891912}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: This study evaluated the safety of intravitreal avacincaptad pegol in treating geographic atrophy (GA) secondary to age-related macular degeneration (AMD).<br><br>PATIENTS AND METHODS: A retrospective review was conducted of patients treated with avacincaptad pegol at Bascom Palmer Eye Institute from January 2024 to January 2025. Adverse events, side effects, and potential risk factors were recorded.<br><br>RESULTS: The study analyzed 124 eyes from 83 patients (mean age 81.8 &#xb1; 6.4 years; 49.4% male; 91.6% White) who received 409 injections in total. Injection intervals varied: 54 eyes monthly, 55 every other month, and others less frequently. The variability in injection frequency was mostly due to patient difficulty with follow-up. Follow-up ranged 3 to 12 months (median: 5 months). Baseline visual acuity averaged 0.40 (approx. 20/50 Snellen) decreasing slightly to 0.38 (20/53 Snellen)-not statistically significant (P = .628). Most eyes (85.2%) were pseudophakic; 47% of patients had prior neovascular AMD treated with anti-vascular endothelial growth factor (anti-VEGF), and 24.2% were simultaneously being treated for active neovascular AMD in the eye receiving avacincaptad pegol. Sixteen eyes had prior pegcetacoplan treatment. Adverse events were rare. One patient developed culture-negative endophthalmitis 4 days after the third injection, presenting with vision loss to hand motion but improving after intravitreal antibiotics. Side effects occurred in 14 eyes (13.8%) across 10 patients, including intraocular pressure elevation (seven eyes), discomfort (four eyes), visual disturbance (two eyes), and subconjunctival hemorrhage (one eye). Five patients discontinued treatment, and one eye (0.8%) had reactivation of neovascular AMD.<br><br>CONCLUSION: Our study highlights the safety profile of avacincaptad pegol for GA, with a low incidence of conversion to neovascular AMD, few adverse events, and manageable side effects.}, }
@article {pmid41892574, year = {2026}, author = {Kim, SJ and Kim, DY and Jeong, D and Lee, C and Cho, HD and Kim, MP}, title = {Food-Grade Microgels for Age-Related Macular Degeneration: Design, Fabrication, and Targeted Delivery.}, journal = {Gels (Basel, Switzerland)}, volume = {12}, number = {3}, pages = {}, doi = {10.3390/gels12030252}, pmid = {41892574}, issn = {2310-2861}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide and is driven by complex pathophysiological processes, including oxidative stress, chronic inflammation, complement dysregulation, and vascular endothelial growth factor (VEGF)-mediated neovascularization. Nutritional interventions-particularly supplementation with carotenoids, omega-3 fatty acids, polyphenols, and essential micronutrients-have demonstrated clinical benefits in slowing disease progression, as evidenced by landmark trials such as AREDS and AREDS2. However, many AMD-relevant bioactives exhibit poor aqueous solubility, low chemical stability, and limited gastrointestinal bioavailability, which significantly constrain their therapeutic efficacy. Food-grade microgels have emerged as versatile colloidal delivery platforms capable of addressing these limitations through rational structural and physicochemical design. This review provides a systematic roadmap for developing food-grade microgels, organized into: (1) the molecular design of protein- and polysaccharide-based networks; (2) advanced fabrication strategies such as microfluidics and atomization; (3) spatiotemporal release programming within the gastrointestinal tract; and (4) multi-nutrient synergy for retinal protection. This approach highlights how controlled crosslinking, interfacial assembly, and tunable network architectures enhance nutrient stabilization. Particular emphasis is placed on spatiotemporal release programming within the gastrointestinal tract, including diffusion-limited gastric retention, pH- and bile-responsive swelling in the small intestine, and microbiota-triggered degradation in the colon. These mechanisms collectively enable region-specific release, improved micellar incorporation, enhanced systemic absorption, and more consistent retinal delivery. Furthermore, we discuss co-encapsulation strategies that accommodate both hydrophilic and lipophilic bioactives, thereby minimizing antagonistic interactions and enabling synergistic nutritional modulation of oxidative and inflammatory pathways implicated in AMD. A central novelty of this review is the integration of the gut-eye axis, framing microgel-based oral delivery as a systemic pathway to modulate retinal health via the intestinal environment. By bridging retinal disease biology with food colloid science, this review proposes food-grade microgels as a translational platform for next-generation nutraceutical interventions. The integration of programmable release behavior with clinically validated nutrient regimens offers a promising pathway toward more effective and mechanistically informed dietary management of AMD.}, }
@article {pmid41893318, year = {2026}, author = {Greiner, JV and Glonek, T}, title = {Metabolomics of Ocular Tissues with High and Low Metabolic Activity.}, journal = {Metabolites}, volume = {16}, number = {3}, pages = {}, doi = {10.3390/metabo16030167}, pmid = {41893318}, issn = {2218-1989}, support = {EY-03988/EY/NEI NIH HHS/United States ; Grant 533181//Valerie and Walter Winchester Grant/ ; }, abstract = {BACKGROUND/OBJECTIVES: An unexplainably high millimolar (~3 mM) concentration of adenosine triphosphate (ATP), herein designated as nucleoside triphosphate (NTP), exists in the crystalline lens even though all of the known functions of NTP combined require only micromolar (μM) concentrations. Since the lens is one of the most metabolically quiescent tissues in the body and the retina is one of the most metabolically active tissues in the body, we compared their phosphorus metabolomics and related metabolic indices that measure their metabolic health status. As such, the purpose of this report was to compare the NTP concentrations in lenticular and retinal tissues and the metabolic indices that include NTP as well as their phosphorus-31 spectral modulus (PSM).<br><br>METHODS: Known phosphatic metabolic profiles of rat lenses and retinas were compared and quantified in mole % phosphorus using phosphorus-31 nuclear magnetic resonance spectroscopy. Metabolic indices measuring health status, where ATP is a principal component, were calculated, including the PSM.<br><br>RESULTS: In this secondary analysis, the NTP concentration calculated in the lens was 41.0% of the total phosphate detected, whereas it was similarly 37.6% in the sensory retina. The PSM values were 1.28 for the lens and similarly 1.42 for the retina.<br><br>CONCLUSIONS: Due to the lens tissue's low quiescent metabolic activity, one might expect the NTP concentration to be lower in the lens than in the highly metabolically active retina: a similar difference is expected in the PSM. However, this was not the case with the mM concentrations of NTP in both the lens (&#x2265;2.3 mM) and the retina (2.4 mM). The similarly high mM NTP concentration coupled with the PSM-calculated measure of metabolic health in these tissues is a novel finding. The novel findings of such similarly high concentrations of NTP in these metabolically diverse eye tissues further support and are consistent with the hypothesized role of NTP as a hydrotrope, preventing protein aggregation resulting in age-related cataractogenesis and age-related macular degeneration.}, }
@article {pmid41893888, year = {2026}, author = {Azizmohammad Looha, M and Amanollahi, M and Hashemi, E and Jameie, M and Mohammadpoor, A and Mozafar, M and Samiee, R and Jalalinejad, M and Arevalo, JF}, title = {Global burden of age-related macular degeneration: Trends, regional disparities, and projections from the Global Burden of Disease study 2021.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41893888}, issn = {1435-702X}, }
@article {pmid41893991, year = {2026}, author = {Venugopal, D and Wood, J and Black, A and Bradley, C and Bentley, S}, title = {Development and Validation of the Assessment of Low Luminance Vision-Related Activities.}, journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)}, volume = {46}, number = {1}, pages = {81-89}, pmid = {41893991}, issn = {1475-1313}, mesh = {Humans ; Cross-Sectional Studies ; Aged ; Male ; Female ; *Visual Acuity/physiology ; Reproducibility of Results ; *Vision, Low/physiopathology/diagnosis ; Middle Aged ; *Vision, Binocular/physiology ; Aged, 80 and over ; *Vision Tests/methods ; Adult ; Psychometrics ; }, abstract = {PURPOSE: To develop a new comprehensive vision-related low luminance performance-based measure, the 'Assessment of Low Luminance Vision-Related Activities' (ALLVA), and evaluate its construct validity and test-retest reliability using Rasch analysis.<br><br>METHODS: A cross-sectional observational study of 75 adults with vision impairment from various ocular conditions (mean age 70 years [SD: 15 years]; mean binocular visual acuity 0.63 logMAR [SD: 0.45 logMAR]) was conducted. Seventeen tasks were developed as items and administered to participants under low luminance, with completion time and number of errors recorded. As some items could not be completed by all participants, five categories of completion time were created for analysis (quartiles and a fifth category representing non-completion). The 'method of successive dichotomisations'-a polytomous Rasch model that always estimates ordered response category thresholds, enabling its application to binned continuous data-was applied to create a single combined measure of performance. Errors were not analysed as they occurred infrequently and generally increased completion time. Eleven participants with age-related macular degeneration were retested after 2-4 weeks. Clinical vision measures, including visual acuity, contrast sensitivity and visual fields, were also collected.<br><br>RESULTS: Initial analysis of the 17-task ALLVA led to removal of one item, walking a mobility course, due to infit and outfit mean square statistics being outside the acceptable range. For the remaining 16 tasks, item difficulty was well targeted to person ability, with only a minor floor effect. Item and person reliability values were 0.98 and 0.93, respectively. Clinical vision measures were significantly correlated with person measures. Bland-Altman analysis indicated a mean difference between test and retest person measures of -0.08 logits (95% limits of agreement 2.16 to -2.32 logits).<br><br>CONCLUSION: The ALLVA is the first comprehensive vision-related low luminance performance-based measure. It demonstrated strong Rasch psychometric properties, validity and good test-retest reliability.}, }
@article {pmid41896032, year = {2026}, author = {Chen, F and Shi, Y}, title = {Lipid peroxidation as a driver of oxidative and neuroinflammatory damage in ocular disease: review and perspectives.}, journal = {Archives of physiology and biochemistry}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/13813455.2026.2628183}, pmid = {41896032}, issn = {1744-4160}, abstract = {Context: Lipid peroxidation (LPO) causes oxidative stress and neuroinflammation in eye diseases. Malondialdehyde and 4-hydroxy-2-nonenal are produced in the eye via polyunsaturated fatty acid oxidation. Objective: Electrophiles damage biological components. LPO damages the retina and optic nerve, causing age-related macular degeneration, diabetic retinopathy, and glaucoma. Materials and Methods: LPO also causes cataracts and dry eye in the anterior area. It also stimulates NLRP3 and NF-κB pathways, causing inflammation. Results: Electrophiles damage biological components. LPO damages the retina and optic nerve, causing age-related macular degeneration, diabetic retinopathy, and glaucoma. LPO also causes cataracts and dry eye in the anterior area. It also stimulates NLRP3 and NF-κB pathways, causing inflammation. Conclusion: Understanding how lipid peroxidation, oxidative stress, and neuroinflammation interact is crucial to developing effective eye health and vision loss therapies.}, }
@article {pmid41896127, year = {2027}, author = {Zhao, X and Wen, Y and Yang, Z and Gu, X and Zeng, Y and Lai, A and Cao, W and He, M and Shi, Z and Zhang, W and Zhao, Q and Cheng, T and Meng, L and Wang, Y and Cheng, S and Wang, C and Liu, X and Yu, Q and Cai, X and Liu, G and Lu, L and Lv, L and Wei, W and Yuan, D and Zhang, J and Cun, Y and Chen, M and Zhang, T and Li, Z and Zeng, Q and Xiao, Z and Wang, C and Su, Y and Wang, Z and Sha, Q and Sheng, B and Chen, Y}, title = {Development and validation of a deep learning model to predict visual and anatomical prognosis of anti-VEGF therapy for neovascular age-related macular degeneration (KongMing Study): a prospective, nationwide, multicentre study.}, journal = {The Lancet. Digital health}, volume = {}, number = {}, pages = {100971}, doi = {10.1016/j.landig.2025.100971}, pmid = {41896127}, issn = {2589-7500}, abstract = {BACKGROUND: The financial burden and the uncertain response of the anti-vascular endothelial growth factor (anti-VEGF) treatment often cause hesitation among patients with neovascular age-related macular degeneration (nAMD), highlighting the need for a reliable method to predict treatment outcomes. We aimed to develop and validate a deep learning model that can predict the visual and anatomical prognosis of patients with nAMD undergoing anti-VEGF therapy.<br><br>METHODS: This prospective, nationwide, multicentre study involved 18 tertiary referral hospitals from 12 provinces across China. A large dataset of patients (aged 50-85 years) with nAMD treated with anti-VEGF therapy (Conbercept, 0&#xb7;5&#x2009;mg/0&#xb7;05&#x2009;mL, Chengdu, China) under a 3+PRN regimen was established. All participants underwent comprehensive ophthalmological examinations, including best-corrected visual acuity (BCVA) assessment and optical coherence tomography (OCT) imaging at baseline, follow-up, and 4-6 weeks after treatment. Patients with other ocular diseases that could confound the diagnosis or prognosis of nAMD were excluded. A Structural-Attention Guided Therapeutic Response Predicting Model (KongMing Model) was developed based on the lesion-aware, transformer-based multitask architecture to facilitate post-single-injection (4-6 weeks after any single injection during the treatment), post-three-loading-injections (4-6 weeks after the first three consecutive injections), and 1-year-post-three doses plus pro re nata (3+PRN; 1-year after treatment) dual predictions of visual and anatomical prognoses. For the prediction of BCVA changes, model performance was evaluated with the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, precision, average precision, and human-machine comparison. The prediction of BCVA values was evaluated with mean absolute error (MAE) and coefficient of determination (R[2]). The prediction of post-treatment OCT images was evaluated by the structural similarity index measure (SSIM) compared with the true post-treatment OCT images. Heatmaps and Shapley additive explanation images were used to identify features related to the prognosis of nAMD.<br><br>FINDINGS: From July 1, 2020, to Dec 31, 2023, we collected 29&#x2009;772 OCT images from 1226 participants after screening to form the internal dataset. From Jan 1, 2023, to May 1, 2024, we collected 3308 OCT images from 172 participants after screening to form the external dataset. In total, we included 603 (43&#xb7;1%) women and 795 (56&#xb7;9%) men. For the prediction of post-single-injection, post-three-loading-injections, and 1-year-post-3+PRN BCVA changes, our model achieved AUCs of 0&#xb7;948 (95% CI 0&#xb7;942-0&#xb7;954) in the internal test and 0&#xb7;941 (0&#xb7;934-0&#xb7;948) in the external test, also significantly outperforming ophthalmologists with different levels of experience in the human-machine comparison (all p<0&#xb7;0001). For the prediction of the post-treatment BCVA values, our model had a remarkably low MAE across the three predictions (range 0&#xb7;048 [0&#xb7;039-0&#xb7;057] to 0&#xb7;058 [0&#xb7;044-0&#xb7;072]) and high R[2] (range 0&#xb7;7140-0&#xb7;9012) across both internal and external tests. The model achieved an SSIM exceeding 0&#xb7;57, indicating a close similarity between the predicted and true post-treatment OCT images. In all aspects, our model outperformed the convolutional neural network-based models. Heatmaps and SHAP plots precisely located the features related to the prognosis of nAMD.<br><br>INTERPRETATION: The KongMing Model, developed and tested by a nationwide, multicentre dataset, showed excellent performance in predicting the post-single-injection, post-three-loading-injections, and 1-year-post-3+PRN visual and anatomical prognosis of patients with nAMD undergoing anti-VEGF therapy. It provides a robust and non-invasive method for more informed personalised treatment planning, potentially improving treatment adherence and avoiding unnecessary interventions.<br><br>FUNDING: National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences, Lumitin Vision to Brightness Research Funding for the Young and middle-aged Ophthalmologists, Peking Union Medical College Hospital Talent Cultivation Program, Fundamental Research Funds for the Central Universities, Peking Union Medical College, National High-Level Hospital Clinical Research Funding, Beijing Students' Funding for Innovation and Entrepreneurship Training Program, Guangdong Basic and Applied Basic Research Foundation, Guangdong Provincial Key Laboratory.}, }
@article {pmid41896129, year = {2027}, author = {Tsai, CY and Lai, TT}, title = {Artificial intelligence for post-treatment prediction in age-related macular degeneration.}, journal = {The Lancet. Digital health}, volume = {}, number = {}, pages = {100997}, doi = {10.1016/j.landig.2026.100997}, pmid = {41896129}, issn = {2589-7500}, }
@article {pmid41883753, year = {2026}, author = {Vidal-Alaball, J and Arocas Bonache, A and Solé-Casals, J and Royo Fibla, D and Marin-Gomez, FX and Distéfano, LN and Boixadera, A and Casado-García, &#xc1; and García-Domínguez, M and Inés, A and Heras, J and Zapata, MA}, title = {Clinical validation of artificial intelligence algorithms for the detection of different central-involved retinal pathologies and glaucoma from non-mydriatic images.}, journal = {Frontiers in artificial intelligence}, volume = {9}, number = {}, pages = {1754682}, pmid = {41883753}, issn = {2624-8212}, abstract = {UNLABELLED: The use of Artificial intelligence (AI) algorithms for detecting different ophthalmic diseases, especially diabetic retinopathy (DR), has become increasingly popular. In this paper, we evaluate the screening performance of different AI algorithms based on convolutional neural networks (CNNs) in a real-world scenario. To that aim, we conducted an observational and cross-sectional study on patients aged ≥18 years with type-2 diabetes mellitus, who had undergone fundus examination for DR screening using a teleophthalmology program. We used the UPRETINA diagnostic system, which consists of 8 AI algorithms based on CNNs. A total of 1,652 eyes from 871 patients were analyzed. The AI algorithms had a sensitivity/specificity of 86.8%/95.6% for detecting DR; 94.9%/94.3% for detecting age-related macular degeneration (AMD); 82.7%/92.4% for detecting glaucomatous optic neuropathy (GON); 87.0%/87.5% for detecting epiretinal membrane; and 89.7%/98.0% for detecting nevus. Additionally, the sensitivity/specificity for correctly classifying images as right eye/left eye and to correctly classifying images gradeability (medium or high quality) were 100% /100 and 92.9%/90.5%, respectively. The AUROC of the AI algorithms ranged between 0.9777 (AMD) and 0.9122 (GON). UPRETINA system was capable of automatically and accurately classifying the screening retinographies, reducing workload and leading to a scenario of more efficient optimization of resources.<br><br>CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04132401 NCT04132401.}, }
@article {pmid41885533, year = {2026}, author = {Michaud, C and Faurite, C and Guénot, J and Gallice, M and Chiquet, C and Vayssière, N and Berry, I and Trotter, Y and Baurès, R and Rosito, M and Soler, V and Peyrin, C and Cottereau, BR}, title = {Perceptual Learning as a Rehabilitation Approach to Enhance Motion Processing in Maculopathy Patients.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {52}, doi = {10.1167/iovs.67.3.52}, pmid = {41885533}, issn = {1552-5783}, mesh = {Humans ; Male ; *Motion Perception/physiology ; Female ; *Macular Degeneration/rehabilitation/physiopathology ; Magnetic Resonance Imaging ; Aged ; *Learning/physiology ; Middle Aged ; Visual Acuity/physiology ; }, abstract = {PURPOSE: Macular degeneration (MD) is a disease affecting the central retina and significantly impairing vision. Given the absence of a cure, rehabilitation strategies are vital for enhancing visual perception.<br><br>METHODS: This study introduces a perceptual learning (PL) protocol for MD patients, focusing on improving motion perception, a key ability for navigating environments and social interactions. Patients underwent four weeks of motion discrimination training, with pretraining and post-training functional magnetic resonance imaging scans to study the underlying neural mechanisms. We also assessed generalization to an untrained multiobject tracking task in a subset of participants. A control group, matched by age and gender with simulated scotomata, followed the same procedures.<br><br>RESULTS: Results in both groups indicated improved motion discrimination and increased responses in the human middle temporal complex (hMT+), a critical neural hub for motion processing. Improvements in the multiobject tracking task suggested transferable learning effects.<br><br>CONCLUSIONS: These findings highlight perceptual learning as a promising rehabilitation strategy for MD and potentially other eye conditions.}, }
@article {pmid41885545, year = {2026}, author = {Zhang, K and Jia, L and Zhao, C and Wang, Y and Wei, P and Han, G}, title = {Genetic Evidence for Causal Effects of Blood Metabolites on Age-Related Macular Degeneration and its Subtypes.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {3}, pages = {31}, doi = {10.1167/tvst.15.3.31}, pmid = {41885545}, issn = {2164-2591}, mesh = {Humans ; Mendelian Randomization Analysis ; *Macular Degeneration/genetics/blood/metabolism/classification ; Aged ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is a predominant cause of permanent vision impairment among older individuals. Despite available treatments for advanced disease, a comprehensive understanding of the pathogenesis, specifically the pivotal causal pathways, remains elusive. This study aims to assess the causal effects of 1400 serum metabolites and their ratios on 3 AMD subtypes using Mendelian randomization (MR).<br><br>METHODS: This study leveraged an integrated MR analytical framework to systematically investigate the causal relationships of 1400 circulating metabolites and metabolite ratios with 3 AMD subtypes: early, dry, and wet AMD. The robustness and consistency of the findings were validated via comprehensive sensitivity analyses, alongside assessments for heterogeneity and horizontal pleiotropy.<br><br>RESULTS: Of the 1400 metabolites and metabolite ratios examined, inverse variance weighting identified 77, 62, and 80 metabolites with statistically significant causal associations with early, dry, wet AMD, respectively. Most of these associations demonstrated consistency across complementary MR methodologies. Furthermore, most of the identified metabolites did not show significant evidence of heterogeneity or horizontal pleiotropy. Notably, among lipid classes, glycerophosphoethanolamine (GPE) metabolites consistently exhibited protective effects.<br><br>CONCLUSIONS: Multiple metabolite classes, including glycerophospholipids, fatty acids, steroid hormones, and energy metabolism intermediates, are involved in AMD pathogenesis. These findings confirm that metabolic dysregulation is the principal driver of AMD at the causal level, in addition to revealing heterogeneous effect sizes of distinct metabolic pathways across disease subtypes. This study reveals potential molecular targets for developing strategies based on metabolism for AMD prevention, diagnosis, and precision therapeutics.<br><br>TRANSLATIONAL RELEVANCE: This work bridges fundamental metabolic discoveries to clinical application by identifying causal metabolites as novel therapeutic targets and informing strategies specific to disease subtypes for precision medicine and diagnostics in AMD.}, }
@article {pmid41887320, year = {2026}, author = {Boscia, G and Feo, A and Quarta, A and Stradiotto, E and Forte, P and Termite, AC and Mastropasqua, R and Savastano, A and Reibaldi, M and Eandi, CM and Boscia, F and Cicinelli, MV and Au, A and Tsui, E and Vujosevic, S and Schmidt-Erfurth, U and Sarraf, D and Sadda, SR and Romano, MR and Borrelli, E and Viggiano, P}, title = {Intraretinal Hyperreflective Foci: Pathophysiology, Imaging Features, and Clinical Implications Across Retinal Diseases.}, journal = {Progress in retinal and eye research}, volume = {}, number = {}, pages = {101464}, doi = {10.1016/j.preteyeres.2026.101464}, pmid = {41887320}, issn = {1873-1635}, abstract = {Intraretinal hyperreflective foci (IHRF) are a common but pathologically diverse optical coherence tomography (OCT) finding, increasingly recognized as a hallmark of retinal disease activity. IHRF have been described in age-related macular degeneration (AMD), where they may represent migrating retinal pigment epithelium cells, in diabetic retinopathy, retinal vein and artery occlusions, pachychoroid spectrum disorders, inherited retinal dystrophies, and ocular inflammatory diseases. Their appearance reflects a spectrum of underlying processes, including inflammatory cell recruitment, lipid or proteinaceous material deposition, and degenerative tissue remodeling. Advances in OCT technology and multimodal imaging have refined the characterization of IHRF, enabling correlations with histopathology, cytokine profiles, and genetic risk variants. Across diseases, their presence, number, distribution, and temporal evolution have been linked to structural progression, functional decline, and treatment response-serving as early indicators of atrophy or neovascularization in AMD, markers of inflammation and therapeutic responsiveness in vascular retinopathies, and predictors of recurrence or complication in pachychoroid disease. This review provides a comprehensive synthesis of the current literature on IHRF, summarizing their proposed histopathological correlates, multimodal imaging features, molecular associations, prognostic significance, and potential role as biomarkers in a wide range of retinal disorders.}, }
@article {pmid41879246, year = {2026}, author = {Pu, J and Gao, L and Thomas, TN and Goerdt, L and Corradetti, G and Kar, D and McGwin, G and Crosson, JN and Owsley, C and Curcio, CA}, title = {Choriocapillaris Flow Signal Deficits Are Associated With AMD Onset and Early Progression Over Three Years: ALSTAR2 Follow-Up.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {51}, doi = {10.1167/iovs.67.3.51}, pmid = {41879246}, issn = {1552-5783}, mesh = {Humans ; Disease Progression ; Male ; Female ; Aged ; *Choroid/blood supply ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; Fluorescein Angiography/methods ; Middle Aged ; *Macular Degeneration/physiopathology/diagnosis ; Regional Blood Flow/physiology ; Aged, 80 and over ; *Capillaries/physiopathology ; *Retinal Vessels/physiopathology ; }, abstract = {PURPOSE: To determine if a baseline choriocapillaris flow signal deficits (CCFD%), as a marker of impaired transport, is associated with age-related macular degeneration (AMD) onset and progression at the 3-year follow-up.<br><br>METHODS: Participants &#x2265; 60 years old with normal macular health, early AMD (eAMD), and intermediate AMD (iAMD) were staged at baseline and follow-up with the Age-Related Eye Disease Study (AREDS) 9-step classification system and were then classified as stable and progressing based on whether their stage advanced. Spectral-domain optical coherence tomography angiography (OCTA) quantified baseline CCFD% across the Early Treatment Diabetic Retinopathy Study (ETDRS) central subfield (CS), inner ring (IR), and an outer area (OA, extending superiorly). Adjusted baseline CCFD% values were compared between stable and progressing eyes.<br><br>RESULTS: Of 332 included eyes at baseline (mean age, 71.1 &#xb1; 5.8 years), 173 eyes were normal, 101 were eAMD, and 58 were iAMD. Over 3 years, 284 eyes remained stable (85.5%), and 48 eyes progressed (14.5%). In the overall cohort, progressing eyes demonstrated significantly higher baseline CCFD% than stable eyes in the CS (57.7% vs. 53.5%; P = 0.007) and IR (56.1% vs. 53.9%; P = 0.045), but not in the OA. When stratified by baseline AMD stage, stable versus progressor differences were exclusively observed in eAMD (51.4% vs. 60.7% and 52.6 vs. 58.0% for CS and IR, respectively) but not in OA or in normal eyes (all P > 0.05).<br><br>CONCLUSIONS: CCFD% in the CS and IR, one aspect of impaired transport between circulation and photoreceptors, is associated with AMD progression in early-stage disease; this spatial specificity implicates the fovea.}, }
@article {pmid41879420, year = {2026}, author = {Lishinsky-Fischer, N and Jaskoll, S and Kramer, A and Grunin, M and Elbaz-Hayoun, S and Rinsky, B and Chowers, I and Levy, J}, title = {Distinct Genetic Profiles Associated With Subretinal Drusenoid Deposits and Cardiovascular Risk in Age-Related Macular Degeneration.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {3}, pages = {27}, doi = {10.1167/tvst.15.3.27}, pmid = {41879420}, issn = {2164-2591}, mesh = {Humans ; *Macular Degeneration/genetics/complications ; Female ; *Retinal Drusen/genetics ; Male ; Aged ; Retrospective Studies ; *Polymorphism, Single Nucleotide ; *Cardiovascular Diseases/genetics ; Aged, 80 and over ; Middle Aged ; Tomography, Optical Coherence ; Genetic Predisposition to Disease ; Gene Frequency ; Genotype ; Risk Factors ; Phenotype ; }, abstract = {PURPOSE: Subretinal drusenoid deposits (SDDs) are increasingly recognized as a distinct phenotype in age-related macular degeneration (AMD) and may be linked to cardiovascular disease (CVD). This study aims to explore whether AMD patients with SDDs carry a distinct genetic profile related to CVD risk compared to those without SDDs.<br><br>METHODS: In a retrospective cohort of 459 AMD patients with genotyping and spectral-domain OCT data, we annotated SDD status and extracted cardiovascular diagnoses and procedures from electronic medical records. Fifty-two AMD-associated single-nucleotide polymorphisms (SNPs) were used to calculate weighted genetic risk scores (GRSs), and minor allele frequencies (MAFs) were compared between groups. Principal component analysis (PCA) was performed to assess clustering by SDD status within CVD subgroups.<br><br>RESULTS: Patients with SDDs exhibited distinct MAFs in several SNPs, including CFH, ARMS2, COL4A3, and ARHGAP21. Certain variants were more strongly associated with cardiovascular subtypes in patients with SDDs compared to those without. GRSs related to lipid metabolism and complement pathways were higher among SDD-positive patients within selected CVD subgroups. PCA suggested modest but significant separation between genetic profiles of patients with and without SDDs.<br><br>CONCLUSIONS: AMD patients with SDDs show distinct genetic signatures potentially relevant to cardiovascular health. These findings suggest that SDDs may represent a genetically and systemically unique AMD phenotype. Further investigation is warranted to understand the shared pathophysiology and potential for systemic risk stratification.<br><br>TRANSLATIONAL RELEVANCE: Integrating OCT phenotyping and genomic profiling in AMD may uncover systemic disease associations with implications for precision medicine.}, }
@article {pmid41879644, year = {2026}, author = {Capuano, V and Fragiotta, S and Abadou, J and Sacconi, R and Miere, A and Amoroso, F and Souied, EH and Querques, G}, title = {Centenarian patients with neovascular age-related macular degeneration.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004837}, pmid = {41879644}, issn = {1539-2864}, abstract = {PURPOSE: To report clinical characteristics of exudative neovascular age-related macular degeneration (AMD) in centenarian patients.<br><br>METHODS: A retrospective, longitudinal study conducted in two retinal referral centers in Europe. Clinical characteristics of neovascular AMD patients having at last follow up at least &#x2265; 100 years were reviewed.<br><br>RESULTS: Twenty-eight eyes from 14 patients (13 females), with a mean baseline age of 95.7 (SD 4.1) years and a mean follow-up duration of 89 months (39.9). The mean age at last follow-up was 102.4 (1.7) years. Most eyes (86%) presented type 1 macular neovascularization (MNV). At the last follow-up, best corrected visual acuity (BCVA) was stable or improved in 57% of eyes, with a mean final BCVA of 53 letters (21.8) Snellen equivalent 20/100. Eyes with better visual outcomes (>50 letters) had significantly higher baseline BCVA (p<0.001) and thicker subfoveal choroidal thickness (p=0.03). Macular hemorrhage (25%) and macular atrophy (53.6%) were associated with poorer BCVA.<br><br>CONCLUSION: Centenarian patients with neovascular AMD can maintain vision with long-term anti-VEGF therapy. These findings underscore the need for tailored management strategies for the challenges faced by centenarians with neovascular AMD.}, }
@article {pmid41880726, year = {2026}, author = {Karapapak, M and Özal, E and Ermiş, S and Önal, I and Gül, C and Özal, SA}, title = {Prevalence and progression of non-exudative macular neovascularization in age-related macular degeneration.}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {4}, pages = {104835}, doi = {10.1016/j.jfo.2026.104835}, pmid = {41880726}, issn = {1773-0597}, abstract = {PURPOSE: To determine the prevalence of non-exudative macular neovascularization (neMNV) in age-related macular degeneration (AMD) and to identify potential markers for activation and disease progression using findings from optical coherence tomography angiography (OCTA).<br><br>MATERIALS AND METHODS: This retrospective longitudinal study included patients with treatment-na&#xef;ve neMNV secondary to AMD who presented to a tertiary retina clinic between January 2021 and July 2024. Patients were evaluated using OCT and OCTA at each visit, with a definitive diagnosis of neMNV established using OCTA. Exclusion criteria included prior anti-VEGF therapy, pachychoroid spectrum diseases, vitreoretinal surgery, chorioretinal conditions, and unreliable OCTA images. Parameters assessed included best-corrected visual acuity (BCVA), and lens status.<br><br>RESULTS: neMNV was identified in 186 out of 3119 patients (5.96%). The mean age was 72.73&#xb1;8.60 years, with a mean follow-up of 22.11&#xb1;7.51&#xa0;months. Transition from the non-exudative to the exudative form occurred in 34 (18.3%) patients, with an average activation duration of 14.71&#xb1;8.42 months. BCVA improved significantly in neMNV eyes over time (P<0.01) but remained stable in fellow eyes. No significant correlations were found between activation time and age, gender, or laterality. The prevalence of exudative MNV in fellow eyes was 67%.<br><br>CONCLUSIONS: neMNV is relatively common among AMD patients, with a prevalence of 5.96%. Regular monitoring using OCTA is essential for early detection and management, given the significant potential for these lesions to progress to an exudative state. Future research should focus on identifying specific biomarkers and imaging characteristics predictive of neMNV activation.}, }
@article {pmid41881234, year = {2026}, author = {Goerdt, L and Basten, V and Terheyden, JH and Dunbar, H and Luhmann, U and Zakaria, N and Leal, S and Moll, KP and Poor, S and Tufail, A and Schmid, M and Finger, RP and Schmitz-Valckenberg, S and Holz, FG and Saßmannshausen, M and , }, title = {Hyperreflective foci contiguous with the RPE associate with visual function in aging, early and intermediate AMD: MACUSTAR study report.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.03.020}, pmid = {41881234}, issn = {1879-1891}, abstract = {PURPOSE: To evaluate the association of hyperreflective foci contiguous with the retinal pigment epithelium (rpeHRF) with visual function impairment in aged normals, early (e) age-related macular degeneration (AMD), and intermediate (i) AMD.<br><br>DESIGN: Prospective cohort study.<br><br>SUBJECTS: Participants of the MACUSTAR study.<br><br>METHODS: MACUSTAR participants underwent color fundus photography, optical coherence tomography (OCT) imaging, best-corrected visual acuity (BCVA), low luminance VA (LLVA), rod-mediated dark adaptation (RMDA) at 12&#xb0;, contrast sensitivity (CS), mesopic, and scotopic pointwise sensitivity deviation (mesPSD, scPSD) testing. rpeHRF presence and count were determined using custom FiJi software. Group comparisons and associations with visual function were analyzed using ANOVA, linear regression, and Spearman correlation.<br><br>MAIN OUTCOME MEASURES: Presence, burden, topographic distribution of rpeHRF; association with functional parameters.<br><br>RESULTS: Fifty-six normal aged (33 female (f), mean age 68.1 &#xb1; 6.4 years), 34 eAMD (27 f, 71.7 &#xb1; 6.4 years), and 583 iAMD eyes (387 f, 72.0 &#xb1; 7.0 years) were included. rpeHRF counts were 0.16 &#xb1; 0.85 in normals, 0.33 &#xb1; 0.96 in eAMD, and 1.61 &#xb1; 2.49 in iAMD (p < 0.001). BCVA, LLVA, CS (all p < 0.001), and scPSD (p&#x202f;=&#x202f;0.001) differed between disease groups. Whereas RMDA and mesPSD did not. In iAMD, eyes with rpeHRF showed worse BCVA, LLVA, CS, scPSD (all p < 0.001), and mesPSD (p&#x202f;=&#x202f;0.02). rpeHRF cound associated modestly with only CS, scPSD, LLVA, and BCVA.<br><br>CONCLUSIONS: Presence and burden of rpeHRF were independently associated with impaired visual function and may thus serve as a prognostic biomarker for disease progression and enrichment criterion for future interventional trials.}, }
@article {pmid41881262, year = {2026}, author = {Yasuda, H and Nakamura, S and Shirakawa, A and Kuse, Y and Mori, K and Shimazawa, M}, title = {Age-dependent induction of ER stress in retinal pigment epithelium impairs phagocytosis via ADAM17-dependent MERTK shedding.}, journal = {The Journal of biological chemistry}, volume = {}, number = {}, pages = {111397}, doi = {10.1016/j.jbc.2026.111397}, pmid = {41881262}, issn = {1083-351X}, abstract = {Retinal pigment epithelium (RPE) plays a crucial role in maintaining visual function by phagocytosing photoreceptor outer segments (POS). Age-related decline in RPE phagocytic activity has been linked to the development of degenerative retinal diseases, including age-related macular degeneration (AMD). However, the underlying mechanisms of RPE phagocytic dysfunction remain poorly understood. In this study, we examined age-related induction of endoplasmic reticulum (ER) stress in RPE cells and its association with POS phagocytosis using tissues from middle-aged mice and cultured RPE cells. In the RPE-choroid complex of 12-month-old mice, ER stress marker proteins were significantly upregulated compared to younger mice. Notably, this increase was absent in the neural retina at the same age. In cultured RPE cells, pharmacological induction of ER stress by tunicamycin (Tm) significantly reduced both phagocytic activity and lysosomal function. Treatment with sodium 4-phenylbutyrate, a chemical chaperone, and transfection with chaperone protein-inducible plasmids alleviated the ER stress-induced phagocytic dysfunction in RPE cells. In the lysates of ER stress-induced RPE cells, the extracellular domain of Mer tyrosine kinase receptor (MERTK) and phosphorylation of focal adhesion kinase were significantly decreased. Mechanistically, ER stress promoted the maturation of a disintegrin and metalloprotease 17 (ADAM17) through Ca[2+]-dependent activation of the Furin protease, leading to MERTK shedding. Furthermore, ADAM17 knockdown attenuated the Tm-induced impairment of POS internalization. Collectively, our findings suggest that ER stress impairs RPE phagocytosis through an integrated mechanism and may contribute to the pathogenesis of AMD.}, }
@article {pmid41881267, year = {2026}, author = {Dong, H and Ding, Q and Liu, M}, title = {Exploring the causal link between long-term elevated plasma caffeine levels and age-related eye diseases using Mendelian randomization.}, journal = {Experimental gerontology}, volume = {}, number = {}, pages = {113106}, doi = {10.1016/j.exger.2026.113106}, pmid = {41881267}, issn = {1873-6815}, abstract = {OBJECTIVE: Experimental evidence suggests that caffeine has the potential to reduce the risk of age-related eye diseases (AREDs). However, there is a lack of population-based evidence directly assessing whether long-term caffeine exposure benefits these conditions. In this study, we employ Mendelian randomization (MR) to evaluate the causal effects of long-term elevated plasma caffeine levels (PCL) on AREDs, including age-related macular degeneration (AMD), age-related cataract (ARC), and glaucoma.<br><br>METHODS AND ANALYSIS: Single-nucleotide polymorphisms strongly associated with PCL and located near the CYP1A2 and AHR genes, both key in caffeine metabolism, were selected as instrumental variables. The MR analyses then calculated the Wald ratio for each variant, with variant-specific estimates combined through a multiplicative random effects meta-analysis.<br><br>RESULTS: Our MR analysis showed that higher genetically predicted PCL were significantly associated with a reduced risk of dry AMD (odds ratio [OR], 0.651; 95% confidence interval [CI], 0.527-0.805; pFDR&#x202f;<&#x202f;0.001), wet AMD (OR, 0.582; 95% CI, 0.433-0.781; pFDR&#x202f;=&#x202f;0.001), ARC (OR, 0.812; 95% CI, 0.720-0.916; pFDR&#x202f;=&#x202f;0.001), and primary open-angle glaucoma (POAG) (OR, 0.753; 95% CI, 0.633-0.896; pFDR&#x202f;=&#x202f;0.002). Notably, an estimated 54.05% (95% CI: 19.25%-88.84%) of the protective effect of PCL on POAG was mediated through reduced intraocular pressure (IOP).<br><br>CONCLUSION: This MR study provides evidence that long-term higher plasma caffeine levels may reduce the risk of age-related eye diseases, including AMD, ARC, and POAG. Notably, approximately half of the protective effect of PCL on POAG is mediated through IOP reduction.<br><br>This study provides novel evidence on the long-term effects of caffeine on age-related eye diseases, including age-related macular degeneration (AMD), age-related cataract (ARC), and primary open-angle glaucoma (POAG). Unlike previous studies that used imprecise measures of caffeine exposure, such as caffeinated beverage intake, we utilized fasting plasma caffeine levels, offering a more accurate assessment of individual exposure. Through Mendelian randomization, we demonstrate that long-term caffeine exposure is independently associated with reduced risks of AMD and ARC, and is also linked to a lower risk of POAG, with approximately half of this effect mediated through intraocular pressure (IOP) reduction. Our findings suggest that caffeine could play a protective role in ocular health, offering new insights into potential prevention strategies for age-related eye diseases.}, }
@article {pmid41108153, year = {2025}, author = {Beckers, D and Lockington, D and Kretz, F and Beckers, L}, title = {Beyond the Label: Inconsistencies in AREDS2 Eye Supplements and a Call for Standardisation.}, journal = {Seminars in ophthalmology}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/08820538.2025.2577391}, pmid = {41108153}, issn = {1744-5205}, abstract = {PURPOSE: Age-related macular degeneration (AMD) remains a major cause of vision impairment among older adults globally. While treatment exists for the more aggressive, exudative form, options for managing nonexudative AMD are limited. One of the few interventions with scientific backing is the AREDS2 micronutrient formula, which has demonstrated an ability to slow disease progression in patients with intermediate AMD.This investigation set out to systematically assess over-the-counter supplements in the UK that are promoted for macular support, measuring how closely their contents align with the evidence-based AREDS2 formulation.<br><br>METHODS: Products marketed as beneficial for AMD were collected and analyzed. Their labeled ingredients and dosages were directly compared with the standardized nutrient profile outlined in the AREDS2 clinical trials.<br><br>RESULTS: The analysis revealed that most commercially available supplements deviated markedly from the AREDS2 formula. On average, vitamin C levels were 52.3% lower than recommended, vitamin E levels were 61.2% lower, and zinc content was reduced by 40.1%. Only a small subset of products fully matched both the composition and dosage of the reference formulation.<br><br>CONCLUSION: These findings highlight a significant gap between marketed claims and clinical evidence. Most supplements do not meet the established AREDS2 standards, potentially limiting their efficacy. Some were promoted specifically for AMD, while others used general "macular health" claims, adding to patient confusion. This inconsistency underscores the need for regulatory measures to enforce standardized labeling and formulation requirements to ensure informed clinical recommendations.}, }
@article {pmid41108452, year = {2025}, author = {Shen, LL and Applegate, CA and Rubin, GS and Sunness, JS}, title = {Patient-reported visual difficulties associated with geographic atrophy from age-related macular degeneration.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {412}, pmid = {41108452}, issn = {1573-2630}, support = {R01EY08552/NH/NIH HHS/United States ; }, mesh = {Humans ; *Geographic Atrophy/physiopathology/diagnosis/complications/etiology ; Male ; Female ; *Visual Acuity/physiology ; Prospective Studies ; Aged ; *Macular Degeneration/complications/diagnosis/physiopathology ; *Vision Disorders/etiology/physiopathology/diagnosis ; Tomography, Optical Coherence/methods ; Surveys and Questionnaires ; Cross-Sectional Studies ; Aged, 80 and over ; Follow-Up Studies ; Middle Aged ; }, abstract = {PURPOSE: To characterize visual difficulties associated with geographic atrophy (GA).<br><br>METHODS: A prospective study included 91 participants with bilateral GA. A visual activities questionnaire was administered at baseline and annually for 2&#xa0;years along with best-corrected visual acuity (BCVA) and GA size. Baseline questionnaire responses were compared using logistic regressions, and longitudinal changes were analyzed with generalized linear mixed-effect models. A small group of 12 participants with drusen without GA served as a comparison to participants with GA and good VA.<br><br>RESULTS: Compared to drusen participants, bilateral GA participants with BCVA of 20/50 or better reported significantly more difficulties in 8 vision-specific tasks. The frequencies of difficulty in reading small print, trouble with face recognition, and stopping driving were positively associated with GA severity cross-sectionally, measured by either BCVA or GA size, and increased over 2&#xa0;years (P&#x2009;<&#x2009;0.05 for each). Additional significant longitudinal changes included difficulty seeing in dim light (P&#x2009;=&#x2009;0.005) and locating a sign (P&#x2009;=&#x2009;0.008).<br><br>CONCLUSION: Reading, vision in dim illumination, face recognition, locating signs, and driving worsen over 2&#xa0;years in patients with GA, and may be the appropriate self-reported items to monitor in a clinical trial. These findings highlight the need for therapies addressing both GA enlargement and visual function decline.}, }
@article {pmid41109779, year = {2025}, author = {Lai, TYY and Kataoka, K and Hsieh, YT and Apte, RS and Bhende, M and Chang, A and Chaikitmongkol, V and Chen, Y and Chen, LJ and Cheung, GCM and Chhablani, J and Fong, KCS and Guymer, RH and Gomi, F and Huang, SS and Kim, JE and Kokame, GT and Koh, A and Li, X and Lim, JI and Ng, DSC and Okada, AA and Radke, NV and Sadda, SR and Sasaki, M and Sivaprasad, S and Shanmugam, MP and Verma, L and Wong, TY and Zhang, X and Lam, DSC}, title = {Corrigendum to "International consensuses and guidelines on etiology, diagnosis, treatment, and future developments of neovascular age-related macular degeneration (nAMD) by the Asia-Pacific Vitreo-retina Society (APVRS), the Asia-Pacific Ocular Imaging Society (APOIS) and the Academy of the Asia-Pacific Professors of Ophthalmology (AAPPO)" [Asia-Pac J Ophthalmol, Available online 29 August 2025, 100242 (2025) DOI:10.1016/j.apjo.2025.100242].}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {100249}, doi = {10.1016/j.apjo.2025.100249}, pmid = {41109779}, issn = {2162-0989}, }
@article {pmid41110782, year = {2025}, author = {Liu, H and Wong, DSL and Parikh, BH and Hao, M and Tan, QSW and Chee, PL and Lou, X and Kai, D and Lingam, G and Huang, D and Su, X and Liu, Z}, title = {Single-cell-pore-sized 3D printed scaffolds for retinal pigment epithelial cell therapy.}, journal = {Acta biomaterialia}, volume = {207}, number = {}, pages = {294-310}, doi = {10.1016/j.actbio.2025.10.033}, pmid = {41110782}, issn = {1878-7568}, mesh = {*Printing, Three-Dimensional ; *Tissue Scaffolds/chemistry ; *Retinal Pigment Epithelium/cytology/metabolism ; Humans ; Animals ; Rabbits ; Polyesters/chemistry ; Swine ; Porosity ; *Human Embryonic Stem Cells/cytology/metabolism ; *Cell- and Tissue-Based Therapy ; }, abstract = {Cell therapy is one of the most promising methods to treat retinal degenerative diseases, and crucial to its success is optimizing biomaterials to facilitate the delivery of retinal pigment epithelial (RPE) cells. This study explores the application of single-cell-pore-sized 3D printed polycaprolactone (PCL) scaffolds for cultivating human embryonic stem cell-derived RPE cell sheets. It compares them with track-etched polyethylene terephthalate (PET) membranes, the commercial products used in clinical trials for RPE cell delivery. We engineered two types of scaffolds at the microscale to optimize cell culture conditions, specifically focusing on pore size and fiber spacing. Protein expression analysis demonstrated that one scaffold with a pore size of ∼10 µm facilitated superior cellular integrity and function. Functional assessments, including barrier integrity, permeability, and phagocytosis assays, indicated that this scaffold enhanced nutrient exchange and maintained effective RPE functions akin to PET membranes. In an in vivo study, color fundus, optical coherence tomography, immunohistochemistry, and electroretinography revealed that 3D printed scaffolds exhibited biocompatibility, stability, and minimal inflammatory responses in the subretinal space of porcine models for 2 months and rabbit models for 14 months, with no adverse impact on retinal structure or function over either period. The findings suggest that 3D-printed biodegradable scaffolds present a viable alternative for RPE cell delivery, potentially advancing therapies for retinal degenerative conditions. STATEMENT OF SIGNIFICANCE: Cell therapy shows great promise for treating eye diseases that lead to vision loss. A crucial aspect of this therapy is delivering specialized retinal pigment epithelial (RPE) cells effectively. Our research presents a 3D-printed scaffold made from polycaprolactone (PCL), designed to carry RPE cells derived from human stem cells and dissolve after placement in the eye. We tested this scaffold in rabbits and pigs to evaluate its surgical handling, cell delivery effectiveness, and safety for human application. Our results refine implant design, paving the way for safer and more effective treatments for retinal diseases. Overall, this research enhances the application of cell therapy with scaffolds and offers valuable insights for future medical practices.}, }
@article {pmid41111635, year = {2025}, author = {Koksaldi, S and Karti, O and Saatci, AO}, title = {Anti-vascular endothelial growth factor therapies in ophthalmology.}, journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal}, volume = {14}, number = {3}, pages = {107-135}, pmid = {41111635}, issn = {2322-3219}, abstract = {BACKGROUND: Retinal diseases, including neovascular age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion, are leading causes of vision loss worldwide. The introduction of anti-vascular endothelial growth factor (anti-VEGF) therapies has dramatically changed the management of these conditions, offering targeted treatment that can preserve and even improve vision. We aimed to provide a comprehensive review of the development, clinical applications, and emerging indications of anti-VEGF therapies in ophthalmology, including biosimilar agents.<br><br>METHODS: A comprehensive literature search was conducted in PubMed/MEDLINE for English-language articles published up to 31 July 2025. Additional sources were identified through manual screening of reference lists. Included studies spanned various designs: clinical trials, meta-analyses, observational studies, and preclinical research. Keywords used in the search strategy included terms such as "anti-VEGF therapy", "biosimilar pharmaceuticals", "intravitreal and intrastromal anti-VEGF injections", "retinal diseases" including "macular degeneration" and "retinal neovascularization", "ranibizumab", and "bevacizumab", as well as relevant MeSH terms where applicable.<br><br>RESULTS: Anti-VEGF agents have transformed the management of retinal diseases such as neovascular age-related macular degeneration, diabetic macular edema, proliferative diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Newer agents such as brolucizumab and faricimab offer prolonged durability and enhanced anatomic outcomes, while biosimilars provide cost-effective alternatives. Anti-VEGF therapy has also shown promise in off-label or emerging indications such as neovascular glaucoma, corneal neovascularization, and other retinal or choroidal disorders including secondary macular edema and/or macular neovascularization associated with various forms of uveitis, diffuse choroidal hemangioma in Sturge-Weber Syndrome, hereditary retinal disorders such as fundus flavimaculatus, Coats-Like retinitis pigmentosa, Peripherin-2-associated retinopathy, immune checkpoint inhibitor use, radiation retinopathy, retinitis pigmentosa, Bietti crystalline dystrophy, autosomal recessive bestrophinopathy, melanocytoma-associated macular neovascular membrane, Best disease, Wyburn-Mason syndrome, choroidal osteoma, peripheral exudative hemorrhagic chorioretinopathy, traumatic choroidal rupture, torpedo maculopathy, optic disc melanocytoma, type 2 proliferative macular telangiectasia, and Coats disease. High-dose formulations and innovative delivery systems are under active investigation to reduce the treatment burden and extend dosing intervals.<br><br>CONCLUSIONS: Anti-VEGF therapies have revolutionized the field of ophthalmology, providing sight-saving treatment for a range of retinal diseases that were once considered untreatable or inevitably blinding. Today, anti-VEGF drugs are the go-to option for managing neovascular retinal disorders, thanks to their proven efficacy, favorable safety profile, and transformative impact on modern eye care.}, }
@article {pmid41111640, year = {2025}, author = {Abukhaled, Y}, title = {Reactive oxygen species and oxidative stress in ocular disease: from molecular mechanisms to targeted therapies.}, journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal}, volume = {14}, number = {3}, pages = {136-145}, pmid = {41111640}, issn = {2322-3219}, abstract = {BACKGROUND: Reactive oxygen species and oxidative stress are increasingly recognized as central drivers in the development of major ocular diseases, including cataracts, age-related macular degeneration, glaucoma, and diabetic retinopathy. The eye's unique environment-continuous light exposure, high oxygen tension, and abundant photosensitizers-renders it particularly vulnerable to ROS-mediated damage. This narrative review aims to synthesize current evidence on the molecular mechanisms of oxidative stress in ocular disease and highlight emerging therapeutic approaches.<br><br>METHODS: Targeted searches of PubMed, Scopus, and Google Scholar for literature published between 2000 and June 2025 were conducted. Keywords included "oxidative stress", "reactive oxygen species", "ocular disease", "cataract", "age-related macular degeneration", "glaucoma", and "diabetic retinopathy". Only English-language, peer-reviewed articles were considered. Relevant primary studies, clinical trials, reviews, and experimental reports were selectively incorporated, with an emphasis on recent publications and high-impact contributions to the field.<br><br>RESULTS: Evidence consistently demonstrates that ROS induce lipid peroxidation, protein oxidation, DNA damage, mitochondrial dysfunction, and disruption of redox-sensitive cellular signaling pathways across ocular tissues. In cataracts, oxidation of crystalline proteins and glutathione depletion are primary drivers of lens opacification. In age-related macular degeneration, mitochondrial dysfunction and lipofuscin accumulation promote retinal pigment epithelium degeneration and neovascularization. Glaucoma involves both trabecular meshwork oxidative injury, contributing to elevated intraocular pressure, and mitochondrial-driven retinal ganglion cell apoptosis. In diabetic retinopathy, hyperglycemia-induced ROS overload activates pathogenic pathways, leading to microvascular damage and neuronal dysfunction. Clinical and experimental studies support antioxidant therapies as adjunctive strategies, with the strongest evidence for Age-Related Eye Disease Study-based formulations in age-related macular degeneration and promising results for agents such as Coenzyme Q10 in glaucoma and sulforaphane in diabetic retinopathy. For cataracts, supplementation trials have yielded mixed outcomes and surgery remains the definitive treatment.<br><br>CONCLUSIONS: Oxidative stress represents a unifying mechanism in the pathogenesis of vision-threatening ocular diseases. Antioxidant-based interventions show potential, particularly when integrated with existing treatment regimens, but their translation into routine practice remains limited by heterogeneous trial results and the absence of robust biomarkers for patient selection. Future research should focus on precision antioxidant therapy, leveraging stage-specific interventions, novel delivery systems, and pathway-targeted compounds, to transform ocular care from reactive management toward prevention.}, }
@article {pmid41112795, year = {2025}, author = {Dhaliwal, KK and Simmons, J and Wong, A and Hudson, C and Wright, T and Ballios, BG and Bizheva, K}, title = {Visual stimulus-evoked transient blood flow and blood vessel diameter changes in the healthy human retina measured with a combined OCT+ERG system.}, journal = {Biomedical optics express}, volume = {16}, number = {10}, pages = {3958-3976}, pmid = {41112795}, issn = {2156-7085}, abstract = {Neurodegenerative retinal diseases, such as glaucoma, age-related macular degeneration and diabetic retinopathy, cause gradual damage to the retinal morphology, blood vasculature, and neuronal function, and ultimately lead to blindness. In this study, a retinal OCT system was combined with a clinical electroretinography (ERG) system to investigate visually-evoked transient changes in the retinal blood flow (RBF) and blood vessel diameter (BVD) in the healthy human retina. The OCT system offered 2.7 µm axial resolution in retinal tissue and 98 dB sensitivity for 1.1 mW imaging power and 250 kHz image acquisition rate. Doppler OCT (double circular scans around the optic nerve head) and ERG traces were acquired from healthy subjects in response to 10 Hz, white light flicker stimuli and different stimulus intensities. The ERG system was used to generate visual stimuli of precise timing, duration, luminance, and flicker frequency, as well as to confirm the retinal neuronal response to the visual stimulation. MATLAB-based custom algorithms were developed to track time-dependent changes in the RBF and BVD from the OCT images. Results from this study revealed a rapid transient increase in the RBF accompanied by transient vasoconstriction and vasodilation of the retinal blood vessels in response to the flicker stimulation. The amplitude and latency of the RBF and BVD responses were dependent on the stimulus intensity as well as the blood vessel type (arteries or veins).}, }
@article {pmid41114788, year = {2026}, author = {Zhou, Y and Liu, C and Yin, J and Zhao, D and Xue, F}, title = {From environmental exposure to retinal pathology: epidemiological and mechanistic insights into multi-metal driven ocular diseases.}, journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine}, volume = {39}, number = {1}, pages = {181-202}, pmid = {41114788}, issn = {1572-8773}, mesh = {Humans ; *Environmental Exposure/adverse effects ; Male ; *Macular Degeneration/epidemiology/chemically induced/pathology ; Female ; Middle Aged ; *Cataract/epidemiology/chemically induced ; *Cadmium/urine/toxicity ; Aged ; *Diabetic Retinopathy/epidemiology/chemically induced ; *Glaucoma/epidemiology/chemically induced ; *Retina/pathology/drug effects ; }, abstract = {With aging and environmental pollution, heavy metal exposure has become a growing concern for age-related eye diseases. However, the relationship between heavy metals and age-related macular degeneration (AMD), cataracts, glaucoma, and diabetic retinopathy (DR) remains unclear. This study investigates the association between urinary heavy metals and these eye diseases, focusing on the molecular mechanisms of cadmium (Cd) in driving AMD. Data from the 2005-2008 NHANES (n = 1865) were analyzed using multivariable logistic regression, weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), restricted cubic spline (RCS) modeling, and sensitivity analyses. Potential molecular mechanisms of Cd in AMD were explored via intersection gene screening, protein-protein interaction network construction, and GO/KEGG enrichment analyses. In single-metal exposure models, Cd was significantly associated with AMD (OR = 1.563, 95% CI: 1.177-2.077, P = 0.00205), Co with cataract (OR = 1.386), U with glaucoma (OR = 1.300), and As with DR (OR = 1.214). In the WQS model, only AMD remained significantly associated with the overall metal mixture (OR = 1.89, 95% CI: 1.22-2.91, P = 0.0041). BKMR identified Cd as the most influential contributor to AMD (PIP = 0.523). The exposure-response curve for Cd and AMD demonstrated an upward trend, with the risk of AMD increasing as Cd exposure levels rose. Additionally, the overall metal mixture was positively associated with AMD risk. Subgroup and RCS analyses confirmed the stability of results, with no significant interaction across demographic subgroups. Sensitivity analyses further validated the findings: the highest quartile of Cd exposure was associated with increased AMD risk (OR = 2.45), and a significant dose-response trend was observed (P for trend = 0.0187). The association remained robust after excluding outliers (OR = 1.31, P = 0.0483).Mechanistically, Cd may induce retinal pigment epithelium damage via oxidative stress (SIRT1/TP53 axis), inflammation (TLR4/NF-κB pathway and pro-inflammatory cytokines), dysregulated apoptosis (BCL2/BAX imbalance), and hypoxia-induced metabolic disruption (HIF-1 signaling). Cd is an independent risk factor for AMD, likely acting through multiple toxic pathways. The effects of U, Co, and As may depend on exposure thresholds or confounders. These findings highlight the need for stricter Cd control and targeted antioxidant or anti-inflammatory strategies for age-related eye disease prevention and treatment.}, }
@article {pmid41117141, year = {2026}, author = {Chen, C and Zhu, M and Fan, X and Lv, K and Jiang, K and Zhang, Y and Zhang, H and Qi, X and Lee, BT and Wan, Y and Wei, G and Liu, K and Xu, X}, title = {Continuous Suppression of Pathological Retinal and Choroidal Neovascularization in Cynomolgus Monkeys via Noninvasive Ophthalmic Delivery of a Novel Anti-VEGFA Nanobody and Proprietary Penetratin Analog Formulation.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {13}, number = {1}, pages = {e04660}, pmid = {41117141}, issn = {2198-3844}, support = {82271096//National Natural Science Foundation of China/ ; 81800835//National Natural Science Foundation of China/ ; 82273864//National Natural Science Foundation of China/ ; 21S11905300//Shanghai Science and Technology Program/ ; 21ZR1407100//Shanghai Science and Technology Program/ ; 18YF1419700//Shanghai Sailing Program/ ; //Shanghai Talent Development Fund/ ; //Shanghai Jiao Tong University K. C. Wong Medical Fellowship Fund/ ; //Lumitin Vision to Brightness Research Funding/ ; }, mesh = {Animals ; Macaca fascicularis ; *Choroidal Neovascularization/drug therapy/pathology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Disease Models, Animal ; *Single-Domain Antibodies/administration &amp; dosage/pharmacology ; *Retinal Neovascularization/drug therapy/pathology ; Ophthalmic Solutions ; Angiogenesis Inhibitors/pharmacology/administration &amp; dosage ; Retina/drug effects ; }, abstract = {Pathological retinal and choroidal neovascularization is a hallmark of several blinding diseases, including diabetic retinopathy and age-related macular degeneration. While intravitreal anti-VEGF therapies remain the standard of care, they necessitate frequent injections, posing risks such as endophthalmitis and elevated intraocular pressure, alongside economic and adherence challenges. Here, we present Pene/LQ015, a novel eye drop formulation comprising the anti-VEGFA nanobody (LQ015) and a proprietary penetratin analog for noninvasive delivery. LQ015 demonstrates superior VEGF-blocking activity, broad binding specificity across species, and robust stability and scalability using a yeast expression system. Topical administration of Pene/LQ015 achieved effective retinal-choroid complex drug levels and suppressed neovascularization in preclinical models. Notably, in the cynomolgus monkey laser-induced choroidal neovascularization model, 30 days of continuous topical application significantly reduced neovascularization and vascular leakage, with excellent safety and tolerability. These findings highlight Pene/LQ015's potential as a game-changer in treating neovascular eye diseases. It offers a groundbreaking, noninvasive alternative to intravitreal injections, addressing key limitations of current therapies by enabling continuous dosing, improving patient adherence, and reducing treatment burden. These findings underscore its potential to transform the management of neovascular retinal and choroidal diseases, with promising implications for clinical application.}, }
@article {pmid41117255, year = {2025}, author = {Yang, W and Jia, J and Liu, X and Wan, P}, title = {Evaluating the Impact of Age-Related Macular Degeneration on Seasonal Affective Disorder: A Retrospective Cohort Study in a Chinese Population.}, journal = {Actas espanolas de psiquiatria}, volume = {53}, number = {5}, pages = {939-946}, pmid = {41117255}, issn = {1578-2735}, mesh = {Humans ; Male ; Female ; Retrospective Studies ; *Seasonal Affective Disorder/complications/psychology/epidemiology ; *Macular Degeneration/complications/psychology ; China/epidemiology ; Aged ; Middle Aged ; Life Style ; East Asian People ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) usually affects the macular region of the retina, while seasonal affective disorder (SAD) is a complex mental disorder. However, the interaction between these two clinical conditions remains unexplored. Therefore, this study aimed to explore the influence of AMD on SAD and to assess the correlation of ocular pathology with lifestyle and mental health factors.<br><br>METHODS: This study recruited 158 AMD patients admitted to the Second Affiliated Hospital of Xi'an Medical University, China, between January 2020 and October 2023. Based on their affection status, the patients were divided into two groups: the SAD group (n = 58) and the non-SAD group (n = 100). Baseline characteristics, including blood pressure, hematological parameters, ocular parameters, and lifestyle factors, were compared between the two groups to evaluate the potential influence of AMD on SAD.<br><br>RESULTS: We observed specific differences in the family history of mental illness between the non-SAD and SAD groups (p < 0.001). However, the two groups' other baseline characteristics, such as blood pressure and hematological parameters, were comparable (p > 0.05). Additionally, significant differences were also observed in central retinal thickness (CRT), choroidal thickness, lesion atrophy area, and macular volume between the two groups (p < 0.001). Moreover, intraocular pressure (IOP) did not reveal a~significant difference between the two groups (p > 0.05). Compared with the SAD group, the non-SAD group had significantly better vision, longer exercise duration, sunlight exposure time, outdoor activity, and lower sedentary behavior (all p < 0.001). The logistic regression analysis indicated that increased macular volume (odds ratio (OR) = 3.054, p = 0.008) and sedentary behavior (OR = 4.382, p < 0.001) significantly increased SAD risk. Additionally, the absence of a family history of mental illness did not reach statistical significance (OR = 0.375, p = 0.129), but a specific correlation was still observed.<br><br>CONCLUSION: This study shows a correlation between SAD and AMD. The significant differences in ocular pathological characteristics, lifestyle factors, and mental health status between the SAD and non-SAD groups suggest the crucial role of visual function and lifestyle in regulating mood and circadian rhythm in AMD patients.}, }
@article {pmid41117364, year = {2026}, author = {García-Serrano Fuertes, R and Romero Martínez, A and Suarez Pérez, J and López Herrero, F and Cabanás Jiménez, M and Flores Córdoba, A and Sánchez Vicente, JL}, title = {Cost-effectiveness analysis of Brolucizumab compared to Aflibercept and Ranibizumab in nAMD with persistent retinal fluid.}, journal = {European journal of ophthalmology}, volume = {36}, number = {2}, pages = {231-239}, pmid = {41117364}, issn = {1724-6016}, mesh = {Humans ; *Recombinant Fusion Proteins/economics/therapeutic use/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; Cost-Benefit Analysis ; *Ranibizumab/economics/therapeutic use ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/economics/diagnosis ; *Angiogenesis Inhibitors/economics/therapeutic use ; Aged ; Female ; Male ; Visual Acuity ; *Antibodies, Monoclonal, Humanized/economics/therapeutic use ; *Subretinal Fluid ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Drug Costs ; Aged, 80 and over ; Cost-Effectiveness Analysis ; }, abstract = {Purpose of the researchThis study aimed to evaluate the cost-effectiveness of Brolucizumab in patients with exudative age-related macular degeneration (AMD) and persistent retinal fluid unresponsive to previous therapies, within the context of a real-world clinical practice setting in a Spanish referral hospital. Furthermore, the study examined the probabilities of transitioning between therapies.Major findingsA 6-month treatment projection demonstrated that Brolucizumab was not cost-effective compared to Ranibizumab (incremental cost-effectiveness ratio [ICER]: -12.98) and Aflibercept (ICER: -47.64). Conversely, when assessing only drug and administration visit costs, Brolucizumab appeared cost-effective (ICER of 9.14 versus Aflibercept and 35.01 versus Ranibizumab). The increased burden of follow-up costs, which were €348.96 higher than those for Ranibizumab and €174.48 higher than Aflibercept, likely drove the trend towards non-cost-effectiveness. Additionally, the analysis indicated a 43% probability of transitioning to Faricimab within the studied population.ConclusionsBrolucizumab was determined to be not cost-effective compared to Ranibizumab and Aflibercept in patients with exudative AMD and persistent retinal fluid, primarily due to a higher number of follow-up visits necessitated by its safety profile. Furthermore, newly observed vitreous opacities and a tendency towards the use of Faricimab were noted.}, }
@article {pmid41120131, year = {2025}, author = {Phan, LT and Hong, T and Chang, JH and Mehta, H and Fraser-Bell, S and Cheung, GCM and Broadhead, GK and Chang, AA}, title = {A prospective, open-label, single-arm, investigator-initiated clinical trial to assess the efficacy, safety and durability of faricimab in patients with inadequate response to current treatment for neovascular age-related macular degeneration: protocol design and rationale for the FURGGHORN Study.}, journal = {BMJ open ophthalmology}, volume = {10}, number = {1}, pages = {}, pmid = {41120131}, issn = {2397-3269}, mesh = {Aged ; Female ; Humans ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Intravitreal Injections ; Multicenter Studies as Topic ; Prospective Studies ; Research Design ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity/physiology ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Clinical Trials, Phase IV as Topic ; Antibodies, Bispecific ; }, abstract = {INTRODUCTION: Anti-vascular endothelial growth factor therapy has revolutionised the treatment of neovascular age-related macular degeneration (nAMD). However, some patients face recurrent and persistent disease activity despite ongoing treatment. Faricimab (trade name: Vabysmo) is a recently approved therapy which targets two pathways involved in nAMD. This study aims to assess changes in best-corrected visual acuity (BCVA) and treatment frequency among patients currently treated for nAMD who switch to intravitreal faricimab therapy under a treat-and-extend regimen.<br><br>METHODS AND ANALYSIS: The FURGGHORN Study is a prospective, open-label, single-arm, multicentre investigator-initiated clinical trial. 102 patients with nAMD meeting inclusion criteria were recruited from 12 clinical sites across Australia and Singapore. Following 4&#x2009;monthly loading doses of faricimab, treatment intervals were adjusted according to a regimen developed based on real-world practice patterns and consensus guidelines. The primary endpoint is the change from BCVA at week 52. Secondary endpoints include the proportions of patients at different treatment intervals, changes in central macular thickness and retinal fluid dimensions.<br><br>ETHICS AND DISSEMINATION: This study was designed, implemented and reported in accordance with the International Conference on Harmonisation Harmonised Tripartite Guidelines for Good Clinical Practice, with applicable local regulations and with the ethical principles laid down in the Declaration of Helsinki. Ethics approval was obtained from Bellberry Limited (2022-12-1388), St Vincent's Hospital Human Research Ethics Committee (2023/STE01568) and Singhealth Centralized Institutional Review Board (2023-2190). Results will be disseminated at scientific meetings and through peer-reviewed publications.<br><br>TRIAL REGISTRATION NUMBER: ACTRN12623000215628.}, }
@article {pmid41122382, year = {2025}, author = {Wang, W}, title = {LLM-based multi-agent system for neuro-ophthalmic diagnosis and personalized treatment planning.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1688509}, pmid = {41122382}, issn = {1662-4548}, abstract = {INTRODUCTION: Ophthalmic findings can non-invasively reflect nervous-system status. We present an LLM-based multi-agent framework that preserves diagnostic uncertainty to support neuro-ophthalmic screening and referral.<br><br>METHODS: Heterogeneous inputs (clinical text/PDFs and optional fundus/OCT images) are normalized by an Information Collection Agent. A Diagnosis Agent ensembles multiple LLMs and, when available, a CNN image branch; outputs are aggregated with an uncertainty-aware fusion.<br><br>RESULTS: Across a curated ophthalmic corpus, the multi-agent framework improves robustness over single-model baselines and produces multi-candidate distributions suitable for downstream triage and monitoring.<br><br>DISCUSSION: Uncertainty-aware, multi-candidate predictions align with clinical decision-making under ambiguity and suggest future work on calibration and knowledge-layer fusion.}, }
@article {pmid41122527, year = {2025}, author = {Bates, BA and Mansour, HA and Al-Khersan, H and Wood, E and Momenaei, B and Schneider, E and Richards, CJ and DeYoung, C and Wykoff, CC and Quinn, K and Hsu, J and Regillo, CD and Ho, AC and Fineman, MS and Klufas, MA and Storey, PP}, title = {The Efficacy and Safety of Intravitreal Aflibercept 8 mg in Clinical Practice.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251383384}, pmid = {41122527}, issn = {2474-1272}, abstract = {Purpose: To characterize real-world use of intravitreal aflibercept 8 mg across 22 US retina practices. Methods: Retrospective review of patients who received at least 1 intravitreal aflibercept 8 mg injection for treatment of neovascular age-related macular degeneration, diabetic macular edema, or diabetic retinopathy through April 1, 2024. Data from health records were collected retrospectively, including best-corrected visual acuity (BCVA), interval between treatments, and adverse events. Results: A total of 8323 eyes of 6271 patients received 20 385 intravitreal aflibercept 8 mg injections. A total of 669 eyes (8.0%) were not previously treated. Among treatment-naive eyes, mean logMAR BCVA improved from 0.57 (Snellen equivalent ~20/80) at the time of the first intravitreal aflibercept 8 mg injection, to 0.47 (Snellen equivalent ~20/60) (P < .001), 0.46 (Snellen equivalent ~20/60) (P < .001), and 0.48 (Snellen equivalent ~20/60) (P = .012) at the second, third, and fourth intravitreal aflibercept 8 mg injections, respectively. Among previously treated eyes, mean logMAR BCVA improved from 0.46 (Snellen equivalent ~20/60) at the time of the first intravitreal aflibercept 8 mg injection, to 0.42 (Snellen equivalent ~20/50) (P < .001), 0.43 (Snellen equivalent ~20/50) (P < .001), and 0.45 (Snellen equivalent ~20/60) (P = .70) at the second, third, and fourth intravitreal aflibercept 8 mg injections, respectively. Treatment intervals to time of second, third, and fourth intravitreal aflibercept 8 mg injections increased compared to baseline intervals, by a mean of 2.2 days (P < .001), 2.5 days (P < .001), and 13.5 days (P < .001), respectively. Intraocular inflammation was observed in 11 eyes (1 in 1853 injections). Nine eyes (1 in 2265 injections) developed suspected endophthalmitis. Conclusions: In this real-world clinical setting, intravitreal aflibercept 8 mg treatment demonstrated improvements in BCVA outcomes, with increased intervals between injections. Rates of intraocular inflammation and endophthalmitis were low.}, }
@article {pmid41123658, year = {2026}, author = {Chakravarthy, U and Foss, AJE and Panos, GD and Peto, T and Rotsos, T and Sadda, S and De Cock, E and Empeslidis, T}, title = {Management of fibrosis in neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {1}, pages = {19-34}, pmid = {41123658}, issn = {1435-702X}, mesh = {Humans ; Fibrosis/etiology/drug therapy ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis/complications ; *Visual Acuity ; *Disease Management ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; *Retinal Pigment Epithelium/pathology ; }, abstract = {Subretinal fibrosis is a common end-stage sequela of neovascular age-related macular degeneration (nAMD), and it is associated with poor long-term visual outcomes. The pathogenesis of subretinal fibrosis in nAMD is largely driven by epithelial-mesenchymal and endothelial-mesenchymal transition within the retinal pigment epithelium and endothelium of the choroidal circulation. Upregulation of vascular endothelial growth factor (VEGF) expression further contributes to the observed fibrovascular content and increased vascular permeability. There is a substantial need for direct therapeutic strategies for fibrosis in nAMD, including anti-fibrotic agents. Until direct treatment strategies are developed, the management of nAMD using anti-VEGF agents must be optimized. However, fibrosis can occur in some patients otherwise successfully treated with anti-VEGF therapy, resulting in the loss of previous visual acuity (VA) gains experienced after treatment initiation. This review summarizes the current understanding of the mechanisms driving fibrosis in nAMD, risk factors for fibrosis development, and limitations of current detection methods. Available evidence on how different factors relating to anti-VEGF therapy (e.g., specific agent, delays in administration, extended administration intervals, dosing or treatment regimen) and the early detection of nAMD impact the risk of fibrosis is also discussed. Lastly, insights into potential future directions for the management of fibrosis in nAMD, particularly the development of anti-fibrotic agents, are deliberated.}, }
@article {pmid41124203, year = {2026}, author = {Holz, FG and Le Mer, Y and Muqit, MMK and Hattenbach, LO and Cusumano, A and Grisanti, S and Kodjikian, L and Pileri, MA and Matonti, F and Souied, E and Stanzel, BV and Szurman, P and Weber, M and Bartz-Schmidt, KU and Eter, N and Delyfer, MN and Girmens, JF and van Overdam, KA and Wolf, A and Hornig, R and Corazzol, M and Brodie, F and Olmos de Koo, L and Palanker, D and Sahel, JA}, title = {Subretinal Photovoltaic Implant to Restore Vision in Geographic Atrophy Due to AMD.}, journal = {The New England journal of medicine}, volume = {394}, number = {3}, pages = {232-242}, pmid = {41124203}, issn = {1533-4406}, support = {NIHR203322/DH_/Department of Health/United Kingdom ; R01 EY035227/EY/NEI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Eyeglasses ; *Geographic Atrophy/etiology/pathology/surgery ; *Macular Degeneration/complications/pathology/surgery ; Prospective Studies ; Retina/pathology/surgery ; *Visual Acuity ; *Visual Prosthesis/adverse effects ; Follow-Up Studies ; Minimal Clinically Important Difference ; Treatment Outcome ; }, abstract = {BACKGROUND: Geographic atrophy due to age-related macular degeneration (AMD) is the leading cause of irreversible blindness and affects more than 5 million persons worldwide. No therapies to restore vision in such persons currently exist. The photovoltaic retina implant microarray (PRIMA) system combines a subretinal photovoltaic implant and glasses that project near-infrared light to the implant in order to restore sight to areas of central retinal atrophy.<br><br>METHODS: We conducted an open-label, multicenter, prospective, single-group, baseline-controlled clinical study in which the vision of participants with geographic atrophy and a visual acuity of at least 1.2 logMAR (logarithm of the minimum angle of resolution) was assessed with PRIMA glasses and without PRIMA glasses at 6 and 12 months. The primary end points were a clinically meaningful improvement in visual acuity (defined as &#x2265;0.2 logMAR) from baseline to month 12 after implantation and the number and severity of serious adverse events related to the procedure or device through month 12.<br><br>RESULTS: A total of 38 participants received a PRIMA implant, of whom 32 were assessed at 12 months. Of the 6 participants who were not assessed, 3 had died, 1 had withdrawn, and 2 were unavailable for testing. Among the 32 participants who completed 12 months of follow-up, the PRIMA system led to a clinically meaningful improvement in visual acuity from baseline in 26 (81%; 95% confidence interval, 64 to 93; P<0.001). Using multiple imputation to account for the 6 participants with missing data, we estimated that 80% (95% CI, 66 to 94; P<0.001) of all participants would have had a clinically meaningful improvement at 12 months. A total of 26 serious adverse events occurred in 19 participants. Twenty-one of these events (81%) occurred within 2 months after surgery, of which 20 (95%) resolved within 2 months after onset. The mean natural peripheral visual acuity after implantation was equivalent to that at baseline.<br><br>CONCLUSIONS: In this study involving 38 participants with geographic atrophy due to AMD, the PRIMA system restored central vision and led to a significant improvement in visual acuity from baseline to month 12. (Funded by Science Corporation and the Moorfields National Institute for Health and Care Research Biomedical Research Centre; PRIMAvera ClinicalTrials.gov number, NCT04676854.).}, }
@article {pmid41125297, year = {2026}, author = {Li, Z and Pan, Z and Huang, Y and Xie, H and Wu, X and Zhang, C and Wong, TY and Jonas, JB and Wang, YX}, title = {Cigarette smoking and retinal ganglion cell layer and photoreceptor outer segment thickness: The Beijing Eye Study.}, journal = {The British journal of ophthalmology}, volume = {110}, number = {4}, pages = {446-451}, doi = {10.1136/bjo-2024-326789}, pmid = {41125297}, issn = {1468-2079}, mesh = {Humans ; Male ; Female ; Middle Aged ; Tomography, Optical Coherence/methods ; *Retinal Ganglion Cells/pathology ; Aged ; Beijing/epidemiology ; *Cigarette Smoking/adverse effects/epidemiology ; *Retinal Photoreceptor Cell Outer Segment/pathology ; Cross-Sectional Studies ; China/epidemiology ; Prevalence ; Surveys and Questionnaires ; }, abstract = {PURPOSE: To examine an association of cigarette smoking on retinal layer thickness.<br><br>METHODS: The population-based Beijing Eye Study 2011 included 3468 individuals aged 50+ years. All participants underwent optical coherence tomography (OCT) of the macula. Using a multiple-surface OCT segmentation algorithm, the retina was segmented into nine layers. Information about cigarette smoking was assessed in an interview with a standardised questionnaire. The exclusion criterion was the presence of any retinal or optic nerve disease.<br><br>RESULTS: The study included 2173 participants (mean age: 61.7&#xb1;8.4 years; mean axial length: 23.1&#xb1;0.8&#x2009;mm) with 660 (30.4%) participants with a smoking history and 1513 (69.6%) non-smokers. Mean duration of the smoking period was 8.7&#xb1;14.9 years, and mean smoking quantity was 9.5&#xb1;18.2 pack-years. In multivariable analysis, higher prevalence of smoking was associated with thinner whole retina (p=0.024; B=-1.64; 95% CIs -3.07 to -0.22), thinner ganglion cell layer (GCL) (p=.044; B=-0.39; 95%&#x2009;CI -0.78 to -0.01) and thinner photoreceptor outer segment layer (POS) (p=0.024; B=-0.38; 95%&#x2009;CI -0.72 to -0.05) with adjustments of age, gender, axial length, education level and hypertension. Similar results were obtained if the retinal thickness measurements were obtained in the various macular subfields. A longer period of smoking was related to thinner whole retina (p=0.009; B=-0.06; 95%&#x2009;CI -0.10 to -0.01), thinner retinal nerve fibre layer (RNFL) (p=0.011; B=-0.01; 95%&#x2009;CI -0.02 to -0.002), thinner GCL (p=0.006; B=-0.02; 95%&#x2009;CI -0.03 to -0.01) and thinner POS (p=0.025; B=-0.01; 95%&#x2009;CI -0.02 to -0.001) with adjustments of age, gender, axial length, education level and hypertension. Higher smoking pack-years were significantly associated with thinner GCL (p=0.022; B=-0.01; 95%&#x2009;CI -0.02 to -0.002).<br><br>CONCLUSIONS: Smoking was related to thinner GCL and POS in this population-based investigation, pointing towards and agreeing with an association between smoking and optic nerve damage or age-related macular degeneration.}, }
@article {pmid41129131, year = {2025}, author = {Shor, R and Popovic, MM and Muni, RH}, title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs-Reply.}, journal = {JAMA ophthalmology}, volume = {143}, number = {12}, pages = {1077-1078}, doi = {10.1001/jamaophthalmol.2025.3723}, pmid = {41129131}, issn = {2168-6173}, }
@article {pmid41129133, year = {2025}, author = {Ahuja, AS and Paredes, AA and Young, BK}, title = {Glucagon-Like Peptide-1 Receptor Agonists and Age-Related Macular Degeneration.}, journal = {JAMA ophthalmology}, volume = {143}, number = {12}, pages = {999-1003}, pmid = {41129133}, issn = {2168-6173}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; Aged ; *Glucagon-Like Peptide-1 Receptor Agonists ; Middle Aged ; Hypoglycemic Agents/therapeutic use ; *Macular Degeneration/epidemiology ; Obesity/drug therapy/complications ; Glucagon-Like Peptides/therapeutic use ; Liraglutide/therapeutic use ; Disease Progression ; Diabetes Mellitus, Type 2/drug therapy ; Risk Factors ; Glucagon-Like Peptide 1 ; Semaglutide ; }, abstract = {IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for weight loss, but their ocular effects in nondiabetic individuals remain unclear. Prior studies suggest GLP-1RA use reduced age-related macular degeneration (AMD) risk in patients with diabetes, but applicability to nondiabetic populations is unknown.<br><br>OBJECTIVE: To evaluate the risk of developing nonexudative AMD and its progression to exudative AMD among patients with obesity but not diabetes prescribed GLP-1RAs compared with those prescribed other weight-loss drugs (OWLDs).<br><br>This retrospective cohort study used electronic health record data obtained from the multicenter TriNetX Global Collaborative Network on patients aged 55 years or older diagnosed with overweight or obesity but not diabetes from January 2004 to July 2025. For the primary analysis, patients with preexisting nonexudative AMD were excluded. For the secondary analysis, patients with preexisting nonexudative AMD were included, while those with preexisting exudative AMD were excluded. Propensity score matching balanced baseline demographics and comorbidities. Data were analyzed on March 21, 2025, and August 2, 2025.<br><br>EXPOSURES: Patients were prescribed either the GLP-1RAs liraglutide or semaglutide or OWLDs including lorcaserin, sibutramine, setmelanotide, fenfluramine, mazindol, orlistat, phentermine, and diethylpropion.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was development of nonexudative AMD at 5, 7, and 10 years. The secondary outcome was progression to exudative AMD at 10 years. Risk ratios (RRs) with 95% CIs were calculated. Standardized mean differences were used to assess covariate balance after matching.<br><br>RESULTS: A total of 91&#x202f;408 patients were included. After propensity score matching for the primary analysis, 45&#x202f;704 patients remained in each of the GLP-1RA and OWLD cohorts. The GLP-1RA cohort included 35&#x202f;753 (78.2%) females and 7852 (17.2%) males with a mean (SD) age of 61.1 (5.76) years, while the OWLD cohort included 35&#x202f;732 (78.2%) females and 7815 (17.1%) males with a mean [SD] age of 61.0 (5.86) years. Covariate balance was achieved across all variables for the GLP-1RA and OWLD cohorts in the primary analysis. GLP-1RA use was associated with reduced risk of nonexudative AMD compared with OWLDs at 5 years (RR, 0.16; 95% CI, 0.10-0.28; P&#x2009;<&#x2009;.001), 7 years (RR, 0.13; 95% CI, 0.08-0.22; P&#x2009;<&#x2009;.001), and 10 years (RR, 0.09; 95% CI, 0.05-0.16; P&#x2009;<&#x2009;.001). No differences were observed in progression to exudative AMD.<br><br>CONCLUSIONS AND RELEVANCE: In this cohort study, GLP-1RA use was associated with reduced risk of developing nonexudative AMD but was not associated with progression to exudative AMD among individuals with nonexudative AMD. These findings may inform future randomized trials evaluating the ocular effects of GLP-1RAs in nondiabetic populations.}, }
@article {pmid41129138, year = {2025}, author = {Talcott, KE and Rachitskaya, AV and Singh, RP}, title = {Glucagon-Like Peptide-1 Receptor Agonist Use and Age-Related Macular Degeneration-Where Do We Stand?.}, journal = {JAMA ophthalmology}, volume = {143}, number = {12}, pages = {1004-1005}, doi = {10.1001/jamaophthalmol.2025.4090}, pmid = {41129138}, issn = {2168-6173}, }
@article {pmid41129165, year = {2025}, author = {Ziemssen, F and Helbig, H}, title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs.}, journal = {JAMA ophthalmology}, volume = {143}, number = {12}, pages = {1075}, doi = {10.1001/jamaophthalmol.2025.3711}, pmid = {41129165}, issn = {2168-6173}, }
@article {pmid41129166, year = {2025}, author = {Mammo, DA and Talcott, KE and Singh, RP}, title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs.}, journal = {JAMA ophthalmology}, volume = {143}, number = {12}, pages = {1075-1076}, doi = {10.1001/jamaophthalmol.2025.3714}, pmid = {41129166}, issn = {2168-6173}, }
@article {pmid41129172, year = {2025}, author = {Feldman-Billard, S and Girmens, JF and Ayello-Scheer, S}, title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs.}, journal = {JAMA ophthalmology}, volume = {143}, number = {12}, pages = {1076-1077}, doi = {10.1001/jamaophthalmol.2025.3717}, pmid = {41129172}, issn = {2168-6173}, }
@article {pmid41129178, year = {2025}, author = {Alkabbani, W and Cromer, SJ and Patorno, E}, title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs.}, journal = {JAMA ophthalmology}, volume = {143}, number = {12}, pages = {1077}, doi = {10.1001/jamaophthalmol.2025.3720}, pmid = {41129178}, issn = {2168-6173}, }
@article {pmid41129903, year = {2025}, author = {Rajendran, N and Singh, A and Runyon, W and Hu, S and Kumar, R and Ratnapriya, R and Csaky, K and Sripathi, SR}, title = {Derivation of pluripotent stem cell lines (RFSCi005-A, RFSCi006-A) from siblings harboring identical high-risk complement variants with discordant age-related macular degeneration.}, journal = {Stem cell research}, volume = {89}, number = {}, pages = {103852}, doi = {10.1016/j.scr.2025.103852}, pmid = {41129903}, issn = {1876-7753}, mesh = {Humans ; *Macular Degeneration/genetics/pathology/metabolism ; Siblings ; *Induced Pluripotent Stem Cells/metabolism/cytology ; Cell Line ; Male ; Female ; Cell Differentiation ; }, abstract = {Age-related macular degeneration (AMD) is a complex disease influenced by genetic and environmental factors. Variants in the complement pathway, especially in the CFH gene, increase AMD risk, yet disease severity can differ among individuals with identical high-risk genotypes. We generated induced pluripotent stem cell (iPSC) lines from siblings carrying identical high-risk complement variants but displaying discordant AMD phenotypes. These lines provide a unique platform to study epigenetic, transcriptomic, and environmental factors driving AMD heterogeneity. By comparing differentiated retinal cells, we aim to reveal mechanisms behind variable disease susceptibility and inform personalized therapies for AMD.}, }
@article {pmid41130334, year = {2026}, author = {Li, HY and Dong, L and Shao, L and Wei, WB}, title = {Multiomics data reveal microglia's promotion for choroidal neovascularization in endothelial cells.}, journal = {Experimental eye research}, volume = {262}, number = {}, pages = {110701}, doi = {10.1016/j.exer.2025.110701}, pmid = {41130334}, issn = {1096-0007}, mesh = {Humans ; *Microglia/metabolism/pathology ; *Choroidal Neovascularization/metabolism/genetics/pathology ; *Endothelial Cells/metabolism/pathology ; Retinal Pigment Epithelium/metabolism/pathology ; Choroid/metabolism/pathology ; Male ; *Gene Expression Regulation/physiology ; Female ; Vascular Endothelial Growth Factor A/metabolism ; Aged ; Signal Transduction ; Wet Macular Degeneration/metabolism/genetics ; Cells, Cultured ; Multiomics ; }, abstract = {Choroidal neovascularization (CNV) stands as one of the leading causes of blindness worldwide, driven by the dysregulation of key signaling pathways, including vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β). This study aimed to elucidate the specific cell types within the retina and retinal pigment epithelium (RPE)/choroid complex that contribute to CNV progression, as well as to explore how the expression levels of cysteine-rich protein 2 (CSRP2), a downstream effector, are altered in the pathological mechanisms underlying CNV. By investigating these molecular and cellular dynamics, we seek to provide deeper insights into the disease's progression and identify potential therapeutic targets. Retinal tissues, RPE/choroid complexes, and blood samples from both age-related macular degeneration (AMD) caused CNV patients and healthy controls were obtained from the GEO database for differential gene expression analysis. Integrated analysis of tissue and blood samples from wet AMD patients and healthy controls identified CSRP2 as a critical biomarker gene associated with pathogenesis. To uncover potential underlying mechanisms, we conducted immune infiltration analysis and further validated our findings using single-cell RNA sequencing (scRNA-seq) data from the GEO database. Additionally, scRNA-seq data were utilized to investigate cell-cell communication networks and perform Gene Set Enrichment Analysis (GSEA). scRNA-seq analysis demonstrated that CSRP2 was significantly upregulated in microglia and endothelial cells, with concurrent activation of the VEGF and TGF-β signaling pathways. Microglia emerged as a central hub for outgoing interactions, while endothelial cells were identified as the primary target of incoming signals within these pathways. GSEA further implicated CSRP2 in CNV progression, highlighting its role in angioimmunoblastic regulated by VEGF and TGF-β signaling pathways. In the in-vitro experiments, we found that activated microglia stimulated VEGFA, TGF-β and CSRP2, which enhanced angiogenesis, migration, proliferation, permeability, and altered the phenotype of co-cultured choroidal endothelial cells. These findings underscore the pivotal involvement of CSRP2 in mediating cellular crosstalk and signaling dynamics critical to CNV development. Microglia and endothelial cells emerged as the primary cell clusters interacting under this signaling regulation, driving angiogenesis and contributing to the pathological progression of CNV. The findings provide promise alternative therapy for CNV patients casued by AMD.}, }
@article {pmid41130930, year = {2025}, author = {Ostrovsky, M and Tuli, R and Kozlov, Y and Robart, ACW and Ruparelia, S and Lebreton, L and Gou, A and Shoham-Hazon, N and Lee, TKM and Berco, E}, title = {To ac tap or not to ac tap: Multi-centre outcomes of patients receiving anti-VEGF injections.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721251389427}, doi = {10.1177/11206721251389427}, pmid = {41130930}, issn = {1724-6016}, abstract = {PurposeTo compare intraocular pressure (IOP) and retinal nerve fibre layer (RNFL) thickness in patients receiving intravitreal anti-vascular endothelial growth factor (VEGF) injections with and without anterior chamber paracentesis (ACP).MethodsThis multicentre retrospective cohort study included 269 injection-naïve eyes from 210 patients with neovascular age-related macular degeneration (AMD) or diabetic macular oedema (DME). A matched subset of 140 eyes (70 with ACP, 70 without) was selected based on age, sex, diagnosis, laterality, and number of injections. RNFL thickness (overall and by quadrant) was measured at baseline and one-year follow-up. Additional outcomes included IOP, visual acuity (VA), and central retinal thickness (CRT).ResultsThe matched cohort had a mean age of 71.06 ± 11.44 years, with 61.4% female participants. ACP eyes had worse baseline VA, higher IOP, and thicker CRT (p < 0.050, for all), but showed greater VA improvement (p = 0.023) and a trend towards greater CRT reduction (p = 0.061). RNFL thinning over one year did not differ between the groups (-3.24 ± 11.82 µm vs -2.95 ± 7.81 µm, p = 0.883). No major complications were observed.ConclusionACP did not significantly reduce RNFL thinning over one year but was well tolerated. It may be considered in patients at higher risk from transient IOP elevations. Future prospective studies are warranted to clarify its role in specific patient subgroups.}, }
@article {pmid41131180, year = {2025}, author = {Graham, F}, title = {Daily briefing: People with macular degeneration can read again after retinal implant.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-025-03442-5}, pmid = {41131180}, issn = {1476-4687}, }
@article {pmid41131329, year = {2025}, author = {Peto, T and Pearce, I and Talks, J and de Salvo, G and Patel, PJ and de Silva, SR and Gale, RP and Sivaprasad, S and Varma, D and Reynolds, R and Bailey, C and Downey, L and Kiire, C and Chi, GC and Dodds, M and James, N and Downey, AK and Dayal, P}, title = {Real-world treatment patterns and visual outcomes of faricimab in patients with diabetic macular oedema in the UK at 12 months: the FARWIDE-DMO study.}, journal = {Eye (London, England)}, volume = {39}, number = {18}, pages = {3350-3358}, pmid = {41131329}, issn = {1476-5454}, mesh = {Humans ; *Visual Acuity ; *Diabetic Retinopathy/drug therapy/physiopathology/complications/diagnosis ; Female ; Male ; *Macular Edema/drug therapy/physiopathology/etiology/diagnosis ; Intravitreal Injections ; United Kingdom/epidemiology ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Middle Aged ; Treatment Outcome ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retrospective Studies ; Time Factors ; Tomography, Optical Coherence ; Antibodies, Bispecific ; }, abstract = {BACKGROUND: The Faricimab Real-World Evidence (FARWIDE) studies are evaluating real-world outcomes of eyes with diabetic macular oedema (DMO)/neovascular age-related macular degeneration (nAMD) treated with faricimab in the UK. We present results from FARWIDE-DMO for eyes with 12 months of follow-up after faricimab initiation.<br><br>METHODS: FARWIDE-DMO includes patients with diagnosis of DMO who received &#x2265;1 intravitreal faricimab injection after May 2022 in the diagnosed eye(s) at 1 of 35 UK National Health Service sites. All eyes had &#x2265;12 months of follow-up after faricimab initiation as of July 2024. Treatment-na&#xef;ve (TN) eyes had no prior anti-VEGF therapy or steroid implant. Previously treated (PT) eyes switched to faricimab. Baseline characteristics, visual acuity (VA) outcomes and treatment patterns were evaluated. Intraocular inflammation (IOI) and presumed infectious endophthalmitis (PIE) incidences were pooled for all nAMD/DMO eyes with any follow-up duration. Analyses are descriptive.<br><br>RESULTS: 2147 eyes (1564 patients) were included (TN, 32.1%; PT, 67.9%). For TN eyes, mean (standard deviation [SD]) VA at baseline and 12 months were 63.9 (15.2) and 68.4 (16.3) Early Treatment Diabetic Retinopathy Study letters, respectively. VA remained stable in PT eyes. TN eyes received a mean (SD) of 4.5 (1.0) faricimab injections in months 1-6 and 1.9 (1.2) injections in months 7-12. PT eyes received 4.5 (1.2) injections in months 1-6 and 2.4 (1.3) in months 7-12. IOI and PIE rates were consistent with faricimab phase 3 trials.<br><br>CONCLUSIONS: These 1-year data support real-world effectiveness, durability and safety of faricimab in DMO.}, }
@article {pmid41132126, year = {2025}, author = {Schmidt-Erfurth, U and Mai, J and Reiter, GS and Riedl, S and Vogl, WD and Sadeghipour, A and McKeown, A and Foos, E and Scheibler, L and Bogunovic, H}, title = {Plain language summary of disease activity and therapeutic response to pegcetacoplan for geographic atrophy identified by deep learning-based analysis of OCT.}, journal = {Immunotherapy}, volume = {17}, number = {14}, pages = {971-981}, doi = {10.1080/1750743X.2025.2569302}, pmid = {41132126}, issn = {1750-7448}, }
@article {pmid41132628, year = {2025}, author = {Ou, S and Shi, F and Cai, M and Wu, Y}, title = {Conbercept Treatment for Heart-Shaped Vascular Intertwined Nets in Macular Neovascularization: Anti-VEGF Drug Therapy Strategy Based on Vascular Geometry Diagnosed by OCTA.}, journal = {Clinical case reports}, volume = {13}, number = {10}, pages = {e71250}, pmid = {41132628}, issn = {2050-0904}, abstract = {Macular neovascularization (MNV), a hallmark of several retinal disorders including ocular trauma and wet age-related macular degeneration, remains a major cause of vision impairment due to the proliferation of abnormal, fragile blood vessels. Anti-VEGF therapies, such as Aflibercept (Eylea), Bevacizumab (Avastin), Brolucizumab (Beovu), Conbercept (Lumitin), Faricimab (Vabysmo), Ranibizumab (Lucentis), and Pegaptanib (Macugen), have significantly transformed MNV management, targeting VEGF to curb this pathological vascular growth. In this report, we describe a 63-year-old male with a history of hypertension and diabetes who developed acute vision loss attributed to MNV secondary to hypertensive retinopathy. Optical coherence tomography angiography (OCTA) revealed unusual heart-shaped, intertwined vascular nets, informing the choice of Conbercept for intravitreal injection. This personalized therapeutic decision led to marked visual improvement over a 12-month period. The case exemplifies the importance of vascular geometry in guiding anti-VEGF selection, supported by existing literature that links specific neovascular geometries to differential drug responsiveness. Conbercept, in particular, proved effective against the complex intertwined nets observed in this patient. These findings emphasize the promise of individualized treatment strategies and the potential of OCTA-based vascular geometry classification as a tool for precision medicine.}, }
@article {pmid41134689, year = {2025}, author = {Xue, Q and Huang, J and Wang, B and Ji, J and Wang, L and Kumari, S and Lan, C and Xiao, M}, title = {FTO Fuels Aβ1-40-Induced Retinal Pigment Epithelium Cell Injury Associated With Pyroptosis by Erasing m6A Methylation of the lncRNA Neat1.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {20}, pages = {e71166}, doi = {10.1096/fj.202500272RRRR}, pmid = {41134689}, issn = {1530-6860}, support = {82101139//MOST | National Natural Science Foundation of China (NSFC)/ ; 2021J01750//| Natural Science Foundation of Fujian Province (Fujian Natural Science Foundation)/ ; 2023J01690//| Natural Science Foundation of Fujian Province (Fujian Natural Science Foundation)/ ; 2023GGA019//| Fujian Provincial Health Technology Project (Provincial Health Technology Project of Fujian Province)/ ; 2022QNA015//| Fujian Provincial Health Technology Project (Provincial Health Technology Project of Fujian Province)/ ; 2024Y9260//Fujian Provincial Department of Science and Technology ()/ ; }, mesh = {*RNA, Long Noncoding/metabolism/genetics ; *Pyroptosis ; *Retinal Pigment Epithelium/metabolism/pathology ; Humans ; Animals ; *Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism/genetics ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; Methylation ; *Adenosine/analogs &amp; derivatives/metabolism ; Macular Degeneration/metabolism/pathology/genetics ; Inflammasomes/metabolism ; Epigenesis, Genetic ; Mice, Inbred C57BL ; }, abstract = {Retinal pigment epithelium (RPE) degeneration in association with inflammation is a key feature of age-related macular degeneration (AMD) pathology. Amyloid β (Aβ) in drusenoid deposits, the hallmark of AMD, is a critical initiating component that causes RPE cell damage through the activation of the NLR family pyrin domain containing 3 (NLRP3)-mediated inflammatory response. Epigenetic mechanisms have been reported to contribute to the pathogenesis of AMD. However, the extent to which epigenetic modifications regulate Aβ-mediated RPE inflammatory damage and cell death remains unclear. N6-methyladenosine (m6A) is the most abundant RNA epigenetic regulation in eukaryotes. Herein, based on bioinformatics analysis, we identified that fat mass and obesity-associated protein (FTO) acts as an essential epigenetic regulator in Aβ1-40-mediated RPE inflammatory cell death. Activation of NLRP3 inflammasome-related RPE pyroptosis was evident through enhanced NLRP3, gasdermin D immunoreactivity, increased caspase-1 cleavage, elevated IL-1β secretion, and higher LDH activity. Deletion of FTO resulted in the inhibition of RPE pyroptosis in vitro and in vivo. Mechanistically, methylated RNA immunoprecipitation (MeRIP) combined with RNA-seq demonstrated that long noncoding RNA (lncRNA) Neat1 served as a downstream target of FTO, with FTO knockdown suppressing Neat1 expression in an m6A-dependent manner. Neat1 depletion deactivated inflammatory factors, thereby hindering Aβ1-40-induced RPE pyroptosis. Furthermore, FTO silencing attenuated Neat1-mediated pyroptosis, resulting in compromised retinal structure and function. These findings suggest that the FTO-Neat1-NLRP3 network provides potential targets to treat AMD while expanding our understanding of the role of epigenetically modified lncRNAs in Aβ-driven RPE injury.}, }
@article {pmid41135050, year = {2025}, author = {Pinhas, A and Pinhas, B and Dmitruk, E and Pinhas, S}, title = {Eye and Systemic Disease Management Changes After Teleophthalmology Screening in Primary Care: Retrospective Cross-Sectional Pilot Study of 200 Consecutive Patients.}, journal = {JMIR formative research}, volume = {9}, number = {}, pages = {e81918}, pmid = {41135050}, issn = {2561-326X}, mesh = {Humans ; Cross-Sectional Studies ; Pilot Projects ; Retrospective Studies ; Female ; Male ; Middle Aged ; *Primary Health Care ; Aged ; Adult ; Telemedicine ; *Eye Diseases/diagnosis/therapy ; Aged, 80 and over ; Adolescent ; Young Adult ; Child ; Disease Management ; *Mass Screening/methods ; Diabetic Retinopathy/diagnosis ; Ophthalmology/methods ; }, abstract = {BACKGROUND: Undiagnosed ocular diseases and ocular complications from systemic diseases are common in primary care populations, and many can be detected through retinal imaging before symptoms develop. Asynchronous store-and-forward teleophthalmology offers a scalable way to integrate eye screening into primary care, yet its broader impact beyond diabetes and diabetic retinopathy detection remains underexplored.<br><br>OBJECTIVE: This study evaluated the outcomes of asynchronous store-and-forward teleophthalmology screening in a primary care clinic, including detection and triage of ocular conditions and subsequent changes in eye and systemic management.<br><br>METHODS: This was a retrospective cross-sectional analysis of the first 200 patients screened in a single primary care clinic in Elmhurst, New York, between January and May 2025. Each patient underwent nonmydriatic external and posterior eye imaging, which was reviewed by a remote reading eye clinician. Reports included eye findings, triage decisions (routine monitoring vs in-person referral), and management recommendations. Subsequent changes in care were extracted from primary care and in-person specialist consult notes.<br><br>RESULTS: Of 200 patients (mean age 62.1, SD 19.0, range 11-100 years), 71.5% (143/200, 95% CI 64.9-77.3) had positive eye findings, and 40% (80/200, 95% CI 33.5-46.9) were referred for in-person eye examinations. Only 8.8% (7/80, 95% CI 4.3-17.0) of referrals were for diabetic retinopathy; most were for glaucoma suspects, age-related macular degeneration, cataracts, and other eye diseases. Image quality was high, with 98.2% (390/397, 95% CI 96.4-99.1) of fundus images being at least partially adequate. Of the 32 patients with documented in-person eye follow-up, 87.5% (28/32) of evaluations confirmed the screening findings. Eye management changes were initiated in 11 patients, whereas systemic management changes occurred in 70 patients, including new prescriptions for Age-Related Eye Disease Study 2 supplements, antihypertensives, diabetes medications, and lipid-lowering agents.<br><br>CONCLUSIONS: Asynchronous teleophthalmology screening in a primary care setting effectively identified both ocular diseases and ocular complications from systemic diseases, leading to meaningful changes in eye and systemic management. The low rate of diabetic retinopathy among referrals highlights the broader diagnostic value of retinal imaging beyond diabetes management. This care model offers a scalable, high-yield strategy for proactive disease detection and interdisciplinary intervention at the primary care level.}, }
@article {pmid41135684, year = {2025}, author = {Saadane, A and von Lintig, J}, title = {The retinol-binding protein receptor STRA6 and melanin cooperatively sustain retinoid signaling and outer blood-retinal barrier integrity.}, journal = {The Journal of biological chemistry}, volume = {301}, number = {12}, pages = {110846}, pmid = {41135684}, issn = {1083-351X}, support = {P30 EY011373/EY/NEI NIH HHS/United States ; R01 EY020551/EY/NEI NIH HHS/United States ; R01 EY028121/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Mice ; Mice, Knockout ; *Blood-Retinal Barrier/metabolism/pathology ; *Membrane Proteins/metabolism/genetics ; *Melanins/metabolism/genetics ; *Signal Transduction ; *Retinoids/metabolism ; Vitamin A/metabolism ; Retinal Pigment Epithelium/metabolism ; Retinol-Binding Proteins, Plasma/metabolism/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; }, abstract = {Disruption of the outer blood-retinal barrier (oBRB) is a central feature of retinal degenerative diseases, including age-related macular degeneration, yet the molecular mechanisms maintaining this barrier in the adult eye remain poorly defined. STRA6, a high-affinity receptor for retinol-binding protein (RBP4), mediates vitamin A uptake at the basolateral membrane of the retinal pigment epithelium (RPE), while melanin protects ocular retinoid stores from photooxidative stress. We previously showed that STRA6 deficiency leads to downregulation of junctional proteins in the RPE. Here, we demonstrate that STRA6 and melanin act synergistically to preserve the integrity of the oBRB. In albino Stra6 knockout mice, ocular retinoid levels were severely reduced despite normal circulating retinol levels, and dietary vitamin A delivered via chylomicrons failed to compensate for the loss of RBP4-mediated transport. This led to a functional impairment of both rod- and cone-mediated responses, even under vitamin A-sufficient conditions. Mice also showed downregulated tight junction proteins (ZO-1, Claudin-1, Claudin-3), RPE disorganization, barrier leakage, and immune cell infiltration into the subretinal space. These defects were further exacerbated under dietary vitamin A restriction. Importantly, systemic treatment with the pan-retinoic acid receptor (RAR) agonist TTNPB restored junctional gene expression and oBRB function in Stra6[-/-] mice, providing evidence that barrier failure arises from impaired retinoid signaling rather than structural loss of STRA6 and melanin. These findings define a novel role for retinoic acid in sustaining RPE barrier function and highlight the combined importance of STRA6-mediated transport and melanin-dependent photoprotection in retinal homeostasis.}, }
@article {pmid41136840, year = {2025}, author = {Jha, S and Hua, F and Dejene, R and Sarkar, S and Sharma, R and Bharti, K}, title = {Development of a Manufacturing Process for Clinical Autologous hiPSC-Derived Retinal Pigment Epithelium.}, journal = {Advances in experimental medicine and biology}, volume = {1486}, number = {}, pages = {165-178}, pmid = {41136840}, issn = {0065-2598}, mesh = {Humans ; Cell Differentiation ; *Induced Pluripotent Stem Cells/cytology/transplantation ; *Macular Degeneration/therapy/pathology ; *Retinal Pigment Epithelium/cytology/transplantation ; Tissue Engineering/methods ; Transplantation, Autologous ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss. The disease progresses through early, intermediate, and advanced stages, with late forms including dry AMD (geographic atrophy) and wet AMD (choroidal neovascularization). Currently, there is no cure for dry AMD, which results from retinal pigment epithelium (RPE) cell loss. Induced pluripotent stem cell (iPSC)-based transplants offer a potential therapy by replacing atrophied RPE. This chapter outlines the manufacturing process, key parameters, and challenges of developing iPSC-derived RPE therapy. We engineered a clinical-grade iPSC-RPE patch using autologous cells from AMD patients. Starting from the patient blood, CD34+ cells were isolated, expanded, and reprogrammed using episomal plasmids. Twelve iPSC clones were generated, quality-tested, and three were selected for differentiation into mature RPE on a biodegradable scaffold. The final patch underwent QC assays for donor identity, sterility, and phenotype confirmation before transplantation. This work has led to a Phase I/IIa clinical trial to evaluate the safety and feasibility of auto-iPSC-RPE patches in AMD patients.}, }
@article {pmid41136844, year = {2025}, author = {Wang, L and Wang, YK and Li, D and Ma, J and Sun, Y and Li, X and Wang, H and Niu, S and Stacey, GN and Zhao, T and Hu, B and Zhou, Q and Wang, L and Hao, J}, title = {The Programme for Manufacture of hPSC‑Based Products for AMD and PD.}, journal = {Advances in experimental medicine and biology}, volume = {1486}, number = {}, pages = {227-236}, pmid = {41136844}, issn = {0065-2598}, mesh = {Humans ; *Macular Degeneration/therapy/pathology ; *Parkinson Disease/therapy/pathology ; *Pluripotent Stem Cells/cytology/transplantation ; Retinal Pigment Epithelium/cytology/pathology ; Cell Differentiation ; Animals ; Dopaminergic Neurons/transplantation/pathology ; *Stem Cell Transplantation/methods ; Regenerative Medicine/methods ; }, abstract = {Pluripotent stem cells (hPSCs) possess the unique ability to self-renew and differentiate into various functional cell types, positioning them as key "seed cells" in regenerative medicine. The development of PSC-based therapies offers new hope for treating complex diseases, and degenerative diseases, particularly those caused by the loss of specific cellular functions, such as macular degeneration, Parkinson's disease, spinal cord injury, diabetes, and cartilage damage. Cell replacement therapies using hPSC-committed cells can help halt disease progression or potentially cure these conditions. The Retinal Pigment Epithelium (RPE) is crucial for visual function and photoreceptor support, with its dysfunction implicated in age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Parkinson's disease (PD), a rapidly progressing neurodegenerative disorder marked by the loss of midbrain dopaminergic neurons (mDA), remains one of the most difficult neurological conditions to treat. Traditional therapies for these diseases have largely been ineffective. RPE and mDA neurons differentiated from hPSCs offer promising solutions for treating AMD and PD, their treatment methods are both cell replacement therapy, and they are the products used in the first batch of stem cell clinical research registration projects in China, so we will put these two products together. This chapter summarizes the differentiation and quality control strategies for hESC-derived RPE and mDA neurons as examples of the potential hPSC-derived cell therapies, under development at the Chinese Academy of Sciences and Beijing Institute for Stem Cell and Regenerative Medicine, for these complex, treatment-resistant diseases.}, }
@article {pmid41136910, year = {2025}, author = {Cho, Y and Yoo, WS and Kim, SJ and Chung, I}, title = {Characteristics of patients lost to follow-up after intravitreal anti-vascular endothelial growth factor therapy for exudative age-related macular degeneration.}, journal = {BMC ophthalmology}, volume = {25}, number = {1}, pages = {598}, pmid = {41136910}, issn = {1471-2415}, mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; Male ; Female ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Aged ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Aged, 80 and over ; Visual Acuity ; *Lost to Follow-Up ; Follow-Up Studies ; Tomography, Optical Coherence ; }, abstract = {BACKGROUND: This study aimed to analyze and compare the characteristics of patients with exudative age-related macular degeneration who were lost to follow-up after receiving intravitreal anti-vascular endothelial growth factor(anti-VEGF) injections versus those who maintained regular follow-up.<br><br>METHODS: This retrospective study included patients who were lost to follow-up for more than 1 year (n&#x2009;=&#x2009;79) or maintained follow-up (n&#x2009;=&#x2009;186) after treatment with intravitreal injections of ranibizumab or aflibercept for exudative age-related macular degeneration. Age, sex, place of residence, type of health insurance, distance from the hospital, laterality of involvement, and follow-up duration were analyzed.<br><br>RESULTS: There were no significant differences between the two groups in terms of age, sex, or type of health insurance. However, patients lost to follow-up resided significantly further from the hospital versus those with regular follow-up (33.1&#x2009;&#xb1;&#x2009;26.8 vs. 21.6&#x2009;&#xb1;&#x2009;8.5&#xa0;km; P&#x2009;=&#x2009;0.001). A significantly higher proportion of patients that were lost to follow-up had unilateral involvement (P&#x2009;<&#x2009;0.001) and resided in rural areas (P&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Distance from the hospital, rural residency, and unilateral involvement are significantly associated with nonadherence to follow-up among patients with exudative age-related macular degeneration receiving intravitreal anti-VEGF injections.}, }
@article {pmid41138048, year = {2025}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {Can Gene Therapy Transform the Treatment Landscape of Posterior Segment Eye Diseases? A Comprehensive Review of Recent Advancements.}, journal = {Drugs}, volume = {85}, number = {12}, pages = {1585-1608}, pmid = {41138048}, issn = {1179-1950}, mesh = {Humans ; *Genetic Therapy/methods ; Animals ; Macular Degeneration/therapy/genetics ; *Eye Diseases/therapy/genetics ; Gene Editing ; *Retinal Diseases/therapy/genetics ; Gene Transfer Techniques ; Genetic Vectors ; *Posterior Eye Segment/pathology ; }, abstract = {Posterior segment eye diseases (PSEDs) encompass a diverse group of conditions affecting the retina, choroid, optic nerve, and vitreous humor, often leading to progressive and irreversible vision loss. Age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), and inherited retinal diseases (IRDs) are among the most clinically significant PSEDs with a substantial global burden and economic impact. Conventional treatments for PSEDs have limitations that necessitate the development of novel therapies that address the underlying molecular drivers of the disease. Gene therapy has emerged as a promising approach, offering the potential for durable and curative outcomes through precise genetic manipulation. Advancements in gene therapy strategies, including gene augmentation, gene editing, RNA-based therapies, and optogenetics, have led to significant progress in preclinical studies and clinical trials across various PSED subtypes. US Food and Drug Administration (FDA) approval of voretigene neparvovec (Luxturna[®]) for RPE65-associated IRDs validated the clinical viability of ocular gene therapy, while ongoing trials for AMD, DR, and other IRDs continue to expand the therapeutic landscape. Innovations in viral and non-viral delivery systems, such as dual AAV vectors, lipid nanoparticles, and novel biomaterials, have enhanced the efficiency and specificity of gene delivery to the retina. However, challenges persist, including immune responses to viral vectors, limited transduction efficiency in certain cell types, and anatomical barriers posed by the blood-retinal barrier. Future directions in ocular gene therapy include the development of precision genome editing techniques, such as prime editing, miRNA-based regulation, and combinatorial approaches integrating gene therapy with stem cell transplantation or neuroprotective agents. As the field continues to evolve, addressing these challenges and optimizing gene therapy strategies will be crucial in translating the transformative potential of ocular gene therapy into clinical reality for patients with PSEDs.}, }
@article {pmid41138285, year = {2025}, author = {Demiot, C and De Sousa, C and Labrunie, A and Danigo, A and Authier, D and Delavaud, JM and Robert, PY and Rocher, M}, title = {Descriptive analysis of the knowledge amongst French patients about neovascular age-related macular degeneration as a function of social vulnerability, health literacy and date of diagnosis.}, journal = {Journal francais d'ophtalmologie}, volume = {48}, number = {9}, pages = {104666}, doi = {10.1016/j.jfo.2025.104666}, pmid = {41138285}, issn = {1773-0597}, mesh = {Humans ; *Health Literacy/statistics &amp; numerical data ; Female ; Male ; *Health Knowledge, Attitudes, Practice ; Aged ; France/epidemiology ; Aged, 80 and over ; *Macular Degeneration/diagnosis/epidemiology/psychology ; Patient Education as Topic ; *Vulnerable Populations/statistics &amp; numerical data/psychology ; Surveys and Questionnaires ; *Wet Macular Degeneration/diagnosis/epidemiology/psychology ; Time Factors ; Socioeconomic Factors ; Risk Factors ; Quality of Life ; }, abstract = {Patient education (PE) programs for patients with neovascular age-related macular degeneration (nAMD) are essential to reduce the disease's impact on quality of life. To establish a PE program for nAMD, a descriptive quantitative study was conducted to (i) describe the population and their knowledge concerning nAMD, (ii) classify patients according to their knowledge of disease, and (iii) their social vulnerability, health literacy and the duration since diagnosis. Socio-demographic data of 100 nAMD patients (70 women and 30 men, 80±7 years of age) were collected and compared with data on their social vulnerability (simplified EPICES score) and health knowledge (health literacy questionnaire). Patients were classified into three groups according to their knowledge, evaluated with questionnaires including the themes of pathology, information retrieval, treatment, risk factors and self-monitoring. A subgroup analysis of these knowledge profiles was assessed according to social vulnerability, health literacy and duration since diagnosis. False beliefs and lack of knowledge about nAMD were noted in almost 50% of patients. Only 15 patients were familiar with the Amsler grid. Three groups of patients were identified according to their knowledge of disease. No link was found between knowledge levels and health literacy. Patients who did not understand their disease were the most vulnerable, searched for less information, and had the most recent diagnosis. There is a significant need to improve the knowledge of nAMD patients. Social vulnerability, duration since diagnosis and heterogeneity in patient knowledge must be considered when establishing a PE program.}, }
@article {pmid41139156, year = {2025}, author = {Habot-Wilner, Z and Ostrovsky, M and Zur, D and Schwartz, S and Hagin, D and Gadoth, A and Ben-Ami, R and Paran, Y and Goldshmidt, H and Slutzkin, M and Adler, A and Levytskyi, K}, title = {Metagenomic next-generation sequencing: a game-changer in the diagnosis of unique intraocular infections.}, journal = {Eye (London, England)}, volume = {39}, number = {18}, pages = {3365-3371}, pmid = {41139156}, issn = {1476-5454}, mesh = {Humans ; *Endophthalmitis/diagnosis/microbiology ; *Eye Infections, Bacterial/diagnosis/microbiology ; *High-Throughput Nucleotide Sequencing/methods ; *Metagenomics/methods ; Retrospective Studies ; }, abstract = {OBJECTIVE: To thoroughly describe unique intraocular infections diagnosed by metagenomic next-generation sequencing (mNGS).<br><br>METHODS: A retrospective case series of patients presenting with challenging atypical intraocular infections at Tel Aviv Sourasky Medical Center during 2024. Clinical and demographic data, as well as mNGS results were extracted from patient records. mNGS was performed on the Illumina NextSeq500 platform using a custom bioinformatics pipeline. The following parameters were examined: Reads Per Million, Reads Per Million-ratio to negative control and E-index (K-mers*coverage/reads).<br><br>RESULTS: The study included three patients with novel presentations of intraocular infections, manifesting with atypical clinical manifestations and negative routine diagnostic workups. mNGS allowed the identification of Cytomegalovirus in a 43-year-old male with a history of autosomal dominant hyper-IgE syndrome, Bartonella henselae infection manifesting with photoreceptoritis, retinal vasculitis and global retinal dysfunction in a healthy 28-year-old female, and polymicrobial endophthalmitis with Rothia mucilaginosa and Pantoea agglomerans following intravitreal faricimab injection for neovascular age-related macular degeneration in an 81-year-old male. Treatment regimens were adjusted based on mNGS results.<br><br>CONCLUSIONS: Metagenomic next-generation sequencing has an important role in the diagnosis of challenging intraocular infections. It enables comprehensive pathogen identification and enhances the precision of treatment strategies.}, }
@article {pmid41140136, year = {2025}, author = {Erbezci, M and Özen Tunay, Z and Öztürk, T}, title = {Preferred Retinal Locus in Juvenile Macular Dystrophy.}, journal = {Turkish journal of ophthalmology}, volume = {55}, number = {5}, pages = {239-244}, pmid = {41140136}, issn = {2149-8709}, mesh = {Humans ; *Visual Acuity/physiology ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; Adolescent ; Young Adult ; Adult ; Child ; *Macular Degeneration/physiopathology/diagnosis ; *Fovea Centralis/pathology ; Fluorescein Angiography/methods ; Follow-Up Studies ; Ophthalmoscopy ; }, abstract = {OBJECTIVES: To evaluate foveal lesion and preferred retinal locus (PRL) locations and their effects on visual acuity in juvenile macular dystrophy (JMD) patients.<br><br>MATERIALS AND METHODS: In this retrospective study, 14 JMD patients (28 eyes) with bilateral central vision loss were examined using scanning laser ophthalmoscope/optical coherence tomography. Best-corrected visual acuity (BCVA), dimensions and location of the macular lesion, PRL location, and PRL stability were evaluated.<br><br>RESULTS: Mean BCVA was 0.84&#xb1;0.17 logarithm of the minimum angle of resolution. PRL was superiorly located in 64.3% of eyes and nasally located in 35.7%. PRL location was significantly associated with patient age (r=0.541, p=0.002); nasally located PRLs were more common in younger patients (mean age 15.1&#xb1;2.8 years) while superiorly located PRLs were more common in older patients (mean age 22.4&#xb1;6.9 years). Superiorly located PRLs were significantly closer to the fovea than nasally located PRLs (p=0.014). Visual acuity worsened as lesion size increased and PRL-fovea distance increased. PRL-fovea distance was longer in younger patients and positively correlated with lesion dimensions and PRL-lesion distance.<br><br>CONCLUSION: In JMD patients, PRLs are predominantly located superiorly or nasally. In younger patients, PRLs are typically located nasally and farther from the fovea, with poorer visual acuity compared to older patients. Cortical adaptation mechanisms may play a role in changing PRL location with age. Understanding PRL characteristics in JMD is crucial for developing effective low-vision rehabilitation strategies.}, }
@article {pmid41140340, year = {2025}, author = {Christensen, CA and Gupta, N and Breazzano, MP}, title = {Novel Bilateral Geographic Atrophy Phenotype Associated With CRX Mutation.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251386364}, pmid = {41140340}, issn = {2474-1272}, abstract = {Purpose: To describe an atypical phenotype of retinal dystrophy in the setting of a heterozygous missense mutation (CRX-RD). Methods: The case is a 71-year-old woman previously diagnosed with advanced, non-neovascular, nonexudative age-related macular degeneration (AMD) who presented with longstanding blurry vision for consideration of intravitreal anti-complement factor therapy. Results: Ophthalmic examination showed geographic atrophy (GA) in both eyes, without evidence of drusen or drusenoid deposits. Genetic panel testing revealed a pathogenic, heterozygous missense mutation in CRX, the NM_000554.6(CRX) variant c.128G>A (p.Arg43His) (RCV001228802.6). Although CRX-RD is known to have phenotypic heterogeneity, cases with macular atrophy most commonly display bullseye maculopathy or benign concentric annular macular dystrophy. Conclusions: This case presenting with bilateral GA is consistent with a novel phenotype associated with a pathogenic variant of CRX and is an atypical presentation of RD simulating AMD.}, }
@article {pmid41140895, year = {2026}, author = {Xu, Z and Lin, R and Wang, X and Liu, Y and Huang, C and Wang, C and Bao, Z}, title = {Association of Physical Frailty and Genetic Predisposition with Risk of Irreversible Eye Diseases.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100910}, pmid = {41140895}, issn = {2666-9145}, abstract = {OBJECTIVE: The evidence linking frailty to overall and specific irreversible eye diseases is limited. Moreover, it is unclear whether frailty is associated with similar increased risk across individuals with different genetic risk profiles. The aim of this study was to examine the association between frailty and overall and specific irreversible eye diseases and explore the modification effect of genetic risk of glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) in such associations.<br><br>DESIGN: Prospective cohort study.<br><br>PARTICIPANTS: The study included a total of 409 579 White participants in the UK Biobank study.<br><br>METHODS: Physical frailty was defined by 5 components: weight loss, exhaustion, low physical activity, slow walking speed, and low grip strength. Participants were classified as nonfrail, prefrail, or frail. Polygenic risk score was categorized as low (tertile 1), intermediate (tertile 2), or high (tertile 3). Cox regression was used to assess the association of physical frailty with irreversible eye diseases.<br><br>MAIN OUTCOMES AND MEASURES: Irreversible eye diseases were identified using hospital admission electronic health records and death registries.<br><br>RESULTS: Among 409 579 individuals (mean age, 56.5 years; 46.5% male) with a median follow-up of 13.1 years, 10 927, 7 095, and 919 were diagnosed with irreversible eye disease in the nonfrail, prefrail, and frail groups, respectively. Prefrail and frail individuals showed increased risks of overall irreversible eye diseases, with a 12% higher risk for prefrail individuals (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.09-1.16) and a 47% higher risk for frail individuals (HR, 1.47; 95% CI, 1.37-1.58). Increased risks were also observed for specific irreversible eye diseases, including glaucoma (HR, 1.11 [95% CI, 1.06-1.17] for prefrailty; HR, 1.43 [95% CI, 1.28-1.61] for frailty), diabetic retinopathy (HR, 1.12 [95% CI, 1.03-1.21] for prefrailty; HR, 1.53 [95% CI, 1.34-1.73] for frailty), and AMD (HR, 1.13 [95% CI, 1.08-1.19] for prefrailty; HR, 1.35 [95% CI, 1.20-1.52] for frailty). Furthermore, individuals with more severe frailty status and higher genetic risk exhibited higher risks of irreversible eye diseases than those with low genetic risk and nonfrailty.<br><br>CONCLUSIONS: Frailty was associated with an increased risk of irreversible eye diseases, particularly among individuals with higher genetic risk. These findings suggest that targeted strategies to prevent and manage frailty may contribute to reducing the risk of irreversible eye diseases.<br><br>FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid41140896, year = {2026}, author = {Dadgar, N and Fung, K and McClintic, S and Metea, C and Llorenç, V and Saleh, M and Nakamura, YK and Jahrig, C and Kiang, L and Janowitz, C and Davin, S and Balter, A and Le Cao, KA and Karstens, L and Martin, TM and Klein, ML and Lin, P}, title = {Age-related Eye Disease Studies Supplements and Genetic Risk Score Are Crucial Determinants of Intestinal Microbial Alterations in Advanced Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100920}, pmid = {41140896}, issn = {2666-9145}, abstract = {OBJECTIVE: Determine whether an intestinal microbial signature is associated with advanced age-related macular degeneration (AMD); investigate the relationship between the microbiota and AMD genetic risk, intestinal immunoglobulin-A (IgA), and Age-Related Eye Disease Studies (AREDS) supplementation.<br><br>DESIGN: Case-control study.<br><br>METHODS: Fecal 16S rRNA sequencing, DESeq2 differential abundance, and IgA-sequencing.<br><br>SUBJECTS: Advanced AMD and age-similar non-AMD control subjects.<br><br>MAIN OUTCOME MEASURES: Differential abundance plots using DESeq2, &#x3b1; and &#x3b2; diversity, and impact of AREDS supplementation and genetic risk on AMD microbiota.<br><br>RESULTS: In 85 advanced AMD compared with 49 healthy control subjects' intestinal microbiota, exploratory partial least-squares-discriminant analysis (PLS-DA) showed that gut microbiome composition was able to predict AMD with moderate confidence (cross validation error rates, 0.28-0.36) with the potential for overfitting. A higher AMD genetic risk score was associated with lower gut microbial diversity (P = 0.0086; Spearman r = -0.3), a finding confirmed by multiple linear regression with confounding covariates, whereas AREDS supplementation was associated with increased gut bacterial diversity (coefficient, 2.64; P < 0.05). Differential abundance plots showed increased Proteobacteria and many differentially abundant genera (including Prevotella, Desulfovibrio, Oscillospira, and Ruminococcaceae) in AMD versus controls. Flow cytometry and IgA-sequencing suggested increased IgA-coating of gut bacteria in the age-related maculopathy susceptibility 2 (ARMS2) gene risk genotype, including higher IgA indices for Prevotella. These findings are hypothesis-generating and require functional validation. Predicted metabolic pathways (via piphillin) that differed between AMD and controls included lipid metabolism and xenobiotic processing by cytochrome P450; these findings are inferred and require confirmation by metabolomic studies.<br><br>CONCLUSIONS: The intestinal microbiome is able to predict advanced AMD via PLS-DA. AREDS supplementation and genetic risk are crucial determinants of the AMD microbiome, which interacts with gut immunity by increasing IgA binding to certain bacteria. Understanding how the gut microbiome and its metabolites interact with gut immunity and host genetics will allow us to further investigate the microbiome to find potentially novel therapeutic targets in AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41140906, year = {2026}, author = {Goldberg, EA and Ross, CJ and Douglas, VP and Ivanov, A and Elze, T and Miller, JW and Lorch, AC and , }, title = {Data Duplication and Errors in Large Medical Data Sets: A Case Study in the IRIS® Registry.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100933}, pmid = {41140906}, issn = {2666-9145}, abstract = {PURPOSE: To investigate entry errors and data duplication within the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) utilizing cataract surgery (CS), neodymium-doped: yttrium aluminum garnet (YAG) capsulotomy, age-related macular degeneration (AMD), and diabetic retinopathy (DR) records.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Patients in the IRIS Registry.<br><br>METHODS: We collected records of CS and YAG capsulotomy with specified laterality within the IRIS Registry (years 2013-2023), identifying eyes having >1 record and eyes having &#x2265;1 record on a date after the first entry (different date duplication, D d). Additionally, we identified eyes amongst records of DR and AMD with (1) a diagnosis indicating a more severe stage then reversion to the less severe stage or (2) a transition to a more severe stage before later being diagnosed with the less severe stage, defined as transition errors. We investigated potential predictors of D d and transition errors among patient and practice characteristics by evaluating the permutation feature importance (PFI) of classification models.<br><br>MAIN OUTCOME MEASURES: For CS and YAG capsulotomy, we measure the proportion of eyes having >1 procedure record, having >1 record only on the initial procedure date, and having &#x2265;1 procedure record on a date after the first entry. For DR and AMD, we measure the proportion of eyes reverting to an earlier stage after starting at a later stage and the proportion reverting to an earlier stage after transitioning to a later stage.<br><br>RESULTS: Of the 14 718 896 CS-treated eyes, 30.9% had duplicates, with 5.5% having D d . For YAG capsulotomy, out of 5 113 679 eyes, 29.1% had duplicates, with 4.1% having D d . For AMD and DR, 13.6% and 12.7% of eyes, respectively, exhibited transition errors. Models captured a relationship between the eye's first practice on record and the data errors under study, indicated by F1-loss = 0.230 (D d model), 0.062 (transition error model) on average by PFI.<br><br>CONCLUSIONS: Data duplication in large medical data sets necessitates caution when analyzing repeated procedures or relapsing conditions. Addressing problematic errors requires transparency and communication amongst stakeholders across organizations. Within the IRIS Registry, the results indicated an association between the first record's originating practice and data errors, providing an investigative entry point for upstream data stewards.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41140907, year = {2026}, author = {Nagai, N and Shinoda, H and Matsubara, H and Terasaki, H and Hirano, T and Kato, A and Miki, A and Hirai, H and Murao, F and Imaizumi, H and Gomi, F and Mitamura, Y and Ogata, N and Kusuhara, S and Yasukawa, T and Murata, T and Sakamoto, T and Kondo, M and Ozawa, Y}, title = {Associations between Progression of Retinal Pigment Epithelial and Outer Retinal Atrophy and Choroidal Thickness: A 2-Year observation.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100939}, pmid = {41140907}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the clinical course of retinal pigment epithelial and outer retinal atrophy (RORA) with best-corrected visual acuity (BCVA) and risk factors for rapid progression to explore the pathogenesis.<br><br>DESIGN: Retrospective observational study.<br><br>SUBJECTS: Data on eyes with fovea-involved RORA associated with age-related macular degeneration were collected over time from 10 hospitals in Japan.<br><br>METHODS: Data on ophthalmic examination, BCVA, and OCT images were analyzed.<br><br>MAIN OUTCOME MEASURES: Relationships between changes in BCVA and extents of RORA and outer plexiform layer (OPL) deterioration and their associations with central choroidal thickness (CCT) and pachychoroid characteristics at baseline were evaluated.<br><br>RESULTS: Of the 53 eyes of 53 patients (mean age; 74.9 &#xb1; 1.4 years), 32 eyes (60.4%) belonged to men. The progression in the mean extent of OPL deterioration was evident at year 1, whereas that of RORA, BCVA impairment, thinning of the central retinal thickness, and CCT became apparent at year 2 (P < 0.05). Changes in the extents of RORA and OPL deterioration and BCVA were correlated (P < 0.05). Baseline CCT negatively correlated with baseline RORA and the changes in extent of RORA (P < 0.05). After adjusting for age and sex, a longer extent of RORA at baseline predicted BCVA worsening &#x2265;0.04 per year (odds ratio [OR], 3.444; 95% confidence interval [CI], 1.015-11.691; P = 0.047). Greater horizontal extension of RORA &#x2265;175 &#x3bc;m/y was frequently observed in eyes with thinner CCT <180 &#x3bc;m (OR, 4.684; 95% CI, 1.288-17.036; P = 0.019), subretinal drusenoid deposits (SDDs) (OR, 6.714; 95% CI, 1.555-28.988; P = 0.011), and drusen (OR, 4.392; 95% CI, 1.176-16.410; P = 0.028) and less observed in eyes with pachychoroid characteristics (OR, 0.038; 95% CI, 0.003-0.454, P = 0.010) at baseline after adjusting for age and baseline extent of RORA; similar risks for greater vertical extension of RORA were observed.<br><br>CONCLUSIONS: The change in BCVA paralleled the changes in the extents of RORA and OPL deterioration. Rapid BCVA impairment was observed in eyes with longer RORA at baseline. A thinner choroid, SDD, and drusen were risk factors, and pachychoroid characteristics were protective factors against RORA progression. Further studies are warranted to better understand the progression of RORA and vision loss.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41141822, year = {2025}, author = {Wang, T and Zhang, Y and Xiao, W and Jin, Y and Yi, Q and Chen, Q and Xiang, J and Wang, R and Li, J and Liu, L}, title = {Tetrahedral DNA Framework Penetrating Ocular Barrier for Treatment of Retinal Oxidative Stress.}, journal = {ACS omega}, volume = {10}, number = {41}, pages = {48984-48990}, pmid = {41141822}, issn = {2470-1343}, abstract = {Excessive accumulation of reactive oxygen species in the retina is the predominant pathogenic mechanism underlying dry age-related macular degeneration (dAMD). Although antioxidant chemicals have been shown to be effective in reducing ROS levels, their bioavailability and therapeutic efficacy are restricted by ocular barriers. Herein, we developed a tetrahedral framework nucleic acid (tFNA)-based antioxidant drug for the treatment of retinal oxidative stress diseases. By exploiting their penetration capability, these tFNAs penetrated multiple ocular tissues and cellular barriers. These tFNAs protected retinal pigment epithelium cells from glyoxal-induced oxidative stress damage by exerting their intrinsic antioxidant properties through the JNK and AKT pathways upon entering the cells. The subconjunctival administration of tFNAs alleviated structural damage and reduced retinal cell apoptosis in a retinal oxidative stress rat model. These results indicated that tFNAs are a promising therapeutic drug for the treatment of retinal oxidative stress diseases, which sheds light on the development of dAMD therapy.}, }
@article {pmid41143143, year = {2025}, author = {Biswas, RK and Sheth, JU and Shrivastava, V and Kaur, J and Sinha, S and Pal, SS and Nandi, K and Das, S}, title = {Faricimab for Refractory Neovascular Age-Related Macular Degeneration: Retrospective Real-World Evidence from India.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {3881-3887}, pmid = {41143143}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate the anatomical and functional outcomes of faricimab in eyes with refractory neovascular age-related macular degeneration (nAMD) in a real-world Indian cohort over a six-month period.<br><br>PATIENTS AND METHODS: In this retrospective, multicenter study, 24 eyes with refractory nAMD were switched to faricimab on a pro-re-nata regimen between January 2024 and December 2024. Patients underwent monthly evaluation for three months, then per physician discretion, with measurement of best-corrected visual acuity (BCVA), central foveal thickness (CFT), and proportions of eyes with intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED).<br><br>RESULTS: The cohort's mean age was 68.1 (&#xb1;10.6) years, and prior to switching had received an average of 11.4 (&#xb1;9.1) anti-VEGF injections. During the six-month period, eyes underwent a mean of 2.63 (&#xb1; 1.34) faricimab injections (range, 1-5): 25.0% received one injection, 29.2% two, 16.7% three, 16.7% four, and 12.5% five. Mean BCVA improved from 0.66 (&#xb1;0.4) logMAR at baseline to 0.47 (&#xb1;0.34) at month 1, 0.35 (&#xb1;0.32) at month 2, and 0.27 (&#xb1;0.27) at months 3 and 6 (P&#x2264;0.0003). Mean CFT decreased from 471.1 (&#xb1;246.4) &#xb5;m to 337.3 (&#xb1;198.3) &#xb5;m (month 1), 265.1 (&#xb1;90.7) &#xb5;m (month 2), 217.7 (&#xb1;41.3) &#xb5;m (month 3), and 209.4 (&#xb1;36.0) &#xb5;m (month 6) (P<0.0001). SRF resolved in 90.9% of affected eyes (P<0.001), IRF in 87.5% (P=0.0006), and PED in 54.5% (P=0.32), with complete fluid resolution in 83.3% of eyes (P=0.00002). No ocular or systemic adverse events occurred.<br><br>CONCLUSION: In this real-world Indian cohort of refractory nAMD, faricimab delivered robust visual gains, significant CFT reduction, and high rates of fluid resolution, with over half of eyes requiring &#x2264;2 injections over six months, supporting its role as an effective switch therapy. Further prospective studies are warranted to optimize dosing intervals and long-term outcomes.}, }
@article {pmid41143474, year = {2025}, author = {Habibi, A and Ashrafkhorasani, M and Emamverdi, M and Chinasigari, PR and Goerdt, L and Gao, L and McGwin, G and Clark, ME and Abbasgholizadeh, R and Fasih-Ahmad, S and Vatanatham, C and Wang, ZC and Mishra, Z and Nittala, MG and Owsley, C and Curcio, CA and Hu, ZJ and Sadda, SR}, title = {Total Retinal Pigment Epithelium Thickness and Reflectivity, in Relation to Histology and Vision, at the Aging-AMD Transition: ALSTAR2 Baseline.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {13}, pages = {42}, pmid = {41143474}, issn = {1552-5783}, support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Tomography, Optical Coherence/methods ; Female ; Aged ; Male ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Visual Acuity/physiology ; *Aging/physiology ; *Macular Degeneration/physiopathology/pathology/diagnosis ; Aged, 80 and over ; Middle Aged ; Dark Adaptation/physiology ; }, abstract = {PURPOSE: The retinal pigment epithelium (RPE) is critical in age-related macular degeneration (AMD) pathophysiology. We compare total RPE thickness (TRPET) and normalized reflectivity intensity (TNRR) on optical coherence tomography (OCT) among healthy aged and early AMD (eAMD) and intermediate AMD (iAMD) eyes, and to visual function.<br><br>METHODS: Spectralis OCT volume scans from aged, eAMD, and iAMD eyes (per Age-Related Eye Disease Study [AREDS] 9-step) of the Alabama Study on Early Age-related Macular Degeneration 2 (ALSTAR2) baseline sample were automatically segmented for vitreous, nerve fiber layer (NFL), and total RPE (measured up to the centerline of the interdigitation zone) and manually corrected. TNRR was normalized with reference to vitreous and NFL within zones of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Vision tests included rod-mediated dark adaptation (RMDA), a functional benchmark for AMD risk (reported as rod intercept time [RIT]), and other tests of rod- and cone-mediated function.<br><br>RESULTS: Of 502 eyes of 502 participants (71.8 &#xb1; 6.1 years, 59.6% female participants), 252 were healthy, 147 had eAMD, and 103 had iAMD. TRPET was significantly thinner in iAMD compared with eAMD and healthy eyes (P < 0.001) and moderately correlated with longer RIT in all eyes (r = 0.12-0.35). TNRR was lower in iAMD eyes compared to eAMD and healthy eyes (P < 0.01); correlation with RIT was weaker but significant.<br><br>CONCLUSIONS: Reduced TRPET and TNRR in AMD and their correlation with RMDA are statistically significant due to the large sample. Whether they have practical utility for AMD detection will be learned from ongoing longitudinal studies. In ALSTAR2, non-RPE layers may contribute to delayed RMDA.}, }
@article {pmid41144243, year = {2026}, author = {Perilli, R and Mastropasqua, R and Mastropasqua, L}, title = {Turning diabetic retinopathy telescreening into a multi-telescreening.}, journal = {European journal of ophthalmology}, volume = {36}, number = {2}, pages = {NP12-NP13}, doi = {10.1177/11206721251389641}, pmid = {41144243}, issn = {1724-6016}, }
@article {pmid41146323, year = {2025}, author = {Lee, Y and Rahman, S and Tao, BK and Fang, T and Akil, H and Ferrara, D and Lam, S and Navajas, EV}, title = {Recognition and treatment of polypoidal choroidal vasculopathy and age-related macular degeneration in British Columbia.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {118}, pmid = {41146323}, issn = {2056-9920}, abstract = {OBJECTIVE: To assess ethnic differences in the prevalence, diagnosis, and management of polypoidal choroidal vasculopathy (PCV) compared to typical neovascular age-related macular degeneration (nAMD) among Chinese and Caucasian patients in British Columbia.<br><br>METHODS: A retrospective chart review was conducted between 2008 and 2013 based on predefined inclusion criteria. Demographic, diagnostic, and clinical outcome data&#x2014;including race, lesion type, diagnostic modality, and treatment response&#x2014;were extracted and analyzed using RStudio.<br><br>RESULTS: Of the 416 eyes reviewed, 92.07% (383/416, N&#x2009;=&#x2009;Total sample number) were from Caucasian patients and 7.93% (33/416, N&#x2009;=&#x2009;Total sample number) from Chinese patients. No statistically significant difference in median age at diagnosis was observed between ethnic groups. ICGA was used in 3.57% (2/56, N&#x2009;=&#x2009;Total number of PCV cases) of PCV cases. Anti-VEGF monotherapy was the predominant treatment modality, while combination therapy with photodynamic therapy (PDT) was employed in 5.38% (22/353&#x2009;+&#x2009;56) of cases. There were no significant differences in visual acuity (VA) gains or central retinal thickness (CRT) reductions between PCV and nAMD diagnoses, nor between ethnic groups. Under anti-VEGF monotherapy, visual acuity and central retinal thickness outcomes were similar between PCV and nAMD and across the ethnic groups evaluated, within the limitations of the study design.<br><br>CONCLUSION: PCV, though less common than typical nAMD, was identified in both Chinese and Caucasian patients, with a trend toward younger age at presentation compared to nAMD. The low utilization of ICGA may contribute to the underdiagnosis of PCV. Nevertheless, anti-VEGF monotherapy yielded comparable outcomes across diagnoses and ethnicities, underscoring the importance of equitable diagnostic and therapeutic strategies in nAMD care.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40942-025-00744-8.}, }
@article {pmid41146803, year = {2025}, author = {Kominami, T and Ota, J and Takeuchi, J and Yuki, K and Ushida, H}, title = {Extensive Macular Atrophy With Pseudodrusen Complicated by Macular Neovascularization in a Japanese Patient: A Case Report.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e93258}, pmid = {41146803}, issn = {2168-8184}, abstract = {Recognizing the characteristic vertically oriented atrophy, pseudodrusen distribution, and retinal pigment epithelium-Bruch's membrane separation is critical for distinguishing extensive macular atrophy with a pseudodrusen-like appearance (EMAP) from age-related macular degeneration (AMD). Early identification of neovascular complications and prompt anti-vascular endothelial growth factor therapy can stabilize macular neovascularization (MNV) and help preserve residual vision in this rare retinal disorder. To the best of our knowledge, this is the first reported case of EMAP with MNV in an Asian patient. This report aims to describe the clinical presentation, imaging features, genetic findings, and therapeutic response in a Japanese woman with EMAP complicated by MNV, which is rarely reported in Asia. A 63-year-old woman presented with decades-long nyctalopia and progressive visual loss. Fundus examination and fundus autofluorescence showed vertically oriented macular atrophy, widespread pseudodrusen, and peripheral paving-stone degeneration. Optical coherence tomography (OCT) demonstrated diffuse separation of the retinal pigment epithelium from Bruch's membrane. These findings lead to the diagnosis of EMAP. Fluorescein angiography, indocyanine green angiography, and OCT angiography revealed type 1 MNV in the left eye. Whole-exome sequencing detected no pathogenic variants associated with inherited retinal disease or AMD. The neovascular lesion was treated with intravitreal aflibercept on a treat-and-extend regimen; after seven injections, the MNV became inactive.}, }
@article {pmid41147690, year = {2025}, author = {Wang, M and Gao, FJ and Tang, W and Lei, B and Hu, F and Ma, J and Sadda, SR and Kannan, R and Sreekumar, PG and Xu, G}, title = {Deficiency of 2-Oxoglutarate Carrier (Slc25a11) Drives RPE Epithelial-to-Mesenchymal Transition and Exacerbates Subretinal Fibrosis in Neovascular Age-Related Macular Degeneration.}, journal = {Aging cell}, volume = {24}, number = {12}, pages = {e70271}, pmid = {41147690}, issn = {1474-9726}, support = {R01 EY030141/EY/NEI NIH HHS/United States ; //Keck Foundation/ ; R01EY30141/EY/NEI NIH HHS/United States ; 82101124//National Natural Science Foundation of China/ ; 82101150//National Natural Science Foundation of China/ ; }, mesh = {*Epithelial-Mesenchymal Transition/genetics ; Animals ; Mice ; Fibrosis ; *Retinal Pigment Epithelium/pathology/metabolism ; Humans ; *Macular Degeneration/pathology/metabolism/genetics ; Signal Transduction ; Mitochondria/metabolism ; Mice, Inbred C57BL ; }, abstract = {Subretinal fibrosis significantly contributes to vision loss in neovascular age-related macular degeneration (nAMD). Epithelial-to-mesenchymal transition (EMT) in RPE cells is a key early step in subretinal fibrosis. While mitochondrial dysfunction in RPE is involved, the metabolic and molecular connections between EMT and mitochondria are not well understood. This study explores the role of oxoglutarate carrier (OGC; Slc25a11) on EMT and investigates the molecular mechanisms, focusing on its role in mitochondrial metabolism and GSH transport. OGC-silenced or overexpressed ARPE-19 cells were treated with TGF-β2 (10 ng/mL) for 48 h. EMT markers, cell migration, mtGSH, and mitochondrial bioenergetics and signaling pathways were assessed. In vivo, subretinal fibrosis was induced in wild-type and OGC[+/-] mice via laser photocoagulation. Fibrosis volume was measured using optical coherence tomography and immunostaining in RPE-choroid flat mounts. OGC silencing aggravated EMT, while overexpression attenuated TGF-β2-induced EMT, cell proliferation, and migration. OGC knockdown significantly enhanced RPE EMT, as evidenced by upregulated expression of α-SMA, fibronectin, collagen type I, and Slug, while E-cadherin was downregulated. OGC overexpression improved mitochondrial bioenergetics, whereas its inhibition reduced mitochondrial respiration, which was further aggravated by co-treatment with TGF-β2. Loss of OGC promoted cell proliferation and migration through Slug-mediated EMT. OGC depletion stimulated EMT via pSmad2/3 upregulation, dependent on the PI3K/AKT signaling pathway activation. In vivo studies further demonstrate that subretinal fibrosis was significantly augmented in OGC[+/-] mice via TGF-β2-dependent PI3K signaling. In conclusion, modulating OGC expression in RPE affects EMT and mitochondrial function, making OGC a potential therapeutic target for subretinal fibrosis in nAMD.}, }
@article {pmid41147841, year = {2025}, author = {Gallagher, D and Hurley, D and O'Brien, L and Petronzi, V and Connell, P and Dooley, I}, title = {VISUAL AND ANATOMICAL OUTCOMES AFTER VITRECTOMY WITH SUBRETINAL TISSUE PLASMINOGEN ACTIVATOR INJECTION IN PATIENTS WITH SUBMACULAR HEMORRHAGES SECONDARY TO WET AGE-RELATED MACULAR DEGENERATION.}, journal = {Retinal cases &amp; brief reports}, volume = {19}, number = {6}, pages = {744-748}, doi = {10.1097/ICB.0000000000001660}, pmid = {41147841}, issn = {1937-1578}, mesh = {Humans ; *Tissue Plasminogen Activator/administration &amp; dosage ; *Vitrectomy/methods ; *Retinal Hemorrhage/etiology/therapy/diagnosis ; Male ; Female ; *Fibrinolytic Agents/administration &amp; dosage ; *Visual Acuity ; Aged ; *Wet Macular Degeneration/complications/diagnosis ; Aged, 80 and over ; Tomography, Optical Coherence ; Retrospective Studies ; Injections, Intraocular ; Treatment Outcome ; Middle Aged ; }, abstract = {PURPOSE: Submacular hemorrhages (SMHs) are most commonly associated with wet age-related macular degeneration and their size and duration are strong prognostic factors for visual outcome. The aim of this audit was to evaluate outcomes of direct injection of submacular tissue plasminogen activator into these lesions during pars plana vitrectomy.<br><br>METHODS: All patients presenting to the Mater Misericordiae Hospital from January 2017 to December 2019 with large submacular hemorrhages secondary to wet age-related macular degeneration who underwent this treatment were included for review. All 10 patients underwent complete pars plana vitrectomy, injection of 0.2 mL (50 &#x3bc;g) of subretinal tissue plasminogen activator, and air tamponade. Preoperative and postoperative evaluations included VA testing, optical coherence tomography, and slit lamp examination.<br><br>RESULTS: Eight patients (80%) showed improvement of their VA, with four patients achieving a VA of &#x2264;0.4 LogMAR (20/50). Six patients had a total clearing of the macular hemorrhage, with a further two patients having subtotal clearance. One patient subsequently developed a retinal detachment requiring oil tamponade.<br><br>CONCLUSION: Submacular hemorrhage secondary to wet age-related macular degeneration is a sight threatening event with a varied prognosis, but in most cases, vitrectomy with subretinal tissue plasminogen activator injection results in improved anatomical and visual outcomes.}, }
@article {pmid41148250, year = {2026}, author = {Terao, R and Kitamoto, K and Aoki, S and Totani, K and Sugiyama, S and Yamanari, M and Inoue, T and Azuma, K and Obata, R}, title = {Short-term changes in retinal pigment epithelium after anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration evaluated by polarization-sensitive optical coherence tomography.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {1}, pages = {129-139}, pmid = {41148250}, issn = {1435-702X}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/pathology/metabolism ; Prospective Studies ; Angiogenesis Inhibitors/administration &amp; dosage ; Intravitreal Injections ; Female ; Male ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged ; *Ranibizumab/administration &amp; dosage ; Follow-Up Studies ; Fluorescein Angiography ; Fundus Oculi ; Time Factors ; Aged, 80 and over ; Middle Aged ; }, abstract = {PURPOSE: To characterize changes in retinal pigment epithelium (RPE) melanin distribution after anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective study enrolled treatment-na&#xef;ve nAMD eyes with macular neovascularization (MNV) type 1 and type 2. Eyes were treated with intravitreal faricimab injection every four weeks. Visual acuity and anatomical changes were assessed with multimodal imaging. Polarization-sensitive OCT (PS-OCT) was used to examine the polarimetric entropy, quantitative indicator of melanin distribution, at the RPE segment. Retinal sensitivity was assessed with microperimetry.<br><br>RESULTS: Twelve patients with MNV type 1 and seven eyes with MNV type 2 were included. Faricimab significantly improved visual acuity and central subfield thickness (p&#x2009;=&#x2009;0.0064,&#x2009;<&#x2009;0.0001, respectively). In MNV type 1, faricimab significantly increased mean entropy in the overall Early Treatment Diabetic Retinopathy Study (ETDRS) grid area (p&#x2009;=&#x2009;0.0386). In the per-grid analysis, entropy of type 1 also significantly increased, whereas type 2 showed significant reduction (p&#x2009;=&#x2009;0.0071, 0.0389, respectively). As MNV type 2 regresses, high-entropy area corresponding to MNV decreased and low-entropy area surrounding them increased (p&#x2009;=&#x2009;0.019, 0.0058, respectively), suggesting RPE migration onto MNV. RPE entropy was significantly associated with visual acuity or retinal sensitivity after the treatment (p&#x2009;=&#x2009;0.00475, 0.0307, respectively).<br><br>CONCLUSIONS: After anti-VEGF treatment for type 1 or type 2 MNV, RPE melanin distribution at the MNV and the surrounding area distinctly changed. They were associated with visual function. The present study supported deterioration of visual function in eyes with type 2 MNV after anti-VEGF treatment resulted not only from subretinal scar formation but RPE atrophy surrounding the MNV.}, }
@article {pmid41149584, year = {2025}, author = {Fang, Y and Zheng, H and Chen, Y and Ryu, B and Qian, ZJ}, title = {A Sulfated Polysaccharide from Gelidium crinale Suppresses Oxidative Stress and Epithelial-Mesenchymal Transition in Cultured Retinal Pigment Epithelial Cells.}, journal = {Marine drugs}, volume = {23}, number = {10}, pages = {}, pmid = {41149584}, issn = {1660-3397}, mesh = {*Epithelial-Mesenchymal Transition/drug effects ; *Oxidative Stress/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/cytology ; Humans ; *Polysaccharides/pharmacology/isolation &amp; purification/chemistry ; Hydrogen Peroxide/pharmacology ; Cell Line ; Apoptosis/drug effects ; Reactive Oxygen Species/metabolism ; Macular Degeneration/drug therapy ; *Rhodophyta/chemistry ; Signal Transduction/drug effects ; NF-kappa B/metabolism ; Epithelial Cells/drug effects/metabolism ; Sulfates/pharmacology/chemistry ; Edible Seaweeds ; }, abstract = {Age-related macular degeneration (AMD) progresses to vision-threatening dry and wet forms, with no effective dry AMD treatments available. The sulfated polysaccharide (GNP, 25.8 kDa) derived from Gelidium crinale exhibits diverse biological activities and represents a potential source of novel therapeutic agents. This study employed a hydrogen peroxide (H2O2)-induced oxidative stress and epithelial-mesenchymal transition (EMT) model in retinal pigment epithelial (RPE) cells to investigate GNP's protective mechanisms against both oxidative damage and EMT. The results demonstrated that GNP effectively suppressed oxidative stress, with the 600 μg/mL dose significantly inhibiting excessive reactive oxygen species (ROS) generation to levels comparable to untreated controls. Concurrently, at concentrations of 200-600 μg/mL, GNP inhibited NF-κB signaling and increased the Bax/Bcl-2 ratio, effectively counteracting H2O2-induced oxidative damage and cell apoptosis. Furthermore, in H2O2-treated ARPE-19 cells, 600 μg/mL GNP significantly reduced the secretion of N-cadherin (N-cad), Vimentin (Vim), and α-smooth muscle actin (α-SMA), while increasing E-cadherin (E-cad) expression, consequently inhibiting cell migration. Mechanistically, GNP activated the Nrf2/HO-1 pathway, thereby mitigating oxidative stress. These findings suggest that GNP may serve as a potential therapeutic agent for dry AMD.}, }
@article {pmid41149849, year = {2025}, author = {Bennie, J and Ramsey, DJ}, title = {Navigating the Decision to Discontinue Intravitreal Injection Therapy in End-Stage Neovascular Age-Related Macular Degeneration.}, journal = {Journal of personalized medicine}, volume = {15}, number = {10}, pages = {}, pmid = {41149849}, issn = {2075-4426}, abstract = {Introduction: The management of neovascular age-related macular degeneration (nAMD) is constrained by diminishing therapeutic options for retina specialists and their patients when the disease reaches its end stages. Methods: Clinical insights emerge from two case narratives in which patients benefitted from discontinuation of anti-VEGF therapy. Results: Long-term management of nAMD with intravitreal injections of agents targeting vascular endothelial growth factor (VEGF) is crucial for slowing progression of the disease and is generally well-tolerated. However, vision often declines as the disease progresses over time, even with treatment. This article presents strategies for aligning therapeutic goals with their expected visual outcome when an eye has reached end-stage disease. It addresses considerations for how and when to stop treatment when vision becomes limited, taking into consideration the visual status of the fellow eye and incorporating input from low vision specialists who can better assess best-corrected visual acuity (BCVA) and optimize the visual function of patients. We also acknowledge the potential benefits of switching either the dose or the agent that targets VEGF to alter the long-term visual outcome of treatment. Finally, we discuss the importance of taking into consideration related manifestations of the disease, such as macular scarring, geographic atrophy, or other retinal or optic nerve diseases which may limit vision and thus the utility of continued nAMD treatment. Conclusions: Building a strong patient-physician relationship is essential for navigating the shared decision-making process of when to stop treatment for nAMD.}, }
@article {pmid41151537, year = {2026}, author = {Lee, JK and Lee, J and Park, JB and Kim, K and Yu, SY}, title = {Topographic Progression of Geographic Atrophy and Visual Acuity in Nonexudative Age-Related Macular Degeneration.}, journal = {Korean journal of ophthalmology : KJO}, volume = {40}, number = {1}, pages = {1-11}, pmid = {41151537}, issn = {2092-9382}, mesh = {Humans ; *Visual Acuity/physiology ; *Geographic Atrophy/diagnosis/physiopathology/etiology ; Male ; Retrospective Studies ; Female ; *Tomography, Optical Coherence/methods ; Aged ; Disease Progression ; Follow-Up Studies ; *Fluorescein Angiography/methods ; *Macular Degeneration/complications/diagnosis/physiopathology ; Fundus Oculi ; Aged, 80 and over ; Middle Aged ; }, abstract = {PURPOSE: To investigate long-term topographic progression of the geographic atrophy (GA) area based on location and analyze its correlation with visual acuity in patient with GA secondary to non-neovascular age-related macular degeneration in South Korean patient cohort.<br><br>METHODS: Medical records and imaging data of 58 eyes from 34 patients with GA were retrospectively reviewed using fundus autofluorescence (FAF). Regions of interest were defined as concentric ring-shaped zones with diameters of 1, 2, 3, and 4 mm centered on the fovea (zones 0-3), each subdivided into superior, temporal, inferior, and nasal sectors. The foveal center was determined using optical coherence tomography, and sectoral GA areas were measured on FAF with the semiautomated software (RegionFinder ver. 2.6.2.0). Correlations among GA area enlargement, GA growth rate, and changes in best-corrected visual acuity (BCVA) were evaluated.<br><br>RESULTS: The mean GA area enlarged from 4.10 to 16.57 mm2 and mean BCVA decreased from 0.34 to 1.06 logMAR at 5 years of follow-up. The mean overall GA area growth rate was 1.96 mm2/yr. During yearly follow-up from baseline to 5 years, there were significant differences in GA growth rate of zone 3 inferior (p < 0.005). The GA area changes of zone 3 inferior was significantly correlated with BCVA. In the subgroup with BCVA decreased under 1.0 logMAR during follow-up, there was a higher growth rate in zone 2 nasal sector, 2 to 3 years before.<br><br>CONCLUSIONS: The overall GA growth rate was 1.96 mm2/yr in the 5-year follow-up of our cohort. Changes in the GA growth rate in the nasal perifoveal region (zone 2) may be associated with subsequent clinically meaningful visual decline.}, }
@article {pmid41152160, year = {2025}, author = {Chen, M and Yang, W and Xu, S and Lu, Y and Yang, Z and Li, F and Gu, Z}, title = {[Research on attention-enhanced networks for subtype classification of age-related macular degeneration in optical coherence tomography].}, journal = {Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi}, volume = {42}, number = {5}, pages = {901-909}, pmid = {41152160}, issn = {1001-5515}, mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Macular Degeneration/classification/diagnostic imaging ; *Neural Networks, Computer ; }, abstract = {Subtype classification of age-related macular degeneration (AMD) based on optical coherence tomography (OCT) images serves as an effective auxiliary tool for clinicians in diagnosing disease progression and formulating treatment plans. To improve the classification accuracy of AMD subtypes, this study proposes a keypoint-based, attention-enhanced residual network (KPA-ResNet). The proposed architecture adopts a 50-layer residual network (ResNet-50) as the backbone, preceded by a keypoint localization module based on heatmap regression to outline critical lesion regions. A two-dimensional relative self-attention mechanism is incorporated into convolutional layers to enhance the representation of key lesion areas. Furthermore, the network depth is appropriately increased and an improved residual module, ConvNeXt, is introduced to enable comprehensive extraction of high-dimensional features and enrich the detail of lesion boundary contours, ultimately achieving higher classification accuracy of AMD subtypes. Experimental results demonstrate that KPA-ResNet achieves significant improvements in overall classification accuracy compared with conventional convolutional neural networks. Specifically, for the wet AMD subtypes, the classification accuracies for inactive choroidal neovascularization (CNV) and active CNV reach 92.8% and 95.2%, respectively, representing substantial improvement over ResNet-50. These findings validate the superior performance of KPA-ResNet in AMD subtype classification tasks. This work provides a high-accuracy, generalizable network architecture for OCT-based AMD subtype classification and offers new insights into integrating attention mechanisms with convolutional neural networks in ophthalmic image analysis.}, }
@article {pmid41153254, year = {2025}, author = {Al-Khersan, H and Sodhi, SK and Cao, JA and Saju, SM and Pattathil, N and Zhou, AW and Choudhry, N and Russakoff, DB and Oakley, JD and Boyer, D and Wykoff, CC}, title = {Deep Learning-Based Segmentation of Geographic Atrophy: A Multi-Center, Multi-Device Validation in a Real-World Clinical Cohort.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {20}, pages = {}, pmid = {41153254}, issn = {2075-4418}, abstract = {Background: To report a deep learning-based algorithm for automated segmentation of geographic atrophy (GA) among patients with age-related macular degeneration (AMD). Methods: Validation of a deep learning algorithm was performed using optical coherence tomography (OCT) images from patients in routine clinical care diagnosed with GA, with and without concurrent nAMD. For model construction, a 3D U-Net architecture was used with the output modified to generate a 2D mask. Accuracy of the model was assessed relative to the manual labeling of GA with the Dice similarity coefficient (DSC) and correlation r[2] scores. Results: The OCT data set included 367 scans from the Spectralis (Heidelberg, Germany) from 55 eyes in 33 subjects; 267 (73%) scans had concurrent nAMD. In parallel, 348 scans were collected using the Cirrus (Zeiss), from 348 eyes in 326 subjects; 101 (29%) scans had concurrent nAMD. For Spectralis data, the mean DSC score was 0.83 and r[2] was 0.91. For Cirrus data, the mean DSC score was 0.82 and r[2] was 0.88. Conclusions: The reported deep learning algorithm demonstrated strong agreement with manual grading of GA secondary to AMD on the OCT data set from routine clinical practice. The model performed well across two OCT devices as well as amongst patients with GA with concurrent nAMD, suggesting applicability in the clinical space.}, }
@article {pmid41153266, year = {2025}, author = {Perkins, SW and Shah, N and Whitney, J and Matar, K and Yu, HJ and Wykoff, CC and Ehlers, JP}, title = {Radiomic Characterization and Automated Classification of Drusen Substructure Phenotype Associated with High-Risk Dry Age-Related Macular Degeneration.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {20}, pages = {}, pmid = {41153266}, issn = {2075-4418}, support = {T32 EY024236/EY/NEI NIH HHS/United States ; T32EY024236/NH/NIH HHS/United States ; }, abstract = {Background/Objectives: Optical coherence tomography (OCT)-reflective drusen substructures (ODSs) are associated with the conversion of intermediate AMD to geographic atrophy (GA). However, ODSs must be manually identified, a laborious process introducing bias and variation. This study proposes objective radiomic metrics of drusen phenotypes and validates them for the prediction of GA development and GA growth rate. Methods: A total of 104 drusen with high-reflective cores (H-type), 105 with low-reflective cores (L-type), 129 conical drusen (C-type), and 101 normal drusen (N-type) were segmented from OCT images. Radiomic features were extracted from these drusen, and the most important features for drusen classification were extracted from the retinal pigment epithelium-Bruch's membrane compartment of 743 OCT scans of eyes with dry AMD and used to predict GA conversion and fast growth. Results: Radiomic features classified drusen phenotypes with AUC = 0.87-0.95. H-type drusen have a higher reflectivity, greater variation in reflectivity, and coarser texture (p < 0.001). L-type drusen have a lower reflectivity and greater variation in reflectivity (p < 0.0001). C-type drusen have a less spherical shape and more disordered internal reflectivity (p < 0.001). N-type drusen have a more spherical shape and more uniform internal reflectivity (p < 0.001). These radiomic features predict the conversion from intermediate AMD to GA and top-quartile GA growth rate with AUC = 0.59-0.74 at years 1-3. Conclusions: These results demonstrate the potential of clinical phenotype-grounded radiomics for objective automated drusen analysis, GA risk stratification, and clinical prediction.}, }
@article {pmid41153316, year = {2025}, author = {Romero-Oraá, R and Herrero-Tudela, M and López, MI and Hornero, R and Romero-Aroca, P and García, M}, title = {An Ensemble Model for Fundus Images to Aid in Age-Related Macular Degeneration Grading.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {20}, pages = {}, pmid = {41153316}, issn = {2075-4418}, support = {TED2021-131913B-I00//Ministerio de Ciencia, Innovaci&#xf3;n y Universidades/ ; PID2023-148895OB-I00//Ministerio de Ciencia, Innovaci&#xf3;n y Universidades/ ; TED2021-131913B-I00//European Regional Development Fund/ ; PID2023-148895OB-I00//European Regional Development Fund/ ; Instituto de Salud Carlos III//Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine/ ; PIF-UVa//Universidad de Valladolid/ ; }, abstract = {Background: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly population. Periodic examinations through fundus image analysis are paramount for early diagnosis and adequate treatment. Automatic artificial intelligence algorithms have proven useful for AMD grading, with the ensemble strategies recently gaining special attention. Methods: This study presents an ensemble model that combines 2 individual models of a different nature. The first model was based on the ResNetRS architecture and supervised learning. The second model, known as RETFound, was based on a visual transformer architecture and self-supervised learning. Results: Our experiments were conducted using 149,819 fundus images from the Age-Related Eye Disease Study (AREDS) public dataset. An additional private dataset of 1679 images was used to validate our approach. The results on AREDS achieved a quadratic weighted kappa of 0.7364 and an accuracy of 66.03%, which outperforms the previous methods in the literature. Conclusions: The ensemble strategy presented in this study could be useful for the screening of AMD in a clinical setting. Consequently, eye care for AMD patients would be improved while clinical costs and workload would be reduced.}, }
@article {pmid41154560, year = {2025}, author = {Mimura, T and Noma, H}, title = {Title Oxidative Stress in Age-Related Macular Degeneration: From Molecular Mechanisms to Emerging Therapeutic Targets.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {41154560}, issn = {2076-3921}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the elderly, and oxidative stress, primarily mediated by reactive oxygen species (ROS), is widely recognized as a central driver of its onset and progression. The retina is highly susceptible to oxidative damage due to its elevated oxygen consumption, abundant polyunsaturated fatty acids, and continuous exposure to light. Recent studies have elucidated molecular mechanisms in which mitochondrial dysfunction, disruption of redox homeostasis, inflammation, and complement activation interact to promote degeneration of retinal pigment epithelium (RPE) and photoreceptor cells. In addition to age-related oxidative stress, environmental factors such as motor vehicle exhaust and volatile organic compounds (VOCs) can accelerate the accumulation of lipofuscin and drusen, thereby fostering a chronic pro-inflammatory milieu. From a therapeutic perspective, beyond conventional antioxidant supplementation, emerging strategies targeting oxidative stress-related pathways have gained attention, including mitochondrial protectants, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, anti-inflammatory agents, and gene therapy. Importantly, several innovative approaches are under investigation, such as saffron supplementation with neuroprotective properties, drug repositioning of levodopa, and nanotechnology-based delivery systems to enhance retinal bioavailability of antioxidants and gene therapies. This review summarizes the pathophysiological role of oxidative stress in AMD from a molecular mechanistic perspective and discusses recent advances in research and novel therapeutic targets.}, }
@article {pmid41155071, year = {2025}, author = {Barthelemy, N and Sridhar, J and Sengillo, JD}, title = {Gene Therapy for Wet Age-Related Macular Degeneration.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {41155071}, issn = {2306-5354}, abstract = {The prevalence of wet age-related macular degeneration (AMD) in the US is expected to increase to 82 million by 2050. Addressing the specialized needs for this population will become increasingly challenging as prevalence rises. Frequent anti-vascular endothelial growth factor (anti-VEGF) injections have been the recourse for this population; however, the burden wet AMD places on patients underscores the critical need for durable therapeutic approaches. Gene therapy is a bioengineered treatment that has transformed the management of previously untreatable disorders. Ongoing advancements and refinements in its biomechanism could lead to more sustainable treatment options for wet AMD. In this article, we provide recent updates on gene therapy trials for wet AMD.}, }
@article {pmid41155120, year = {2025}, author = {Patel, MJ and Sheth, S and Mar, J and Gregori, NZ and Sengillo, JD}, title = {Surgical Approaches to Retinal Gene Therapy: 2025 Update.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {41155120}, issn = {2306-5354}, abstract = {Gene therapy offers a promising new frontier in the treatment of inherited and acquired retinal disease. This review describes the current surgical delivery approaches for gene therapy to the retina-subretinal, suprachoroidal, and intravitreal-and provides an update on the state of the art for each method in 2025.}, }
@article {pmid41155961, year = {2025}, author = {Hassan, MSA and Zhong, C and Hassan, F and Li, SK}, title = {Targeting the Eye: RNA-Based Therapies, Interferences, and Delivery Strategies.}, journal = {Pharmaceutics}, volume = {17}, number = {10}, pages = {}, pmid = {41155961}, issn = {1999-4923}, support = {R01 EY031452/EY/NEI NIH HHS/United States ; R01EY031452/EY/NEI NIH HHS/United States ; }, abstract = {Recent advances in molecular biology have led to the development of RNA-based therapeutics, offering significant promise for treating various eye diseases. Current RNA therapeutics include RNA aptamers, antisense oligonucleotides (ASOs), small interfering RNA (siRNA), and messenger RNA (mRNA) that can target specific genetic and molecular pathways involved in eye disorders. In addition to their potential in therapy, RNA technologies have also provided tools for mechanistic studies to improve the understanding of eye diseases, expanding the possibilities of RNA-based treatments. Despite the utility of RNA in studying eye disease mechanisms and its potential in disease treatment, only a few RNA-based therapies have been approved for posterior eye diseases. This paper reviews RNA interference and related ocular delivery and posterior eye diseases, focusing on the use of RNA aptamers, siRNA, short hairpin RNA (shRNA), and microRNA (miRNA). Approaches using RNA to advance our understanding of eye diseases and disease treatments, particularly in the posterior segment of the eye, are discussed. It is concluded that RNA therapeutics offer a novel approach to treating a variety of eye diseases by targeting their molecular causes. siRNA, shRNA, miRNA, and ASO can directly silence disease-driving genes, while RNA aptamers bind to specific targets. Although many RNA-based therapies are still in experimental stages, they hold promise for conditions such as age-related macular degeneration (AMD), diabetic macular edema (DME), glaucoma, and inherited retinal disorders. Effective delivery methods and long-term safety are key challenges that need to be addressed for these treatments to become widely available.}, }
@article {pmid41156023, year = {2025}, author = {Yu, HS and Cho, H and Shin, YU and Hong, EH and Koh, SH}, title = {Protective Effect of Curcumin in Oxidative Stress-Induced Injury on Retinal Pigment Epithelial Cells.}, journal = {Journal of clinical medicine}, volume = {14}, number = {20}, pages = {}, pmid = {41156023}, issn = {2077-0383}, support = {2020R1A2C1010229//National Research Foundation of Korea/ ; 2021R1I1A1A01059690//National Research Foundation of Korea/ ; 202400000000843//Hanyang University/ ; }, abstract = {Background/Objectives: Oxidative stress is the major cause of retinal pigment epithelial cell death. We used oxidative stress-injured retinal pigment epithelial cells to investigate the protective effects of curcumin, a strong antioxidant, on the Nod-like receptor protein 3 (NLRP3) inflammasome pathway. Methods: To evaluate the effect of curcumin, cell viability was measured with cell counting kit-8 and lactate dehydrogenase assays. Hydrogen peroxide (H2O2)-injured ARPE-19 cells were treated with different curcumin concentrations. We performed a wound healing assay and dichlorodihydrofluorescein diacetate staining. Western blotting and immunofluorescence staining were performed to evaluate the changes in inflammasome levels in the ARPE-19 cells. Result: H2O2 (300 μM) reduced the viability of ARPE-19 cells. However, treatment with 7.5 μM curcumin enhanced ARPE-19 cell viability and reduced cell toxicity. Curcumin also reduced reactive oxygen species (ROS) levels in the H2O2-induced damaged ARPE-19 cells and attenuated the H2O2-dependent levels of the NLRP3 inflammasome and its related signaling proteins. Conclusions: Curcumin demonstrated protective effects against oxidative stress in retinal pigment epithelial cells by attenuating the activation of the NLRP3 inflammasome pathway. These findings suggest the therapeutic potential of curcumin as an anti-inflammatory and antioxidant agent for macular degeneration.}, }
@article {pmid41156127, year = {2025}, author = {Nishiyama, T and Hirai, H and Miyata, K and Nishi, T and Ueda, T and Kase, S}, title = {A Pilot Study on Structural Changes of Choroidal Vasculature Following Intravitreal Anti-VEGF Injection in Neovascular Age-Related Macular Degeneration: Faricimab vs Ranibizumab.}, journal = {Journal of clinical medicine}, volume = {14}, number = {20}, pages = {}, pmid = {41156127}, issn = {2077-0383}, abstract = {Objectives: This paper aims to explore optical coherence tomography (OCT)-based choroidal vascular changes in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents, faricimab and ranibizumab, in a pilot study. Methods: This retrospective pilot cohort study enrolled 28 treatment-naïve nAMD patients who received three consecutive intravitreal anti-VEGF injections at Nara Medical University Hospital. In total, 17 patients (61%) were Type 1 MNV and 11 patients (39%) were Type 2 MNV. Patients were divided into a faricimab group (13 eyes) and a ranibizumab group (15 eyes). The type of macular neovascularization (MNV) and the presence of polyps were recorded. The central choroidal thickness (CCT) and the ratio of luminal area to choroidal area (L/C ratio), derived from binarized OCT images, were measured at baseline after the first and third injections. Results: Type 1 MNV was observed in 61% of eyes, with polyps confirmed in 53%. There was no significant difference in best corrected visual acuity (BCVA) for both faricimab and ranibizumab during treatment (p = 0.12, 0.94, respectively). After the third injection, a dry macula was achieved in 62% of the faricimab group and 60% of the ranibizumab group. In the ranibizumab group, CCT significantly decreased after the first injection, while no significant change was observed in the faricimab group. Conversely, the L/C ratio significantly decreased in the faricimab group after the third injection (p = 0.010). Among faricimab-treated eyes, those with type 1 MNV showed a significantly greater reduction in the L/C ratio compared to type 2 MNV (p = 0.017). Conclusions: This pilot study suggests that faricimab may exert combined anti-VEGF and Ang-2 effects predominantly on type 1 MNV, potentially leading to vascular constriction. These exploratory findings warrant confirmation in larger studies.}, }
@article {pmid41156216, year = {2025}, author = {Kucharczuk, J and Kasprzak, H and Gawęcki, M}, title = {Switching from Aflibercept to Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration: Short-Term Results from Real-Life Study.}, journal = {Journal of clinical medicine}, volume = {14}, number = {20}, pages = {}, pmid = {41156216}, issn = {2077-0383}, abstract = {Purpose: To evaluate anatomical and functional outcomes after switching from aflibercept to faricimab in patients with neovascular age-related macular degeneration (nAMD) with suboptimal response. Methods: This retrospective study included 72 eyes of 66 patients with nAMD previously treated with intravitreal aflibercept using a treat-and-extend regimen. Indications for switching included persistent retinal fluid, pigment epithelial detachment (PED), lack of best-corrected visual acuity (BCVA) improvement, or inability to extend treatment intervals beyond four weeks. Patients received three monthly loading doses of faricimab followed by individualized 8- to 16-week dosing. Follow-up comprised six visits over a mean of 8.5 ± 1.4 months. Outcomes included BCVA (logMAR), retinal morphology (subretinal fluid-SRF; intraretinal fluid-IRF; pigment epithelial detachment-PED), central subfoveal thickness (CST), and treatment interval changes. Results: Switching to faricimab led to significant short-term anatomical improvement, primarily reduction in subretinal fluid (p < 0.0001), with maximal effect during the loading phase. Resolution of SRF was significant at the end of the follow up; however, IRF changes were transient and not sustained beyond three months. PED reduction reached borderline significance (p = 0.0455). CST decreased during the loading phase (p < 0.0001) but returned to baseline thereafter. BCVA improved only after loading (p = 0.0287) but not at final follow-up. Treatment intervals were extended by a mean of ~2 weeks (p < 0.0001), increasing in 80% of eyes. Eyes with fewer prior injections and better baseline BCVA achieved superior final visual outcomes. Conclusions: Switching to faricimab provides short-term anatomical benefits and treatment-interval extension without sustained visual gain. Functional improvements tended to be greater in patients with fewer injections and shorter treatment duration prior to switch.}, }
@article {pmid41156523, year = {2025}, author = {Pieńczykowska, K and Bryl, A and Mrugacz, M}, title = {The Impact of a High-Fat Diet on Eye Health.}, journal = {Nutrients}, volume = {17}, number = {20}, pages = {}, pmid = {41156523}, issn = {2072-6643}, mesh = {Humans ; *Diet, High-Fat/adverse effects ; Oxidative Stress ; Fatty Acids, Omega-3/administration &amp; dosage ; *Eye Diseases/etiology ; Lipid Metabolism ; Dietary Supplements ; Inflammation/etiology ; Retina/metabolism ; Animals ; *Eye ; Retinal Pigment Epithelium/metabolism ; }, abstract = {Background: The increasing prevalence of high-fat diets is associated with a rise in metabolic and neurodegenerative diseases. The retina and retinal pigment epithelium are metabolically active tissues exposed to oxidative stress, making them particularly vulnerable to lipid excess. Materials and Methods: A systematic literature review was conducted covering years until 2025 inclusive. Results: High-fat diets lead to cholesterol accumulation and lipid metabolism disturbances in the retina, retinal pigment epithelium, and ocular vessels. They activate inflammatory and oxidative stress pathways, resulting in structural and functional damage. Omega-3 deficiency exacerbates inflammation, while supplementation improves the tear film stability, corneal epithelial function, intraocular pressure regulation, and exerts neuroprotective effects. Conclusions: High-fat diets represent a significant risk factor for ocular diseases by disrupting lipid metabolism, enhancing inflammation, and inducing oxidative stress. Omega-3 fatty acid supplementation reduces inflammation and supports ocular functions.}, }
@article {pmid41157186, year = {2025}, author = {Chujo, S and Chung, YC and Quarta, A and Kwak, H and Soylu, C and Abbasgholizadeh, R and Alhelaly, M and Rattu, R and Corradetti, G and Nittala, MG and Sadda, SR}, title = {Improving OCTA Visualization of Macular Neovascularization via a Grayscale Inversion Method.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {10}, pages = {}, pmid = {41157186}, issn = {2075-1729}, abstract = {BACKGROUND: Age-related macular degeneration is a major cause of vision loss, and improved visualization of macular neovascularization (MNV) on OCT angiography (OCTA) could enhance clinical assessment. This study aimed to establish a simple and accessible image enhancement method.<br><br>METHODS: We retrospectively analyzed 24 eyes from 22 patients with MNV at the Doheny UCLA Eye Centers. Grayscale-inverted OCTA images were generated using the basic "Invert" function in ImageJ 1.51 23. Each original and inverted image pair was assessed for seven MNV-related features: structure and area within 3 &#xd7; 3 mm, 6 &#xd7; 6 mm and 12 &#xd7; 12 mm scans, and presence of polypoidal lesions. Twenty-one ophthalmologists graded visibility using a standardized five-point scale. Paired comparisons were performed using the Wilcoxon signed-rank test.<br><br>RESULTS: Grayscale inversion significantly improved the visualization of MNV structure in 6 &#xd7; 6 mm scans (mean difference: +0.67 &#xb1; 1.02; p = 0.008), 12 &#xd7; 12 mm scans (+0.62 &#xb1; 1.07; p = 0.013), and detection of polypoidal lesions (+0.43 &#xb1; 0.98; p = 0.030). No significant differences were found for 3 &#xd7; 3 mm structure (p = 0.793) or area-related features (all p > 0.3).<br><br>CONCLUSIONS: Grayscale inversion may enhance MNV visibility and polypoidal lesion detection on OCTA. As this study relied solely on subjective assessments, future work should incorporate quantitative image analysis.}, }
@article {pmid41157282, year = {2025}, author = {Iliadis, I and Pechnikova, NA and Poimenidou, M and Almaliotis, DD and Tsinopoulos, I and Yaremenko, TV and Yaremenko, AV}, title = {Applications of Modern Cell Therapies: The Latest Data in Ophthalmology.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {10}, pages = {}, pmid = {41157282}, issn = {2075-1729}, abstract = {Cell-based therapeutics are redefining interventions for vision loss by enabling tissue replacement, regeneration, and neuroprotection. This review surveys contemporary cellular strategies in ophthalmology through the lenses of therapeutic effectiveness, translational readiness, and governance. We profile principal sources-embryonic and induced pluripotent stem cells, mesenchymal stromal cells, retinal pigment epithelium, retinal progenitor and limbal stem cells-and enabling platforms including extracellular vesicles, encapsulated cell technology and biomaterial scaffolds. We synthesize clinical evidence across age-related macular degeneration, inherited retinal dystrophies, and corneal injury/limbal stem-cell deficiency, and highlight emerging applications for glaucoma and diabetic retinopathy. Delivery routes (subretinal, intravitreal, anterior segment) and graft formats (single cells, sheets/patches, organoids) are compared using standardized structural and functional endpoints. Persistent barriers include GMP-compliant derivation and release testing; differentiation fidelity, maturation, and potency; genomic stability and tumorigenicity risk; graft survival, synaptic integration, and immune rejection despite ocular immune privilege; the scarcity of validated biomarkers and harmonized outcome measures and ethical, regulatory, and health-economic constraints. Promising trajectories span off-the-shelf allogeneic products, patient-specific iPSC-derived grafts, organoid and 3D-bioprinted tissues, gene-plus-cell combinations, and cell-free extracellular-vesicle therapeutics. Overall, cell-based therapies remain investigational. With adequately powered trials, methodological harmonization, long-term surveillance, scalable xeno-free manufacturing, and equitable access frameworks, they may eventually become standards of care; at present, approvals are limited to specific products/indications and regions, and no cell therapy is the standard of care for retinal disease.}, }
@article {pmid41158172, year = {2025}, author = {Guo, YJ and Chen, ZQ and Zhao, J}, title = {Integrating plasma proteomics and genome-wide association data to identify therapeutic targets for retinal neurodegenerative diseases in Europeans.}, journal = {International journal of ophthalmology}, volume = {18}, number = {11}, pages = {2170-2182}, pmid = {41158172}, issn = {2222-3959}, abstract = {AIM: To employ proteome-wide Mendelian randomization (MR) to explore novel protein and drug targets for retinal neurodegenerative diseases (RND) in individuals of European ancestry.<br><br>METHODS: This study used summary data-based MR to analyze the correlation between plasma protein levels and three RND, with protein data derived from two independent large-scale proteomics datasets. Potential drug targets were identified using Bayesian colocalization, followed by MR analysis, sensitivity testing, and external validation. Drug prediction and molecular docking were conducted to evaluate the druggability of the target proteins.<br><br>RESULTS: The study identified six promising protein targets, each successfully replicated at least twice. The results included three proteins related to diabetic retinopathy (ICAM1, GCKR, WARS), two proteins related to age-related macular degeneration (WARS, BRD2), and two proteins related to glaucoma (SVEP1, NPTXR). Additionally, drug prediction and molecular docking indicated that five drugs (fenofibrate, trofinetide, ticagrelor, lifitegrast, acetaminophen) effectively bound to the target proteins.<br><br>CONCLUSION: This study identified six potential protein targets for RND and five existing drugs with therapeutic potential. By integrating plasma proteomics with genetic data, it provides a cost-effective framework for drug discovery.}, }
@article {pmid41158183, year = {2025}, author = {Ai, LQ and Zhu, LY and Yang, H and Ye, J}, title = {Critical role of lipid metabolism in axial myopia development.}, journal = {International journal of ophthalmology}, volume = {18}, number = {11}, pages = {2195-2204}, pmid = {41158183}, issn = {2222-3959}, abstract = {The global prevalence of myopia is becoming increasingly severe, with epidemiological models predicting that by 2050, approximately 50% of the world's population will be affected by myopia, and about 10% will suffer from high myopia. The incidence of high myopia is projected to increase fivefold, making it the leading cause of irreversible vision impairment. Myopia often leads to various complications and has been associated with other ocular diseases, including early-onset cataracts, age-related macular degeneration, and primary open angle glaucoma. As a result, the control and management of myopia have become ongoing and long-term research priorities. The pathogenesis of myopia involves complex multisystem interactions. Current mainstream theories focus primarily on choroidal hypoxia-induced scleral remodeling, with neurotransmitters such as acetylcholine and dopamine playing regulatory roles. However, recent studies have increasingly suggested that changes in nutritional intake, including proteins, fats, and cholesterol, may also be related to myopia development. The role of lipid metabolism in the onset and progression of myopia has gradually attracted growing attention. Therefore, this review aims to systematically elucidate the molecular mechanisms of lipid metabolism regulatory networks in axial myopia, integrating multidimensional factors to provide a theoretical foundation for precision intervention strategies.}, }
@article {pmid41158184, year = {2025}, author = {Kananen, F}, title = {Treatment results switching from aflibercept to bevacizumab in wet age-related macular degeneration.}, journal = {International journal of ophthalmology}, volume = {18}, number = {11}, pages = {2116-2121}, pmid = {41158184}, issn = {2222-3959}, abstract = {AIM: To examine effects of switching intravitreal aflibercept to bevacizumab in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Data from patients treated for nAMD with anti-vascular endothelial growth factor (VEGF) injections at &#xd6;rebro University Hospital between January 2014 and June 2020, were extracted from the Swedish macular register (SMR). A total of 230 eyes were included in the study: 116 in the study/bevacizumab switch group and 114 in the control/aflibercept group. Central retinal thickness (CRT) was measured at baseline and after 2y. Primary outcome was mean change in best corrected visual acuity (BCVA) between baseline and 2y. Secondary outcome variables included proportion of patients with a clinically significant change in BCVA [increase or decrease of &#x2265;15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters], mean change in CRT, number of anti-VEGF injections, number of visits assessing disease activity and number of visits with active disease.<br><br>RESULTS: The mean difference in BCVA between baseline and 2y was 1.13&#xb1;14.47 ETDRS letters in the bevacizumab switch group and 1.81&#xb1;13.01 ETDRS letters in the aflibercept group. The lower bound of the 95% confidence interval of the difference in BCVA was -4.25, indicating non-inferiority within a 5 ETDRS letter limit. No significant differences in mean change of CRT between baseline and 2y were detected (study -185.9&#xb1;167.0 versus control -149.4&#xb1;193.1 &#xb5;m, P=0.127). The distribution of clinically significant improvement (P=0.598) or worsening (P=0.508) of BCVA during follow-up did not show statistically significant differences between groups. The number of anti-VEGF injections administered (study 12.76&#xb1;2.20 versus control 13.10&#xb1;4.20, P=0.442), the number of visits assessing disease activity (P=0.301), and the number of visits with active disease (P=0.065) did not show differences between subjects receiving bevacizumab and aflibercept treatment. No significant differences were detected in baseline characteristics between the study and control groups, including age, BCVA, CRT, neovascular membrane type or location, duration of symptoms or prior cataract surgery.<br><br>CONCLUSION: Switching to off-label bevacizumab in patients responding to initial aflibercept treatment is non-inferior to continued aflibercept treatment with respect to change in visual acuity at 2y. Switching anti-VEGF from aflibercept to bevacizumab may be a viable option in clinical settings with limited resources.}, }
@article {pmid41158821, year = {2025}, author = {Sanfelippo, WA and Oley, M and Harrelson, H and Vilar, N}, title = {Artery of Percheron infarct with multiple cranial nerve palsies and Horner Syndrome.}, journal = {American journal of ophthalmology case reports}, volume = {40}, number = {}, pages = {102458}, pmid = {41158821}, issn = {2451-9936}, abstract = {PURPOSE: To report a case of a rare stroke variant involving the artery of Percheron leading to ocular motility compromise.<br><br>OBSERVATIONS: A 65-year-old man presented to the neuro-ophthalmology clinic with multiple cranial nerve palsies and Horner Syndrome. He was three weeks post-thrombolytic therapy to treat an ischemic stroke, and his pertinent medical history consisted of hyperlipidemia and macular degeneration. On physical exam, the patient experienced bilateral vertical gaze paresis, incomplete left Horner syndrome, right-sided cranial nerve VI palsy, and partial left-sided cranial nerve VII palsy. Based on the infarction patterns demonstrated on MRI, the patient was diagnosed with an artery of Percheron infarct.<br><br>CONCLUSIONS AND IMPORTANCE: The artery of Percheron is a rare variant of posterior cerebral circulation that supplies both paramedian thalamic zones in addition to variably supplying the midbrain. Overall, this case highlights the importance of considering rare anatomical variants when working up ophthalmic deficits in a stroke patient. Early diagnosis can lead to adequate therapy and prevent complications in the future.}, }
@article {pmid41159651, year = {2025}, author = {Gorski, M and Grunin, M and Herold, JM and Fröhlich, B and Behr, M and Wheeler, N and Bush, WS and Song, YE and Zhu, X and Blanton, SH and Pericak-Vance, MA and Heid, IM and Haines, JL and , }, title = {Diverse-Ancestry GWAS of Age-Related Macular Degeneration on 16,108 Examined Cases and 18,038 Controls.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {13}, pages = {51}, pmid = {41159651}, issn = {1552-5783}, support = {R01 EY012118/EY/NEI NIH HHS/United States ; R01 EY022310/EY/NEI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Case-Control Studies ; Complement Factor H/genetics ; *Genetic Predisposition to Disease/ethnology ; *Genome-Wide Association Study ; *Macular Degeneration/ethnology/genetics ; *Polymorphism, Single Nucleotide ; *Population Groups/ethnology/genetics ; }, abstract = {PURPOSE: In 2016, the International Age-related Macular Degeneration Genomics Consortium analyzed data from approximately 50,000 individuals (IAMDGC 1.0) and identified 52 variants across 34 loci associated with advanced AMD (adAMD) in individuals of European ancestry and did not include diverse ancestries, fine-mapping per ancestry, or a predictive model with/without the contributions of one lead genetic risk locus, CFH. Therefore, we analyzed full cross-ancestry IAMDGC data, utilizing the newest imputation panel, and identified genetic risk loci across and between ancestries contributing to AMD.<br><br>METHODS: In this IAMDGC 2.0 analysis, we included cross-ancestry data via custom exome chip imputed genome-wide via TOPMedv2, in 16,108 ophthalmologically confirmed adAMD cases and 18,038 examined AMD-free controls. We included both male and female subjects and four diverse ancestries. Data were analyzed from June 2021 to May 2024.<br><br>RESULTS: Utilizing diverse ancestry data (cases/controls&#xa0;=&#xa0;15,616/16,723 European, 50/357 African, 207/322 Asian, and 235/636 Other), we identified 28 loci at P&#xa0;<&#xa0;5 &#xd7; 10-8, including 2 additional AMD loci compared to IAMDGC 1.0 (SERPINA1 and CPN1). Fine-mapping supported one ancestry-shared signal around HTRA1/ARMS2 and nine signals around CFH without African ancestry contribution. The 52-variant genetic risk score with and the 44-variant score without CFH predicted adAMD in all ancestries (area under the curve [AUC] = 0.80/0.75, 0.65/0.64, and 0.80/0.79, respectively).<br><br>CONCLUSIONS: Our results indicate that the genetic underpinning of adAMD is mostly shared between ancestries. We also identify the CFH variant as being less relevant in specific ancestries, indicating a difference in pathogenic burden between ancestries. We increased the available genomic data for AMD over 300-fold with the IAMDGC 2.0 imputation, making it a valuable resource for further AMD genetic analysis.}, }
@article {pmid41160616, year = {2025}, author = {Jia, S and Liu, Q and Liu, P and Zhao, W and Li, S}, title = {Association of perchlorate, nitrate, and thiocyanate with age-related macular degeneration in the United States.}, journal = {PloS one}, volume = {20}, number = {10}, pages = {e0334919}, pmid = {41160616}, issn = {1932-6203}, mesh = {Humans ; *Nitrates/urine/adverse effects ; *Thiocyanates/urine/adverse effects ; Female ; Male ; United States/epidemiology ; Middle Aged ; *Macular Degeneration/epidemiology/chemically induced/urine ; Aged ; *Perchlorates/urine/adverse effects ; Adult ; Nutrition Surveys ; Risk Factors ; }, abstract = {Perchlorate, nitrate, and thiocyanate are endocrine-disrupting chemicals, but their associations with AMD is unclear. This study aims to investigate this relationship. We included 4727 participants aged 40 years and older from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. Logistic regression analysis, restricted cubic spline (RCS), and weighted quantile sum (WQS) were applied to investigate the single, non-linear, and combined effects on AMD risk. Nitrate exposure was positively associated with any AMD risk (OR Any AMD, 1.19; 95% CI, 1.05-1.35; P = 0.010) and early AMD risk (OR Early AMD, 1.19; 95% CI, 1.05-1.36; P = 0.010); compared to the first quartile, the highest quartile of nitrate (OR, 1.94; 95% CI, 1.18-3.19; P = 0.012) and thiocyanate (OR, 1.70; 95% CI, 1.19-2.42; P = 0.006) levels were positively associated with AMD risk. The results of RCS showed a nonlinear relationship between nitrate exposure (P for nonlinearity = 0.020), thiocyanate (P for nonlinearity = 0.041), and AMD risk. WQS analysis indicated a positive relationship between mixed exposure and AMD risk (OR, 1.24; 95% CI, 1.01 to 1.51; P = 0.037). This study indicated that high urinary nitrate and thiocyanate levels were associated with an increased AMD risk among US adults. However, the cross-sectional design precludes causal inference.}, }
@article {pmid41162371, year = {2025}, author = {Amirkavei, M and Kaikkonen, O and Turunen, T and Meller, A and Åhlgren, J and Kvanta, A and André, H and Koskelainen, A}, title = {Non-damaging laser treatment with electroretinography-based thermal dosimetry activates hormetic heat response in pig retinal pigment epithelium.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {9533}, pmid = {41162371}, issn = {2041-1723}, mesh = {Animals ; *Retinal Pigment Epithelium/radiation effects/metabolism/pathology ; *Electroretinography/methods ; Swine ; Male ; *Heat-Shock Response/physiology ; *Laser Therapy/methods ; Autophagy/radiation effects ; Apoptosis/radiation effects ; Oxidative Stress ; Retina ; Lasers ; Hot Temperature ; Heat-Shock Proteins/metabolism ; }, abstract = {Enhancing protein homeostasis and antioxidant defense mechanisms in the retinal pigment epithelium (RPE) holds significant promise as a treatment option for various retinal diseases, including age-related macular degeneration. However, patient responses to laser-induced RPE hyperthermia varies substantially. To address this, we introduce a focal electroretinography (fERG)-based method for retinal temperature monitoring during laser exposure. Applying the method to anaesthetized male pigs in vivo, we study the biological effects of controlled retinal hyperthermia. Our findings reveal that temperature elevation to 44 °C with 60-second laser exposure triggers heat shock protein production and autophagy activation in RPE/choroid while avoiding oxidative stress, apoptosis, and structural damage. Importantly, our results demonstrate that visible lesions occur at temperatures above 48 °C, and that the temperature determination precision was 0.6 °C. These outcomes highlight that fERG-controlled retinal laser treatment enables reliable and safe activation of cytoprotective mechanisms in the RPE, providing a promising new therapeutic approach.}, }
@article {pmid41162502, year = {2025}, author = {Luo, M and Zhang, M and Xing, Z and Yu, W and Lv, H}, title = {Mechanistic analysis of luteolin in mitigating dry age-related macular degeneration through network pharmacology and experimental validation.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {37862}, pmid = {41162502}, issn = {2045-2322}, support = {2024ZYD0114//Sichuan Provincial Department of Science and Technology/ ; S2024001//Sichuan Medical Association/ ; }, mesh = {*Luteolin/pharmacology/chemistry ; Humans ; *Macular Degeneration/drug therapy/metabolism/pathology ; Molecular Docking Simulation ; *Network Pharmacology ; Cell Survival/drug effects ; Protein Interaction Maps/drug effects ; Reactive Oxygen Species/metabolism ; Cell Line ; Retinal Pigment Epithelium/drug effects/metabolism ; Membrane Potential, Mitochondrial/drug effects ; Iodates ; }, abstract = {Dry age-related macular degeneration (AMD) ranks among the primary causes of irreversible vision loss in the elderly. Luteolin, with its diverse biological activities, has attracted significant attention as a promising candidate for intervening in dry AMD. Explore the protective effect of luteolin on dry AMD to address the unmet need for current therapeutic agents. Luteolin's target information and dry AMD-related genes were retrieved from public databases. Shared targets of luteolin and dry AMD were used to construct a protein‒protein interaction network, followed by Gene Ontology and pathway enrichment analyses. Finally, molecular docking between the active ingredient and core targets was validated. In vitro, sodium iodate was used to induce ARPE-19 cells, after which cell viability was analyzed via a Cell Counting Kit-8 (CCK-8) assay. Reactive oxygen species (ROS) levels and mitochondrial membrane potential were detected via fluorescent dye staining. In the network pharmacology analysis, a total of 213 potential therapeutic targets associated with luteolin's activity against dry AMD were identified. Among these genes, TP53, TNF, IL6, AKT1, BCL2, STAT3, JUN, and CASP3 were identified as core therapeutic targets. These targets are primarily involved in pathways including lipid and atherosclerosis, cancer-related pathways, and the AGE-RAGE signaling pathway in diabetic complications. Molecular docking analyses revealed strong binding affinities between luteolin and the core targets, validating the molecular mechanisms underlying luteolin's efficacy against dry AMD. Experimental data demonstrated that luteolin not only mitigated sodium iodate-induced reductions in ARPE-19 cell viability but also decreased intracellular ROS levels and restored mitochondrial membrane potential. Luteolin effectively enhances the viability of damaged RPE cells, reduces oxidative stress levels, and protects mitochondrial function. This protective effect is likely mediated through the coordinated action of multiple targets and pathways, highlighting luteolin's promising potential in the prevention and management of dry AMD. However, this study is limited by its sole reliance on in vitro cell validation and inability to fully reflect real in vivo effects and potential side effects.}, }
@article {pmid41162529, year = {2025}, author = {Misson, GP and Anderson, SJ and Armstrong, RA and Heitmar, R}, title = {A novel computational model for human macular pigment optical density and its relationship to foveal structure.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {37865}, pmid = {41162529}, issn = {2045-2322}, mesh = {Humans ; *Macular Pigment/metabolism ; *Fovea Centralis/diagnostic imaging/metabolism ; Tomography, Optical Coherence ; Female ; Male ; Macular Degeneration/metabolism/diagnostic imaging ; Aged ; Middle Aged ; *Computer Simulation ; Xanthophylls/metabolism ; Macula Lutea/metabolism ; }, abstract = {Macular pigment optical density (MPOD) models enhance understanding of macular xanthophyll distribution, particularly relevant to age-related macular degeneration. This study investigates an existing model and introduces a novel, more accurate and biologically relevant approach. MPOD spatial profiles of 48 eyes were obtained using dual-wavelength autofluorescence imaging, with structural data from OCT and OCT-angiography. MPOD data were analyzed using (a) an existing sum of exponential and Gaussian model (MEG) and (b) a novel sum of three Gaussians model (M3G). Extracted parameters generated individualized MPOD models, from which gradients and volumes were derived. M3G-derived variables were analyzed against OCT/OCTA data using factor analysis and multiple regression. M3G demonstrated a superior fit to MPOD data (SSE = 2.60 × 10[- 3]) compared to MEG, (SSE = 35.7 × 10[- 3]) enabling automated fitting consistent over small and large datasets. M3G provided meaningful variables, including MPOD gradients, volumes and critical point eccentricities. Correlations included those between dependent variables of critical point eccentricities and central macular pigment volume with foveal avascular zone and foveal pit radii.The excellent data fit of M3G enables automated extraction of physiologically relevant parameters. Its three-component configuration is consistent with the location of macular xanthophylls. M3G is similar to models of foveal structure, suggesting a fundamental relationship.}, }
@article {pmid41162760, year = {2025}, author = {Brandl, C and Schuster, AK and Finger, RP}, title = {[Nutrition and dietary supplements in eye diseases-Part 1: age-related macular degeneration and diabetic eye diseases].}, journal = {Die Ophthalmologie}, volume = {122}, number = {11}, pages = {871-872}, doi = {10.1007/s00347-025-02326-3}, pmid = {41162760}, issn = {2731-7218}, }
@article {pmid41164518, year = {2025}, author = {Namdeo, TS and Ashok, AA}, title = {Transformative Algal Interventions in Ophthalmology, Mechanisms, and Future Potential: A Review.}, journal = {Journal of pharmacy &amp; bioallied sciences}, volume = {17}, number = {Suppl 3}, pages = {S2044-S2048}, pmid = {41164518}, issn = {0976-4879}, abstract = {Microalgae have become the focus of many studies concerning ocular health due to the varied chemical composition of algae. These organisms contain bioactive compounds especially carotenoids, polyunsaturated fatty acids (PUFAs), and antioxidants, which have proven beneficial in some diseases of the eyes. This review is focused on summarizing the potential therapeutic use of algae in treating eye diseases, including macular degeneration, glaucoma, cataracts, diabetic retinopathy (DR), and dry eye syndrome. We will also describe the pathways by which algae produce benefits, review cases of clinical studies, and explore future uses for algae in treatments.}, }
@article {pmid41165404, year = {2025}, author = {Faurite, C and Michaud, C and Cousin, E and Olivier, P and Gallice, M and Chiquet, C and Pietras, J and Attyé, A and Soler, V and Berry, I and Mermillod, M and Cottereau, BR and Peyrin, C}, title = {Neurobehavioral Changes in Macular Degeneration: Spatial Frequency Use in Scene Recognition.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {13}, pages = {54}, pmid = {41165404}, issn = {1552-5783}, mesh = {Humans ; *Macular Degeneration/physiopathology/psychology ; Male ; Female ; Magnetic Resonance Imaging ; Aged ; Middle Aged ; *Scotoma/physiopathology ; *Pattern Recognition, Visual/physiology ; Visual Acuity/physiology ; *Visual Perception/physiology ; Aged, 80 and over ; }, abstract = {PURPOSE: Central vision loss in macular diseases severely affects visual perception and cognition, particularly scene recognition. A key question is whether observed impairments result solely from reduced input or reflect functional changes in spatial frequency processing. This study investigated how macular diseases affects this processing at both behavioral and brain levels.<br><br>METHODS: We compared patients with macular diseases with age-matched controls using an artificial scotoma simulating each patient's central vision loss. Participants performed a scene categorization task with images filtered in high spatial frequencies (HSFs; fine details) or low spatial frequencies (LSFs; global shape). Patients fixated using their preferred retinal locus (PRL), whereas controls fixated on the location corresponding to the patient's fovea, within the artificial scotoma. Behavioral performance and functional magnetic resonance imaging (fMRI) responses were analyzed.<br><br>RESULTS: Patients performed worse than the healthy controls for both HSF and LSF scenes, with a more pronounced deficit for HSFs. These deficits were associated with reduced activation in occipital cortex and in the parahippocampal place area (PPA), particularly for HSF scenes. In contrast, LSF processing was relatively preserved and accompanied by increased recruitment of higher-level cognitive and oculomotor areas in patients.<br><br>CONCLUSIONS: These findings demonstrate that macular diseases leads to altered spatial frequency processing within residual vision itself, particularly affecting fine-detail analysis. This perceptual degradation is accompanied by functional brain reorganization supporting partial compensation. The results highlight the importance of considering both degraded input and adaptive mechanisms when designing rehabilitation strategies based on residual peripheral vision.}, }
@article {pmid41166891, year = {2025}, author = {Zhang, M and Shen, J and Luly, KM and Lim, Y and Shannon, SR and Jain, M and Tzeng, SY and Hackett, S and Kanan, Y and Green, JJ and Campochiaro, PA}, title = {Suppression of choroidal neovascularization by nonviral gene transfer of pigment epithelium-derived factor.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {193}, number = {}, pages = {118711}, doi = {10.1016/j.biopha.2025.118711}, pmid = {41166891}, issn = {1950-6007}, support = {R01 EY031097/EY/NEI NIH HHS/United States ; }, mesh = {*Serpins/genetics/metabolism ; Animals ; *Nerve Growth Factors/genetics/metabolism ; *Choroidal Neovascularization/therapy/genetics/pathology ; *Eye Proteins/genetics/metabolism ; *Gene Transfer Techniques ; Rats ; *Genetic Therapy/methods ; Nanoparticles/chemistry ; Mice ; Mice, Inbred C57BL ; Male ; Plasmids/administration &amp; dosage ; Retina/metabolism/pathology ; Macular Degeneration/therapy/genetics ; Rats, Sprague-Dawley ; Polymers ; Pigment Epithelium-Derived Factor ; }, abstract = {Age-related macular degeneration (AMD), a leading cause of vision loss among individuals over 60, is characterized by progressive retinal degeneration in a critical area for vision, the macula, and neovascular complications. Pigment epithelium-derived factor (PEDF) has the potential to address both of these pathologic processes because it has both neuroprotective and anti-angiogenic activities. In this study, we used a polymeric nonviral gene transfer platform to express PEDF in the eyes of mice and rats. In mice, there was high expression of PEDF in the retina and eyecup two weeks after subretinal injection of poly(β-amino ester) (PBAE) nanoparticles (NPs) containing a plasmid encoding PEDF, and at 2 or 4 weeks after injection there was a significant reduction in the area of choroidal neovascularization (CNV) at Bruch's membrane rupture sites compared with eyes that had received subretinal injection of a control vector. As suprachoroidal injection is a route of vector delivery that can be done in an outpatient setting and may limit certain negative side effects associated with subretinal injection, this route of administration was also investigated for PEDF plasmid delivery. In rats, there was high expression of PEDF in the retina and eyecup 4 weeks after suprachoroidal injection of PEDF NPs, and a significant reduction in CNV area at Bruch's membrane rupture sites compared with those in eyes injected with control vector. These data suggest that ocular nonviral gene transfer of PEDF may provide a new treatment approach for AMD.}, }
@article {pmid41167282, year = {2026}, author = {Chen, Y and Jiang, F and Zhang, M}, title = {Response to comments on refining the translational pathway for senotherapeutics in age-related macular degeneration: Insights on biomarkers, delivery strategies, and clinical trial design.}, journal = {Survey of ophthalmology}, volume = {71}, number = {3}, pages = {1012-1013}, doi = {10.1016/j.survophthal.2025.10.006}, pmid = {41167282}, issn = {1879-3304}, }
@article {pmid41167797, year = {2025}, author = {Huang, X and Chen, J and Li, J and Zhang, G and Zhu, X and Zhou, M and Bo, Q and Sun, X}, title = {Choroidal changes correlate with type 1 neovascular activity in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-327839}, pmid = {41167797}, issn = {1468-2079}, abstract = {PURPOSE: To investigate the association among choroidal factors and lesion activity of polypoidal choroidal vasculopathy (PCV) and type I neovascular age-related macular degeneration (nAMD) using swept-source optical coherence tomography angiography (SS-OCTA).<br><br>METHODS: 69 eyes with PCV or type I nAMD were retrospectively included. All eyes had either &#x2265;2 consecutive non-exudative visits without treatment or no exudation/treatment within 6-month SS-OCTA follow-up. Lesions were categorised into active and inactive based on progression, defined as exudation, branching vascular network (BVN)/macular neovascularisation enlargement or recurrence/new/growth of polypoidal lesions. Choroidal parameters, including mean choroidal thickness (MCT), choroidal vascularity index (CVI) and choroidal volume (CV), were evaluated before and after lesion progression. The association between CVI variation and lesion area growth in PCV was also analysed.<br><br>RESULTS: No baseline differences in MCT or CVI were found between PCV and nAMD. However, significant differences in CVI and MCT variation were observed between active and inactive lesions (p<0.05). In PCV, lesion activity was characterised by decreased CVI and increased MCT, while in nAMD, only MCT and CV increased. Notably, combined CVI decrease and MCT increase served as a sensitive marker for active PCV (p<0.05), but not for nAMD. CVI reduction also correlated with BVN growth in PCV (R=-0.722, p<0.01).<br><br>CONCLUSION: Choroidal parameters varied significantly during lesion progression. Combined CVI decrease and MCT increase sensitively reflected active PCV lesions and were correlated with lesion location, size and progression, highlighting the differences in the choroidal microenvironment in the activities of PCV and nAMD.}, }
@article {pmid41168499, year = {2025}, author = {Fink, DJ and Finger, RP and Terheyden, JH}, title = {[Importance of vision in old age].}, journal = {Zeitschrift fur Gerontologie und Geriatrie}, volume = {58}, number = {8}, pages = {639-644}, pmid = {41168499}, issn = {1435-1269}, mesh = {Humans ; Aged ; *Vision Disorders/diagnosis/therapy/rehabilitation/prevention &amp; control/psychology ; Aged, 80 and over ; Female ; Male ; *Quality of Life/psychology ; Germany ; }, abstract = {Vision is a significant determinant of quality of life and autonomy in older people. It declines with age due to natural processes. In the general population this is exacerbated by age-related eye diseases, such as cataract, age-related macular degeneration, glaucoma and diabetic retinopathy. The resulting impairments can lead to reduced mobility, independence and mental health and physiological ageing processes of the eye and disease-related changes in visual function are therefore associated with increased morbidity, such as an increased risk of falls and depression. Treatment, prevention and rehabilitation measures can significantly reduce the impairment of older people caused by age-related eye diseases. In order to keep pace with the increasing demand for care and to maintain vision at the highest possible level into old age, not only targeted and timely ophthalmological care are necessary but also more prevention in the field of age-related eye diseases.}, }
@article {pmid41168502, year = {2025}, author = {Jiménez-Loygorri, JI and Shang, P and Bayramoglu, I and Gómez-Sintes, R and Martín-Segura, A and Ambrosino, H and Hoang, J and Díaz, A and Geng, Z and Gavathiotis, E and Dutton, JR and Dengjel, J and Cuervo, AM and Ferrington, DA and Boya, P}, title = {Defective chaperone-mediated autophagy in the retinal pigment epithelium of age-related macular degeneration patients.}, journal = {EMBO molecular medicine}, volume = {17}, number = {12}, pages = {3472-3495}, pmid = {41168502}, issn = {1757-4684}, support = {310030_215271//SNSF/ ; R01 AG021904/AG/NIA NIH HHS/United States ; AG031782//NIH/NIA/ ; R37 AG021904/AG/NIA NIH HHS/United States ; Ram&#xf3;n Areces Postdoctoral Fellowship//Ramon Areces Foundation/ ; R01EY028554//NIH/NEI/ ; PID2021-126864NBI00//MCIN/ ; R01 EY028554/EY/NEI NIH HHS/United States ; P01 AG031782/AG/NIA NIH HHS/United States ; AG021904//NIH/NIA/ ; CRSII5_189952//SNSF/ ; 310030_212187//SNSF/ ; PRE2019-088222//MCIN/ ; }, mesh = {Humans ; *Retinal Pigment Epithelium/pathology/metabolism ; *Macular Degeneration/pathology/metabolism ; *Chaperone-Mediated Autophagy ; Induced Pluripotent Stem Cells ; Oxidative Stress ; Aged ; Female ; Male ; Proteostasis ; *Autophagy ; Mitochondria/metabolism ; }, abstract = {Autophagy is one of the main intracellular recycling systems and its impairment is considered a primary hallmark of the aging process. Defective macroautophagy in the retinal pigment epithelium (RPE) has been described in age-related macular degeneration (AMD), a blindness-causing disease that affects roughly 200 million patients worldwide. The relevance of chaperone-mediated autophagy (CMA), a selective type of autophagy for proteins containing a KFERQ-like motif, in RPE cell biology and homeostasis remains to be elucidated. Here we describe decreased CMA activity in the RPE of AMD patients compared to healthy age-matched controls, along with accumulation of substrate proteins, and in donor-derived iPSC-RPE cells, which we used to further characterize AMD-associated alterations of cellular homeostasis derived from proteotoxicity. Treatment with CA77.1 (CMA activator) restores proteostasis and remodels specific subsets of the proteome in cells from healthy and AMD donors. CA77.1-treated AMD iPSC-RPE display reduced oxidative stress and improved mitochondrial function. These findings may explain the specific vulnerability of the RPE during AMD and shed light on CMA as a new druggable target for this as-of-now incurable disease.}, }
@article {pmid41169217, year = {2025}, author = {Mirshahvaladi, S and Gaire, BP and Kashani, SA and Guha, A and Koronyo, Y and Fuchs, DT and You, Y and Black, KL and Paulo, JA and Graham, SL and Gupta, V and Mirzaei, M and Koronyo-Hamaoui, M}, title = {Retinal proteomics in neurodegeneration: Insights into ocular and brain disorders.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-00291}, pmid = {41169217}, issn = {1673-5374}, support = {R01 AG055865/AG/NIA NIH HHS/United States ; R01 AG056478/AG/NIA NIH HHS/United States ; }, abstract = {Dysregulated proteome in the retina represents a promising avenue for discovering novel therapeutic targets and noninvasive diagnostic biomarkers for neurodegenerative diseases with ocular manifestations. Advanced mass spectrometry-based proteomics techniques have shown considerable potential in investigating the retinal proteome in diseases such as glaucoma, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, as well as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. Recent proteomics innovations are overcoming challenges such as limited sample size and protein coverage that previously hindered comprehensive retinal proteome analysis. Notably, the incorporation of artificial intelligence-driven computational pipelines, including Graphics Processing Unit-accelerated deep learning architectures, has markedly enhanced the precision and effectiveness of retinal proteomics. These advances facilitate high-resolution identification of novel protein signatures within large-scale multi-omics datasets. Furthermore, the integration of advanced artificial intelligence with state-of-the-art big data infrastructures supports the early detection of biomarkers and therapeutic targets in neurodegenerative diseases with ocular involvement, offering unprecedented disease specificity and sensitivity. In addition to these computational strides, emerging complementary and alternative technologies continue to provide valuable tools for retinal analysis, expanding the potential for identifying biomarker and therapeutic targets in both ophthalmic and neurodegenerative disorders. This review summarizes recent advancements in retinal proteomics, with a particular focus on neurodegenerative and ocular diseases.}, }
@article {pmid41169746, year = {2025}, author = {Abuleil, D and Gorbet, D and McCulloch, DL and Cohan, R and Steeves, JEK and Bang, JW and Chan, KC and Thompson, B}, title = {Anodal transcranial direct current stimulation does not alter GABA concentration or functional connectivity in the normal visual cortex.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1639838}, pmid = {41169746}, issn = {1662-4548}, abstract = {INTRODUCTION: Anodal direct current stimulation (a-tDCS) of the visual cortex is a potential rehabilitation tool for vision disorders such as amblyopia and macular degeneration. However, the underlying neural mechanisms are currently unknown. When applied to the human motor cortex, a-tDCS reduces the concentration of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter that modulates neuroplasticity. Our primary aim was to assess whether the same a-tDCS paradigm alters local GABA concentration when applied to the healthy primary visual cortex. We also measured the effect of a-tDCS on visual cortex resting-state connectivity and sought to replicate reported observations of an association between visual cortex GABA concentration and the dynamics of binocular rivalry.<br><br>METHODS: Fourteen participants with normal vision completed two brain imaging sessions at least 48 hours apart. In each session, binocular rivalry dynamics, primary visual cortex GABA and glutamate-glutamine (Glx) concentrations (via magnetic resonance spectroscopy (MRS)) and resting-state functional connectivity (via task-free fMRI) were measured at baseline. Real or sham a-tDCS (20 min, 2mA) was then applied to the visual cortex in a randomized sequence followed by a second set of MRS and fMRI measurements.<br><br>RESULTS: No between-session effects of a-tDCS on GABA or Glx concentration or resting-state functional connectivity were observed. A pre-planned within-session analysis revealed a significant increase in Glx following a-tDCS that did not withstand multiple comparisons correction. No consistent relationships between binocular rivalry dynamics and GABA concentration were apparent.<br><br>DISCUSSION: Together, our results suggest that a-tDCS effects on the visual cortex may differ from the GABA-associated mechanism in motor cortex.}, }
@article {pmid41170269, year = {2025}, author = {Lloyd, A and Elbalawi, M and Kurc, M and Hussain, M and Abugreen, S}, title = {The Implementation of Faricimab in East Lancashire NHS Trust: Highlighting the Real-World Efficacy and Safety in Patients With Neovascular Age-Related Macular Degeneration.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e93478}, pmid = {41170269}, issn = {2168-8184}, abstract = {PURPOSE: To report the safety and efficacy of intravitreal faricimab injections (IVTF) in both treatment-naïve and treatment-resistant patients with neovascular age-related macular degeneration (nAMD).<br><br>PATIENTS AND METHODS: This study was a retrospective real-world evidence trial where patients with nAMD were given IVTF. Group 1 (treatment-na&#xef;ve) and group 2 (switch loading dose, SLD)&#xa0;were given a course of four loading doses of IVTF four weeks apart. Group 3 (switch pro re nata, SPRN)&#xa0;was given a single IVTF and then reviewed at eight weeks. The outcome was based on visual acuity (VA) and optical coherence tomography (OCT), showing central retinal thickness (CRT), subretinal, and intraretinal fluid.<br><br>RESULTS: A total of 99 eyes from 89 patients were included. A total of 350 IVTF were given. The mean follow-up duration was 6.33 &#xb1; 1.11 months (range: 2-8 months).&#xa0;The mean change in CRT at final follow-up was&#xa0;-127.09 &#xb1; 97.39 &#xb5;m (p < 0.001) for na&#xef;ve eyes, -115.59 &#xb1; 145.02 &#xb5;m (p < 0.001) for SLD, and -57.61 &#xb1; 58.06 &#xb5;m (p < 0.001) for SPRN. The mean VA change was&#xa0;-3.47 ETDRS (Early Treatment Diabetic Retinopathy Study) (p = 0.256) for na&#xef;ve eyes, -0.79 (p = 0.45) for SLD, and +1.25 (p = 0.304) for SPRN. A total of 48 eyes (48.48%) had better VA, 22 (22.22%) had no change in VA, and 29 (29.29%) had worse VA. One patient developed bilateral sterile intraocular inflammation.<br><br>CONCLUSION: IVTF was associated with an improvement in CRT in both treatment-naive and treatment-resistant nAMD patients. There was no evidence of vasculitis or vein occlusion, highlighting the safety of faricimab in our real-world study.}, }
@article {pmid41172710, year = {2025}, author = {Singh, S and Runyon, W and Hu, S and Kennedy, PG and Singh, A and Ratnapriya, R and Kumar, R and Csaky, K and Sripathi, SR}, title = {Generation of iPSCs (RFSCi007-A, RFSCi008-A) from a patient with early-onset bilateral drusen and a healthy sibling for retinal disease modeling.}, journal = {Stem cell research}, volume = {89}, number = {}, pages = {103862}, doi = {10.1016/j.scr.2025.103862}, pmid = {41172710}, issn = {1876-7753}, mesh = {Humans ; *Induced Pluripotent Stem Cells/metabolism/cytology/pathology ; Siblings ; *Retinal Drusen/pathology ; Male ; Macular Degeneration/pathology ; Female ; }, abstract = {Drusen are extracellular deposits between the retinal pigment epithelium and Bruch's membrane, commonly linked to age-related macular degeneration (AMD). However, their presence in younger individuals offers a unique opportunity to study early disease mechanisms before extensive degeneration. We generated two human induced pluripotent stem cell (hiPSC) lines from siblings' peripheral blood mononuclear cells-one with early-onset bilateral drusen and the other unaffected. This genetically matched iPSC pair enables investigation of early drusen associated pathological changes driving retinal disease development.}, }
@article {pmid41173219, year = {2026}, author = {Deimazar, G and Sabbaghi, H and Ahmadieh, H and Sheikhtaheri, A}, title = {Artificial intelligence for detection of age-related macular degeneration based on fundus images: A systematic review.}, journal = {Survey of ophthalmology}, volume = {71}, number = {3}, pages = {980-991}, doi = {10.1016/j.survophthal.2025.10.004}, pmid = {41173219}, issn = {1879-3304}, mesh = {Humans ; *Macular Degeneration/diagnosis ; Fundus Oculi ; *Artificial Intelligence ; Neural Networks, Computer ; Deep Learning ; Algorithms ; *Diagnostic Techniques, Ophthalmological ; Machine Learning ; }, abstract = {Age-related macular degeneration (AMD) is one of the most common types of eye diseases that generally affect the elderly population over 50 years of age. The effects of AMD on the quality of vision and life are devastating. We systematically review applications and performance of machine/deep learning algorithms for AMD detection and prediction using color fundus photos. We reviewed the studies that focused on machine learning and deep learning techniques and algorithms to analyze the fundus images for AMD. The data were collected by searching Scopus, PubMed (Medline), Web of Science and IEEE Xplore databases. After screening, 42 papers were included. The findings showed that the studies used different architectures for model training and testing. Convolutional neural networks (CNN) are used mostly in the diagnosis of AMD. ResNet architecture (11 studies) was used more than other architectures. Twenty-two studies used AREDS dataset. CNN algorithm with ResNet architecture had the highest performance compared to other architectures. Studies have shown that machine learning can diagnose AMD from fundus images with high accuracy; however, calibration, fairness, explainability, external validation, generalization, prospective validation in clinical settings and regulatory requirements should be considered in the future.}, }
@article {pmid41174770, year = {2025}, author = {Trinh, M and Tee, YG and Nam, J and Chen, S and Schiller, G and Friedrich, J and Ng, D and Ly, A and Hodge, C and Nivison-Smith, L}, title = {Localising OCTA changes induced by the isometric hand-grip test to the superficial retina in neovascular age-related macular degeneration.}, journal = {Eye and vision (London, England)}, volume = {12}, number = {1}, pages = {44}, pmid = {41174770}, issn = {2326-0254}, support = {2023//Future Vision Foundation/ ; }, abstract = {PURPOSE: This study uses optical coherence tomography angiography (OCTA) topographical cluster analysis to localise where vascular changes occur during the isometric hand-grip test (IHGT) in eyes with neovascular age-related macular degeneration (AMD).<br><br>METHODS: This prospective study included single eyes from 44 participants with neovascular&#xa0;AMD. Systemic blood pressure (BP) and macular 6&#x2009;&#xd7;&#x2009;6&#xa0;mm OCTA scans were obtained before the IHGT, during the IHGT, and after the IHGT. The main outcome was the change in processed OCTA signal (%), measured within high-density (126&#x2009;&#xd7;&#x2009;126) grids and analysed by topographical clusters across the superficial retina, deep retina, and choriocapillaris. Results were compared against test-retest thresholds to differentiate true IHGT-induced changes from measurement variability.<br><br>RESULTS: The IHGT increased systolic (13.83 [3.28, 24.39] mmHg) and diastolic BP (7.04 [3.57, 10.52] mmHg; P&#x2009;<&#x2009;0.01). Adjusted for test-retest thresholds, the IHGT increased processed OCTA signal (12.84 [8.49, 26.77] %, P&#x2009;<&#x2009;0.0001) at nasal clusters in the superficial retina. These changes were moderately correlated with systolic BP increases (Spearman r&#x2009;=&#x2009;0.43, P&#x2009;<&#x2009;0.05), but not with diastolic BP. No changes were observed in the deep retina or choriocapillaris. Systemic BP and processed OCTA signal returned to baseline within 30&#xa0;s after IHGT release.<br><br>CONCLUSION: Hand-squeezing temporarily increases processed OCTA signal in the nasal superficial retina. This response may serve as a valuable marker of vascular function. Consequently, caution is warranted when interpreting OCTA following BP changes, such as those induced by physical activity or medication changes.}, }
@article {pmid41175224, year = {2026}, author = {Yang-Seeger, D and Schellstede, A and Pauleikhoff, LJB and Spitzer, MS and Birtel, J}, title = {Travel-associated emissions of intravitreal injections.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {347-353}, pmid = {41175224}, issn = {1435-702X}, mesh = {Humans ; *Intravitreal Injections ; Female ; Male ; *Travel ; Aged ; Middle Aged ; *Carbon Footprint/statistics &amp; numerical data ; Germany/epidemiology ; *Angiogenesis Inhibitors/administration &amp; dosage ; Retrospective Studies ; Follow-Up Studies ; Aged, 80 and over ; }, abstract = {PURPOSE: Intravitreal injections (IVIs) are among the most frequently performed ophthalmic procedures and have been associated with a substantial carbon footprint. Travel-associated emissions are considered a key driver of IVIs' carbon footprint; however, no study in a country with a decentralised healthcare system has assessed IVI-related emissions. Here, the IVI-associated carbon footprint in an urban German tertiary referral centre was investigated.<br><br>METHODS: In total, 340 patients were included. The carbon footprint was assessed based on the distance travelled by patients and accompanying persons, the mode of transport, and postoperative follow-up visits. Demographic data, treatment indication, and the injected medication were collected.<br><br>RESULTS: The average travel-associated CO2 equivalent (CO2eq) for a single IVI was 11.1&#xa0;kg. Of this,&#xa0;9.1&#xa0;kg CO2eq and 2&#xa0;kg CO2eq were due to travel to the injection clinic and to follow-up visits, respectively. Anti-VEGF treatment for common diseases such as age-related macular degeneration and diabetic macular edema was associated with a lower CO2eq compared with treatment of patients suffering from&#xa0;less prevalent conditions such as uveitis (10.8&#xa0;kg vs. 15.6&#xa0;kg). The majority of patients (49%) travelled by public transport (median distance: 22.4&#xa0;km); patients travelling by car (33%) usually covered longer distances (median distance: 61.5&#xa0;km).<br><br>CONCLUSION: Travel is a meaningful contributor to the carbon footprint of IVIs. Mitigation may be achieved by various approaches, such as longer-acting therapeutic agents or bilateral injections. To implement strategies for more sustainable IVIs, ophthalmologists may be encouraged by local and national bodies to incorporate environmental criteria into their practice.}, }
@article {pmid41175863, year = {2025}, author = {Xin, Y and Jin, Y and Qian, C and Blackshaw, S and Qian, J}, title = {MetaLigand provides a prior-knowledge-guided framework for predicting non-peptide ligand mediated cell-cell communication.}, journal = {Cell reports methods}, volume = {5}, number = {11}, pages = {101217}, pmid = {41175863}, issn = {2667-2375}, mesh = {*Cell Communication ; Humans ; Ligands ; Transcriptome ; Animals ; *Computational Biology/methods ; }, abstract = {Non-peptide ligands (NPLs), including lipids, amino acids, carbohydrates, and non-peptide neurotransmitters and hormones, play a critical role in ligand-receptor-mediated cell-cell communication, driving diverse physiological and pathological processes. To facilitate the study of NPL-dependent intercellular interactions, we introduce MetaLigand, a tool designed to infer NPL availability and NPL-receptor interactions using transcriptomic data. MetaLigand compiles data for 233 NPLs, including their biosynthetic enzymes, transporter genes, and receptor genes, through a combination of automated pipelines and manual curation from comprehensive databases. The tool integrates both de novo and salvage synthesis pathways, incorporating multiple biosynthetic steps and transport mechanisms. Comparisons with existing tools demonstrate MetaLigand's ability to account for complex biogenesis pathways and model NPL availability across diverse tissues and cell types. Furthermore, analysis of single-nucleus RNA sequencing (RNA-seq) datasets from age-related macular degeneration samples revealed that distinct retinal cell types exhibit unique NPL profiles and participate in specific NPL-mediated pathological cell-cell interactions.}, }
@article {pmid41177551, year = {2025}, author = {Brunner, P and Havanur, P and Papukchieva, S and Friedrich, B and Ziemssen, F}, title = {Tracking real-world persistence and adherence to anti-VEGF intravitreal therapy with prefilled syringes: a German prescription sales analysis.}, journal = {BMJ open ophthalmology}, volume = {10}, number = {1}, pages = {}, pmid = {41177551}, issn = {2397-3269}, mesh = {Humans ; Germany/epidemiology ; Retrospective Studies ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Male ; Female ; Aged ; *Syringes ; *Drug Prescriptions/statistics &amp; numerical data ; *Bevacizumab/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy ; *Ranibizumab/administration &amp; dosage ; Aged, 80 and over ; Middle Aged ; Follow-Up Studies ; }, abstract = {OBJECTIVE: Intravitreal antivascular endothelial growth factor (anti-VEGF) therapy is the standard treatment for neovascular age-related macular degeneration and other retinal vascular diseases. Despite proven efficacy in clinical trials, real-world data suggest suboptimal persistence and adherence. This study aimed to assess therapy continuity in routine practice using pharmacy-based dispensing data in Germany, focusing on treatment with prefilled syringes (PFS).<br><br>METHODS AND ANALYSIS: This retrospective cohort study used anonymised nationwide pharmacy sales data from Germany to evaluate patients who initiated anti-VEGF therapy with PFS between 2020 and 2023. Patient trajectories were followed from treatment initiation for up to 12 months. 46&#x2009;546 therapy beginners with 297&#x2009;454 anti-VEGF PFS purchases were included. Discontinuation of treatment was defined by not purchasing a relevant medication for >6 months.<br><br>RESULTS: Mean time on therapy for all patients was 8.1&#xb1;8.2 months (median=5.5) with 6.9&#xb1;6.1 purchases (median=5). 20.5% of patients initiating anti-VEGF treatment stopped therapy before completing the loading phase (first three injections), and more than half of all patients discontinued treatment after 6 months. 49.4% of the patients who completed the loading phase (n all=34&#x2009;895) adhered to the recommended monthly regimen. Non-adherence significantly decreased the number of injections later on (average of 7.5 vs 8.7 injections). Further, patients who stayed longer on therapy bought more PFSs within the first 6 and 12 months.<br><br>CONCLUSIONS: Real-world adherence and persistence to intravitreal anti-VEGF therapy in Germany are suboptimal, even with the use of PFS formulation. The high rate of early treatment discontinuation, especially during the loading phase, underscores the need for improved patient support, education and flexible treatment approaches to sustain long-term outcomes. A 'breaking point' or sensitive phase already seems to exist right at the beginning of therapy.}, }
@article {pmid41177553, year = {2025}, author = {Sawires, K and Nithianandan, H and Somani, S}, title = {Comparative outcomes of aflibercept biosimilars and reference aflibercept in nAMD: a systematic review and meta-analysis.}, journal = {BMJ open ophthalmology}, volume = {10}, number = {1}, pages = {}, pmid = {41177553}, issn = {2397-3269}, mesh = {Humans ; *Biosimilar Pharmaceuticals/therapeutic use/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Intravitreal Injections ; *Recombinant Fusion Proteins/administration &amp; dosage ; Treatment Outcome ; *Visual Acuity ; Randomized Controlled Trials as Topic ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; }, abstract = {OBJECTIVE: To evaluate the literature-pooled functional, anatomical and safety outcomes of aflibercept biosimilars compared with reference aflibercept for neovascular age-related macular degeneration (nAMD).<br><br>METHODS AND ANALYSIS: Systematic review and meta-analysis. Medline, Embase and CENTRAL were searched from inception to 2 June 2025. Phase 3 randomised controlled trials (RCTs) comparing aflibercept biosimilars with the reference product in patients with nAMD were included. Two independent reviewers conducted screening, data extraction, risk of bias (RoB 2) assessment and certainty of evidence assessment (Grading of Recommendations, Assessment, Development and Evaluation), with a third reviewer resolving discrepancies. Primary outcomes included mean difference (MD) change in best-corrected visual acuity (BCVA) and retinal thickness over time, risk ratio (RR) for proportion of participants gaining >15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and RR for adverse events. Meta-regression was used to evaluate the temporal stability of continuous outcomes.<br><br>RESULTS: Six RCTs involving 2044 participants (1026 biosimilar, 1018 reference) were included. Five aflibercept biosimilars were evaluated, representing more than 50% of the eight biosimilars currently approved worldwide. Meta-regression revealed no significant difference in MD change in BCVA over time between biosimilar and reference aflibercept (slope: 0.0321 letters/week; p=0.1013). For MD change in retinal thickness, an initial anatomical advantage for reference aflibercept at week 0 (intercept: 9.58&#x2009;&#xb5;m; p=0.0449) was not sustained over time (slope: -0.1685&#x2009;&#xb5;m/week; p=0.2303). The pooled RR for gaining >15 ETDRS letters from baseline was 1.19 (95% CI 0.98 to 1.45; p=0.079). No statistically significant differences were observed across 15 safety outcomes.<br><br>CONCLUSION: This systematic review and meta-analysis found no statistically significant differences in functional, anatomical or safety outcomes between aflibercept biosimilars and the reference product for nAMD, based on moderate to high certainty evidence. Functional and anatomical outcomes appeared stable across multiple timepoints. Further long-term pharmacovigilance studies and real-world data beyond 56 weeks are warranted.<br><br>PROSPERO REGISTRATION NUMBER: CRD420251048633.}, }
@article {pmid41178994, year = {2025}, author = {Li, Y and Wang, C and Deng, T and Li, X and Xu, R and Shang, Q}, title = {RARRES1 attenuates H2O2-induced RPE cell injury and inhibits choroidal neovascularization.}, journal = {Frontiers in physiology}, volume = {16}, number = {}, pages = {1641653}, pmid = {41178994}, issn = {1664-042X}, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in the elderly, yet its underlying molecular mechanisms remain incompletely understood, and novel biomarkers and therapeutic targets are urgently needed. This study aimed to identify and functionally characterize potential biomarkers and therapeutic candidates for nAMD, with a focus on retinoic acid receptor responder protein 1 (RARRES1).<br><br>METHODS: Tandem mass tag (TMT)-based proteomic analysis was performed on aqueous humor samples from patients with nAMD and age-related cataracts. RARRES1 expression was examined in aqueous humor, laser-induced choroidal neovascularization (CNV) model mice, and human ARPE-19 cells exposed to H2O2. Functional studies assessed the effects of RARRES1 on oxidative stress, cell death, inflammatory and angiogenic factor expression, and signaling pathways in ARPE-19 cells. Its effects on proliferation, migration, and tube formation were tested in HUVECs. In vivo, a RARRES1-overexpressing AAV2 vector was injected intraocularly into CNV model mice, and lesion size and vascular leakage were evaluated using fundus fluorescein angiography, hematoxylin and eosin staining, and isolectin B-4 fluorescence staining.<br><br>RESULTS: RARRES1 was significantly reduced in the aqueous humor of nAMD patients, in CNV model mice, and in H2O2-treated ARPE-19 cells. Overexpression of RARRES1 in ARPE-19 cells mitigated oxidative stress-induced damage, suppressed inflammatory and angiogenic factor expression, inhibited JNK phosphorylation, and increased Sirtuin 1 and Nrf2 expression. In HUVECs, RARRES1 reduced proliferation, migration, and tube formation. In vivo, intraocular delivery of RARRES1 significantly reduced CNV lesion size and vascular leakage.<br><br>CONCLUSION: RARRES1 protects retinal pigment epithelial cells from oxidative stress, inhibits choroidal neovascularization, and modulates inflammatory and angiogenic pathways. These findings identify RARRES1 as a potential biomarker and therapeutic target for nAMD.}, }
@article {pmid41179910, year = {2026}, author = {Doshi, U and Davis, E and Al-Sheikh, M and Sahel, JA and Chhablani, J and Vupparaboina, KK and Bollepalli, SC}, title = {Generalizable Multimodal Retinal Image Registration via Label-free Vessel Segmentation.}, journal = {Biomedical signal processing and control}, volume = {113}, number = {Pt B}, pages = {}, pmid = {41179910}, issn = {1746-8094}, support = {P30 EY008098/EY/NEI NIH HHS/United States ; }, abstract = {Multimodal retinal imaging plays a crucial role in diagnosing and managing various retinal diseases such as diabetic retinopathy and age-related macular degeneration (AMD). The majority of retinal imaging modalities including Color Fundus Photography (CF), Fluorescein Angiography (FAG), Fundus Autofluorescence (FAF), Indocyanine Green Angiography (ICG), and Optical Coherence Tomography (OCT), along with infrared imaging (IR) and B-scans, capture different aspects of the same pathology within the retina. Consequently, accurate disease quantification, monitoring, and automated diagnosis require integrating their complementary insights, which relies on accurate registration of these images. To this end, developing a robust registration algorithm applicable across all modalities assumes significance. This paper presents a generalizable, label-free approach to retinal image registration, using vessel structure, extracted using DexiNed algorithm. The proposed method was evaluated across various imaging modalities, including CF-IR, CF-FAF, CF-FAG, CF-ICG, FAF-FAG, FAF-ICG, and FAG-ICG, achieving a mean landmark error (MLE) ranging from 1.91±0.44 to 4.9±2.32 pixels. In particular, CF-IR and CF-FAF registration attained an MLE of 3.08±1.47 and 4.9±2.32 pixels respectively, performing favorably when compared to human grader annotations. Furthermore, the proposed solution eliminates the need for large labeled training datasets while effectively extracting vessel structures to enable multimodal retinal image registration, improving diagnostic precision and disease monitoring.}, }
@article {pmid41181297, year = {2025}, author = {Agius, D and Mamo, JJ and Calleja, N and Cassar, D and Marku, X and Nappa, MC and Zammit, M and Pace, ME and Carbonaro, F}, title = {Markedly Lower Rates of Age-Related Macular Degeneration in Malta Compared to European Countries: Results from The Malta Eye Study, Indicating Possible Divergent Genetic Ancestry?.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {3961-3971}, pmid = {41181297}, issn = {1177-5467}, abstract = {PURPOSE: To estimate the prevalence of age-related macular degeneration (ARMD) in a nationally representative sample of older adults from Malta, evaluate associations with established risk factors, and compare rates with those reported in other European populations, where substantial variation has been observed.<br><br>PATIENTS AND METHODS: A population-based cross-sectional study was conducted involving 1794 participants aged 50-80 years from Malta (1% of the represented population), recruited as part of The Malta Eye Study. Standardized ophthalmic examinations were performed, including retinal imaging graded for ARMD according to Age-Related Eye Disease Study criteria and optical coherence tomography scans. Data on demographics, medical history, behavioural risk factors, and ocular characteristics were collected via structured questionnaires. Associations were assessed using multivariable logistic regression. DNA samples were also collected for future genetic analyses.<br><br>RESULTS: The overall prevalence of ARMD was 6.5% (95% CI 5.4-7.8%), with early ARMD accounting for 5.6% (95% CI 4.6-6.7%) and late ARMD for 0.4% (95% CI 0.2-0.8%). Multivariate analysis showed that ARMD prevalence increased significantly with age (OR per year 1.08; 95% CI 1.05-1.11, p<0.001) and in the male sex (OR 1.57; 95% CI 1.01-2.44, p=0.043). The other traditional ARMD risk factors did not show significant associations in this cohort. Compared to other European populations, ARMD prevalence was notably lower.<br><br>CONCLUSION: This study reports a relatively low prevalence of ARMD compared to other European settings, with age and male sex emerging as the only significant risk factors. The absence of association with other traditional risk factors may reflect underlying genetic differences or distinct gene-environment interactions. As DNA samples were collected, further investigation incorporating genetic data is warranted to better understand ARMD susceptibility in this population.}, }
@article {pmid41181732, year = {2025}, author = {Tamai, R and Nizawa, T and Kawamata, Y and Iwase, T and Baba, T}, title = {Switching From Aflibercept 2 mg to 8 mg in Vitrectomized Eyes With Neovascular Age-Related Macular Degeneration.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e93645}, pmid = {41181732}, issn = {2168-8184}, abstract = {Vitrectomy may alter intravitreal pharmacokinetics through the removal of the vitreous gel, potentially accelerating the clearance of anti-vascular endothelial growth factor (VEGF) agents. Clinical trials and most real-world studies on neovascular age-related macular degeneration (nAMD) generally exclude vitrectomized eyes, and the efficacy of anti-VEGF therapy in this subgroup remains unclear. Aflibercept 8 mg, approved in Japan in 2024, delivers four times the dose of the conventional 2 mg formulation and is designed to improve durability and extend treatment intervals. We report three vitrectomized eyes from three patients with nAMD who exhibited persistent or recurrent exudation despite short-interval (≤8 weeks) aflibercept 2 mg therapy under a treat-and-extend regimen. Switching to aflibercept 8 mg led to the resolution of fluid in all cases and enabled interval extension. No ocular or systemic adverse events were observed. These findings suggest that aflibercept 8 mg can achieve improved anatomical outcomes and greater treatment durability in vitrectomized eyes with nAMD, thereby potentially reducing the treatment burden in this challenging subgroup. Larger prospective studies are required to validate these findings.}, }
@article {pmid41182355, year = {2026}, author = {Shmueli, O and Batash, T and Nitzan, I and Chowers, I and Tiosano, L}, title = {Cataract surgery in eyes with adult-onset foveomacular-vitelliform dystrophy.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {355-364}, pmid = {41182355}, issn = {1435-702X}, mesh = {Humans ; Retrospective Studies ; Male ; *Visual Acuity ; Female ; Tomography, Optical Coherence/methods ; Aged ; Middle Aged ; Follow-Up Studies ; *Cataract/complications/diagnosis ; *Vitelliform Macular Dystrophy/complications/diagnosis/physiopathology ; *Cataract Extraction/methods ; *Fovea Centralis/pathology ; Fluorescein Angiography ; Treatment Outcome ; Aged, 80 and over ; Adult ; }, abstract = {PURPOSE: To assess the outcomes and safety of cataract surgery in Adult-Onset Foveomacular-Vitelliform dystrophy (AFVD) patients.<br><br>METHODS: This retrospective study analyzed eyes with AFVD that underwent cataract surgery in a tertiary center, comparing them with eyes affected by none and neovascular age-related macular degeneration (NVAMD). Data included demographics, best-corrected visual acuity LogMAR (VA), eye examination results, and optical coherence tomography (OCT) results. The primary outcome was improvement in VA. A secondary outcome was AFVD progression such as the development of choroidal neovascularization (CNV) or retinal atrophy.<br><br>RESULTS: The cohort included 83 eyes (18 with AFVD, 27 with none-NV AMD, and 38 with NVAMD). AFVD eyes showed significant improvement in VA&#xb1;SD from pre-surgery (0.60&#x2009;&#xb1;&#x2009;0.34) to 1 month (0.23&#x2009;&#xb1;&#x2009;0.11; P&#x2009;<&#x2009;0.0001) and 12 months post-operatively (0.26&#x2009;&#xb1;&#x2009;0.12; P&#x2009;<&#x2009;0.0001). No cases of CNV or major AFVD progression changes were observed over 12 months of follow up. However, at last follow-up (62.20&#x2009;&#xb1;&#x2009;39.30 months) there was increased proportion of atrophic AFVD (44.40% compared to 5.50% at baseline; P&#x2009;=&#x2009;0.10). No difference was found comparing VA improvement one month after surgery of none-NV AMD, NVAMD and AFVD (AFVD&#x2009;=&#x2009;0.37&#x2009;&#xb1;&#x2009;0.36, none-NV AMD&#x2009;=&#x2009;0.47&#x2009;&#xb1;&#x2009;0.68, NVAMD&#x2009;=&#x2009;0.28&#x2009;&#xb1;&#x2009;0.37; P&#x2009;=&#x2009;0.29). In the none-NV AMD group, one eye developed CNV ten months post-operatively and another eye demonstrated worsening retinal atrophy one-month post-surgery. In the NVAMD group, 9 eyes developed retinal atrophy at last follow up.<br><br>CONCLUSION: Cataract surgery in&#xa0;AFVD eyes led to significant visual acuity improvement and demonstrated good safety with no&#xa0;new CNV or retinal atrophy. The similar visual improvement across the AFVD, none-NV AMD&#xa0;and NVAMD groups suggests the procedure's efficacy and safety for AFVD patients.}, }
@article {pmid41182446, year = {2025}, author = {Entezari, Z and Mahootchi, M and Eskandari, M and Ahmadieh, H}, title = {Artificial intelligence-driven diagnosis for age-related macular degeneration bridging pathology and engineering: a survey.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {456}, pmid = {41182446}, issn = {1573-2630}, mesh = {Humans ; *Macular Degeneration/diagnosis ; *Artificial Intelligence ; Tomography, Optical Coherence/methods ; Disease Progression ; Early Diagnosis ; Risk Factors ; }, abstract = {Age-related macular degeneration (AMD) is the primary reason for severe visual impairments, making early diagnosis critically important. This paper provides a comprehensive review of the methods used to support screening and diagnostic decisions, focusing on four categories: early, intermediate, and advanced stages of AMD, in addition to AMD across all stages. In this regard, a reference framework is initially proposed to describe research perspectives in pathology. Utilizing this framework, a literature review is conducted to identify the most reliable demographic, environmental, and comorbidity-related risk factors, clinical symptoms, and various aspects of AMD pathology, setting the necessary prerequisites for subsequent sections. The potential application of risk factors is also explained for personalized medicine. While phenotypic risk factors and genetic variants play a crucial role in predicting the progression of AMD, it is more vital to examine demographic and environmental factors at earlier stages for developing effective prevention plans. Therefore, the selection of appropriate risk factors emerges as a critical area of research. Afterward, we present a comparative analysis of different screening and diagnostic methods pertinent to AMD from an industrial engineering perspective. This analysis brings attention to the suite of artificial intelligence (AI) to describe, analyze, and evaluate diagnostic models, thereby providing a reference outline for clinical practice. AI methods can automate the interpretation of retinal images, serving as a supportive tool for clinical decision-making to improve the management of disease progression. In general, this survey highlights the necessity of developing more integrated methods to support decisions at different planning levels.}, }
@article {pmid41182913, year = {2025}, author = {Akçay, G and Kutlutürk Karagöz, I and Doğan Gökçe, G}, title = {Evaluating anxiety and depression levels in patients undergoing intravitreal injections and investigation of contributing factors.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721251392036}, doi = {10.1177/11206721251392036}, pmid = {41182913}, issn = {1724-6016}, abstract = {PurposeTo evaluate anxiety and depression levels in patients receiving intravitreal injections for diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO), and their associations with visual acuity, disease type, and demographic factors.MethodsThe study included 90 patients (43 males and 47 females) mean age 73.9 ± 12.4 years; (range: 22-92 years). Anxiety levels were assessed using the state anxiety form of the State-Trait Anxiety Inventory (STAI-S), and depression symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). Best-corrected visual acuity (BCVA) was recorded, and patients were evaluated according to disease type, severity of visual impairment, and number of injections.ResultsThe mean STAI-S score was 36.2 ± 8.9, and that of HADS was 13.9 ± 12.6. There were no significant differences in STAI-S scores between the disease groups (p = 0.17). However, HADS scores were significantly lower in the RVO group than in the DME and AMD groups (p = 0.02, p = 0.04). A significant association was observed between severity of visual impairment and STAI-S scores (p = 0.016), with moderate visual impairment showing higher anxiety levels than mild and severe impairment (p = 0.07, p = 0.02). However, HADS scores were not significantly associated with visual acuity (p = 0.058). Women exhibited higher HADS scores (p = 0.036). Neither injection frequency nor waiting time significantly affected STAI-S or HADS scores (p > 0.05).ConclusionPatients receiving intravitreal injections have varying levels of anxiety and depression, considering disease type, sex, and severity of visual impairment affecting these psychological parameters. These findings provide invaluable insights into the importance of psychological support in ophthalmic care.}, }
@article {pmid41183001, year = {2025}, author = {Hu, X and Tang, Y and Zhang, H and Wang, Z and Sun, J}, title = {Alu RNA-transfected Primary Mouse Retinal Pigment Epithelium: A Pathologically Relevant In Vitro Model for Age-related Macular Degeneration.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {224}, pages = {}, doi = {10.3791/68570}, pmid = {41183001}, issn = {1940-087X}, mesh = {Animals ; Mice ; *Retinal Pigment Epithelium/pathology/metabolism/cytology ; *Macular Degeneration/pathology/genetics ; *Disease Models, Animal ; *Alu Elements/genetics ; *Transfection/methods ; *RNA/genetics ; Mice, Inbred C57BL ; }, abstract = {Age-related macular degeneration (AMD), particularly non-exudative AMD, requires experimental models that better replicate human pathology. Current in vivo models remain technically demanding and time-intensive, whereas conventional in vitro systems fail to recapitulate disease-specific pathological triggers. Here, we present a method to establish a retinal pigment epithelial (RPE) degeneration model using primary mouse RPE cells transfected with Alu RNA, a retrotransposon directly implicated in geographic atrophy pathology. This protocol details the enzymatic isolation of primary mouse RPE cells, followed by Alu RNA transfection to induce RPE degeneration. Validation integrates morphological (hexagonal architecture), functional (polarity loss and mouse protein ZO-1 disruption), and molecular analysis (quantitative PCR). As a result, we observed multifactorial changes triggered by Alu RNA transfection: inflammatory cytokine secretion (mouse genes Ifn-β, Il-6, Tnf-α; p < 0.05) and cellular senescence (mouse genes p21 and p53 upregulation; p < 0.05). Compared to traditional acute stress models, this system recapitulates chronic inflammatory-degenerative cascades of AMD through standardized techniques, ensuring reproducibility. By combining aspects of simplified in vitro assays and complex in vivo models, this approach could serve as a preliminary platform for exploring retrotransposon-driven mechanisms and screening potential therapeutic candidates.}, }
@article {pmid41183353, year = {2025}, author = {Sabbagh, F and Zargarian, SS and Kosik-Kozioł, A and Nakielski, P and Pierini, F}, title = {Hydrogel-based ocular drug delivery systems.}, journal = {Journal of materials chemistry. B}, volume = {13}, number = {46}, pages = {14982-15006}, doi = {10.1039/d5tb01575h}, pmid = {41183353}, issn = {2050-7518}, mesh = {*Hydrogels/chemistry ; Humans ; *Drug Delivery Systems ; Animals ; *Ophthalmic Solutions/chemistry ; }, abstract = {Ocular drug delivery is challenging due to physical and physiological barriers, such as the corneal epithelium and blood-retinal barrier, resulting in limited bioavailability (<5% for eye drops) and fast degradation. For the reason of improving drug delivery to the anterior and posterior ocular segments, this review attempts to assess hydrogel-based systems as versatile systems to overcome these barriers. We thoroughly explore physicochemical and performance characterization approaches (e.g., swelling, rheology, drug release kinetics), hydrogel fabrication methods (e.g., chemical crosslinking, 3D printing), and their uses in new and commercial products. Significant advances highlight the controlled release, mucoadhesion, and biocompatibility of hydrogels, which allow prolonged drug delivery as demonstrated by commercial products such as DEXTENZA® and ReSure® Sealant for corneal sealing and post-operative inflammation control. New technologies provide greater accuracy and less invasiveness. Examples include bioengineered hydrogels for retinal regeneration, systems integrated with nanotechnology, and stimuli-responsive hydrogels (such as pH-sensitive chitosan for glaucoma). By addressing mechanical stability and regulatory criteria, characterization techniques guarantee the suitability of the hydrogel for ocular applications. Hydrogels exhibit considerable promise for personal and least invasive treatments, despite challenges like scalability and high production costs. With implications for improving clinical outcomes and patient compliance through novel biomaterials, this review highlights the important role of hydrogels in ocular drug delivery and offers an outline for future advancements in the treatment of diseases like glaucoma, age-related macular degeneration, and dry eye syndrome.}, }
@article {pmid41183696, year = {2026}, author = {Cheng, Y and Gu, S and Yu, H and Jin, J and Cheng, H and Zhang, H and Lin, J and Li, M and Zhu, H and Wang, T and Huang, Q and Liu, Y and Yue, P and Li, W and Ling, S}, title = {PYGM downregulates necroptosis signaling to attenuate sodium iodate-induced RPE cell degeneration.}, journal = {Cellular signalling}, volume = {137}, number = {}, pages = {112206}, doi = {10.1016/j.cellsig.2025.112206}, pmid = {41183696}, issn = {1873-3913}, mesh = {*Iodates/toxicity ; *Necroptosis/drug effects ; Animals ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Humans ; Mice ; *Macular Degeneration/metabolism/pathology/genetics/chemically induced ; Signal Transduction/drug effects ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Down-Regulation ; Mice, Inbred C57BL ; Disease Models, Animal ; Cell Line ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) causes incurable vision loss in elderly individuals, and there is currently only a rarely effective treatment for dry AMD. Necroptosis is attracting increasing attention in the context of AMD. This study aimed to elucidate the mechanisms underlying the induction of abnormal necroptosis in AMD.<br><br>METHODS: Sodium iodate (SI) was used to establish in vitro and in vivo retinal pigment epithelium cell (RPE) degeneration models and to simulate dry AMD-like conditions. Phenotypes and classic necroptosis markers were identified. RNA-seq was performed on the retinas of RPE-degeneration mice and combined with the GSE29801 microarray data of human AMD retinal samples to identify the key genes regulating necroptosis. Key genes were overexpressed both in vivo and in vitro to further validate their function in necroptosis and RPE degeneration.<br><br>RESULTS: Necroptosis phenotypes and the expression of the necroptosis markers RIPK1, RIPK3, and MLKL were upregulated in both SI-treated ARPE-19 cells and the RPE layer of mice. Transcriptome data from SI-treated mice and patients with AMD revealed that the reduced expression of PYGM is implicated in the regulation of necroptosis. PYGM overexpression in RPE cells and mouse retinas alleviated SI-induced RPE degeneration.<br><br>CONCLUSIONS: This study confirmed that PYGM attenuates necroptosis in cellular and animal models resembling dry AMD, providing a new perspective on exploring novel AMD treatment targets.}, }
@article {pmid41183785, year = {2025}, author = {Basilious, A and Yuan, AT and Sheidow, TG}, title = {Outcomes of 16-week extension of anti-VEGF therapy in neovascular age-related macular degeneration.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcjo.2025.10.002}, pmid = {41183785}, issn = {1715-3360}, abstract = {OBJECTIVE: To determine the outcomes of extending anti-VEGF injection intervals to 4 months in neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: A prospective cohort study.<br><br>PARTICIPANTS: Patients undergoing injections with standard-dose anti-VEGF (aflibercept, ranibizumab) with documented disease stability at 3-month injection intervals for &#x2265;2 years.<br><br>METHODS: The injection interval was extended to 4 months. The primary outcome of disease stability was defined as no clinical evidence of lesion growth, blood, or intraretinal or new subretinal fluid seen on ocular coherence tomography (OCT). Demographic data, visual acuity, exam findings, and OCT data were collected.<br><br>RESULTS: This study included 88 eyes (83.4 &#xb1; 7.3 years, 64.8% female) with nAMD extended to injection intervals of 4 months (56 eyes with aflibercept and 32 with ranibizumab). The recurrence rate was 10.2% (9/88). Four eyes recurred after the first 4-month extension interval, 2 eyes at the 8-month follow-up, 2 eyes at 16 months, and 1 eye at 22 months. In eyes with a recurrence (n&#x202f;=&#x202f;9), there was no significant difference (p > .05) between mean visual acuity prior to recurrence (0.18 &#xb1; 0.13 [20/30]) and at final follow-up postrecurrence (0.21 &#xb1; 0.17 [20/30]). All but 1 case returned to within 1 Snellen line of visual acuity at final follow-up. All eyes were able to regain stability at 3- or 4-month injection intervals.<br><br>CONCLUSIONS: In nAMD patients with disease stability at 3-month injection intervals for at least 2 years, the majority remained stable when extended to 4 months. Recurrences were able to achieve stability again with shorter injection intervals, without a persistent decline in visual acuity.}, }
@article {pmid41184811, year = {2025}, author = {Wang, Y and Wei, W and Pei, X and Zhan, H and Tang, Y and Li, Y and Bai, J and Li, J}, title = {PDC-DETR: a Parallel Dilated Convolutional Detection Transformer for preliminary screening of multiple macular degeneration.}, journal = {BMC medical imaging}, volume = {25}, number = {1}, pages = {439}, pmid = {41184811}, issn = {1471-2342}, support = {2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; }, abstract = {Current diagnostic approaches for macular degeneration in optical coherence tomography (OCT) images often lead to misdiagnosis due to their limited ability to capture the disease’s multiscale and irregular features. We present PDC-DETR, a Parallel Dilated Convolutional Detection Transformer, which introduces three major innovations for accurate and efficient macular degeneration analysis. First, a Parallel Feature-Optimized Attention Pyramid Network (PFOAPN) enables simultaneous modeling of global context and local details through multi-scale feature pathways. Second, a novel Wise-MPDIoU loss dynamically adjusts to variations in image quality while improving lesion localization accuracy. Third, the lightweight design ensures real-time clinical applicability, requiring only 38.2 MB parameters and 58.5 GFLOPs, while achieving 94.1% accuracy across five macular degeneration categories at 71 FPS. This study establishes a new benchmark for automated OCT-based retinal disease detection, providing both high diagnostic accuracy and practical clinical deployment potential.}, }
@article {pmid41186544, year = {2026}, author = {Lou, J and Liao, X}, title = {Re: Friedman et al: Randomized trial of biosimilar ABP 938 compared with reference aflibercept in adults with neovascular age-related macular degeneration (2025 Aug 5:S2468-6530(25)00351-3. doi: 10.1016/j.oret.2025.07.015. Online ahead of print.).}, journal = {Ophthalmology. Retina}, volume = {10}, number = {1}, pages = {e1}, doi = {10.1016/j.oret.2025.10.003}, pmid = {41186544}, issn = {2468-6530}, }
@article {pmid41187156, year = {2025}, author = {Li, Y and Wang, B and Luo, X and Zhang, M and Hu, Q and Li, X}, title = {Machine learning models for risk prediction of age-related macular degeneration in Fujian eye study.}, journal = {PloS one}, volume = {20}, number = {11}, pages = {e0335620}, pmid = {41187156}, issn = {1932-6203}, mesh = {Humans ; *Macular Degeneration/epidemiology/diagnosis ; *Machine Learning ; Female ; Male ; Aged ; Cross-Sectional Studies ; Risk Factors ; Logistic Models ; Middle Aged ; Aged, 80 and over ; Support Vector Machine ; }, abstract = {OBJECTIVE: Age-related macular degeneration (AMD) is a retinal disorder that significantly impairs vision. This study investigates various machine learning models for predicting AMD risk, laying the groundwork for further research using big data and determining the most effective predictive model.<br><br>METHODS: Utilizing data from 8211 records with 39 features from the Fujian Eye Study, a cross-sectional epidemiological investigation, several machine learning models were developed and assessed. The models included logistic regression (LR), K-nearest neighbors (KNN), support vector machine (SVM), decision tree (DT), random forest (RF), light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost). Data preprocessing, feature selection, and model training were all key components of the study.<br><br>RESULTS: After evaluating multiple models, the logistic regression model emerged as the most accurate, achieving a balanced accuracy of 0.6364. Among the predictive features, educational background had the highest influence on the model's predictions, with an average SHAP (SHapley Additive exPlanations) value of 0.8199. Other significant factors included outdoor time and left eye spherical equivalent (OSSE), with SHAP values of 0.6474 and 0.6377, respectively.<br><br>CONCLUSION: This study confirms that logistic regression is the most effective machine learning model for predicting AMD risk, with educational background identified as the most critical risk factor.}, }
@article {pmid41187450, year = {2025}, author = {Dashti, R and Safaei, F and Sadeghian, G and Hosseini, SA and Salimibani, M}, title = {Peptide-functionalized nanomaterials for controlled drug delivery and regenerative therapies in retinal diseases.}, journal = {Journal of biomaterials applications}, volume = {}, number = {}, pages = {8853282251395196}, doi = {10.1177/08853282251395196}, pmid = {41187450}, issn = {1530-8022}, abstract = {Degenerative retinal diseases, such as diabetic retinopathy, age-related macular degeneration (AMD), and retinitis pigmentosa, cause irreversible vision loss by destroying vital retinal cells and represent major global health concerns. Traditional therapies have limited success in fully restoring vision due to the complex retinal structure and blood-retinal barriers (BRBs), though they may help alleviate symptoms or slow disease progression in some cases. Nanochemistry and peptide-based systems represent breakthrough approaches by leveraging nanoscale precision and biological specificity. This review examines the chemical design and synthesis of nanoparticles (NPs), nanoscaffolds, and peptide conjugates used in retinal neural regeneration. It also explores their biomedical applications, especially in targeted drug delivery, tissue engineering, and cellular repair. Biodegradable polymeric NPs, liposomes, and hybrid nanostructures are designed to cross barriers, release drugs in a controlled manner, and enhance biocompatibility. PEGylation improves stability and reduces immune responses in the ocular environment, while peptide functionalization enables specific cellular targeting and minimizes inflammatory reactions. Peptide-functionalized platforms, such as RGD-modified NPs and self-assembling hydrogels, provide receptor-mediated targeting and extracellular matrix (ECM) mimicry to support retinal regeneration for improved stem cell differentiation and neuroprotection. We discuss drug/gene delivery mechanisms, cellular interactions, and immune modulation, as well as neuroprotection, stem cell therapy, and diagnostic applications. Preclinical studies have demonstrated promising efficacy in animal models; however, concerns regarding scalability, long-term safety, and non-invasive delivery persist. Next-generation technologies, such as stimuli-responsive NPs, computationally designed peptides, and patient-specific delivery systems, are on the horizon to address unmet clinical needs. By marrying nanochemistry's precision with peptides' bioactivity, these technologies have the potential to transform retinal disease treatment, enabling the restoration of vision and an improvement in quality of life for millions of people worldwide.}, }
@article {pmid41188571, year = {2026}, author = {Eilon, E and Lishinsky-Fischer, N and Levy, J}, title = {Systemic prostacyclin analogues in pulmonary hypertension are associated with reduced risk of age-related macular degeneration: a cohort study.}, journal = {Eye (London, England)}, volume = {40}, number = {1}, pages = {71-76}, pmid = {41188571}, issn = {1476-5454}, mesh = {Humans ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; *Hypertension, Pulmonary/drug therapy/complications ; *Epoprostenol/analogs &amp; derivatives/therapeutic use ; *Macular Degeneration/prevention &amp; control/epidemiology ; *Antihypertensive Agents/therapeutic use ; Risk Factors ; Incidence ; Follow-Up Studies ; *Prostaglandins, Synthetic/therapeutic use ; Proportional Hazards Models ; }, abstract = {BACKGROUND/OBJECTIVES: To assess whether systemic prostacyclin analogue (PCA) therapy in patients with pulmonary arterial hypertension (PAH) is associated with a reduced long-term risk of developing age-related macular degeneration (AMD).<br><br>SUBJECTS/METHODS: A retrospective cohort study was conducted using the TriNetX global health research network. Patients aged &#x2265;50 with a diagnosis of PAH were included and stratified by PCA treatment. Propensity score matching (1:1) was applied to balance demographics and comorbidities. Incident diagnoses of non-neovascular AMD (non-nvAMD) and neovascular AMD (nvAMD) were compared across six follow-up intervals (3-15 years) using Kaplan-Meier analysis and Cox proportional hazards models.<br><br>RESULTS: Following matching, 9862 PCA-treated and 9862 untreated PAH patients were analysed. PCA-treated patients showed a consistently lower risk of non-nvAMD across all follow-up periods (hazard ratios [HRs] 0.30-0.37; all p&#x2009;<&#x2009;0.001). A similar protective trend was observed for nvAMD, with significant associations emerging at longer follow-up (HR&#x2009;=&#x2009;0.37-0.39 at 10-15 years; p&#x2009;<&#x2009;0.05). The protective effect was robust and durable over time.<br><br>CONCLUSIONS: Systemic administration of prostacyclin analogues is associated with a significant and sustained reduction in AMD risk among patients with PAH. These findings suggest a potential preventive role for PCAs in AMD pathogenesis and merit further investigation in broader populations.}, }
@article {pmid41189030, year = {2025}, author = {Arnal, L and Mesfin, Y and Xu, C and Salvi, A and Mishra, K and Ludwig, CA}, title = {Beyond refractive error: myopia's exponential burden on retinal health with each diopter.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {121}, pmid = {41189030}, issn = {2056-9920}, support = {K23 EY035741/EY/NEI NIH HHS/United States ; P30 EY026877/EY/NEI NIH HHS/United States ; NEI P30-EY026877//P30 Vision Research Core Grant/ ; K23EY035741//National Eye Institute K23 Grant/ ; }, abstract = {BACKGROUND: As myopia reaches epidemic levels worldwide, its role in driving vision-threatening retinal complications is increasingly urgent. This study quantifies the burden of myopia by examining its association with key retinal diseases and how risk escalates with increasing severity.<br><br>METHODS: We conducted a retrospective cohort study using the STARR clinical data warehouse, including all patients with &#x2265;&#x2009;1 documented eye visit. Myopia severity was defined by spherical equivalent and axial length, classifying patients as non-myopic, myopic, highly myopic, or severely myopic. Primary outcomes included six retinal diseases associated with myopia: choroidal neovascularization (CNV), myopic macular degeneration (MMD), foveoschisis, macular hole (MH), rhegmatogenous retinal detachment (RRD), and foveal retinal detachment (FRD). Adjusted logistic regression estimated odds by myopia severity and spherical equivalent. Mean age at diagnosis was compared across groups.<br><br>RESULTS: Retinal complications occurred at younger ages with increasing myopia severity. Compared to non-myopes, myopic, highly myopic, and severely myopic patients had 2.45 (95% CI: 2.36-2.55), 2.46 (95% CI: 2.31-2.62), and 8.15 (95% CI: 7.17-9.27) times higher odds, respectively, of developing any retinal complication. Per diopter increase in myopia, the odds of each complication increased: CNV (OR 1.11; 95% CI: 1.09-1.12), MMD (OR 1.22; 95% CI: 1.18-1.25), foveoschisis (OR 1.22; 95% CI: 1.16-1.28), MH (OR 1.06; 95% CI: 1.05-1.08), FRD (OR 1.23; 95% CI: 1.16-1.32), and RRD (OR 1.10; 95% CI: 1.10-1.11). In severe myopes, odds were markedly elevated: CNV (OR 22.90), MMD (OR 60.19), foveoschisis (OR 102.98), MH (OR 6.69), FRD (OR 22.72), and RRD (OR 6.84).<br><br>CONCLUSIONS: Myopia is independently associated with higher odds of retinal diseases, and this risk increases incrementally with severity. These findings support a dose-response relationship and highlight the importance of early risk stratification, tailored monitoring, and timely referral in patients with high and severe myopia.}, }
@article {pmid41189775, year = {2025}, author = {Guzun, OV and Zadorozhnyy, OS and Konovalova, NV and Bezdetko, PA and Korol, AR and Dumbrăveanu, LG and Cușnir, VN and Cușnir, VV}, title = {Reducing the risk of age-related macular degeneration progression - five-year follow-up study in Ukraine and Moldova.}, journal = {Romanian journal of ophthalmology}, volume = {69}, number = {3}, pages = {340-349}, pmid = {41189775}, issn = {2501-2533}, mesh = {Humans ; Ukraine/epidemiology ; Disease Progression ; Follow-Up Studies ; Male ; Female ; Prospective Studies ; Aged ; *Dietary Supplements ; *Macular Degeneration/epidemiology/prevention &amp; control/diagnosis ; Moldova/epidemiology ; *Antioxidants/administration &amp; dosage/therapeutic use ; Time Factors ; *Visual Acuity ; Risk Factors ; Middle Aged ; Vitamins ; *Fatty Acids, Omega-3/administration &amp; dosage ; }, abstract = {This open prospective study aimed to evaluate the dynamics of progression of early and intermediate age-related macular degeneration (AMD) against the background of continuous use of the nutraceutical formula AREDS2, which includes omega-3 polyunsaturated fatty acids (PUFAs), vitamin D, resveratrol, and photobiomodulation (PBM), over a 5-year follow-up in patients from Ukraine and Moldova. Examining 126,400 patients, 163 patients (304 eyes) with early and intermediate stages of AMD were treated (5-year follow-up). Patients were divided into two groups. Patients in the 1st group (149 eyes) were prescribed a nutraceutical formula based on AREDS2 with omega-3 PUFAs, vitamin D, and resveratrol (Nutrof®Forte 1 capsule once a day continuously). The second group (155 eyes) included patients who irregularly took various vitamin-antioxidant complexes. All patients underwent PBM every 6 months. The five-year prevalence of early and intermediate AMD was estimated using data from leading ophthalmological centers in Ukraine (Odesa - 7.1%, Kharkiv - 6.6%) and Moldova (6.3%). AMD progression in the multivariate Cox regression model over five years showed a 3.24-fold reduction in relative risk (95% CI: 2.15-4.79, p=0.000) for patients with early and intermediate AMD who regularly took the recommended nutraceutical (compared to those who irregularly took various vitamin-antioxidant complexes). Patients with early and intermediate AMD are recommended to undergo courses of PBM every six months. Additionally, it is crucial to address cardiovascular issues and consistently use the AREDS2 nutraceutical formula. Adherence to these recommendations can reduce the likelihood of disease progression by at least 3.24 times over the next 5 years.}, }
@article {pmid41189785, year = {2025}, author = {Stoica, AM and Jurja, S and Dervis, N}, title = {Anti-VEGF therapy - a new hope in AMD treatment.}, journal = {Romanian journal of ophthalmology}, volume = {69}, number = {3}, pages = {322-327}, pmid = {41189785}, issn = {2501-2533}, mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Choroidal Neovascularization/drug therapy/etiology ; *Macular Degeneration/drug therapy/complications ; Ranibizumab ; *Wet Macular Degeneration/drug therapy ; Bevacizumab ; }, abstract = {Choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) represents a significant global cause of visual impairment. Contemporary therapeutic approaches for neovascular AMD focus on inducing regression of CNV by inhibiting critical growth factors involved in angiogenesis. For nearly two decades, vascular endothelial growth factor (VEGF) has been the principal therapeutic target, with multiple intravitreally administered agents developed to achieve anatomical restoration and improved visual outcomes through sustained dosing.}, }
@article {pmid41189788, year = {2025}, author = {Stoica, AM and Jurja, S and Dervis, N}, title = {The Role of Vitamin D in Retinal Physiology.}, journal = {Romanian journal of ophthalmology}, volume = {69}, number = {3}, pages = {315-321}, pmid = {41189788}, issn = {2501-2533}, mesh = {Humans ; *Vitamin D/physiology ; *Retina/physiology ; *Retinal Diseases/physiopathology/metabolism/prevention &amp; control ; Oxidative Stress/physiology ; Vitamin D Deficiency/physiopathology ; Animals ; }, abstract = {Vitamin D plays a crucial role in ocular health, particularly in the function and protection of the retina. This fat-soluble vitamin is synthesized in the skin in response to UVB radiation and can also be obtained from dietary sources. Research indicates that vitamin D has neuroprotective properties, which are essential for retinal cell survival and function. The active form of vitamin D, calcitriol, has been shown to modulate inflammation and oxidative stress in retinal tissues, thus potentially preventing retinal degeneration diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. Furthermore, vitamin D receptors are expressed in various retinal cells, suggesting that vitamin D directly influences retinal physiology. Deficiency in vitamin D has been associated with an increased risk of chronic eye diseases, emphasizing the importance of maintaining adequate vitamin D levels for preserving retinal health. Ongoing studies are needed to elucidate further the molecular mechanisms underlying the protective effects of vitamin D on the retina and to explore its therapeutic potential in retinal disorders.}, }
@article {pmid41189793, year = {2025}, author = {Muşat, AAM and Zamfiroiu-Avidis, N and Ştefan, C and Andreea, S and Muşat, G and Udrea, G and Popescu, IS and Muşat, O}, title = {A Case Series of Serious Adverse Events Following Anti-VEGF Intravitreal Injections.}, journal = {Romanian journal of ophthalmology}, volume = {69}, number = {3}, pages = {450-454}, pmid = {41189793}, issn = {2501-2533}, mesh = {Humans ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; *Bevacizumab/adverse effects/administration &amp; dosage ; *Cataract/chemically induced/diagnosis ; *Endophthalmitis/chemically induced/diagnosis ; Intravitreal Injections/adverse effects ; *Ranibizumab/adverse effects/administration &amp; dosage ; *Retinal Detachment/chemically induced/diagnosis ; Retrospective Studies ; Tomography, Optical Coherence ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; }, abstract = {PURPOSE: To highlight serious adverse effects regarding intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, which is widely used for the treatment of retinal diseases, including two cases of post-injection endophthalmitis, one of which was complicated by rhegmatogenous retinal detachment, and one case of secondary cataract following a potentially unnecessary injection.<br><br>METHODS: A retrospective analysis of three cases that developed complications after intravitreal anti-VEGF therapy.<br><br>RESULTS: All cases resulted in a decline in best corrected visual acuity (BCVA) that required additional surgical procedures.<br><br>DISCUSSION: While intravitreal anti-VEGF therapy has become the standard in the treatment of various retinal pathologies, it is not without risks. This case series presents significant adverse outcomes, emphasizing the potential for severe anatomical and functional consequences. As the global volume of anti-VEGF intravitreal injections increases, so must our commitment to patient safety, precision in diagnosis, and ethical decision making.<br><br>CONCLUSION: Although generally safe and commonly used in clinical practice, physicians must be aware of the risks of anti-VEGF therapy and must remain vigilant regarding patient selection and risk-benefit considerations.}, }
@article {pmid41191064, year = {2026}, author = {Hasan, N and Sadeghi, E and Gandhi, P and Vupparaboina, SC and Du, K and Eller, AW and Sahel, JA and Bollepalli, SC and Vupparaboina, KK and Chhablani, J}, title = {Demography, clinical profile and risk of retinal vein occlusion among patients with age-related macular degeneration - a tertiary hospital based study.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {383-392}, pmid = {41191064}, issn = {1435-702X}, mesh = {Humans ; Female ; Male ; *Retinal Vein Occlusion/epidemiology/diagnosis/etiology ; Risk Factors ; Aged ; Incidence ; Prevalence ; Retrospective Studies ; *Tertiary Care Centers/statistics &amp; numerical data ; *Visual Acuity ; Aged, 80 and over ; *Macular Degeneration/complications/diagnosis/epidemiology ; Follow-Up Studies ; Risk Assessment/methods ; Tomography, Optical Coherence/methods ; Middle Aged ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) and retinal vein occlusion (RVO) share common risk factors and the risk of blindness is higher when both diseases coexist. This study aims to evaluate the risk factors of developing RVO among AMD patients and describe their clinical characteristics.<br><br>METHODS: In this single-center cohort study, 5618 Patients with AMD were divided into two groups: those who developed RVO and those who did not. Demographic, clinical and comorbidity profile were compared and multivariable logistic regression was performed to identify risk factors for RVO among patients with AMD. Additionally, baseline characteristics were compared between patients who developed central and branch retinal vein occlusion (CRVO and BRVO).<br><br>RESULTS: Among 5,618 patients with AMD, 55 developed RVO while 5563 did not. The prevalence of RVO among AMD patients was 9.79/1,000 AMD patients (95% CI:7.2-12.4) with an incidence rate of 2.04/1,000 person-years. Multivariate regression analysis revealed patients with lower BMI(OR:0.89,95%CI:0.84-0.95,p&#x2009;=&#x2009;<&#x2009;0.001), higher Charlson comorbidity index(OR:1.12,95%CI:1.02-1.22,p&#x2009;=&#x2009;0.019), African-American ethnicity(OR:4.07,95%CI:1.55-10.73,p&#x2009;=&#x2009;0.004), glaucoma(OR:2.09,95%CI:1.2-3.64,p&#x2009;=&#x2009;0.009) and neovascular AMD(OR:1.92,95%CI:1.07-3.43,p&#x2009;=&#x2009;0.028) have higher risk. On subgroup analysis, 27 patients developed CRVO, while 29 developed BRVO. The mean time to RVO development after the first visit for AMD was 4.42&#xb1;3.6 years. Patients with CRVO had significantly worse visual acuity(p&#x2009;<&#x2009;0.001), higher IOP(p&#x2009;=&#x2009;0.012), and a higher incidence of glaucoma(p&#x2009;=&#x2009;0.006) at baseline.<br><br>CONCLUSION: AMD Patients with lower BMI, higher CCI, African Americans, glaucoma, and neovascular AMD are at a higher risk of developing RVO. Identifying these risk factors is crucial to diagnose RVO promptly in patients with AMD as it has a higher prevalence compared to the general population, with a greater risk for vision loss.}, }
@article {pmid41191163, year = {2025}, author = {Zhang, J and Kamoi, K and Zong, Y and Yang, M and Zou, Y and Ohno-Matsui, K}, title = {Inflammation and Immune Pathways in Myopia: An Overview on Pathomechanisms and Treatment Prospects.}, journal = {Clinical reviews in allergy &amp; immunology}, volume = {68}, number = {1}, pages = {98}, pmid = {41191163}, issn = {1559-0267}, support = {JPMJSP2180//JST SPRING/ ; 25K02864//Japan Society for the Promotion of Science/ ; 22FC0201//Ministry of Health, Labour and Welfare/ ; 23fk0108671h0001, 23fk0108672h000//Japan Agency for Medical Research and Development/ ; FY2023//Takeda Science Foundation/ ; }, mesh = {Humans ; *Myopia/therapy/immunology/etiology/metabolism/epidemiology ; *Inflammation/immunology/metabolism ; Animals ; Cytokines/metabolism ; Anti-Inflammatory Agents/therapeutic use ; Signal Transduction ; Inflammation Mediators/metabolism ; Disease Susceptibility ; Extracellular Matrix/metabolism ; Disease Management ; }, abstract = {Myopia represents a growing global public health challenge, characterized by increasing prevalence and associated complications such as myopic macular degeneration and retinal detachment. Although genetic and environmental factors are well-recognized contributors, emerging evidence supports a pathological link between inflammation and myopia progression. Epidemiological studies indicate a higher incidence of myopia among individuals with systemic or ocular inflammatory conditions. Inflammation perturbs the ocular immune microenvironment by upregulating pro-inflammatory cytokines and matrix metalloproteinase-2, thereby accelerating extracellular matrix (ECM) degradation and scleral remodeling, which culminates in axial elongation. Conversely, excessive axial elongation in high myopia triggers choroidal microvascular dysfunction, tissue hypoxia, and disruption of the blood-retinal barrier, leading to elevated inflammatory cytokines in the aqueous humor and vitreous, thereby raising the possibility of a self-perpetuating loop. Anti-inflammatory agents, including diacerein, resveratrol, and lactoferrin, have demonstrated therapeutic potential in experimental models by modulating inflammatory pathways, reducing pro-inflammatory cytokines, and preserving ECM integrity. However, their clinical efficacy and long-term safety require further validation. Elucidating the complex interplay between inflammation and myopia is pivotal for the development of targeted interventions, moving the focus of myopia management beyond optical correction towards disease-modifying strategies.}, }
@article {pmid41191669, year = {2025}, author = {Zhou, J and He, Y and Wang, J and Cao, J and Huang, X and Chen, M and Ye, J}, title = {Malnutrition and age-related macular degeneration: mechanistic insights from UK Biobank metabolomic and imaging data.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {80}, number = {12}, pages = {}, doi = {10.1093/gerona/glaf229}, pmid = {41191669}, issn = {1758-535X}, support = {82330032//Key Program of the National Natural Science Foundation of China/ ; U20A20386//National Natural Science Foundation Regional Innovation and Development Joint Fund/ ; 2024C03204//Key Research and Development Program of Zhejiang Province/ ; 82301208//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Male ; *Macular Degeneration/epidemiology/etiology/metabolism/diagnostic imaging ; Female ; Middle Aged ; United Kingdom/epidemiology ; *Malnutrition/complications/metabolism/epidemiology ; Metabolomics ; Biological Specimen Banks ; Aged ; Risk Factors ; Cohort Studies ; Tomography, Optical Coherence ; UK Biobank ; }, abstract = {BACKGROUND: Malnutrition, characterized by degeneration of body composition due to reduced intake or inflammation, shares some common mechanisms with age-related macular degeneration (AMD), while their associations remain unexplored.<br><br>METHODS: This cohort study utilized data from the UK Biobank. Participants without pre-existing AMD and with complete malnutrition data were included. Cox regression was employed to evaluate the longitudinal association. An ElasticNet model was used to derive a metabolomic signature of malnutrition, which was subsequently assessed for association with AMD. Malnutrition and the metabolomic signature were further tested for associations with photoreceptor thinning. Structural equation modeling was applied to delineate underlying mechanisms.<br><br>RESULTS: A total of 444&#x2009;681 participants (mean age: 56.4&#x2009;&#xb1;&#x2009;8.1 years; 45.8% male) were included, with 32&#x2009;086 (7.2%) diagnosed with malnutrition at baseline. Over a median follow-up of 13.6 years, 10 009 AMD cases were identified. Malnutrition was associated with an increased risk of AMD (hazard ratio [HR]: 1.221, 95% CI, 1.144-1.304, p&#x2009;<&#x2009;.001). The metabolomic signature of malnutrition, derived from 127 metabolites, was significantly associated with AMD risk (per SD increase: HR: 1.073, 95% CI, 1.037-1.110, p&#x2009;<&#x2009;.001) and thinner photoreceptor layer (&#x3b2;&#x2009;=&#x2009;-.214, 95% CI, -0.314 to -0.114, p&#x2009;<&#x2009;.001). Structural equation modeling revealed that malnutrition increased AMD risk partially through metabolomic changes that induced photoreceptor thinning.<br><br>CONCLUSIONS: Malnutrition in middle-aged adults was significantly associated with increased risk of AMD, which was mediated by metabolomic alterations that impaired photoreceptor health.}, }
@article {pmid41192738, year = {2026}, author = {Aphale, P and Shekhar, H and Dokania, S}, title = {Comments on "Refining the translational pathway for senotherapeutics in age-related macular degeneration: Insights on biomarkers, delivery strategies, and clinical trial design".}, journal = {Survey of ophthalmology}, volume = {71}, number = {3}, pages = {1010-1011}, doi = {10.1016/j.survophthal.2025.10.002}, pmid = {41192738}, issn = {1879-3304}, }
@article {pmid41194409, year = {2026}, author = {Zarei-Ghanavati, S and Motamed Shariati, M and Hadi, Y and Khazaei, S and Yoo, SH}, title = {Cataract surgery in the context of age-related macular degeneration: challenges and considerations.}, journal = {Journal of cataract and refractive surgery}, volume = {52}, number = {4}, pages = {398-405}, pmid = {41194409}, issn = {1873-4502}, mesh = {Humans ; *Cataract Extraction/methods ; *Macular Degeneration/complications ; *Cataract/complications ; Visual Acuity/physiology ; Lens Implantation, Intraocular ; }, abstract = {Age-related macular degeneration (AMD) and cataracts commonly coexist in the aging population, posing unique diagnostic and therapeutic challenges for ophthalmologists. Although cataract surgery can substantially improve visual function, outcomes are often influenced by the type and severity of underlying macular pathology. This narrative review explores current evidence on the impact of cataract surgery in patients with AMD, including preoperative assessment strategies, intraoperative considerations, and postoperative visual expectations. The role of multimodal imaging in detecting subclinical macular changes, advanced intraocular lenses, and the debated relationship between cataract surgery and AMD progression are discussed. Emphasis is placed on personalized patient selection and counseling to optimize outcomes. Overall, with appropriate planning and patient-centered care, cataract surgery remains a safe and beneficial intervention for most individuals with AMD.}, }
@article {pmid41194565, year = {2025}, author = {Singh, RB and Stettler, I and Romano, F and Parmar, UPS and Surico, PL and Ding, X and Kim, J and Rai, KK and Miller, JW and Miller, JB}, title = {Prevalence of Age-Related Macular Degeneration in the United States: A Medicare-Based Analysis from 2014 to 2021.}, journal = {Ophthalmic research}, volume = {68}, number = {1}, pages = {573-582}, pmid = {41194565}, issn = {1423-0259}, mesh = {Humans ; United States/epidemiology ; Aged ; Female ; Male ; Retrospective Studies ; *Medicare/statistics &amp; numerical data ; Prevalence ; Aged, 80 and over ; *Macular Degeneration/epidemiology ; Age Distribution ; }, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of vision loss among older adults in the USA. Understanding its prevalence and demographic distribution is critical for developing targeted public health strategies. This study aimed to assess the prevalence of AMD and its clinical stages among US Medicare beneficiaries aged 65 years and older.<br><br>METHODS: We conducted a retrospective cohort study using the Vision and Eye Health Surveillance System (VEHSS) database of Medicare beneficiaries diagnosed with AMD between 2014 and 2021. Crude prevalence rates for overall AMD, early AMD, intermediate AMD, wet AMD, and geographic atrophy (GA) were calculated at national and state levels. Prevalence was stratified by age, sex, and race/ethnicity. Statistical analyses included the Mann-Whitney U test for age and sex comparisons, the Brown-Forsythe one-way ANOVA for racial/ethnic comparisons, and the Dunnett T3 test for post hoc analyses.<br><br>RESULTS: In 2021, the VEHSS-Medicare dataset included 24,129,807 individuals aged 65 and older, among whom the national prevalence of AMD was 10.40%. Prevalence rates for early AMD, intermediate AMD, wet AMD, and GA were 2.87%, 6.91%, 2.14%, and 0.73%, respectively. The number of AMD cases increased from 2.33 million in 2014 to 2.51 million in 2021. Prevalence was significantly higher in individuals aged &#x2265;85 years compared to those aged 65-84 years, and in females compared to males. Post hoc analyses demonstrated that White individuals had a significantly higher prevalence of AMD compared with all other racial/ethnic groups.<br><br>CONCLUSIONS: The prevalence of AMD among US adults aged 65 years and older was 10.4%, with higher rates observed in the oldest age groups, females, and White individuals. These findings highlight the importance of addressing disparities in AMD prevention and care, particularly in populations at greatest risk.}, }
@article {pmid41194821, year = {2025}, author = {Almpanidou, S and Gounari, E and Goulas, A and Topouzis, F and Talimtzi, P and Kouzi-Koliakou, K and Karampatakis, V and Koliakos, G}, title = {Targeting Angiogenesis and Visual Cycle in Age-Related Macular Degeneration: The Role of Stem Cells and Vinpocetine.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e93878}, pmid = {41194821}, issn = {2168-8184}, abstract = {Purpose The purpose of this study was to evaluate whether bone marrow stem cells (BMSCs), vinpocetine, or their combination can attenuate amyloid-β (Aβ)-induced alterations in angiogenesis and visual cycle gene expression in a cellular model of age-related macular degeneration (AMD). Methods Human retinal pigment epithelium (RPE) cells (ARPE-19) were exposed to Aβ 1-42 for 24h and divided into four groups: (i) co-culture with BMSCs, (ii) treated with vinpocetine, (iii) treated with BMSCs and vinpocetine, and (iv) untreated control. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the mRNA expression levels of angiogenesis-related genes, vascular endothelial growth factor (VEGF-A) and pigment epithelium-derived factor (PEDF), and RPE-associated visual cycle genes: lecithin retinol acyltransferase (LRAT), retinoid isomerohydrolase (RPE65), retinol dehydrogenase 5 (RDH5), retinol dehydrogenase 10 (RDH10), and retinaldehyde-binding protein 1 (RLPB1). Results Aβ1-42 significantly reduced ARPE-19 cell viability (p=0.002); all treatments significantly restored viability. Aβ1-42 upregulated VEGF-A expression, which was significantly downregulated by all treatments. Although Aβ1-42 slightly increased PEDF expression, all treatments significantly enhanced its upregulation, with the combination therapy showing the greatest effect (p=0.006, 0.010, and 0.002, respectively). Furthermore, Aβ 1-42 induced upregulation of most visual cycle genes was reversed by all treatments. Conclusion Aβ1-42 induces cytotoxicity, angiogenesis, and dysregulation of visual cycle genes in RPE cells in vitro. BMSCs, vinpocetine, and their combination attenuate these effects, supporting a potential role in AMD therapy pending further investigation.}, }
@article {pmid41196411, year = {2025}, author = {Furtado, J and Zapadka, TE and Park, H and Boyé, K and Demb, JB and Eichmann, A}, title = {Restoring compromised blood-retina-barrier integrity with Netrin-1 overexpression.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {82}, number = {1}, pages = {389}, pmid = {41196411}, issn = {1420-9071}, support = {R01 HL125811/HL/NHLBI NIH HHS/United States ; 834161/ERC_/European Research Council/International ; 1R01HLI125811//NHLBI Division of Intramural Research/ ; 830299//American Heart Association/ ; }, mesh = {*Netrin-1/genetics/metabolism ; Animals ; *Blood-Retinal Barrier/metabolism/pathology ; Mice ; Diabetic Retinopathy/pathology/metabolism/genetics ; Choroidal Neovascularization/pathology/metabolism/genetics ; Mice, Inbred C57BL ; Humans ; Electroretinography ; Netrin Receptors/genetics ; Mice, Knockout ; Retina/metabolism/pathology ; }, abstract = {The blood-retina barrier (BRB) protects retinal neuronal function and enables vision. A compromised, leaky BRB is a hallmark of vision-threatening retinal diseases such as diabetic retinopathy (DR) and wet age-related macular degeneration (AMD) that affect millions of persons worldwide. Strategies to enhance BRB integrity hold promise as therapeutic interventions to prevent vision loss. Previous studies identified Netrin-1 (NTN1) as a key regulator of BRB stability and revealed reduced Netrin-1 signaling in DR patients, suggesting that Netrin-1 supplementation could help preserve BRB function and prevent disease progression. Herein, we used inducible genetic NTN1 overexpression to investigate effects on BRB development and maintenance. We show that global NTN1 overexpression converted leaky vessels at the P5 angiogenic front into a non-leaky state. In pathological settings, NTN1 overexpression reinforced BRB integrity in oxygen-induced retinopathy (OIR), improving electroretinogram (ERG) amplitudes and rescued vascular leak in laser-induced choroidal neovascularization (CNV). NTN1 overexpression or Ntn1 knockout minimally and transiently affected retinal angiogenesis. Global Unc5b deletion phenocopied vascular leak observed in Ntn1 deficient retinas, while angiogenesis defects differed between Ntn1 and Unc5b knockouts. These findings establish Netrin-1 as a promising therapeutic target for preventing BRB breakdown in retinal vascular diseases and suggest that reinforcing the Netrin-1/Unc5b signaling pathway may provide a strategy to selectively stabilize the BRB.}, }
@article {pmid41197713, year = {2025}, author = {Allan, KC and Cohn, EF and Bala, S and Kim, SB and Kaelber, DC and Singh, RP and Talcott, KE and Mammo, DA and Rachitskaya, AV}, title = {Glucagon-Like Peptide-1 Receptor Agonist Use and Risk of Neovascular Age-Related Macular Degeneration in a National Cohort Study.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2025.10.020}, pmid = {41197713}, issn = {2468-6530}, abstract = {PURPOSE: To investigate the risk of neovascular age-related macular degeneration (AMD) in patients taking glucagon-like peptide-1 receptor agonists (GLP-1RAs).<br><br>DESIGN: A retrospective cohort study.<br><br>PARTICIPANTS: This study used the TriNetX network, a large aggregated electronic health records platform from health care organizations across the United States. Adults over the age of 60 years with &#x2265;1, 2, or 3 years of ophthalmology follow-up and medication prescription documentation were included.<br><br>METHODS: Patients were grouped into those taking GLP-1RAs, alternate glucose-lowering medications, and alternate lipid-lowering medications. Cohorts were propensity matched on demographics, chronic disease prevalence, and disease severity indicators.<br><br>MAIN OUTCOME MEASURES: The primary outcomes were risk of developing nonneovascular and neovascular AMD at 1, 2, and 3 years after initial medication prescription. A secondary analysis evaluated the risk of neovascular AMD in patients with nonneovascular AMD at baseline. Significance was defined as P < 0.05 and hazard ratio (HR) threshold >1.1 or <0.9 to minimize noise in large data sets.<br><br>RESULTS: Patients prescribed GLP-1RA had greater baseline chronic disease burden and worse disease severity metrics than comparator groups. Propensity matching effectively matched chronic disease prevalence at baseline. Glucagon-like peptide-1 receptor agonist prescription was associated with a significant reduction in risk of nonneovascular AMD compared with glucose-lowering medications over 1 (HR, 0.79; 95% confidence interval [CI], 0.66-0.94), 2 (HR, 0.75; 95% CI, 0.64-0.88), and 3 (HR, 0.77; 95% CI, 0.66-0.91) years. Similar protective effects were observed when compared with lipid-lowering medications after 2 (HR, 0.84; 95% CI, 0.71-0.99) and 3 (HR, 0.8; 95% CI, 0.68-0.94) years. There was a significant reduction in risk of neovascular AMD with GLP-1RA prescription across all time points compared with both alternate glucose-lowering and lipid-lowering medications. However, there was no significant impact of GLP-1RA on the risk of conversion from nonneovascular AMD at baseline to neovascular AMD.<br><br>CONCLUSIONS: These findings suggest that GLP-1RAs may provide protective effects against nonneovascular AMD and, importantly, did not show an increased risk of neovascular AMD. Future prospective trials are needed to validate these findings.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41198612, year = {2025}, author = {Ortega, AJ and Daniel, S and Renwick, M and Kambhampati, P and Thompson, KN and Collier, GE and Baker, EL and Zaki, H and Hulleman, JD}, title = {Genetic removal of Nlrp3 protects against age-related and R345W Efemp1-induced basal laminar deposit formation.}, journal = {Cell death &amp; disease}, volume = {16}, number = {1}, pages = {803}, pmid = {41198612}, issn = {2041-4889}, support = {R01 EY027785/EY/NEI NIH HHS/United States ; R01-DK128031//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; R01-EY027785//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; N/A//Edward N. and Della L. Thome Memorial Foundation (Thome Memorial Foundation)/ ; R01 DK128031/DK/NIDDK NIH HHS/United States ; R01 DK125352/DK/NIDDK NIH HHS/United States ; R01-DK125352//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; }, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism/deficiency ; Mice ; Caspase 1/metabolism/genetics ; *Macular Degeneration/genetics/pathology/metabolism ; *Extracellular Matrix Proteins/genetics/metabolism ; *Aging/pathology/genetics ; Inflammasomes/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice, Knockout ; }, abstract = {Chronic, unresolved inflammation has long been speculated to serve as an initiating and propagating factor in numerous neurodegenerative diseases, including a leading cause of irreversible blindness in the elderly, age-related macular degeneration (AMD). Intracellular multiprotein complexes called inflammasomes in combination with activated caspases facilitate production of pro-inflammatory cytokines such as interleukin 1 beta. Specifically, the nucleotide-binding oligomerization (NOD)-like receptor protein 3 (NLRP3) has received heightened attention due to the wide range of stimuli to which it can respond and its potential involvement in AMD. In this study, we directly tested the role of Nlrp3 and its downstream effector, caspase 1 (Casp1) in mediating early AMD-like pathology (i.e., basal laminar deposits [BLamDs]) in wild-type (WT) mice and the Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD) mouse model (p.R345W mutation in Efemp1). Compared to aged-matched controls, R345W[+/+] knockin mice demonstrated increased Muller cell gliosis, subretinal Iba-1[+] cells, higher Nlrp3 immunoreactivity in the retina, as well as significant transcriptional upregulation of complement component 3, Nlrp3, pro-Il1b, pro-caspase-1, and tissue inhibitor of matrix metalloproteinase 3 in the retinal pigmented epithelium (RPE)/choroid. These findings were accompanied by an age-related increase in BLamD formation in the R345W[+/+] mice. Genetic elimination of either Nlrp3 or Casp1 significantly reduced both the size and coverage of BLamDs in the R345W[+/+] background, highlighting an important and underappreciated pathway that could affect ML/DHRD onset and progression. Moreover, Nlrp3 knockout reduced spontaneous, age-related BLamDs in WT mice, suggesting translatability of our findings not only to rare inherited retinal dystrophies, but also potentially to AMD itself.}, }
@article {pmid41198978, year = {2026}, author = {Gelisken, F and Koçak, N and Wenzel, CJ and Atay Dinçer, K and Wenzel, DA}, title = {Intravitreal anti-VEGF therapy for extrafoveal macular neovascularisation secondary to age-related macular degeneration: five-year results in a tertiary centre.}, journal = {Eye (London, England)}, volume = {40}, number = {1}, pages = {83-90}, pmid = {41198978}, issn = {1476-5454}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Visual Acuity/physiology ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Ranibizumab/therapeutic use ; Aged, 80 and over ; Tomography, Optical Coherence ; Tertiary Care Centers ; *Macular Degeneration/complications/drug therapy/physiopathology ; Bevacizumab/therapeutic use ; Follow-Up Studies ; Middle Aged ; *Wet Macular Degeneration/drug therapy/physiopathology ; Fluorescein Angiography ; Treatment Outcome ; Fovea Centralis/pathology ; }, abstract = {OBJECTIVES: To assess the long-term efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy on best-corrected visual acuity (BCVA) and foveal morphology in patients with extrafoveal macular neovascularisation (MNV) secondary to age-related macular degeneration (AMD) over five years.<br><br>METHODS: A total of 104 eyes with treatment-na&#xef;ve extrafoveal MNV treated with intravitreal anti-VEGF injections were analysed retrospectively. BCVA was assessed at baseline and annually for five years. Central foveal thickness (CFT), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachments (PED), subretinal hyperreflective material (SHRM), and foveal atrophy (incomplete/complete retinal pigment epithelium and outer retinal atrophy (iRORA/cRORA))-were documented.<br><br>RESULTS: After five years, 46% of the eyes had unchanged or improved vision by one or more lines, whereas mean BVCA declined from 0.28&#x2009;&#xb1;&#x2009;0.20 logMAR at baseline to 0.50&#x2009;&#xb1;&#x2009;0.49 logMAR after five years (p&#x2009;=&#x2009;0.016). CFT, and the prevalence of IRF and SRF decreased significantly (p&#x2009;<&#x2009;0.001), while iRORA (p&#x2009;=&#x2009;0.041), and cRORA (p&#x2009;<&#x2009;0.001) increased by year five. Presence of cRORA was associated with worse five-year BCVA (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Anti-VEGF therapy for extrafoveal MNV secondary to AMD stabilised or improved BCVA in approximately half of the patients; however, mean BCVA declined after five years. Long-term functional benefits were limited due to morphological changes in the macula, such as subfoveal atrophy.}, }
@article {pmid41198979, year = {2026}, author = {Feo, A and Boscia, G and Borrelli, E and Quarta, A and Stradiotto, E and Forte, P and Viggiano, P and Popovic, MM and Corradetti, G and Savastano, A and Boscia, F and Sarraf, D and Sadda, SR and Romano, MR}, title = {Vitelliform lesions and choroidal changes in chorioretinal disorders: pathophysiological insights and clinical implications.}, journal = {Eye (London, England)}, volume = {40}, number = {1}, pages = {12-23}, pmid = {41198979}, issn = {1476-5454}, mesh = {*Choroid Diseases/diagnostic imaging/pathology/physiopathology ; *Retinal Diseases/diagnostic imaging/pathology/physiopathology ; Humans ; *Vitelliform Macular Dystrophy/diagnostic imaging/pathology/physiopathology ; *Retinal Pigment Epithelium/diagnostic imaging/pathology/physiopathology ; *Choroid/diagnostic imaging/pathology/physiopathology ; Retinal Vessels/pathology/physiopathology ; Tomography, Optical Coherence ; Fluorescein Angiography ; }, abstract = {This narrative review aims to explore the correlation between choroidal thickness (CT), broader choroidal changes, and the development and progression of vitelliform lesions, with a focus on their potential modulatory role-whether primary or secondary- through mechanisms involving choriocapillaris (CC) and retinal pigment epithelium (RPE) dysfunction. CT was found to be significantly increased in various vitelliform maculopathies, including adult-onset foveomacular vitelliform dystrophy (AOFVD), Best disease, autosomal recessive bestrophinopathy, age-related macular degeneration (AMD), and pachychoroid disease spectrum (PDS) disorders. Notably, increased subfoveal CT was associated with the presence and progression of subretinal hyperreflective material and subretinal fluid in AOFVD and Best disease. In PDS disorders, choroidal thickening, pachyvessels, and choroidal vascular hyperpermeability were identified as key contributors to RPE dysfunction and vitelliform lesion formation. Conversely, leptovitelliform maculopathy was characterised by thinner choroid in association with reticular pseudodrusen or subretinal drusenoid deposits. An important feature is CC dysfunction, which is often associated with pachyvessels, even in the absence of a clear pachychoroid-related phenotype or choroidal thickening. These findings underscore the importance of CT evaluation in clinical practice and highlight the need for further research to elucidate the complex relationship between CT and vitelliform maculopathies.}, }
@article {pmid41199263, year = {2025}, author = {Menghini, M and Grimaldi, G and Paris, A and Bachmann, LM and Schmid, MK}, title = {One-year clinical outcomes of four-dose induction versus immediate treat-and-extend faricimab regimens in pretreated neovascular age-related macular degeneration.}, journal = {BMC ophthalmology}, volume = {25}, number = {1}, pages = {624}, pmid = {41199263}, issn = {1471-2415}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; Intravitreal Injections ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Tomography, Optical Coherence ; *Angiogenesis Inhibitors/administration &amp; dosage ; Follow-Up Studies ; Aged, 80 and over ; Treatment Outcome ; Dose-Response Relationship, Drug ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography ; Time Factors ; Antibodies, Bispecific ; }, abstract = {BACKGROUND/OBJECTIVES: This study aimed to compare one-year clinical outcomes of two faricimab treatment strategies in patients with previously treated exudative neovascular age-related macular degeneration (nAMD): (1) immediate switch to treat-and-extend dosing (T&amp;E), and (2) initiation with a four-dose induction ("loading") regimen.<br><br>SUBJECT/METHODS: Retrospective comparing two cohorts of pretreated nAMD patients with 12 months of follow-up who were either switched to Faricimab with immediate T&amp;E dosing (Lucerne protocol, "on-the-fly"), or initiated with a four-dose induction phase (Lugano protocol,"re-loading"). Both cohorts were subsequently managed according to a T&amp;E regimen. Demographic and clinical data, including prior intravitreal agents, best-corrected visual acuity (BCVA), central subfield thickness (CST) on optical coherence tomography (OCT), and length of treatment intervals were analysed. Multivariable models were adjusted for baseline differences.<br><br>RESULTS: Both cohorts (Lucerne, 183 eyes; Lugano, 33 eyes) were similar in baseline characteristics. BCVA improved by 0.81 ETDRS letters in Lucerne and by 2.42 in the Lugano cohort (p&#x2009;=&#x2009;0.250). CRT decreased by -38.3&#xa0;&#x3bc;m in Lucerne and by -57.8&#xa0;&#x3bc;m in Lugano (p&#x2009;=&#x2009;0.053). Treatment intervals increased by 2.2 weeks in Lucerne and 3.4 weeks in Lugano (p&#x2009;=&#x2009;0.092). At 12 months, 15.3% of Lucerne patients and 27.3% of Lugano patients achieved intervals&#x2009;&#x2265;&#x2009;12 weeks, with significantly higher odds of extension in Lugano (OR 3.87; p&#x2009;=&#x2009;0.013).<br><br>CONCLUSIONS: Both cohorts showed anatomical and functional improvements after switching to faricimab. The Lugano cohort, using a four-dose induction phase, showed longer treatment intervals, suggesting better disease stability.<br><br>CLINICAL TRIAL NUMBER: Not applicable.}, }
@article {pmid41199318, year = {2025}, author = {Lennikov, A and Yang, M and Elzaridi, F and Shu, DY and Hu, Z and Miller, WP and Tsonas, M and Huang, L and Yen, C and Chang, K and Chen, J and Vijikumar, A and Ashok, A and Cho, KS and Geniez, MS and Dartt, DA and Chen, DF}, title = {Non-invasive bioelectrical therapy suppresses retinal neovascularization by modulating cellular metabolism and inflammation.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {479}, pmid = {41199318}, issn = {1478-811X}, support = {HT9425-24-1-0788//U.S. Department of Defense/ ; M2021010F//BrightFocus Foundation/ ; R01EY019470/EY/NEI NIH HHS/United States ; R01 EY031696/EY/NEI NIH HHS/United States ; R01EY031696/EY/NEI NIH HHS/United States ; HT9425-23-1-1045//U.S. Department of Defense/ ; R01 EY019470/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Microglia/metabolism ; *Retinal Neovascularization/therapy/pathology/metabolism ; *Electric Stimulation Therapy ; *Inflammation/pathology/therapy/metabolism ; Mice, Inbred C57BL ; Choroidal Neovascularization/therapy/pathology ; Endothelial Cells/metabolism ; Diabetic Retinopathy/therapy/pathology/metabolism ; Adenosine Triphosphate/metabolism ; Male ; Membrane Potential, Mitochondrial ; Retina/pathology ; }, abstract = {BACKGROUND: Pathological retinal neovascularization, a major cause of blindness, occurs in conditions such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Microglial activation and chronic neuroinflammation play critical roles in disease progression by promoting vascular permeability and angiogenesis. While anti-VEGF therapies are the current standard of care, their efficacy is limited, requiring frequent intraocular injections and raising concerns about long-term retinal health. Noninvasive transpalpebral electrical stimulation (TpES) has emerged as a potential alternative therapy, but its mechanism and therapeutic impact remain poorly understood.<br><br>METHODS: To investigate the therapeutic effects of TpES, we applied daily microcurrent stimulation (300 &#xb5;A, 20&#xa0;Hz, 4&#xa0;min) in laser-induced choroidal neovascularization (CNV) and streptozotocin (STZ)-induced DR mouse models. Vascular pathology was assessed using fluorescein angiography, optical coherence tomography (OCT), and immunohistochemistry. Mechanistic studies were conducted using primary microglia and human retinal endothelial cells (HREC) to evaluate TpES-induced changes in intracellular calcium ([Ca&#xb2;&#x207a;]i) signaling, mitochondrial membrane potential, and ATP production. Additionally, human RPE/choroidal explants from healthy, AMD, and DR donors were cultured to assess TpES effects on angiogenesis in healthy and pathological human tissues.<br><br>RESULTS: TpES significantly reduced vascular leakage (by ~&#x2009;30%, p&#x2009;<&#x2009;0.001) and lesion size in the CNV model (p&#x2009;<&#x2009;0.05), while also suppressing microglial infiltration and VEGF-A expression. In the DR model, TpES attenuated microaneurysm formation, preserved endothelial tight junctions (in vitro). Mechanistic studies revealed that TpES suppressed ATP-induced microglial activation by reducing mitochondrial membrane potential and intracellular ATP levels, leading to depletion of ER calcium stores and inhibition of proinflammatory and proangiogenic signaling. TpES also directly suppressed endothelial cell migration and tube formation, as well as angiogenic sprouting in human RPE/choroidal explants.<br><br>CONCLUSIONS: These findings establish TpES as a dual-action therapy that mitigates both inflammation and pathological angiogenesis by modulating microglial and endothelial metabolism. Given its noninvasive nature and ability to target key pathways in retinal pathology, TpES represents a promising therapeutic strategy for AMD, DR, and other retinal vascular diseases.}, }
@article {pmid41200258, year = {2025}, author = {Rizwan Khan, AY and Malik, MB}, title = {Artificial Intelligence in Ophthalmology: Practical Applications, Subspecialty Evidence and Real-World Deployment.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e96121}, pmid = {41200258}, issn = {2168-8184}, abstract = {Artificial Intelligence (AI) has undoubtedly emerged as a transformative technology in the field of medicine. In ophthalmology, it has been a catalyst for innovation in the methods used for the diagnosis, management, and treatment of different eye diseases. This article offers a detailed review of the literature on the application and utilization of AI technology in the field of ophthalmology. A detailed search of available literature on the use of AI in the field of ophthalmology was performed through the PubMed database and Google Scholar. Published literature on the role of AI in screening, diagnosis, and management of common ocular conditions such as diabetic retinopathy (DR), cataract, glaucoma, and age-related macular degeneration (AMD) was reviewed. Special emphasis was laid on the effectiveness and limitations of the recently developed AI systems for the detection and management of ocular conditions. We screened (n=4449) records and included (n=102) studies spanning retina, glaucoma, cornea, pediatric ophthalmology, neuro-ophthalmology, ocular oncology, surgery, emergencies, and tele-ophthalmology. Deep learning (DL) and machine learning (ML) algorithms have demonstrated significant performance in the analysis of ophthalmic data, including optical coherence tomography scans and retinal images, for accurately diagnosing and classifying diseases, predicting disease progression, and personalizing different treatment plans. In addition to the common ocular conditions, the use of AI has now spread to other domains of ophthalmology, such as pediatric ophthalmology, oculoplastics and reconstructive surgery, and triage and management of emergency ocular conditions. Various AI systems have shown accuracy similar to that of clinical experts, with the additional benefit of being less subjective and time-consuming. Despite significant progress, different challenges related to regulatory approval, standardization, data quality, and ethical considerations hamper the wide-scale implementation of AI in ophthalmology. Literature is evident on the transformative role of AI in screening, diagnosis, and management of various ocular conditions. However, currently, there are various challenges and limitations to the implementation of AI. Future research should focus on addressing these challenges while optimizing the utilization of AI algorithms for enhancing patient care in ophthalmology.}, }
@article {pmid41201702, year = {2025}, author = {Zhou, Y and Liu, J and Wang, Z and Huang, C and Wang, Q and Yu, X and Dai, C and Zhao, D and Cai, Y and Wang, T}, title = {Biological aging phenotypes mediate gut microbiota effects on age-related macular degeneration subtype progression: genetic causality by mendelian randomization and mediation analysis.}, journal = {AMB Express}, volume = {15}, number = {1}, pages = {167}, pmid = {41201702}, issn = {2191-0855}, support = {62175156//National Natural Science Foundation of China/ ; 22S31903000//Science and technology innovation project of Shanghai Science and Technology Commission/ ; 2025M771943//China Postdoctoral Science Foundation/ ; 2024409//Shanghai Post-doctoral Excellence Program/ ; 2023030716//Ningbo Top Medical and Health Research Program/ ; }, abstract = {The mechanisms driving age-related macular degeneration (AMD) progression into two major but distinct vision-threatening subtypes, geographic atrophy (GA) and choroidal neovascularization (CNV), are unclear. This study identifies causal gut microbiota (GM) taxa involved in AMD and their connections to biological aging phenotypes, including epigenetic clock acceleration, telomere length, mitochondrial DNA copy number, 731 immune cell traits, and 91 inflammatory proteins through genetic prediction. Analyzing 207 GM taxa and 205 functional pathways alongside AMD progression GWAS data, we found that class_Gammaproteobacteria significantly influences both CNV and GA, and a bidirectional gut-retina axis involving Erysipelotrichaceae was also identified. Genus_Flavonifractor, species_Ruminococcus_obeum, and species_Streptococcus_thermophilus may attenuate AMD progression. Mediation analysis revealed pathways linking Ruminococcus obeum to GA progression via SSC-A expression on CD4 + T cells, and a CNV-associated pathway mediated by CD33dim HLA-DR + CD11b- cell counts. This study provides novel genetic evidence linking GM to dynamic AMD progression, offering genetic insights for future experimental research and clinical strategies.}, }
@article {pmid41202799, year = {2025}, author = {Ryals, RC}, title = {RPE replacement therapy for dry AMD-early success in a phase 1/2 clinical trial.}, journal = {Cell stem cell}, volume = {32}, number = {11}, pages = {1637-1638}, doi = {10.1016/j.stem.2025.10.007}, pmid = {41202799}, issn = {1875-9777}, mesh = {Humans ; Clinical Trials, Phase I as Topic ; *Macular Degeneration/therapy ; *Retinal Pigment Epithelium/transplantation/cytology ; *Stem Cell Transplantation ; Clinical Trials, Phase II as Topic ; }, abstract = {The number of retinal pigment epithelium (RPE) transplantation clinical trials for dry age-related macular degeneration (AMD) is increasing quickly, with groups using different stem cell sources, delivery approaches, and immune suppression. We discuss the recent success in a phase 1/2a clinical trial[1] evaluating allogeneic RPE stem cell-derived RPE cells isolated from the RPE layer of human cadaveric eyes.}, }
@article {pmid41204997, year = {2026}, author = {Gandhi, P and Sadeghi, E and Schulman, A and Singh, SR and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Eller, AW and Chhablani, J}, title = {Correlation of drusen burden and vascular integrity in age-related macular degeneration using three-dimensional choroidal vascular model.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {417-425}, pmid = {41204997}, issn = {1435-702X}, support = {NIH Core Grant P30 EY08098//Eye and Ear Foundation of Pittsburgh/ ; }, mesh = {Humans ; Female ; *Choroid/blood supply ; *Tomography, Optical Coherence/methods ; Male ; *Fluorescein Angiography/methods ; Aged ; *Retinal Drusen/diagnosis/etiology ; *Retinal Vessels/pathology/diagnostic imaging ; Fundus Oculi ; Visual Acuity ; *Imaging, Three-Dimensional/methods ; Aged, 80 and over ; Retrospective Studies ; Follow-Up Studies ; Middle Aged ; }, abstract = {PURPOSE: To study intricate relationship between drusen volume and evolving dynamics of retinal and choroidal vasculature in dry age-related macular degeneration (AMD).<br><br>METHODS: Patients underwent swept-source optical coherence tomography angiography (SS-OCTA) using Plex Elite 9000 device. Retinal thickness, retinal vessel perfusion, drusen volume, choroidal thickness (ChT), choroidal vascularity index (CVI), choroidal vessel diameters (MChVD), and intervessel distance (IVD) were assessed. The Advanced Research and Innovation (ARI) Network, ResUNet model, and Phansalkar thresholding were utilized for image analysis. The linear mixing model was used for the statistical analysis.<br><br>RESULTS: We assessed 53 eyes from 40 patients with dry AMD (22 eyes with early-stage, 31 eyes with intermediate-stage eyes). The mean age was 75.25 years and 62.5% were females. The mean LogMar visual acuity was 0.09&#x2009;&#xb1;&#x2009;0.17 standard deviation (SD) in early-stage and 0.19&#x2009;&#xb1;&#x2009;0.14 SD in intermediate-stage (p&#x2009;=&#x2009;0.03). Mean drusen volume was 0.075&#x2009;&#xb1;&#x2009;0.125 SD mm[3] in early-stage and 0.24&#x2009;&#xb1;&#x2009;0.26 SD mm[3] in intermediate-stage (p&#x2009;=&#x2009;0.005). Mean ChT was thicker, and mean CVI was higher in the early-stage compared to the intermediate-stage (p&#x2009;<&#x2009;0.05). A decrease of 11.48&#xa0;&#x3bc;m in MChVD for every 1&#xa0;mm&#xb3; increase in drusen volume was noted.<br><br>CONCLUSION: With increase in drusen volume, a reduction in CVI and MChVD was noted, without any significant association with changes in retinal metrics, suggesting that choroidal vessels may exhibit early changes during disease progression.}, }
@article {pmid41205411, year = {2025}, author = {Realini, G and Amato, R and Rasa, M and Ceccatelli, R and Cannavale, A and Bottoni, L and Marchini, F and Minetti, A and Giustarini, D and Canovai, A and Melecchi, A and Elia, I and Krepelova, A and Annunziata, F and Cammalleri, M and Rossi, R and Tosi, GM and Orlandini, M and Chiariello, M and Neri, F and Dal Monte, M and Galvagni, F}, title = {N-acetyl-l-cysteine ethyl ester (NACET) induces the transcription factor NRF2 and prevents retinal aging and diabetic retinopathy.}, journal = {Redox biology}, volume = {88}, number = {}, pages = {103914}, pmid = {41205411}, issn = {2213-2317}, mesh = {*NF-E2-Related Factor 2/metabolism/genetics ; Animals ; *Diabetic Retinopathy/metabolism/pathology/drug therapy/genetics/prevention &amp; control ; Mice ; *Acetylcysteine/analogs &amp; derivatives/pharmacology ; Oxidative Stress/drug effects ; Humans ; Kelch-Like ECH-Associated Protein 1/metabolism/genetics ; *Retina/metabolism/drug effects/pathology ; Disease Models, Animal ; Aging/drug effects ; Retinal Pigment Epithelium/metabolism/drug effects ; Macular Degeneration/metabolism/pathology/genetics/drug therapy ; }, abstract = {Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are leading causes of visual impairment in older people, with oxidative stress playing a central role in the development of these diseases. In this study, we showed that N-acetylcysteine ethyl ester (NACET) not only increases intracellular cysteine and glutathione levels, but also strongly stimulates the expression and activity of the transcription factor NRF2, a master regulator of oxidative stress response, in RPE cells. Using RNA interference, mass spectrometry and mutagenesis of the NRF2 regulator KEAP1, we identified direct cysteinylation of the sensor residues Cys226 and Cys613 on KEAP1 as the molecular mechanism underlying NRF2 activation after NACET treatment. Furthermore, we demonstrated that oral administration of NACET induces NRF2 activity in the retina in vivo, attenuates retinal aging hallmarks, and prevents diabetes-induced retinal neurodegeneration in mouse models. These results position NACET as a promising therapeutic candidate for age- and oxidative stress-related retinal diseases such as AMD and DR.}, }
@article {pmid41205703, year = {2025}, author = {Yin, Q and Xie, Y and Chen, R and Lyu, Y and Yao, K and Han, H and Shentu, X}, title = {Multifunctional macrophage membrane biomimetic nanoparticles for targeted therapy of neovascular age-related macular degeneration.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {388}, number = {Pt 2}, pages = {114394}, doi = {10.1016/j.jconrel.2025.114394}, pmid = {41205703}, issn = {1873-4995}, mesh = {Animals ; *Macular Degeneration/drug therapy/pathology ; *Nanoparticles/administration &amp; dosage/chemistry ; *Choroidal Neovascularization/drug therapy/pathology ; *Biomimetic Materials/administration &amp; dosage/chemistry ; Mice, Inbred C57BL ; *Macrophages/metabolism ; Mice ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; *Curcumin/administration &amp; dosage/therapeutic use/chemistry ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Humans ; Male ; *Anti-Inflammatory Agents/administration &amp; dosage/therapeutic use ; Oxidative Stress/drug effects ; Antioxidants/administration &amp; dosage ; Disease Models, Animal ; }, abstract = {Neovascular age-related macular degeneration (nAMD), characterized by choroidal neovascularization (CNV), is a major cause of blindness worldwide. Current anti-vascular endothelial growth factor (VEGF) therapy remains unsatisfactory, as this single-target treatment only alleviates the symptoms without addressing the underlying etiology. Emerging research indicates that inflammation and oxidative stress are closely related to early nAMD, where the retinal pigment epithelium (RPE) is initially impaired, leading to pathological angiogenesis. Herein, biomimetic nanoparticles (termed SHP/Cur@MNPs) are prepared by co-encapsulating SHP099, an anti-inflammatory and anti-angiogenic agent, and curcumin, an antioxidant, into poly (lactic-co-glycolic acid) (PLGA) coated with macrophage membrane. Taking advantage of the macrophage-inherited property, SHP/Cur@MNPs effectively targeted the inflamed foci, specifically the vascular endothelium. Using a laser-induced CNV mouse model, SHP/Cur@MNPs markedly inhibited neovascularization, reduced inflammation and oxidative stress, and improved retinal function. Furthermore, bioinformatics analysis explored the mechanism of the Hippo signaling pathway in the treatment of SHP/Cur@MNPs against nAMD. Collectively, our study describes a strategy using biomimetic nanoparticles to achieve the synergistic effect by targeting major risk factors associated with nAMD, which might be a novel approach for the safe and effective treatment of nAMD.}, }
@article {pmid41205855, year = {2026}, author = {Chen, Y and Jiang, F and Fu, Y and Han, N and Yang, J and Wu, X and Mao, T and Zhang, M}, title = {Transketolase regulates endoplasmic reticulum stress independent of enzymatic activity in human retinal Müller cells.}, journal = {Experimental eye research}, volume = {262}, number = {}, pages = {110732}, doi = {10.1016/j.exer.2025.110732}, pmid = {41205855}, issn = {1096-0007}, mesh = {*Transketolase/genetics/physiology/metabolism/biosynthesis ; *Endoplasmic Reticulum Stress/physiology ; Animals ; Humans ; *Ependymoglial Cells/metabolism/enzymology/pathology ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; *Macular Degeneration/pathology/metabolism/genetics/enzymology ; Cells, Cultured ; Chromatin Immunoprecipitation ; Endoribonucleases/genetics/metabolism ; Protein Serine-Threonine Kinases ; }, abstract = {Transketolase (TKT) expression in the nucleus of the retina has been reported, but its function beyond metabolism remains unclear. In this study, we investigated the role of TKT in the regulation of endoplasmic reticulum (ER) stress in the retina. Using a VEGF-overexpressing mouse model of age-related macular degeneration (AMD), we analyzed the expression and enzymatic activity of Tkt, and found that while expression levels remained unchanged, enzymatic activity was significantly reduced. Tkt localized primarily to the nucleus of the inner nuclear layer in healthy retinae but shifted outside the nuclear center in the lesion area of the AMD mouse model. ChIP-seq analysis revealed that Tkt-targeted genes were enriched in pathways related to metabolism, ER protein processing, and neurogenerative diseases. Among these targets, TKT directly bound to the promoter region of endoplasmic reticulum to nucleus signaling 1 (ERN1) and suppressed its expression, as validated by dual-luciferase reporter assays. In human Müller cells, TKT knockdown elevated ERN1 levels and exacerbated ER stress responses, while enzymatic inhibition alone had no effect on ER stress. Furthermore, TKT knockdown did not alter mitochondria respiration or glycolysis. These findings demonstrate that TKT mitigates ER stress in the human retinal Müller cells by transcriptionally regulating ERN1 in a manner that is independent of its enzymatic activity.}, }
@article {pmid41208951, year = {2025}, author = {Adrean, SD and Hill, L and Amador-Patarroyo, J}, title = {Fibrosis in Patients With Choroidal Neovascularization Based on Spectral-Domain Optical Coherence Tomography: Findings From the HARBOR Trial.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251389993}, pmid = {41208951}, issn = {2474-1272}, abstract = {Purpose: To evaluate the rate and impact of fibrosis on visual outcomes by choroidal neovascularization (CNV) type, based on spectral-domain optical coherence tomography (SD-OCT), in patients with neovascular age-related macular degeneration (nAMD). Methods: Fibrosis status and location at month 24, stratified by baseline CNV type, were evaluated using data from the HARBOR trial (NCT00891735). All patients (n = 1097) received pro re nata or monthly ranibizumab treatment. Results: Fibrosis was most common in eyes with type 2 CNV lesions (53%) compared with other types (type 1, 31%; mixed type 1 or 2, 45%; any type 3, 33%; P < .0001). The rate of fibrosis differed by less than or equal to 6% between monthly and pro re nata treatment regimens. In eyes with subretinal fibrosis, most (65% to 78%) showed subfoveal involvement at month 24. Mean visual acuity gains at month 24 were not negatively affected by the presence of fibrosis (type 1, 8.0 letters; type 2, 11.0; mixed type 1 or 2, 7.8; any type 3, 16.2), regardless of treatment regimen. Male sex and current smoking status were associated with significantly higher rates of fibrosis at month 24 (P < .0001 and P = .003, respectively). Conclusions: Many patients with nAMD develop fibrosis despite antivascular endothelial growth factor therapy, and the prevalence of fibrosis is affected by baseline CNV type.}, }
@article {pmid41211298, year = {2026}, author = {Bai, ZP and Pan, YS and Cai, YX and Chen, C and Tao, D and Zhao, XY and Shen, YF and Chen, F and Li, JH and Qu, J and Huang, XF}, title = {Investigating the Shared Genetic Architecture of 3 Age-Related Ocular Disorders.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100942}, pmid = {41211298}, issn = {2666-9145}, abstract = {PURPOSE: To explore the shared genetic architecture, causal relationships, and cell type-specific expression patterns of pleiotropic genes in age-related macular degeneration (AMD), cataract, and primary open-angle glaucoma (POAG), uncovering molecular mechanisms and informing targeted therapies.<br><br>DESIGN: A genetic association study combined with cross-trait meta-analyses, Mendelian randomization analyses, and single-cell RNA sequencing (scRNA-seq) analysis.<br><br>SUBJECTS: The data related to 3 age-related ocular diseases, including AMD, cataract, and POAG, were obtained from publicly available genome-wide association study (GWAS) databases.<br><br>METHODS: We conducted a comprehensive genetic analysis utilizing GWAS summary statistics to examine genetic correlations among AMD, cataract, and POAG. Cross-trait meta-analyses were performed to identify shared risk loci. Mendelian randomization was employed to investigate potential causal relationships between these conditions. Additionally, we analyzed scRNA-seq data to examine the expression patterns of identified pleiotropic genes across different retinal cell types.<br><br>MAIN OUTCOME MEASURES: Identification of shared risk single nucleotide polymorphisms (SNPs) and pleiotropic loci. Causal relationships between AMD, cataract, and POAG. Cell type-specific expression patterns of pleiotropic genes in retinal cells.<br><br>RESULTS: Our analysis revealed significant genetic correlations, with a negative correlation between AMD and POAG and a positive correlation between cataract and POAG. Cross-trait meta-analyses identified shared risk SNPs, with CDKN2B-AS1 emerging as a notable pleiotropic locus. Mendelian randomization analyses suggested causal relationships between AMD and cataract, as well as between POAG and AMD. Single-cell expression analysis demonstrated cell type-specific expression patterns of pleiotropic genes including ATXN2, HTRA1, SIX6, and THSD7A across retinal cells.<br><br>CONCLUSIONS: This study provides compelling evidence for shared genetic architecture and causal relationships among AMD, cataract, and POAG. The identification of specific pleiotropic genes and their expression patterns across retinal cell types offers new insights into the molecular mechanisms underlying these age-related ocular diseases, potentially informing the development of targeted therapeutic strategies.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41211376, year = {2025}, author = {Kong, H and Feng, H and Wang, H}, title = {Global burden of age-related macular degeneration (1990-2021): trends, age-sex disparities, and socioeconomic dynamics from the GBD study.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1594672}, pmid = {41211376}, issn = {2296-2565}, mesh = {Humans ; *Macular Degeneration/epidemiology ; Male ; Female ; Aged ; Prevalence ; *Global Burden of Disease/trends ; Middle Aged ; *Global Health/statistics &amp; numerical data ; Socioeconomic Factors ; Aged, 80 and over ; Risk Factors ; Adult ; Sex Factors ; *Health Status Disparities ; }, abstract = {OBJECTIVES: This study aimed to assess the global burden of Age-related macular degeneration (AMD) across countries, regions, and age groups by sex, sociodemographic index (SDI) level, and risk factors from 1990 to 2021, using newly updated data from the Global Burden of Disease (GBD) study. The focus was on age-related disparities in AMD burden by sex and SDI.<br><br>METHODS: This population-based study utilized AMD data from GBD 2021 (1990-2021). The burden was evaluated using the number of cases, prevalence rates per 100,000 population, and trends in years lived with disability (YLDs) and prevalence, assessed through average annual percentage changes (AAPCs) and estimated annual percentage changes (EAPCs).<br><br>RESULTS: Globally, AMD prevalence increased from 364,000 cases in 1990 to 806,000 in 2021 (+121%), while YLDs rose from 30,000 to 58,000 (+91%). However, age standardized prevalence and YLD rates (ASPRs and ASYRs) significantly declined (EAPCs: -0.26 and -0.94, respectively). Regional analyses revealed that low SDI regions (e.g., sub-Saharan Africa) bore the highest AMD burden (ASPR: 139.9 per 100,000) and exhibited a younger age distribution, with a significantly higher proportion of cases in individuals aged 55-74&#x202f;years. In contrast, high SDI regions (e.g., high-income Asia-Pacific) had a concentration of cases among those aged 70&#x202f;years or older. While medium SDI regions accounted for one-third of global cases in 2021, age-standardized rates declined most slowly in low SDI regions (EAPC: -1.03) and even trended upward in some countries. AMD cases peaked globally at ages 65-69, yet prevalence was highest among those over 85&#x202f;years (1,349.9 per 100,000), with women generally experiencing a higher burden than men. These findings highlight distinct regional patterns, with younger disease profiles in low SDI regions and aging-driven increases in high SDI regions, underscoring the need for targeted prevention and control strategies.<br><br>CONCLUSION: Although global efforts over the past 30&#x202f;years have led to a decline in AMD prevalence rates and YLDs, the absolute number of cases and YLDs continues to rise, driven by age, sex, socioeconomic status, and geographic location. These findings provide an epidemiological basis for developing global public health strategies to address these ongoing challenges.}, }
@article {pmid41212222, year = {2026}, author = {Honjo, J and Mukai, R and Itagaki, K and Tanaka, K and Norikawa, K and Kato, Y and Kasai, A and Sekiryu, T}, title = {A one-year study on the regression effects of aflibercept and faricimab on retinal pigment epithelial detachment.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {437-444}, pmid = {41212222}, issn = {1435-702X}, mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/antagonists &amp; inhibitors/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; Intravitreal Injections ; *Retinal Detachment/drug therapy/diagnosis/etiology ; Female ; Male ; Tomography, Optical Coherence/methods ; *Visual Acuity ; Fluorescein Angiography/methods ; *Retinal Pigment Epithelium/pathology/drug effects ; Follow-Up Studies ; Fundus Oculi ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged ; Retrospective Studies ; Treatment Outcome ; Middle Aged ; Time Factors ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To compare long-term regressive effects on pigment epithelial detachment (PED) between aflibercept and faricimab in type 1 macular neovascularization (MNV).<br><br>METHODS: We analyzed 94 eyes from 92 patients diagnosed with type 1 MNV using multimodal imaging. Seventy-one eyes received intravitreal aflibercept injections (IVA group), and 23 received intravitreal faricimab injections (IVFa group). After three consecutive monthly injections, intervals were adjusted in 2-4 week increments within drug-specific windows (IVA, 4-12 weeks; IVFa, 8-16 weeks) through 1 year. The maximum height (MH) and horizontal maximum diameter (H-MD) of PED were measured using optical coherence tomography before treatment and at 3 months and 1year post-treatment. We also assessed associations between PED change and 1-year dry macula, and explored visual outcomes with using analysis of covariance and logistic models.<br><br>RESULTS: MH decreased in both IVA (184&#x2009;&#xb1;&#x2009;176&#x2192;126&#x2009;&#xb1;&#x2009;153&#xa0;&#x3bc;m at 3 months, P&#x2009;=&#x2009;0.0003; 124&#x2009;&#xb1;&#x2009;135&#xa0;&#x3bc;m at 1 year, P&#x2009;=&#x2009;0.0005) and IVFa (162&#x2009;&#xb1;&#x2009;124&#x2192;83&#x2009;&#xb1;&#x2009;65&#xa0;&#x3bc;m, P&#x2009;=&#x2009;0.0056; 86&#x2009;&#xb1;&#x2009;71&#xa0;&#x3bc;m, P&#x2009;=&#x2009;0.0053). The mean change in MH was not significantly different between groups (P&#x2009;=&#x2009;0.244). H-MD did not show significant regression in either group. IVFa required fewer injections (6.17&#x2009;&#xb1;&#x2009;0.39 vs. 7.90&#x2009;&#xb1;&#x2009;1.99/year; P&#x2009;<&#x2009;0.0001) and achieved a longer final intended injection interval (14.17&#x2009;&#xb1;&#x2009;2.53 vs. 8.64&#x2009;&#xb1;&#x2009;2.90 weeks; P&#x2009;<&#x2009;0.0001). In multivariable linear regression for percent MH change at 1 year, annual injection number was positively associated with percent change (&#x3b2;&#x2009;=&#x2009;7.62% points/injection, P&#x2009;=&#x2009;0.012), whereas drug type was not (P&#x2009;=&#x2009;0.633), adjusting for baseline MH (&#x3b2; = -0.078/&#xb5;m, P&#x2009;=&#x2009;0.016; all VIFs&#x2009;<&#x2009;2). At 1 year, MH was lower in dry vs. wet macula (90&#x2009;&#xb1;&#x2009;82 vs. 186&#x2009;&#xb1;&#x2009;185&#xa0;&#x3bc;m; P&#x2009;=&#x2009;0.0004). For vision, &#x2265; 0.2logMAR gain was predicted by CMT decrease (OR&#x2009;&#x2248;&#x2009;1.56 per 100&#xa0;&#x3bc;m decrease; P&#x2009;=&#x2009;0.045), while percent PED change was not significant (P&#x2009;=&#x2009;0.283).<br><br>CONCLUSION: In a treat-and-extend regimen with different label constraints, 1-year PED regression was similar for IVA and IVFa and was achieved with less treatment burden in IVFa. PED regression aligned with dry macula rather than with large visual gains, which instead tracked with retinal thickness recovery.}, }
@article {pmid41216067, year = {2025}, author = {Moafa, MA and Albahrawy, SS and Alluwimi, MS and Alrasheed, S and Elmadina, AM and Mutwaly, RF and Abdelhamid, AF and Albarnawi, EH and Alghamdi, WM and Aldebasi, YH}, title = {Assessment of Peripapillary Retinal Nerve Fibre Layer Thickness, Optic Nerve Head Rim Area, Anterior Chamber Parameters, and Axial Length in Myopic Eyes.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e94271}, pmid = {41216067}, issn = {2168-8184}, abstract = {BACKGROUND: Myopic eyes commonly show structural changes, including optic nerve head (ONH) and altered anterior chamber parameters.<br><br>AIM: The study aimed to investigate the associations of peripapillary retinal nerve fibre layer (RNFL) thickness, optic disc rim area, anterior chamber parameters, and axial length in myopic eyes.<br><br>METHODS: This&#xa0;cross-sectional study was conducted at the Royal Commission Medical Centre, Yanbu, Saudi Arabia, between February and May 2025 and included 152 myopic eyes. Refraction was measured using an autorefractometer. Swept-source optical coherence tomography (SS-OCT)&#xa0;scans (optic disc cube 200&#x2009;&#xd7;&#x2009;200) were used to assess peripapillary RNFL thickness and optic disc rim area. Corneal and anterior chamber parameters, along with axial length, were measured using Pentacam AXL (OCULUS Optikger&#xe4;te GmbH, Wetzlar, Germany). Data analysis was conducted to assess the correlation between myopia severity and structural ocular changes.<br><br>RESULTS: Myopic eyes (mean spherical equivalent: -2.02 &#xb1; 1.34 D) showed a significant inverse correlation with both central corneal thickness (r = -0.193, P < 0.05) and corneal thickness at the thinnest point (r = -0.225, P < 0.05). Anterior chamber volume (r = 0.266, P < 0.001) and anterior chamber depth (r = 0.259, P < 0.001) showed significant positive correlations with myopia, while the anterior chamber angle showed no significant association (P > 0.05). Axial length was strongly correlated with myopia severity (r = 0.545, P < 0.001). Inverse correlations were observed between myopia and both peripapillary RNFL thickness (r = -0.100, P > 0.05) and ONH rim area (r = -0.134, P > 0.05). A statistically significant inverse correlation was found between peripapillary RNFL thickness and axial length (r = -0.163, P < 0.05), as well as between ONH rim area and axial length (r = -0.167, P < 0.05).<br><br>CONCLUSION: The study revealed a significant positive correlation between myopia and both anterior chamber volume and anterior chamber depth, while the anterior chamber angle remained unaffected. The increase in myopia severity was correlated with thinning of the peripapillary RNFL and a reduction in ONH rim area. These findings underscore the importance of assessing axial elongation and structural changes in myopic eyes, particularly in the context of ocular diseases such as glaucoma, myopic macular degeneration, and retinal detachment.}, }
@article {pmid41216998, year = {2025}, author = {Brouwer, NJ and Vu, THK and De Jong‐Hesse, Y and van Dijk, EHC}, title = {The prechoroidal cleft in neovascular age-related macular degeneration.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70035}, pmid = {41216998}, issn = {1755-3768}, abstract = {The prechoroidal cleft is a lenticular, hypo-reflective space on optical coherence tomography imaging, located between a band of fibrovascular material underneath the retinal pigment epithelium (RPE) and Bruch's membrane. It occurs in 8%-22% of neovascular age-related macular degeneration (nAMD) eyes, most often with macular neovascularization (MNV) type 1 and 3, and less often with MNV type 2 or polypoidal choroidal vasculopathy. The presence of a prechoroidal cleft is associated with poor visual prognosis, some studies report more frequent occurrence of RPE tears and subretinal haemorrhages. Eyes with a prechoroidal cleft require more frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections to treat the nAMD and more often require a switch to other anti-VEGF medication. Clinicians should be aware of the prechoroidal cleft for diagnostic and prognostic reasons, as it may be misunderstood for other (subretinal) fluid or even a choroidal lesion.}, }
@article {pmid41217603, year = {2025}, author = {Akada, M and Hata, M and Ideyama, M and Kido, A and Miyata, M and Tamura, H and Ooto, S and Tsujikawa, A}, title = {Subtype-specific shifts in age, axial length, and clinical profile of neovascular age-related macular degeneration: a five-year study in Japan.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {41217603}, issn = {1613-2246}, abstract = {PURPOSE: To evaluate 5-year temporal changes in baseline clinical characteristics-age, axial length, and best-corrected visual acuity-among treatment-naïve eyes with neovascular Age-Related Macular Degenaration (nAMD), comparing pachychoroid neovasculopathy (PNV) with drusen-driven (non-PNV) nAMD at a Japanese tertiary center.<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: Registry data from Kyoto University Hospital were analyzed for patients newly diagnosed with nAMD in 2013/2014 and in 2018/2019. Patients were classified as PNV or non-PNV based on findings derived from multimodal imaging-including optical coherence tomography, indocyanine-green angiography, and color fundus photography. Demographic data, axial length, best-corrected visual acuity (BCVA) at baseline and 1 year posttreatment, and the proportion of eyes achieving &#x2265;0.20 logMAR improvement were compared over time.<br><br>RESULTS: A total of 118 patients were included. In the non-PNV group, mean age rose from 74.35 &#xb1; 8.42 years to 77.39 &#xb1; 7.90 years (p = 0.021), whereas the PNV group showed a smaller, non-significant change from 68.88 &#xb1; 7.25 to 70.41 &#xb1; 9.19 years (p = 0.48). Among non-PNV cases, both mean age (p=0.021) and axial length (p=0.017) increased significantly over time. In contrast, PNV cases showed no significant changes in age or axial length. BCVA outcomes and the proportion of patients achieving &#x2265;0.20 logMAR improvement were similar across time points within each subtype. Multivariable logistic regression analysis revealed no significant associations between visual improvement and year, subtype, age, or axial length.<br><br>CONCLUSIONS: This study revealed an aging trend and axial elongation among non-PNV cases over time, underscoring a subtype-specific divergence in clinical trajectory.}, }
@article {pmid41218191, year = {2025}, author = {Călugăru, D and Călugăru, M}, title = {Ten-year follow-up of patients with exudative age-related macular degeneration treated with intravitreal anti-vascular endothelial growth factor injections.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004728}, pmid = {41218191}, issn = {1539-2864}, }
@article {pmid41218567, year = {2025}, author = {Cai, S and Liang, X and Wu, H and Li, X and Pu, Q}, title = {Navigating the ocular barrier: Viral- and nanotechnology-based delivery systems as promising therapeutic agents for ocular diseases.}, journal = {Molecular aspects of medicine}, volume = {106}, number = {}, pages = {101421}, doi = {10.1016/j.mam.2025.101421}, pmid = {41218567}, issn = {1872-9452}, mesh = {Humans ; *Eye Diseases/therapy/drug therapy ; *Drug Delivery Systems/methods ; Animals ; *Nanotechnology/methods ; Viruses/genetics ; Gene Transfer Techniques ; }, abstract = {While the intricate and precisely specialized structure of the human eye is critical for its appropriate function, it also presents a number of anatomical and physiological barriers, such as tight junctions, enzymatic degradation, and dynamic fluid turnover, which highly restrict the intraocular bioavailability of various therapeutic compounds. This is more significant for those therapeutic compounds that are used for complications affecting the posterior segment. Accordingly, conventional therapeutic strategies for common ocular complications such as diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, and infectious keratitis significantly demand invasive administration approaches and multiple injections, frequently resulting in various side effects and suboptimal therapeutic consequences. To address these major challenges, novel technologies, such as viral- and nanotechnology-based delivery systems, have provided emerging opportunities to bypass ocular barriers and facilitate targeted, maintained, and efficient drug and gene delivery. The present review aims to comprehensively describe the current advancements in both viral- and nanotechnology-based strategies for ocular diseases. It discusses the complex molecular structure and physiological functions of the ocular barriers, focusing on the exact mechanisms that restrict drug permeation. Moreover, this review describes the design principles, physicochemical properties, and therapeutic potential of diverse viral- and nanotechnology-based delivery systems. Their efficacy and safety profiles are thoroughly discussed across various pre-clinical and clinical studies. Furthermore, the review discusses the emergence of hybrid viral-nanotechnology delivery systems that combine the strengths of both approaches, offering enhanced targeting precision and biocompatibility. The major challenges linked to the clinical translation of these novel technologies, such as aspects of biocompatibility and immunogenicity are also addressed. This review highlights the significant transformative potential of viral vectors and nanotechnology in reforming ocular disease management and increasing patient quality of life.}, }
@article {pmid41218596, year = {2025}, author = {Debbarma, R and Dos Santos, ACF and Ramirez Gutierrez, D and Erk, KA and Koo, H and da Cunha, F and Ladisch, M}, title = {Imaging of Intra-Matrix IgG Diffusion as an Indicator of Age-Related Vitreous Changes.}, journal = {Molecular pharmaceutics}, volume = {22}, number = {12}, pages = {7445-7454}, doi = {10.1021/acs.molpharmaceut.5c00836}, pmid = {41218596}, issn = {1543-8392}, mesh = {*Immunoglobulin G/metabolism/chemistry ; *Vitreous Body/metabolism ; Hyaluronic Acid/chemistry/metabolism ; Humans ; Aged ; Viscosity ; Aged, 80 and over ; Animals ; Diffusion ; Cattle ; Macular Degeneration/drug therapy/metabolism ; Intravitreal Injections ; *Aging ; }, abstract = {Intravitreal injection of therapeutics that treat age-related macular degeneration and diabetic retinopathy requires diffusion of the protein therapeutic through hyaluronic acid (HA) in the vitreous humor. The tracking of bovine IgG movement in an in vitro HA matrix simulates protein diffusion in the vitreous humor and provides a fundamental understanding of the diffusion properties of injected IgG type biologics. Phase separation of the vitreous humor, creating pockets of liquid rich in HA, begins at about age 40 and steadily progresses, with more than 50% of the vitreous being liquid by age 80-90 years. When formulated to represent viscosity at the injection site for patients between 65 and 80 years old, the HA has a viscosity of 0.1 Pa s. The vitreous humor for patients at ages lower than 65 corresponds to a viscosity of 1 Pa s. This work shows how HA matrices may be formulated to simulate the HA environment in the vitreous humor so that IgG diffusion may be measured using label-free imaging based on tryptophan autofluorescence. A 37% increase in the mean diffusion coefficient occurred as the HA matrix viscosity decreased from 1 to 0.1 Pa s, thus indicating that protein formulations may need to be adjusted if equivalent diffusion rates are to be achieved in the vitreous humor of different ages of patients. This approach provides an in vitro preclinical screening tool that could prove useful for correlating the diffusion properties of protein therapeutics as a function of the viscoelasticity of the vitreous humor.}, }
@article {pmid41218907, year = {2025}, author = {Hong, Y and Bo, QY and Sun, XD}, title = {[Progress on predictive biomarkers for exudation in polypoidal choroidal vasculopathy].}, journal = {[Zhonghua yan ke za zhi] Chinese journal of ophthalmology}, volume = {61}, number = {11}, pages = {915-920}, doi = {10.3760/cma.j.cn112142-20250416-00186}, pmid = {41218907}, issn = {0412-4081}, support = {U22A20311, 82301220, 82388101//National Natural Science Foundation of China/ ; 23YF1434100//"YangFan Program"of Shanghai Municipal Committee of Science and Technology/ ; 20224Y0352//Clinical research project of Shanghai Municipal Health Commission/ ; }, mesh = {Humans ; Biomarkers ; *Choroid/blood supply ; *Choroidal Neovascularization/diagnosis ; *Choroid Diseases/diagnosis ; Macular Degeneration ; Polypoidal Choroidal Vasculopathy ; }, abstract = {Polypoidal choroidal vasculopathy (PCV) is a common subtype of neovascular age-related macular degeneration (nAMD) in Asian populations. Clinical follow-up has revealed varying degrees of activity in PCV lesions. Studies have shown that multimodal retinal imaging techniques can be used to assess the activity of PCV lesions. Abnormal branching vascular networks, polypoidal lesions, and choroidal-related features are important biological markers for predicting lesion activity. Additionally, demographic characteristics and genetic traits of patients may also serve as relevant factors for assessing the activity of PCV lesions. This review summarizes recent updates in the understanding of PCV lesion activity based on multimodal retinal imaging studies and their impact on clinical ophthalmic practice. It also explores the potential applications and prospects of lesion activity characteristics in the treatment and follow-up of PCV, aiming to provide reference for clinicians in assessing and determining the activity of PCV lesions and developing personalized treatment and follow-up plans.}, }
@article {pmid41219247, year = {2025}, author = {Chiu, CJ and Chiu, ES and Chang, ML}, title = {Interaction between serum levels of Porphyromonas gingivalis immunoglobulin G and lutein/zeaxanthin is associated with risk for age-related macular degeneration.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {39400}, pmid = {41219247}, issn = {2045-2322}, support = {R01 EY021826/EY/NEI NIH HHS/United States ; R21 EY028209/EY/NEI NIH HHS/United States ; RO1EY021826 and R21EY028209/GF/NIH HHS/United States ; }, mesh = {Humans ; *Porphyromonas gingivalis/immunology ; *Macular Degeneration/blood/microbiology/etiology ; Female ; Male ; *Immunoglobulin G/blood ; Middle Aged ; Case-Control Studies ; Aged ; Risk Factors ; Periodontitis/microbiology/blood ; Antibodies, Bacterial/blood ; Nutrition Surveys ; *Bacteroidaceae Infections/blood/microbiology ; }, abstract = {Porphyromonas gingivalis (P. gingivalis) functions as a catalyst bacterium in the development of periodontitis, and the serum antibody level against P. gingivalis is considered a surrogate marker for the activity level of periodontopathic microbiota. The chronic systemic inflammation induced by P. gingivalis elevates the risk of various systemic and neurodegenerative disorders, including atherosclerosis, diabetes, and Alzheimer's disease. Although the connection between human microbiota and age-related macular degeneration (AMD) remains relatively unexplored, it is noteworthy that AMD shares risk factors and etiological mechanisms with diseases related to P. gingivalis. To investigate the potential association between periodontopathic microbiota and AMD occurrence, we conducted a candidate microbe approach case-control study in the Third National Health and Nutrition Examination Survey (NHANES-III). Our hypothesis was tested by examining the correlation between serum P. gingivalis immunoglobulin G (IgG) levels and AMD. Comparing the lowest IgG category (≤ 57 enzyme-linked immunosorbent assay units (EU)) with higher categories revealed escalating risks: the second higher category (58-65 EU) conferred almost a 30% increased risk (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.17 to 1.4), the third higher category (66-119 EU) conferred nearly a 60% increase (OR = 1.58, 95% CI: 1.46 to 1.72), and the highest category (> 119 EU) conveyed over a two-fold risk (OR = 2.04, 95% CI: 1.62 to 2.58) of early AMD. Consistent with current evidence that host nutritional status critically modulates immune responses to the microbiota and influences human health, our analysis indicates that sustaining elevated serum levels of lutein/zeaxanthin (≥ 0.35 µmol/L or ≥ 20 µg/dL) might potentially mitigate the P. gingivalis-related AMD risk by as much as 35% (P for interaction < 0.0001). Although the precise mechanism requires additional exploration, these findings suggest a connection between nutrients related to eye health and humoral response to P. gingivalis.Significance statement: While humoral response to P. gingivalis indicates an impact on age-related macular degeneration, nutritional factors may modulate the associated risk.}, }
@article {pmid41219682, year = {2026}, author = {de Angelis, L and Galasso, M and Di Simplicio, S and Raimondi, R and Vidal-Aroca, F and Romano, MR and Toro, MD and Rizzo, S and Barca, F}, title = {In Vivo Evaluation of SING IMT™ Alignment for Late-Stage Age-Related Macular Degeneration Using Anterior Segment OCT.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {1}, pages = {239-249}, pmid = {41219682}, issn = {2193-8245}, abstract = {INTRODUCTION: This study aimed to assess the in vivo positioning, tilt, and decentration of the second-generation implantable miniature telescope (SING-IMT™; Samsara Vision, Inc., Far Hills, NJ, USA) using swept-source anterior segment optical coherence tomography (AS-OCT).<br><br>METHODS: This was a multicentric retrospective observational study conducted at two tertiary referral centers (Palagi Hospital, Florence, Italy, and Royal Victoria Infirmary Hospital, Newcastle upon Tyne, UK). Eleven eyes from 11 patients with end-stage age-related macular degeneration (AMD) underwent secondary SING IMT&#x2122; implantation at these two tertiary centers. Using high-resolution AS-OCT (CASIA2 system [Tomey, Nagoya, Japan] and Anterion system [Heidelberg Engineering, Heidelberg, Germany]), telescope alignment was assessed after 12&#xa0;months. Decentration and tilt were calculated and reported in both Cartesian and polar coordinates. Telescope configuration relative to the iris plane and corneal-telescope (C-T) distance and endothelial cell count was also evaluated.<br><br>RESULTS: The mean (&#xb1; standard deviation) follow-up was&#xa0;15.7&#x2009;&#xb1;&#x2009;2.8&#xa0;months. The mean decentration was 0.33&#x2009;&#xb1;&#x2009;0.12&#xa0;mm, with a predominant superior and nasal displacement. Mean tilt was 3.28&#x2009;&#xb1;&#x2009;1.31&#xb0;, oriented mainly in the supero-temporal direction. Three positional configurations were observed: anterior to the iris plane (36.4%), at the iris plane (36.4%), and posterior to the iris plane (27.3%). The mean C-T distance was 2.71&#x2009;&#xb1;&#x2009;0.48&#xa0;mm. Mean endothelial cell loss at 12&#xa0;months was 13.21%&#x2009;&#xb1;&#x2009;3.57%.<br><br>CONCLUSIONS: After 12&#xa0;months of follow-up, the SING IMT&#x2122; maintained stable in-the-bag fixation, with tilt and decentration values within the ranges previously reported for conventional in-the-bag intraocular lenses.}, }
@article {pmid41221122, year = {2025}, author = {Alqahtani, HB and Votruba, M and Regini, J}, title = {Do retinal implants provide long-term efficacy, safety and improve quality of life? A systematic review.}, journal = {Therapeutic advances in ophthalmology}, volume = {17}, number = {}, pages = {25158414251385884}, pmid = {41221122}, issn = {2515-8414}, abstract = {BACKGROUND: Retinal implants have emerged as interventions to partially restore functional vision such as light perception, motion detection or object localisation in patients with severe vision loss from degenerative retinal conditions, including retinitis pigmentosa (RP) and dry age-related macular degeneration (AMD).<br><br>OBJECTIVES: To evaluate the long-term efficacy, safety and quality of life (QoL) impact of retinal implants with &#x2a7e;1&#x2009;year of follow-up.<br><br>METHODS: Following PRISMA guidelines, a systematic search was conducted (31st July to 31st August 2024) in Web of Science, PubMed, Medline, Scopus, Cochrane Library and Embase, using the terms: ('retinal implant' OR 'retinal prosthesis') AND ('long-term' OR 'follow-up') AND ('efficacy' OR 'safety' OR 'quality of life'). No publication date restrictions were applied. Eligible studies were in English, involved human subjects with retinal degenerations, and reported &#x2a7e;1&#x2009;year follow-up. Risk of bias was assessed using the Critical Appraisal Skills Programme (CASP) cohort study checklist for most studies, as they involved prospective follow-up without randomisation or control groups. The Joanna Briggs Institute (JBI) critical appraisal checklist for case series was applied to studies with a case series design. Narrative synthesis was applied.<br><br>RESULTS: Thirteen studies met the inclusion criteria: 53.85% assessed epiretinal implants (Argus II), 30.77% subretinal (Alpha AMS and PRIMA), and 15.38% suprachoroidal (44 and 49-channel STS). Epiretinal implants improved visual function, with up to 89% better in SLT, 50%-56% in DOM, and 30%-40% reaching &#x2a7e;2.9 logMAR when activated. Subretinal implants enhanced light perception, localisation, and grating acuity (to 3.33 cycles/degree), with acuity of 20/460 and 20/550 in some cases. Suprachoroidal devices improved SLT, DOM and GVA. Adverse events were more frequent with epiretinal than other implant types. QoL outcomes improved, particularly in mobility, orientation, and daily tasks.<br><br>CONCLUSION: Retinal implants confer functional vision, but acuities remain below 20/200, and recipients continue to meet criteria for legal blindness. Given the high risk of bias, lack of controls and potential placebo effects, further high-quality evidence is needed to confirm their efficacy, safety and QoL impact.}, }
@article {pmid41222198, year = {2025}, author = {Cinque, F and de Breuk, A and Mhmud, H and De Jong, S and Vermeulen, J and Liefers, B and den Hollander, AI and Thee, E and Colijn, JM and Heesterbeek, TJ and Klaver, CC and Hoyng, CB and Lechanteur, YTE}, title = {Disease Progression in Age-Related Macular Degeneration Patients Carrying Rare Variants in the Complement Factor H or Complement Factor I Genes.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {14}, pages = {23}, pmid = {41222198}, issn = {1552-5783}, mesh = {Humans ; Female ; Male ; Aged ; *Complement Factor H/genetics/metabolism ; Disease Progression ; *Complement Factor I/genetics/metabolism ; Retrospective Studies ; Visual Acuity/physiology ; Incidence ; *Macular Degeneration/genetics/epidemiology/diagnosis ; Follow-Up Studies ; Middle Aged ; Aged, 80 and over ; Prospective Studies ; Geographic Atrophy/genetics ; }, abstract = {PURPOSE: Rare variants in CFI and CFH genes are associated with AMD. This study aimed to compare the incidence of late AMD in carriers of these variants to a reference cohort using a long follow-up cohort (LF-cohort) and to examine short-term AMD progression in a short follow-up cohort (SF-cohort).<br><br>METHODS: This cohort study included two groups: the LF-cohort, observed for more than five years retrospectively and the SF-cohort, observed for one year prospectively, with patients attending in-hospital visits. One hundred twelve AMD patients with rare CFH/CFI or variants were invited from the European Genetic Database. The LF-cohort's outcome was the incidence of late AMD per 100 person-years compared to a matched reference cohort. In the SF-cohort, geographic atrophy (GA), retinal sensitivity, and visual acuity were measured.<br><br>RESULTS: The LF-cohort included 28 patients (median [interquartile range {IQR}] age, 71.3 [24.3] years; 18 females [64%]) with an incidence rate of 6.2 per 100 person-years which was higher than the reference cohort (1.8 per 100 person years (P = 0.01)). The SF-cohort consisted of 44 patients (median [IQR] age 70.5 [16.5] years; 29 (65% female). Mean annual GA growth (SD) was 0.22 mm (0.13) in 19 eyes of 12 patients. Retinal sensitivity changed for late-staged eyes (right eye: 17.2 dB to 15.7 dB, P = 0.03; left eye 17.3 dB to 16.4 dB, P = 0.06) whereas visual acuity did not.<br><br>CONCLUSIONS: Carriers of rare CFI or CFH variants show a higher incidence of late AMD. These patients may benefit from personalized gene therapy and complement inhibition in future trials.}, }
@article {pmid41222201, year = {2025}, author = {Beqiri, S and Pan, H and Kumar, BS and Berni, A and Shen, M and Hiya, FE and Cheng, Y and El-Mulki, OS and Herrera, G and Badla, O and Kastner, J and Trivizki, O and Di Nicola, M and O'Brien, RC and Waheed, NK and Wang, RK and Gregori, G and Rosenfeld, PJ}, title = {Changes in Choriocapillaris Flow Deficits Before and After the Onset of Large Choroidal Hypertransmission Defects in AMD.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {14}, pages = {20}, pmid = {41222201}, issn = {1552-5783}, support = {P30 EY014801/EY/NEI NIH HHS/United States ; R01 EY028753/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Choroid/blood supply ; Tomography, Optical Coherence/methods ; Retrospective Studies ; Female ; Male ; Aged ; Fluorescein Angiography/methods ; Regional Blood Flow/physiology ; Aged, 80 and over ; *Macular Degeneration/physiopathology/diagnosis ; Capillaries/physiopathology ; Retinal Pigment Epithelium/pathology ; Fundus Oculi ; Follow-Up Studies ; Middle Aged ; Prospective Studies ; }, abstract = {PURPOSE: Eyes with intermediate age-related macular degeneration (iAMD) underwent swept-source optical coherence tomography angiography (SS-OCTA) imaging and were evaluated longitudinally to determine if choriocapillaris flow deficits (CCFDs) developed before or after the formation of large choroidal hypertransmission defects (hyperTDs).<br><br>METHODS: A retrospective review was performed of prospectively collected 6 &#xd7; 6-mm SS-OCTA images from eyes with iAMD that developed large hyperTDs, defined on en face images from subretinal pigment epithelium (sub-RPE) slabs positioned 64 to 400 &#xb5;m beneath Bruch's membrane (BM) as bright lesions with a greatest linear dimension (GLD) &#x2265; 250&#xa0;&#xb5;m. The onset of large hyperTDs was designated as baseline T = 0; additional visits were chosen at 1 year before and at two 1-year intervals after T = 0. A grid box strategy was implemented for the analysis of CCFDs at the site where hyperTDs formed. A change in the percentage of CCFDs greater than 5% was considered to be a true change outside the repeatability limits.<br><br>RESULTS: Twenty-seven targets from 27 eyes eligible for final analysis were followed over four visits separated by 12 &#xb1; 3 months. No targets showed a marked CCFD change above 5% prior to hyperTD onset. Only two targets showed marked increases in CCFDs after hyperTD formation. A grouped analysis of all targets showed no mean CCFD change prior to hyperTD onset, but a significant change only after the onset of hyperTD.<br><br>CONCLUSIONS: CCFD values did not increase prior to the onset of hyperTDs with increases in CCFDs detected after their onset. These results suggest that loss of choriocapillaris perfusion did not precede hyperTD formation but may play a role in hyperTD growth.}, }
@article {pmid41222493, year = {2025}, author = {Pan, SY and Chao, TF and Weng, CH and Lin, JF and Lin, CH and Lin, HJ and Wang, IJ and Chou, CC}, title = {Association between atrial fibrillation and age-related macular degeneration: A multinational cohort study.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70028}, pmid = {41222493}, issn = {1755-3768}, support = {TCVGH-1136902B//Taichung Veterans General Hospital/ ; }, abstract = {PURPOSE: To assess whether atrial fibrillation (AF) is associated with an increased risk of age-related macular degeneration (AMD).<br><br>METHODS: This multinational retrospective cohort study included individuals aged 50&#x2009;years or older, with or without AF at baseline, from healthcare organisations across 21 countries during 2015-2020 in the TriNetX database. Participants were classified into those with and without AF, and followed for up to 5&#x2009;years to observe the occurrence of AMD, including both dry and wet forms, and other cerebrovascular outcomes. The AF and non-AF groups were 1:1 propensity score-matched to balance baseline characteristics and comorbidities. Outcomes were assessed using Cox regression models and Kaplan-Meier analysis.<br><br>RESULTS: A total of 113&#x2009;974 individuals were included in the final analysis. The mean follow-up (standard deviation [SD]) is 4.09 (1.30) years in the AF group and 4.53 (0.95) years in the non-AF group. During follow-up, 1169 individuals developed AMD, 527 developed dry AMD, and 242 developed wet AMD. Compared to individuals without AF, those with AF have a significantly higher risk of developing AMD (hazard ratio [HR], 2.72; 95% confidence interval [CI], 2.42-3.11), dry AMD (HR, 2.55; 95% CI, 2.12-3.07), wet AMD (HR, 2.50; 95% CI, 1.90-3.28), and ischemic stroke (HR, 1.67; 95% CI, 1.60-1.73). Across most subpopulations, AF is consistently linked to higher risks of both dry and wet AMD.<br><br>CONCLUSION: Individuals with AF experience a higher risk of developing both dry and wet forms of AMD compared to individuals without AF.}, }
@article {pmid41222660, year = {2026}, author = {Fragiotta, S and Parravano, M and Costanzo, E and De Geronimo, D and Varano, M and Borrelli, E and Barresi, C and Sacconi, R and Querques, G}, title = {Early prediction of macular neovascularization phenotypes and prognostic evolution.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {445-454}, pmid = {41222660}, issn = {1435-702X}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; *Tomography, Optical Coherence/methods ; Prognosis ; Aged ; *Fluorescein Angiography/methods ; Phenotype ; Follow-Up Studies ; Fundus Oculi ; *Macula Lutea/pathology ; Middle Aged ; Aged, 80 and over ; *Wet Macular Degeneration/diagnosis ; Choroid/pathology ; Time Factors ; Disease Progression ; Angiogenesis Inhibitors/administration &amp; dosage ; }, abstract = {PURPOSE: To investigate baseline predictors of macular neovascularization (MNV) phenotypes and prognostic outcomes, including changes in visual acuity (VA) and the development of macular atrophy (MA) and fibrosis.<br><br>METHODS: A retrospective, observational, cohort study was performed on a total of 102 eyes from 97 patients with intermediate age-related macular degeneration (AMD) converting to MNV subtypes. Baseline features, including age, drusen, reticular pseudodrusen (RPD), subfoveal choroidal thickness (SFCT), and central retinal thickness (CRT), were analyzed. Predictive models that considered the baseline characteristics predicting the different MNV subtypes and prognostic outcomes were developed using Cox regression and generalized linear models.<br><br>RESULTS: Of the included eyes, 68.6% developed type 1 MNV, 15.7% type 2 MNV, and 15.7% type 3 MNV. SFCT was a significant predictor of type 2 MNV, with thicker choroid predisposing to the lesion development (HR: 1.02, CI95%: 1, 1.03, p&#x2009;=&#x2009;0.001). Age was the primary predictor for type 3 MNV (HR: 1.1, CI 95%: 1, 1.2, p&#x2009;=&#x2009;0.02). Type 2 MNV exhibited the highest rate of fibrosis at follow-up (71.4%), compared to both type 1 (43.5%) and type 3 MNV (26.7%) (p&#x2009;=&#x2009;0.04). Age at baseline and best-corrected visual acuity (BCVA) were factors associated with final vision loss (p&#x2009;<&#x2009;0.001), while the presence of drusen alone appeared protective (p&#x2009;=&#x2009;0.03). SFCT at baseline also reduced the risk of outer retinal atrophy (p&#x2009;=&#x2009;0.01).<br><br>CONCLUSIONS: SFCT served as a key indicator for type 2 MNV while aging predominantly predicted type 3 MNV. The findings may improve the early identification and tailored management of MNV phenotypes, optimizing visual outcomes and mitigating complications such as fibrosis and atrophy.}, }
@article {pmid41223116, year = {2026}, author = {Ottaiano-Poli, PA and Germano-Morrel, CS and Tomishige, KS and Macchione, RM and Kasahara, N}, title = {Comparison of balance-confidence between glaucoma and age-related macular degeneration patients who live in a developing country.}, journal = {Clinical rehabilitation}, volume = {40}, number = {3}, pages = {419-426}, doi = {10.1177/02692155251394989}, pmid = {41223116}, issn = {1477-0873}, mesh = {Humans ; Male ; Female ; *Macular Degeneration/psychology/physiopathology ; Aged ; *Postural Balance/physiology ; Brazil ; Developing Countries ; Case-Control Studies ; Middle Aged ; *Glaucoma, Open-Angle/psychology/physiopathology ; Activities of Daily Living ; *Glaucoma/psychology/physiopathology ; }, abstract = {ObjectiveTo compare balance-confidence among patients with primary open-angle glaucoma, age-related macular degeneration, and controls in Brazil.DesignCase-control study.SettingCharity hospital in São Paulo, Brazil.ParticipantsPatients with glaucoma, age-related macular degeneration, and controls without eye diseases.Main outcomes measuresActivities-specific Balance Confidence (ABC) Scale scores.ResultsThe sample consisted of 64 patients with glaucoma, 60 with age-related macular degeneration, and 60 controls. All groups were matched by age, gender, ethnic distribution, and comorbidities. The ABC Scale score was 63.1 (25.9) in the glaucoma group, 69.5 (16.4) in the age-related macular degeneration group, and 95.3 (9.1) for the controls (P < 0.001; Hedges' g -1.65 and -1.93, large effect size); glaucoma patients score did not differ from age-related macular degeneration patients (P = 0.132; Hedges' g 0.30, small effect size).ConclusionBoth glaucoma and age-related macular degeneration patients reported lower balance-confidence in performing daily activities without losing balance as compared to controls.}, }
@article {pmid41223128, year = {2026}, author = {Spooner, KL and Fraser-Bell, S and Mehta, H and Hong, T and Broadhead, G and Wong, JG and Chang, AA}, title = {Lost to Follow-Up in Neovascular Age-Related Macular Degeneration: A Systematic Review of Global Trends, Risk Factors, and Clinical Consequences.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {249}, number = {1}, pages = {79-102}, doi = {10.1159/000549177}, pmid = {41223128}, issn = {1423-0267}, mesh = {Humans ; Risk Factors ; *Wet Macular Degeneration/drug therapy/epidemiology/diagnosis ; *Lost to Follow-Up ; Global Health ; Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; Intravitreal Injections ; }, abstract = {INTRODUCTION: Loss to follow-up (LTFU) among patients receiving anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD) remains a critical challenge for maintaining visual outcomes. This systematic review and meta-analysis evaluated the prevalence, risk factors, and impact on visual prognosis of LTFU across real-world studies.<br><br>METHODS: A comprehensive literature search of PubMed, Embase, Cochrane, Scopus, and Google Scholar identified studies published between 2015 and 2025. Eligible studies included observational cohorts and registry-based analyses that reported the LTFU rates, risk factors, and visual outcomes following treatment discontinuation. Random-effects meta-analysis (DerSimonian-Laird) estimated pooled odds ratios (ORs) and 95% confidence intervals (CIs); heterogeneity was assessed via I2 and Cochran's Q. Continuous predictors were analysed using regression-based ORs or standardized mean differences (SMDs), where appropriate.<br><br>RESULTS: We included 52 studies. Short-term LTFU was defined as 6-12 months without treatment; long-term LTFU as &#x2265;12 months. LTFU rates ranged from <5% to >75% over up to 10 years. Older age was moderately associated with LTFU (SMD = 0.47, 95% CI: 0.37-0.57; &#x2248;6-7 years older). Greater travel distance increased LTFU risk (OR = 1.35 per 10-km increase, 95% CI: 1.14-1.60). Male sex (OR = 1.20, 95% CI: 1.05-1.37) and caregiver/transport dependence (OR = 2.00, 95% CI: 1.45-2.75) were also associated with a higher likelihood of LTFU. Treat-and-extend (T&amp;E) regimens showed lower LTFU than pro re nata. Patients who were LTFU had worse visual outcomes even after resuming care.<br><br>CONCLUSION: LTFU in nAMD treatment is common and driven by demographic (age, sex, and race), socioeconomic (income and insurance), and access (distance and caregiver need) factors. Continuous treatment, early response, and structured regimens (e.g., T&amp;E) mitigate dropout risk. Interventions to improve access and personalize support are essential to reduce LTFU and preserve visual outcomes.}, }
@article {pmid41224521, year = {2025}, author = {Yeo, D and Hwang, SH and Lee, S and Jeong, J and Kong, J and Lee, H and Smith, L and Cho, J and Yim, Y and Lee, J and Kang, J and Yang, JM and Yon, DK}, title = {Global, regional and national burden of major blindness-associated ophthalmologic conditions, 1990-2021, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2021.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-327917}, pmid = {41224521}, issn = {1468-2079}, abstract = {BACKGROUND: The global burden of blindness and vision loss continues to increase, yet comprehensive analyses of underlying causes remain limited. This study estimated the global and regional burden of blindness-related diseases from 1990 to 2021 and projected trends to 2050 to inform public health strategies.<br><br>METHODS: We analysed data from the Global Burden of Disease Study (GBD) 2021 to estimate the prevalence and disability-adjusted life years (DALYs) rates of blindness and vision loss, focusing on six major causes, including glaucoma, cataract, age-related macular degeneration, refraction disorders, near vision loss and other vision loss. We quantified the contribution of risk factors, and future trends were projected to 2050 using GBD's forecast framework.<br><br>RESULTS: In 2021, the global age-standardised prevalence and DALY rates of blindness were 15&#x2009;784.3 (95% uncertainty interval (UI), 12&#x2009;761.4-19&#x2009;502.3) and 342.8 (224.2-503.6) per 100&#x2009;000. Although global age-standardised DALY rates remained statistically stable between 1990 and 2021, regional trends varied numerically. Southern sub-Saharan Africa recorded the highest age-standardised prevalence rate in 2021 at 16&#x2009;741.4 (13&#x2009;187.8-21&#x2009;129.5), whereas the highest DALY rate was observed in South Asia at 497.1 (345.3-691.6). While the overall burden of blindness did not differ significantly by sex, glaucoma showed a higher burden in males. From 1990 to 2021, cataract DALY rates attributable to household air pollution decreased by 38.4%, with projections showing stable age-standardised rates through 2050.<br><br>CONCLUSIONS: As populations age, the global burden of vision loss is projected to grow, with particularly high impact in lower-sociodemographic index regions such as Southern Sub-Saharan Africa and South Asia.}, }
@article {pmid41226778, year = {2025}, author = {Dave, A and Tosevska, A and Morselli, M and Tom, E and Pellegrini, M and Skowronska-Krawczyk, D and Radu, RA}, title = {Dysregulated DNA Methylation in Abca4[-/-] Retinal Pigment Epithelium: Insights into Early Stage of Stargardt Disease.}, journal = {International journal of molecular sciences}, volume = {26}, number = {21}, pages = {}, pmid = {41226778}, issn = {1422-0067}, support = {1R01EY025002-05/NH/NIH HHS/United States ; 1R01EY000331-10/NH/NIH HHS/United States ; na//Research to Prevent Blindness, Inc./ ; }, mesh = {*DNA Methylation/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; *Stargardt Disease/genetics/pathology/metabolism ; Animals ; *ATP-Binding Cassette Transporters/genetics/metabolism ; Mice ; Disease Models, Animal ; Methyl-CpG-Binding Protein 2/metabolism/genetics ; Mice, Knockout ; *Macular Degeneration/genetics/congenital ; Epigenesis, Genetic ; Humans ; }, abstract = {Stargardt disease (STGD1), the most common inherited juvenile macular degeneration, is caused by biallelic mutations in the ABCA4 gene. Currently, there is no approved treatment. In this study, we investigated early-stage epigenomic changes in the retinal pigment epithelium (RPE) of Abca4[-/-] mice, a well-established model of STGD1. Reduced representation bisulfite sequencing (RRBS) revealed hypermethylation of gene regions associated with disease-related pathways, implicating methyl-CpG-binding protein 2 (MeCP2) and RE1-silencing transcription factor (REST) as potential regulators. Notably, DNA methylation of a subset of genes preceded their transcriptional change and disease phenotypes in Abca4[-/-] RPE. Together with the detected age-dependent increase in MeCP2 levels in Abca4[-/-] RPE, these findings suggest that early DNA methylation changes may contribute to RPE dysfunction and eventual cell loss in STGD1.}, }
@article {pmid41229226, year = {2025}, author = {Rakic, N and Van Cauwenberge, F and Georges, A and Rakic, JM}, title = {[Early management of vitreous hemorrhage : clinical experience of the University Hospital of Liege].}, journal = {Revue medicale de Liege}, volume = {80}, number = {11}, pages = {703-707}, pmid = {41229226}, issn = {0370-629X}, mesh = {Humans ; *Vitreous Hemorrhage/surgery/therapy/diagnosis/etiology ; Retrospective Studies ; Male ; Female ; Aged ; Hospitals, University ; Middle Aged ; Vitrectomy ; Adult ; Aged, 80 and over ; Visual Acuity ; Young Adult ; }, abstract = {Hemorrhages occurring in the vitreous body have multiple etiologies. They cause an immediate and severe loss of visual acuity and sometimes require urgent surgical management by vitrectomy. We report in a retrospective series the clinical data of 76 patients treated at the University Hospital of Liège, highlighting the high incidence of retinal tears caused by posterior detachment of the vitreous body, the predominance of proliferative diabetic retinopathy in young patients, and that of age-related macular degeneration in older patients. Surgical intervention allows a very significant and fast improvement in visual acuity while avoiding the natural history of retinal tears which, in a hemorrhagic context, lead to retinal detachment with a very bad prognosis.}, }
@article {pmid41229552, year = {2025}, author = {Schuster, AK and Leisle, L and Picker, N and Vorwerk, H and Hahn, P and Wasem, J and Lewis, P}, title = {Economic and Medical Burden of Non-Exudative Age-Related Macular Degeneration in Germany: A Retrospective Observational Claims Data Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {4129-4144}, pmid = {41229552}, issn = {1177-5467}, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly in higher-income countries. This study aimed to explore the medical and economic burden of non-exudative AMD patients living in Germany.<br><br>METHODS: German claims data (AOK PLUS) were utilized in this retrospective analysis. Prevalent non-exudative AMD only patients were compared to (i) non-exudative AMD patients with a concomitant exudative AMD diagnosis and (ii) propensity score matched non-AMD controls in terms of patient characteristics and eye-related diagnostic/monitoring patterns during baseline (in 2020) as well as in terms of the healthcare resource use and associated costs during the follow-up (in 2021).<br><br>RESULTS: The sample comprised 25,439 patients diagnosed with non-exudative AMD only and 7,153 diagnosed with both types of AMD (mean age: 79/81 years | female: 64.3%/64.5%). The total health insurance costs for non-exudative AMD only patients were estimated to be 6,500 &#x20ac; per person-year (pPY), which was about 500 &#x20ac; pPY higher than in matched non-AMD controls. The total costs further increased by about 3,500 &#x20ac; pPY in the presence of concomitant exudative AMD. Also, the healthcare resources (especially related to ophthalmological care) were utilized more frequently by non-exudative AMD patients compared to non-AMD controls, and even more so by patients with concomitant exudative AMD.<br><br>CONCLUSION: Non-exudative AMD patients were associated with an increased medical and economic burden compared to non-AMD individuals living in Germany.}, }
@article {pmid41230053, year = {2025}, author = {Ambiya, V and Kapoor, G and Sharma, VK}, title = {Large subfoveal pigment epithelial detachment causing macular hole formation: Surgical approach.}, journal = {Oman journal of ophthalmology}, volume = {18}, number = {3}, pages = {382-384}, pmid = {41230053}, issn = {0974-620X}, abstract = {Subfoveal pigment epithelial detachments (PEDs) have been reported to develop full-thickness macular hole (FTMH). The response to treatment has been varied in different reports, with most cases having persistent PED even after successful surgical closure of the macular hole. Here, we report an unusual case of nonneovascular age-related macular degeneration, having a large subfoveal serous PED, leading to the formation of a large FTMH, which showed complete flattening of the PED with a successful closure of the macular hole with the surgical approach.}, }
@article {pmid41230077, year = {2025}, author = {Sriram, R and Manayath, GJ}, title = {Subretinal injection of tissue plasminogen activator for submacular hemorrhage - When and how to do.}, journal = {Oman journal of ophthalmology}, volume = {18}, number = {3}, pages = {284-290}, pmid = {41230077}, issn = {0974-620X}, abstract = {Submacular hemorrhage (SMH) causes irreversible loss of vision as it causes permanent anatomical and functional damage to photoreceptors. The various causes include polypoidal choroidal vasculopathy, neovascular age-related macular degeneration, retinal artery macroaneurysm, high myopia, and trauma. The current treatment modalities include antivascular endothelial growth factor (anti-VEGF) monotherapy, anti-VEGF ± gas pneumatic displacement ± intravitreal recombinant tissue plasminogen activator injection (rtPA), and triple therapy (intravitreal anti-VEGF + intravitreal rtPA + perfluoropropane gas injection). The surgical displacement of the SMH by vitrectomy with subretinal tissue plasminogen activator injection + intravitreal anti-VEGF + gas tamponade has been a valuable addition to our armamentarium. Evidence suggests that this novel technique provides better anatomical and functional outcomes in terms of visual acuity when the surgical displacement is performed within the prompt time frame in comparison to other available modalities of treatment. The current lacuna in the literature is the absence of level 1 evidence to support the surgical displacement as the first-line therapy. Hence, we review the current evidence and provide recommendations regarding this ever-promising therapy that can be vision-saving.}, }
@article {pmid41230290, year = {2025}, author = {Shloush, M and Eleff, A and Eleff, E}, title = {Ophthalmology Considerations in End-of-Life Care.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e94396}, pmid = {41230290}, issn = {2168-8184}, abstract = {Ophthalmologic interventions can significantly impact quality of life, even in the context of end-of-life care. This paper explores the ethical and clinical considerations for ophthalmologic treatments in hospice care, with a focus on cataract surgery, age-related macular degeneration (ARMD) therapy, retinal detachment (RD) repair, glaucoma, painful blind eye (PBE) management, benign and surface ocular tumors, and corneal or anterior segment diseases. A review of published literature and clinical precedent was conducted to assess the benefits, risks, and practical limitations of ophthalmologic procedures in hospice patients, with an emphasis on quality of life. Cataract surgery has been shown to be cost-effective in hospice settings, offering significant improvements in vision and overall quality of life. Treatment for ARMD, though requiring ongoing injections, can provide benefits within weeks and help sustain visual function. RD repair, while more complex, can substantially restore vision when appropriately managed. Palliative glaucoma interventions, including individualized target intraocular pressures and laser therapy, can minimize treatment burden while maintaining comfort. PBEs may be managed with retrobulbar chlorpromazine or alcohol injections, and enucleation or evisceration may be considered when pain persists. Benign or surface ocular tumors and corneal or anterior segment diseases can often be addressed with conservative, comfort-focused measures to reduce symptoms and preserve quality of life. Ophthalmologic procedures should be considered viable options in end-of-life care when clinically indicated, with careful ethical review. Restoration of vision contributes meaningfully to the quality of life and deserves thoughtful inclusion in care planning.}, }
@article {pmid41230723, year = {2026}, author = {Usmani, E and Bahrami, B and Ebneter, A and Chan, WO}, title = {Cessation of Anti-VEGF Treatment Therapy in Age-Related Macular Degeneration: A Narrative Review.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {54}, number = {2}, pages = {275-283}, doi = {10.1111/ceo.70034}, pmid = {41230723}, issn = {1442-9071}, mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis ; Visual Acuity ; *Withholding Treatment ; Quality of Life ; Ranibizumab/administration &amp; dosage ; Bevacizumab/administration &amp; dosage ; }, abstract = {Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionised the treatment of neovascular age-related macular degeneration (nAMD), significantly improving visual outcomes and enhancing the quality of life for affected patients. However, the decision to discontinue anti-VEGF therapy in nAMD management remains complex and lacks consensus, with various criteria being applied. This narrative review examines the available evidence on the cessation of anti-VEGF treatment in nAMD in detail.}, }
@article {pmid41231253, year = {2026}, author = {Yu, Y and Sun, Y and Zhao, T}, title = {The roles of glycerophospholipids in the aging retina and age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {309-323}, pmid = {41231253}, issn = {1435-702X}, support = {No. 2023SK2032//Key Research and Development Program of Hunan Province of China/ ; No. kq2502054//the Changsha Municipal Natural Science Foundation/ ; No. 2025JGB161//Project Program of central south university graduate education teaching reform/ ; }, mesh = {Humans ; *Macular Degeneration/metabolism ; *Aging/physiology/metabolism ; *Glycerophospholipids/metabolism ; *Retina/metabolism/pathology ; Animals ; }, abstract = {Glycerophospholipids (GPs) are integral constituents of cellular membranes, and play a crucial role in the regulation of lipid metabolism homeostasis and physiological conditions. However, pathological alterations associated with aging, such as variations in plasma GP concentrations, disruptions in intercellular GP transport, and local accumulation of excessive GPs, have been observed. These changes induce irreversible cellular degeneration, ultimately leading to tissue damage in organs such as the brain and retina. A growing body of evidences has demonstrated that GPs play significant roles in neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Similarly, GPs have been implicated in the pathogenesis and progression of age-related macular degeneration (AMD), a degenerative condition affecting the choroid and retinal layers of the eye. Understanding the homeostasis of GP metabolism in the aging retina and in AMD is essential for elucidating the pathogenic processes involved in AMD. In this review, we present a comprehensive overview of the mechanisms of GPs in the aging retina and their correlation with degenerative processes associated with AMD. KEY MESSAGES: What is known Metabolic dysregulation of glycerophospholipids (GPs) plays vital roles in age-related macular degeneration (AMD) and neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Patients with age-related neurological disorders exhibit a significantly higher risk of developing AMD compared to healthy individuals, potentially due to shared pathological mechanisms, including mitochondrial metabolic disturbance, chronic inflammation and autophagy dysfunction. What is new The interconnection between multiple GP species and their metabolites has been established to delineate complex pathogenic mechanisms underlying the aging retina and AMD, including cell senescence, autophagy and apoptosis, oxidative stress, inflammation, vascular abnormalities. GPs may serve as potential therapeutic targets to prevent or delay the progression of AMD.}, }
@article {pmid41232598, year = {2026}, author = {Yang, Z and Zhang, W and Gu, X and Zhao, X and Sadda, SR and Cheung, G and Koh, A and Loewenstein, A and Li, B and Wang, C and Zhang, J and Yang, J and Jin, K and Meng, L and Chen, L and He, M and Yuan, M and Luo, M and Li, N and Ruamviboonsuk, P and Yu, Q and Zhao, Q and Cheng, S and Peng, W and Zhang, X and Zhang, X and Liu, X and Wang, Y and Xu, Z and Xie, Z and Xu, Z and Ma, Z and Zhao, C and Chen, Y}, title = {Polypoidal choroidal vasculopathy: In-depth insights and promising future directions.}, journal = {Progress in retinal and eye research}, volume = {110}, number = {}, pages = {101414}, doi = {10.1016/j.preteyeres.2025.101414}, pmid = {41232598}, issn = {1873-1635}, mesh = {Humans ; Tomography, Optical Coherence/methods ; *Choroidal Neovascularization/diagnosis/therapy ; *Choroid/blood supply ; Fluorescein Angiography/methods ; *Polyps/diagnosis/therapy ; Animals ; Angiogenesis Inhibitors/therapeutic use ; *Choroid Diseases/diagnosis ; Polypoidal Choroidal Vasculopathy ; }, abstract = {Polypoidal choroidal vasculopathy (PCV) is an ocular condition predominantly affecting elderly individuals of Asian descent, characterized by the presence of polypoidal lesions and branching neovascular networks in the sub-retinal pigment epithelium (RPE) space. It has garnered increased attention for its potential differences from neovascular age-related macular degeneration. Genetic studies have identified specific genetic markers associated with PCV. Advances in imaging techniques, particularly optical coherence tomography (OCT) and OCT angiography, have significantly enhanced the diagnosis of PCV and our insight into its unique pathogenesis. Treatment strategies for PCV have evolved, with anti-vascular endothelial growth factor (VEGF) monotherapy becoming the primary treatment, and combination therapies including photodynamic therapy showing promising results. Consideration of targets beyond VEGF and the incorporation of artificial intelligence (AI) based analysis strategies may open the door to more personalized, precise, and effective treatments for patients. This review comprehensively discusses the current knowledge and recent advancements in PCV, including its epidemiology, genetics, biomarkers, pathogenesis, diagnosis, and management. It also highlights the need to explore mechanism underlying the higher prevalence of PCV in pigmented races, clarify the roles of pachychoroid and pachydrusen in PCV pathogenesis, and develop animal models that can better recapitulate the disease's pathological features.}, }
@article {pmid41232694, year = {2026}, author = {Rashid, M and Azeem, S and Shahid, IF and Ali, MKB and Shahid, F and Fatima, A and Rashid, A and Azeem, E}, title = {Efficacy and safety of aflibercept biosimilars compared to reference aflibercept for retinal diseases: A systematic review and meta-analysis.}, journal = {Survey of ophthalmology}, volume = {71}, number = {3}, pages = {780-792}, doi = {10.1016/j.survophthal.2025.11.007}, pmid = {41232694}, issn = {1879-3304}, mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/therapeutic use ; *Biosimilar Pharmaceuticals/therapeutic use ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use ; Visual Acuity ; *Diabetic Retinopathy/drug therapy ; Treatment Outcome ; *Macular Edema/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Randomized Controlled Trials as Topic ; }, abstract = {Aflibercept biosimilars offer cost-effective alternatives to reference aflibercept for retinal diseases such as neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). By inhibiting vascular endothelial growth factor-mediated vascular damage, they aim to improve visual outcomes with comparable safety and efficacy, increasing treatment access while reducing cost burden. We evaluate their performance against the reference drug. A comprehensive search was done across Cochrane, Embase, PubMed, Scopus and ClinicalTrials.gov. Randomized controlled trials were included, and quality was assessed via RoB 2.0 tool. A random-effects model estimated standardized mean differences (SMD) and risk ratios. 11 studies (4064 participants) were analyzed, 8 focused on nAMD and 2 on DME. No significant differences in best-corrected visual acuity changes were observed between biosimilars and reference aflibercept in studies on nAMD (SMD = -0.04, 95 % confidence inerval [CI]: -0.15-0.06) or DME (SMD = 0.11, 95 % CI: -0.12-0.33). Central subfield thickness change at week 4 and the endpoint also showed no significant differences. Similarly, no significant differences were seen in choroidal neovacularization size, vision maintenance, anti-drug antibody development, treatment-emergent adverse events, or ocular adverse effects. Biosimilar aflibercept show similar efficacy and safety to the original for nAMD and DME, with no significant differences in key outcomes. They offer a cost-effective alternative that offers similar clinical benefits while improving treatment accessibility.}, }
@article {pmid41235547, year = {2025}, author = {}, title = {Correction to "Peptide-Bound Aflibercept Eye Drops for Treatment of Neovascular Age-Related Macular Degeneration in Nonhuman Primates".}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {48}, pages = {e19902}, doi = {10.1002/advs.202519902}, pmid = {41235547}, issn = {2198-3844}, }
@article {pmid41235805, year = {2026}, author = {Hashimoto, Y and Reddie, I and Louw, Z and Gillies, M}, title = {Macular Atrophy in the Better-Seeing Eye of Australian Patients Treated for Neovascular Age-Related Macular Degeneration.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {54}, number = {2}, pages = {295-297}, doi = {10.1111/ceo.70032}, pmid = {41235805}, issn = {1442-9071}, support = {//Roche/ ; //Bayer/ ; 1195021//National Health and Medical Research Council/ ; //Astellas/ ; //Apellis/ ; }, }
@article {pmid41236117, year = {2025}, author = {Singerman, L and Gugiu, C and Tschosik, E and Doll, H and Singerman, B and Gentile, B}, title = {DERIVATION OF A SHORT FORM OF THE NATIONAL EYE INSTITUTE VISUAL FUNCTION QUESTIONNAIRE-25 IN SUBJECTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {12}, pages = {2319-2328}, pmid = {41236117}, issn = {1539-2864}, mesh = {Humans ; *Visual Acuity/physiology ; Psychometrics ; Female ; Male ; Surveys and Questionnaires ; Aged ; *Wet Macular Degeneration/physiopathology/drug therapy ; *National Eye Institute (U.S.) ; Angiogenesis Inhibitors/therapeutic use ; Reproducibility of Results ; United States ; Ranibizumab/therapeutic use ; *Sickness Impact Profile ; Aged, 80 and over ; *Quality of Life ; Middle Aged ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; }, abstract = {PURPOSE: Develop a short form of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) using Rasch methodology in patients with neovascular age-related macular degeneration.<br><br>METHODS: Data on 32 items of the NEI VFQ-25 were analyzed from 1,294 patients in 3 studies of ranibizumab in neovascular age-related macular degeneration. Items were first grouped by visual function type; iterative multiple-group rating scale Rasch analyses were used to derive the Visual Function Questionnaire-Short Form (VFQ-SF). Item and scale-level VFQ-SF psychometric properties were assessed with estimation of meaningful within-patient change.<br><br>RESULTS: Fourteen of 32 items were eliminated initially; the final optimal subset included 7 items measuring 5 domains. The seven-item VFQ-SF had strong internal consistency (average item-total correlation 0.67, Cronbach alpha 0.88), test-retest reliability (intraclass correlation coefficient 0.79-0.91), and high NEI VFQ-25 composite score correlation (r = 0.93). Convergent (mean r = 0.76) and divergent (mean r = 0.24) validity were demonstrated. Known-groups validity was shown by mean VFQ-SF scores monotonically increasing with best-corrected visual acuity severity categories with large between group effect sizes (>2.8). Responsiveness was confirmed with VFQ-SF change linearly related to best-corrected visual acuity change. A meaningful within-patient change estimate of seven points was derived.<br><br>CONCLUSION: The seven-item VFQ-SF measures composite vision-related functioning, met all psychometric benchmarks, and is fit-for-purpose in neovascular age-related macular degeneration patients.}, }
@article {pmid41237838, year = {2026}, author = {Wei, Y and Hu, X and Liu, Y and Zhang, J and Zhao, L and Yang, J and Xie, Z and Shi, D and Ma, L}, title = {ALKBH5-mediated m6A modification of ID2 mRNA promotes choroidal neovascularization and subretinal fibrosis.}, journal = {Cellular signalling}, volume = {138}, number = {}, pages = {112237}, doi = {10.1016/j.cellsig.2025.112237}, pmid = {41237838}, issn = {1873-3913}, mesh = {*Choroidal Neovascularization/genetics/metabolism/pathology ; Animals ; Humans ; *AlkB Homolog 5, RNA Demethylase/metabolism/genetics ; *RNA, Messenger/metabolism/genetics ; Mice ; Fibrosis ; *Adenosine/analogs &amp; derivatives/metabolism ; Mice, Inbred C57BL ; Retina/pathology/metabolism ; RNA-Binding Proteins/metabolism ; Macular Degeneration/genetics/pathology/metabolism ; Disease Models, Animal ; Cell Movement ; Male ; }, abstract = {Choroidal neovascularization (CNV) and subretinal fibrosis are pivotal in the pathogenesis of wet age-related macular degeneration (wAMD) and contribute significantly to blindness. The role of N6-methyladenosine (m6A) modifications in the progression of wAMD remains unclear. This study identifies a significant upregulation of the RNA demethylase A-ketoglutarate dioxygenase ALKB homolog 5 (ALKBH5) in macular samples of wAMD donors. Mechanistically, ALKBH5 enhances retinal microvascular endothelial cell (RMEC) migration, angiogenesis, and endothelial-mesenchymal transition (EndMT) by upregulating DNA binding/differentiation protein 2 (ID2). Further analysis reveals that ALKBH5 interacts with the YTHDF2 binding domain of the m6A reader, which recognizes the m6A sequence on ID2 mRNA. This interaction stabilizes ID2 mRNA and modulates its m6A methylation, thereby influencing the epigenetic network in wAMD. In laser-induced CNV mouse models, ALKBH5 knockdown significantly inhibits CNV and subretinal fibrosis while protecting the retinal photoreceptor layer, thus preserving visual function. This study highlights the ALKBH5-YTHDF2-ID2 axis as a critical regulator in wAMD and suggests it as a novel therapeutic target for subretinal fibrosis in wAMD.}, }
@article {pmid41237938, year = {2026}, author = {Wang, Y and Xia, Z and Jia, L and Zhang, K and Wei, P and Han, G}, title = {Metabolomic biomarkers across plasma, serum, and ocular fluids in age-related macular degeneration: narrative review and evidence synthesis.}, journal = {Experimental eye research}, volume = {262}, number = {}, pages = {110749}, doi = {10.1016/j.exer.2025.110749}, pmid = {41237938}, issn = {1096-0007}, mesh = {Humans ; *Biomarkers/metabolism/blood ; *Macular Degeneration/metabolism/blood/diagnosis ; *Metabolomics/methods ; *Aqueous Humor/metabolism ; Disease Progression ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss globally. It is a degenerative disorder characterized by progressive macular damage and systemic metabolic dysregulation. Metabolomics elucidates relationships between metabolic alterations and disease phenotypes, providing scientific foundation for biomarker-driven predictive diagnostics. Current AMD staging predominantly relies on a linear classification based on clinical symptoms and imaging phenotypes. But metabolic alterations often precede morphological changes, providing a crucial window for early screening and intervention. Recent multi-biofluid metabolomic studies have identified key metabolic biomarkers, including glycerophospholipid pathway metabolites, acylcarnitines, branched-chain amino acids, and adenosine. They are predictive of transition from non-advanced to advanced stages. This review summarizes stage-specific metabolic biomarkers across AMD progression, such as 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (18:0-20:4 PC), sphingosylphosphorylcholine (LysoSM[d18:1]), lysophosphatidylcholine (LysoPC[18:4]), short-chain acylcarnitines (e.g., acetylcarnitine [C2]), long-chain acylcarnitines (e.g., linoleoylcarnitine [C18:2]), and valerylcarnitine (C5). These biomarkers may allow for timely intervention before irreversible visual impairment and underscore the importance of differential metabolic signatures between stable and progressive stages for early disease management. By unveiling the dynamic changes of these critical metabolites, and providing evidence for their prognostic value in stage transition, this review proposes an evidence-based foundation for early risk stratification and precision intervention in AMD.}, }
@article {pmid41242720, year = {2025}, author = {Zheng, X and Mi, Y and Cao, Y and Tong, L and Wan, M}, title = {Plasma caffeine level as a protective factor against age-related eye diseases: a two-sample Mendelian randomisation study.}, journal = {The British journal of nutrition}, volume = {}, number = {}, pages = {1-7}, doi = {10.1017/S0007114525105291}, pmid = {41242720}, issn = {1475-2662}, abstract = {Traditional studies examining caffeine intake and age-related eye diseases (ARED) have shown inconsistent results, potentially related to variations in caffeine assessment methods. This two-sample Mendelian randomisation study investigated associations between plasma caffeine and four ARED: senile cataract, diabetic retinopathy (DR) and glaucoma and age-related macular degeneration (AMD). Summary data on genetically predicted plasma caffeine came from a genome-wide association study of 9876 European-ancestry participants across six population-based studies. ARED data were extracted from FinnGen Consortium clinical records. We further examined causal effects on glaucoma subtypes: primary open-angle glaucoma (POAG) and primary angle closure glaucoma (PACG) and assessed intraocular pressure (IOP) as a potential mediator. Higher genetically predicted plasma caffeine levels were associated with reduced risk of senile cataract (OR 0·84, 95 % CI 0·78, 0·90, P < 0·001), DR (OR 0·81, 95 % CI 0·74, 0·88, P < 0·001), glaucoma (OR 0·83, 95 % CI 0·73, 0·95, P = 0·008) and PACG (OR 0·74, 95 % CI 0·54, 0·99, P = 0·046). No associations were observed with AMD or POAG. Mediation analysis suggested that 41 % (95 % CI −0·14, −0·01) of caffeine’s effect on glaucoma was mediated by IOP. Our findings indicate that elevated plasma caffeine may protect against senile cataract, DR and glaucoma, but not AMD. Effects differed by glaucoma subtype, with IOP partially explaining the overall association. This study provides genetic evidence supporting caffeine’s role in mitigating ARED risk, highlighting its potential therapeutic implications.}, }
@article {pmid41243864, year = {2025}, author = {Cui, Y and Li, H and Fan, W and Wu, H and Wang, J and Qu, C and Pu, N and Tao, Y}, title = {Dialogue Between the Clock Gene Bmal1 and Retinopathy: What Is the Exact Relationship?.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {31}, number = {11}, pages = {e70490}, pmid = {41243864}, issn = {1755-5949}, support = {221100310200//the Science and Technology Major Project of Henan Province/ ; 224200510013//the Zhongyuan Science and Technology Leading Talent Project/ ; }, mesh = {Humans ; *ARNTL Transcription Factors/genetics/metabolism ; Animals ; Circadian Rhythm/physiology/genetics ; *Retinal Diseases/genetics/metabolism ; Circadian Clocks/genetics/physiology ; Retina/metabolism ; CLOCK Proteins/genetics ; Diabetic Retinopathy/genetics ; }, abstract = {BACKGROUND: Circadian clock coordinates the physiologic and behavioral activities with a 24-hour solar rhythm to maintain the temporal homeostasis of the body. In the mammalian retina, the circadian system regulates the physiological function of this organ. The realm of ocular circadian rhythm has earned kinds of research interest as the circadian rhythms dysfunction will disrupt the retinal homeostasis. Bmal1 functions as a major transcriptional regulator of the circadian clock.<br><br>RESULTS: In the retina, Bmal1 mediates the processing of light information, sustains photoreceptor viability and governs neurotransmitter release. Moreover, Bmal1 gene is believed to be a pathologic cofactor of the diabetic retinopathy (DR), age-related macular degeneration (AMD), premature aging and refractive myopia. To date, the precise mechanisms underlying the pathological effects mediated by Bmal1 remain incompletely elucidated.<br><br>CONCLUSIONS: This review presents recent findings and evidence regarding the contributory role of Bmal1 in retinal degeneration and its deficits, while exploring its therapeutic potential. And th review provides a comprehensive analysis of the underlying mechanisms of the clock gene Bmal1 in other diseases, with the aim of offering insights into innovative therapeutic strategies for retinopathy.}, }
@article {pmid41244030, year = {2025}, author = {Momenaei, B and Wakabayashi, T and Adams, OE and Wang, K and Regillo, CD and Spirn, M and Ho, AC and Hsu, J and Kaiser, R and Yonekawa, Y and Orlin, A and Garg, SJ}, title = {Short-Term Changes in Intraocular Pressure Following Intravitreal Injection of Pegcetacoplan.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251390791}, pmid = {41244030}, issn = {2474-1272}, abstract = {Purpose. To determine short-term changes in intraocular pressure (IOP) after intravitreal injection of 0.1 mL pegcetacoplan (Syfovre; Apellis Pharmaceuticals) for the treatment of geographic atrophy (GA). Methods. This prospective, interventional study evaluated a case series of patients with GA without corneal pathology or a history of vitreoretinal surgery who received pegcetacoplan injections. IOP was measured with a handheld applanation tonometer immediately prior to injection, immediately after injection, and at 5, 10, 20, and 30 minutes postinjection. Results. Fifty-one patients (total 73 eyes) were enrolled. The mean (±SD) preinjection IOP was 15.3 ± 3.3 mm Hg, which significantly increased to 40.2 ± 13.7 mm Hg (P < .001) immediately after injection. Subsequent IOP measurements showed a gradual decrease to 31.3 ± 11.6 mm Hg at 5 minutes (P < .001), 23.2 ± 9.7 mm Hg at 10 minutes (P < .001), 19.6 ± 8.6 mm Hg at 20 minutes (P < .001), and 16.4 ± 4.9 mm Hg at 30 minutes (P = .05) postinjection. No further treatment was required, except that the left eye of 1 patient with a history of primary open-angle glaucoma and persistent IOP elevation underwent anterior chamber tap 20 minutes after injection. Multivariate linear regression analysis revealed that a higher IOP at 30 minutes postinjection was significantly associated with the preinjection IOP (P = .004) and with a history of glaucoma (P = .019). Conclusions. Following pegcetacoplan injections, immediate IOP elevation was observed, which gradually declined within the first 30 minutes. Eyes with higher baseline IOP or a history of glaucoma exhibited higher postinjection IOP.}, }
@article {pmid41244346, year = {2025}, author = {Wang, Y and Jiang, D and Wang, Q and Cao, Y and Guo, H and Lu, Y and Tian, F}, title = {Three-dimensional tissue engineering and organoid technologies for retinal regeneration and therapy.}, journal = {Bioengineering &amp; translational medicine}, volume = {10}, number = {6}, pages = {e70051}, pmid = {41244346}, issn = {2380-6761}, abstract = {The human eye, a masterpiece of evolution, orchestrates the intricate process of vision. The retina is a tissue with a layered structure that plays a critical role in converting light signals into neural impulses interpretable by the brain. Various eye conditions such as glaucoma, retinitis pigmentosa, age-related macular degeneration, and other retinopathies are characterized by damage or degeneration in the retina. Recent strides in organoid cultivation and advanced three-dimensional (3D) bioengineering technologies offer promising avenues for potential therapeutic interventions. Compared to traditional two-dimensional cell culture models, which are non-natural and limited in accuracy, 3D models, including organoids, electrospinning constructs, microfabrication-based scaffolds, and hydrogel systems, are more delicate, especially in recapitulating tissue architecture, offering spatial patterning, and enabling vascularization. Retinal organoids are 3D multicellular structures derived from stem cells that can mimic the retina's layered architecture and functionality. However, their inherent complexity, including the presence of multiple differentiated cell types, may not be necessary for all disease modeling applications. In contrast, engineered 3D technologies can be tailored to specific retinal diseases by incorporating only the most relevant cell types, matrix stiffness, and spatial arrangements, offering greater experimental control and reproducibility in targeted therapeutic testing. In the following paper, we will discuss organoid generation in detail. Besides retinal organoids, bioprinting is another promising avenue for regenerative medicines. We further review a suite of 3D fabrication strategies, including inkjet and laser-assisted bioprinting, electrospun scaffolds, and hydrogel systems, and evaluate their current and potential applications in modeling retinal diseases and developing translational therapies. We will also delve into the contemporary advancements in retinal therapies, particularly emphasizing the roles and prospects of organoid and engineered 3D technologies.}, }
@article {pmid41244990, year = {2026}, author = {Tan, JCK and Montesano, G and Behning, C and Dunbar, HMP and Finger, RP and Tufail, A and Terheyden, JH and Holz, FG and Luhmann, UFO and Crabb, DP and , }, title = {Using the Rate of Global and Pointwise Microperimetry Change to Predict Structural Conversion in Intermediate Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100950}, pmid = {41244990}, issn = {2666-9145}, abstract = {PURPOSE: Studies evaluating functional change in age-related macular degeneration (AMD) using microperimetry often measure the difference in global mean sensitivity at interval time points versus baseline. We evaluate the rate of global and pointwise microperimetry change in intermediate AMD (iAMD) in the multicenter MACUSTAR (Registration NCT03349801) study and assess their prognostic value in structural conversion to late-stage AMD.<br><br>DESIGN: Prospective study.<br><br>SUBJECTS: Four hundred forty-seven subjects with iAMD (Beckman classification) from 20 European sites.<br><br>METHODS: Subjects that underwent mesopic microperimetry on &#x2265;3 follow-up visits were included. Two methods of assessing functional progression were evaluated: (1) global mean sensitivity regression and (2) pointwise sensitivity regression at fastest progressing N number of locations (N from 1 to 10). Rates of microperimetry progression were then evaluated in an initial series of visits prior to structural conversion to late-stage AMD.<br><br>MAIN OUTCOME MEASURES: Area under the receiving operating characteristic (AUC) curves and Cox proportional hazard models were used to assess risk of structural conversion based on rate of functional progression.<br><br>RESULTS: The mean age of subjects was 72 (standard deviation 7) years. The median number of visits and duration of follow-up was 6 visits and 3 years, respectively. Structural conversion to late-stage AMD was observed in 80 (17.9%) eyes. In the visits prior to conversion, there was a greater rate of global mean sensitivity loss in eyes that eventually developed late-stage AMD compared with those that did not (-1.05 vs. -0.30 decibels/year, P < 0.001). The AUC for classifying structural conversion versus no conversion was 0.72 for global sensitivity progression and 0.75-0.76 for between 1 and 10 fastest progressing N pointwise locations. The rate of global (hazard ratio 1.7, confidence interval [CI] 1.4-2.0) and pointwise (hazard ratio 1.2, CI 1.2-1.3) microperimetry progression in the initial series of visits was significantly associated with structural conversion (P < 0.0001).<br><br>CONCLUSIONS: In the analysis of longitudinal microperimetry data from the MACUSTAR study, the rate of global and pointwise sensitivity change was significantly greater and strongly prognostic of eyes that developed structural conversion. Our findings support use of these trend-based pointwise analysis methods in assessing functional progression in iAMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41244992, year = {2026}, author = {Kleinman, DM and Wykoff, CC and Borkar, DS and Guymer, RH and Kocab, AJ and Puscas, L and Wietholter, SC and Kesteloot, LL and Zacks, DN}, title = {ONL1204 for the Treatment of Geographic Atrophy: Phase Ib Study Evaluating Safety, Tolerability, and Efficacy.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100954}, pmid = {41244992}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the safety and tolerability of ONL1204, a novel, small peptide inhibitor of the fragment apoptosis stimulator receptor, for the treatment of patients with geographic atrophy (GA).<br><br>DESIGN: A phase Ib multicenter study involving a dose-escalation/open-label (DE/OL) component and a randomized, double-masked, sham-controlled natural history/treatment (NHS/T) component.<br><br>PARTICIPANTS: Patients aged &#x2265;55 years with GA secondary to age-related macular degeneration.<br><br>METHODS: Dose-escalation/OL patients received a single intravitreal injection of either 50 &#x3bc;g, 100 &#x3bc;g, or 200 &#x3bc;g of ONL1204 and were followed for 24 weeks. Participants in the NHS/T component were randomized (1:1:1) to either 50 &#x3bc;g or 200 &#x3bc;g of ONL1204 or sham injection, after a 24-week NHS phase. Two injections were administered 12 weeks apart, and patients were observed for an additional 12 weeks.<br><br>MAIN OUTCOME MEASURES: The primary endpoint was safety, assessed by monitoring adverse events (AEs), ophthalmic examination, electrophysiology, fundus photography, fundus autofluorescence, and OCT. Additional endpoints included measurement of GA lesion area and best-corrected visual acuity.<br><br>RESULTS: Six patients were enrolled in the DE/OL component and 22 patients in the NHS/T component. All patients in the DE/OL component completed the study with no major safety findings or dose-limiting toxicities. Seventeen patients were randomized in the NHS/T component, with 15 patients completing the study. All ophthalmic AEs were mild or moderate in severity. ONL1204 demonstrated a favorable effect on GA lesion growth, with numerically favorable slower lesion growth compared with the fellow eye in the DE/OL component at 6 months and a numerically slower growth rate (mean difference [standard error of the mean] of -0.524 mm[2] [0.39]; P = 0.202) in the 200 &#x3bc;g ONL1204 group compared with the sham group in the treatment phase of the NHS/T component. There were no changes in the treatment group with respect to visual acuity suggestive of any safety issues.<br><br>CONCLUSIONS: ONL1204 was safe and well tolerated at all evaluated doses, with the potential to reduce GA lesion growth and improve vision. These results support further evaluation of ONL1204 in patients with GA.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41245253, year = {2025}, author = {Cen, S and Xie, S and Ibrahim, KS and Baran, MR and Li, X and Reilly, J and Tan, Z and He, Z and Shu, X}, title = {Modified Zhujing pill regulates RPE cholesterol metabolism and gut microbiota in an age-related macular degeneration mouse model.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1691360}, pmid = {41245253}, issn = {2235-2988}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Macular Degeneration/drug therapy/metabolism ; Mice ; Disease Models, Animal ; *Drugs, Chinese Herbal/pharmacology/administration &amp; dosage ; *Cholesterol/metabolism ; *Retinal Pigment Epithelium/metabolism/drug effects ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; Male ; Cytokines/metabolism ; Cecum/microbiology ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a common retinal disorder, causing blindness in aged individuals. One of the traditional Chinese medicines, modified Zhujing pill (MZP), has been widely used to treat various ocular disorders, including AMD; however, its protective mechanisms remain elusive. In this study, we explored the functional role of MZP in high-fat-diet-fed mice, a commonly used model for AMD.<br><br>METHODS: Compounds of MZP water extract were identified by high-performance liquid chromatography (HPLC)/mass spectrometry (MS)/MS. The mice were divided into three groups: group 1 mice fed with control diet (CD), group 2 mice fed with high-fat diet (HFD), and group 3 mice fed with HFD for 12 weeks; groups 1 and 2 were then treated with physiological saline, while group 3 was treated with MZP for 4 weeks. The cholesterol level and expression of cholesterol homeostasis-associated genes, antioxidant genes, and proinflammatory cytokines in mouse tissues were measured using biochemical approaches. Mouse cecum microbiota compositions and metabolic functions were analyzed using 16rRNA sequencing and bioinformatics approach.<br><br>RESULTS: HFD-fed mice had high levels of cholesterol in the retinal pigment epithelial (RPE) cells, liver, and serum, a decreased expression of cholesterol homeostasis-associated genes and antioxidant genes in the RPE and liver, and an increased expression of proinflammatory cytokines. MZP treatment counteracted HFD-induced pathologic effects. Additionally, HFD altered cecum bacterial compositions and diversities associated with individual metabolic pathways. These metabolic pathways are involved in the biosynthesis of bacterial metabolites, mitochondrial function, oxidative stress, and inflammation. MZP reversed most of the changes back to control characteristics.<br><br>CONCLUSION: We postulate that the beneficial effects of MZP against AMD are possibly related to lowering the cholesterol level, suppressing oxidative stress and inflammation, and modulating gut microbiota and associated functions.}, }
@article {pmid41247474, year = {2026}, author = {Vahldiek, A and Heine, L and Vahldiek, B and Schröter, J and Wolf, JN and Swora, M and Reissberg, L and Pauleikhoff, L and Kleesiek, J and Pauleikhoff, D}, title = {Automated measurement of macular neovascularization lesion size in nAMD using AI segmentation.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {455-463}, pmid = {41247474}, issn = {1435-702X}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; Aged ; *Wet Macular Degeneration/diagnosis/drug therapy/complications ; *Artificial Intelligence ; *Fluorescein Angiography/methods ; Follow-Up Studies ; *Macula Lutea/pathology ; Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; Fundus Oculi ; Intravitreal Injections ; Aged, 80 and over ; }, abstract = {PURPOSE: To compare artificial intelligence (AI)-based annotations of hyperreflective material (HRM) and manual demarcation of macular neovascularization (MNV) on optical coherence tomography (OCT) volume scans in neovascular age-related macular degeneration (nAMD), and to assess the suitability of AI-driven OCT segmentation for longitudinal lesion monitoring.<br><br>METHODS: In this retrospective study, 42 eyes from 36 patients (21 f, 15&#xa0;m; mean age baseline 76.6 y) with exudative nAMD were analyzed using longitudinal spectral-domain OCT data. Manual MNV demarcations on en-face OCT projections served as ground truth and were compared to AI-predicted HRM segmentations generated by a 3D nU-Net model on OCT scans. HRM and MNV lesion areas were quantified at multiple time points, and agreement between manual and AI-based measurements was evaluated using Pearson correlation, ordinary least squares regression and robust regression.<br><br>RESULTS: A highly similar mean lesion growth was observed when comparing HRM/MNV lesion sizes in longitudinal measurements. Point-by-point comparison revealed a strong overall correlation (r&#x2009;=&#x2009;0.78) between AI-predicted and manually annotated HRM areas with increasing significance with longer follow-up. However, two aspects were responsible for some AI measurements being larger than manual measurements: At baseline, AI measurements included hyperreflective subretinal fluid as HRM, which was resorbed after three anti-VEGF injections, and during longer-term follow-up, manually annotated MNV areas were occasionally smaller than those derived from AI-based HRM segmentation due to the manual underestimation of very thin HRM.<br><br>CONCLUSIONS: AI-based segmentation of HRM on OCT scans demonstrates strong overall agreement with manual MNV measurements, particularly on longitudinal assessments. Despite some AI-based overestimations occurring at baseline and some manual MNV underestimations during follow-up, measurements between both methods were highly comparable over time.}, }
@article {pmid41247476, year = {2026}, author = {Rosso, WC and Chakravarthy, U and Girado, SEM and Rosenstiehl, S and Peto, T and Rodriguez, FJ}, title = {Characterization of subretinal hyperreflective material and short-term visual acuity in patients with neovascular age related macular degeneration after loading dose with antiangiogenics.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {465-471}, pmid = {41247476}, issn = {1435-702X}, mesh = {Humans ; *Visual Acuity ; Female ; Aged ; Tomography, Optical Coherence/methods ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Intravitreal Injections ; Fluorescein Angiography/methods ; Follow-Up Studies ; Retrospective Studies ; Fundus Oculi ; *Ranibizumab/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Time Factors ; Dose-Response Relationship, Drug ; Treatment Outcome ; Bevacizumab/administration &amp; dosage ; *Retina/pathology ; Recombinant Fusion Proteins/administration &amp; dosage ; }, abstract = {PURPOSE: This study analyzes the morphological characteristics of subretinal hyperreflective material (SHRM) and its relationship with short-term visual outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial grown factor (anti-VEGF) at the Fundación Oftalmológica Nacional between 2011 and 2017.<br><br>METHODOLOGY: An analytical observational study was conducted on 65 treatment-na&#xef;ve nAMD patients who initiated treatment between January 2011 and December 2017. Spectral-Domain Optical Coherence Tomography (SD-OCT) was graded to determine quantitative and qualitative SHRM characteristics. SHRM features and best corrected visual acuity (BCVA) were correlated before and after treatment, and associations between SHRM characteristics and BCVA improvement after the loading phase were analyzed.<br><br>RESULTS: The median age was 75.5 years (range 68-84), and 56.9% were women. Aflibercept was the most widely used anti-VEGF (40%). Median BCVA improved from 0.8 logMAR (range 0.5-1.2) to 0.7 logMAR (range 0.4-1) after treatment. At baseline, a significant correlation was found between worse BCVA and SHRM horizontal extension (r=0.7, p=0.001), low reflectivity (p=0.017), and undefined margins (p=0.037). SHRM characteristics associated with BCVA improvement after treatment included low reflectivity (p=0.048), non-homogeneity (p=0.048), smaller width (p=0.043), and the presence of the external limiting membrane (ELM) (p=0.002) and ellipsoid zone (EZ) (p=0.017).<br><br>CONCLUSION: SHRM features such as low reflectivity, non-homogeneity, reduced width, and the presence of ELM/EZ were associated with improved short-term visual outcomes. These findings provide insight into favorable short-term SHRM characteristics, which may help establish early treatment criteria and support its role as a prognostic biomarker.<br><br>KEY MESSAGES: WHAT IS KNOWN : Neovascular age-related macular degeneration (nAMD) is a progressive disease that severely impacts vision if untreated. Subretinal hyperreflective material (SHRM) is a recognized biomarker on spectral-domain optical coherence tomography (SD-OCT) and has been studied as a predictor of long-term visual outcomes in patients treated with anti-VEGF therapy.<br><br>WHAT IS NEW: This study evaluates SHRM characteristics and their relationship with short-term visual outcomes after the loading dose of anti-VEGF treatment.SHRM features such as low reflectivity, undefined borders, smaller horizontal extent, and the presence of external limiting membrane (ELM) and ellipsoid zone (EZ) are associated with early visual improvement. SHRM features such as low reflectivity, undefined borders, smaller horizontal extent, and the presence of external limiting membrane (ELM) and ellipsoid zone (EZ) are associated with early visual improvement. These findings suggest that SHRM morphology could serve as an early prognostic biomarker, potentially guiding treatment decisions for better visual outcomes.}, }
@article {pmid41248230, year = {2026}, author = {Fragiotta, S and Sacconi, R and Beretta, F and Querques, G}, title = {Basal Laminar Deposits and Pseudodrusen: Rethinking Their Role in Age-Related Macular Degeneration Progression.}, journal = {Retina (Philadelphia, Pa.)}, volume = {46}, number = {3}, pages = {399-409}, doi = {10.1097/IAE.0000000000004683}, pmid = {41248230}, issn = {1539-2864}, mesh = {Humans ; *Retinal Drusen/diagnosis ; Disease Progression ; *Macular Degeneration/diagnosis ; *Retinal Pigment Epithelium/pathology ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Fundus Oculi ; Eye Diseases, Hereditary ; Bruch Membrane/pathology ; }, abstract = {PURPOSE: To explore the association between basal laminar deposits (BLamD) and pseudodrusen and its clinico-prognostic significance in the context of age-related macular degeneration (AMD).<br><br>METHODS: A comprehensive narrative review of the literature was conducted, focusing on histopathological, clinical, and imaging studies that examine BLamD and subretinal drusenoid deposits (SDD) in AMD. Histopathological and clinical studies were analyzed to understand the composition, distribution, and clinical significance of these deposits.<br><br>RESULTS: Imaging and histologic studies suggest that BLamD may serve as an indicator of AMD severity. BLamD is consistently observed in eyes with pseudodrusen and is characterized by a thin double-layer sign in vivo with a hyporeflective interior. On fundus autofluorescence, BLamD retain an intrinsic autofluorescence, leading to a dark grey appearance of the nascent atrophic lesions. The association with SDD, also known as reticular pseudodrusen, can synergically affect the outer retina and retinal pigment epithelium, leading to a rapidly progressive atrophy.<br><br>CONCLUSION: BLamD is a key pathologic feature in AMD, particularly in eyes with pseudodrusen. Their presence may contribute to disease progression, highlighting the need for further research into their prognostic significance and potential as therapeutic targets. A critical consideration is the need to improve multimodal imaging recognition, facilitating their identification in future clinical studies.}, }
@article {pmid41248269, year = {2025}, author = {Starr, MR and Bakri, SJ}, title = {Response to Letter to the Editor regarding: "10-year Follow-Up of Patients with Exudative Age-Related Macular Degeneration Treated with Intravitreal Anti-VEGF Injections".}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004729}, pmid = {41248269}, issn = {1539-2864}, }
@article {pmid41248379, year = {2025}, author = {Shumye, AF and Desalegn, GK and Tegegn, MT and Worku, EM and Lorato, MM and Bogale, ZM and Tegegne, MM and Alimaw, YA and Mengistu, HG and Bekele, MM and Bayabil, AZ and Birhan, GS and Eticha, BL}, title = {Burden and predictors of age-related macular degeneration among old age patients with diabetes attending comprehensive specialised hospitals in Northwest Ethiopia: a multicentre cross-sectional prospective study.}, journal = {BMJ open}, volume = {15}, number = {11}, pages = {e105305}, pmid = {41248379}, issn = {2044-6055}, mesh = {Humans ; Ethiopia/epidemiology ; Male ; Female ; Cross-Sectional Studies ; *Macular Degeneration/epidemiology/etiology ; Aged ; Middle Aged ; Prospective Studies ; Risk Factors ; Hospitals, Special/statistics &amp; numerical data ; *Diabetes Mellitus/epidemiology ; Prevalence ; Aged, 80 and over ; Adult ; Age Factors ; }, abstract = {OBJECTIVE: This study aims to assess the burden and predictors of age-related macular degeneration (AMD) among older age patients with diabetes attending comprehensive specialised hospitals in Northwest Ethiopia.<br><br>DESIGN: A multicentre cross-sectional study was conducted among older patients with diabetes using a systematic random sampling technique.<br><br>SETTING: The study was conducted at five comprehensive specialised hospitals in Northwest Ethiopia from 8 May to 8 June 2023.<br><br>PARTICIPANTS: The study included 832 diabetic individuals aged 40 years and above.<br><br>MAIN OUTCOME MEASURES: Data were collected using a pretested structured questionnaire and physical examinations.<br><br>RESULT: In this study, a total of 832 participants were involved, with a response rate of 96.85%. The burden of AMD was 15.4% (95% CI 13.0% to 18.0%). Male sex (adjusted OR (AOR) 2.04, 95%&#x2009;CI 1.17 to 3.56), older age (AOR 6.91, 95%&#x2009;CI 3.17 to 15.08), diabetes duration of 10 and more years (AOR 3.00, 95%&#x2009;CI 1.91 to 4.69), higher body mass index (AOR 2.56, 95%&#x2009;CI 1.15 to 5.71), presence of hypertension (AOR 2.45, 95%&#x2009;CI 1.56 to 3.85) and family history of diabetes mellitus (DM) (AOR 2.29, 95%&#x2009;CI 1.40 to 3.76) were positively associated with AMD.<br><br>CONCLUSIONS: This study found that the prevalence of AMD among patients with diabetes was 15.4%. Older age, male sex, longer DM duration, higher body mass index, presence of hypertension and family history of DM were significantly associated with AMD. Targeted screening of at-risk individuals for AMD, public health awareness campaigns focusing on these factors and further research to understand the burden and underlying mechanisms of these associations with AMD are recommended.}, }
@article {pmid41251528, year = {2025}, author = {Singh, SR and Sadeghi, E and Schulman, A and Du, K and Gandhi, P and Narayan, SA and Arora, S and Ibrahim, MN and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Chhablani, J}, title = {Comparison of Three-Dimensional Choroidal Contour in Patients With Neovascular Age-Related Macular Degeneration and Their Fellow Eyes.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {11}, pages = {26}, pmid = {41251528}, issn = {2164-2591}, support = {P30 EY008098/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Cross-Sectional Studies ; *Choroid/diagnostic imaging/pathology ; *Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; *Wet Macular Degeneration/diagnostic imaging ; *Imaging, Three-Dimensional/methods ; Aged, 80 and over ; *Choroidal Neovascularization ; Middle Aged ; Macular Degeneration ; }, abstract = {PURPOSE: To compare the three-dimensional choroidal contour map of patients with neovascular age-related macular degeneration (nAMD) and their fellow eyes.<br><br>METHODS: This cross-sectional study included 30 patients with nAMD in one eye and early/intermediate AMD in the fellow eye. Wide-field (12 &#xd7; 12 mm) swept source optical coherence tomography volumetric scans were obtained. Choroidal inner boundaries (CIBs) and choroidal outer boundaries (COBs) were delineated based on our previously reported deep learning model. Best-fit spherical radius (R, mm) was calculated for CIB and COB and compared in both groups using paired t tests. The regional variation of RCIB and RCOB in different sectors (superior, inferior, nasal, temporal, and central) was compared. P values of &#x2264;0.05 were considered statistically significant.<br><br>RESULTS: The mean RCIB was 32.8 &#xb1; 8.6 mm and 32.5 &#xb1; 9.4 mm in nAMD group and their fellow eyes, respectively (P = 0.80). Similarly, the mean RCOB was 31.3 &#xb1; 7.0 mm in the nAMD group with no statistically significant variation in their fellow eyes (early/intermediate AMD, 31.5 &#xb1; 9.0 mm; P = 0.88). Comparison of RCIB (nAMD, 15.0 &#xb1; 9.1 mm; fellow eye, 15.2 &#xb1; 10.4 mm; P = 0.91) and RCOB (nAMD, 13.6 &#xb1; 8.1 mm; fellow eye, 12.2 &#xb1; 9.0 mm; P = 0.48) in the central sector where AMD lesions were located was not significant. Intragroup sectoral comparisons of RCIB and RCOB in both groups were statistically significant (all P values < .01).<br><br>CONCLUSIONS: RCIB and RCOB exhibited significant regional variations across different sectors in both eyes, including nAMD and fellow eyes. However, the comparison of RCIB and RCOB between the two groups was not significantly different.<br><br>TRANSLATIONAL RELEVANCE: The study of choroidal contour may help to understand the pathological changes in age-related macular degeneration.}, }
@article {pmid41254090, year = {2025}, author = {Wolfram, L and Schwämmle, M and Gimpel, C and Merle, DA and Tang, J and Clark, SJ and Böhringer, D and Schlunck, G}, title = {Extracellular matrix stiffness modulates angiogenic properties of the retinal pigment epithelium.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {40349}, pmid = {41254090}, issn = {2045-2322}, mesh = {*Retinal Pigment Epithelium/metabolism/cytology ; *Extracellular Matrix/metabolism ; Humans ; *Neovascularization, Physiologic ; Cell Line ; Vascular Endothelial Growth Factor A/metabolism ; Culture Media, Conditioned/pharmacology ; Thrombospondin 1/metabolism ; Bruch Membrane/metabolism ; Macular Degeneration/metabolism/pathology ; }, abstract = {Physiological and pathological processes, such as aging and basal deposit aggregation in degenerative retinal diseases like age-related macular degeneration (AMD), alter the mechanical properties of Bruch's membrane (BrM). These mechanical changes in the extracellular matrix (ECM) significantly affect retinal pigment epithelial (RPE) cells, influencing their morphology, transcriptome and angiogenic behavior. ARPE-19 cells were cultured on hydrogels of physiological stiffness (30 and 80 kPa) and on conventional tissue culture plastic (TCP) for comparison. Gene expression was analyzed by droplet digital PCR (ddPCR), while protein-level changes were examined using immunofluorescence (IF), Western blotting (WB) and enzyme-linked immunosorbent assays (ELISA). Stiffness-dependent modulation of endothelial cells by RPE-conditioned media was investigated using in vitro angiogenesis assays. RPE cells cultured on softer substrates exhibited enhanced angiogenic properties, including increased expression of CD44 and vascular endothelial growth factor (VEGF). In contrast, stiffer substrates promoted antiangiogenic responses, associated with altered distribution of thrombospondin 1 (THBS1). These findings underscore the importance of ECM mechanics in modulating angiogenic signaling and highlight their potential relevance in retinal pathologies such as AMD. Local disruptions in adhesion or mechanical cues, potentially caused by basal deposits, may contribute to proangiogenic behavior even in the context of globally increased tissue stiffness with age.}, }
@article {pmid41258038, year = {2025}, author = {Barbosa, M and Bartolomeo, N and Schuetz, YP and Nascimbeni, AC and Castro, DG and Barry, MP and Ambresin, A}, title = {Intravitreal faricimab in patients with aflibercept-refractory neovascular age-related macular degeneration: short and long-term outcomes and assessment of volume dynamics using an artificial intelligence-based tool.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {126}, pmid = {41258038}, issn = {2056-9920}, abstract = {PURPOSE: This study assessed the short- and long-term outcomes of intravitreal (IVT) faricimab treatment in patients with neovascular age-related macular degeneration (nAMD) refractory to aflibercept. The main aim was to investigate whether faricimab might enable longer treatment intervals versus aflibercept through improved fluid control, evaluated through use of an artificial intelligence-based quantification tool to evaluate retinal fluid dynamics.<br><br>METHODS: This observational cohort study involved patients with refractory nAMD who received at least three consecutive IVT aflibercept 2.0&#xa0;mg injections before switching to IVT faricimab (with a four-month loading phase followed by a treat-and-extend regimen) due to persistent or recurrent disease despite 4-8-week treatment intervals. Functional and anatomical outcome measures were recorded, and fluid volume dynamics were quantified, at baseline, monthly to Month 4, and at Months 6, 9, and 12.<br><br>RESULTS: Seventy-four eyes from 60 patients were included, with a mean&#x2009;&#xb1;&#x2009;standard deviation duration of prior aflibercept therapy of 24&#x2009;&#xb1;&#x2009;17 months. Fifty-two eyes completed 12-month follow-up. At Month 12, mean best-corrected visual acuity showed no significant change from baseline (+&#x2009;0.01 Early Treatment of Diabetic Retinopathy Study letters, p&#x2009;=&#x2009;0.64). Significant reductions in mean central retinal thickness (-&#x2009;80.8&#xa0;&#x3bc;m, p&#x2009;=&#x2009;0.0001) and maximal pigment epithelium detachment (PED) height (-&#x2009;28.2&#xa0;&#x3bc;m, p&#x2009;=&#x2009;0.011), were observed at Month 4 and maintained to Month 12. Mean fluid volumes (intraretinal fluid [IRF], subretinal fluid [SRF]), and PED decreased significantly at Month 4 (-&#x2009;26.3 nL, p&#x2009;=&#x2009;0.007; -41.5 nL, p&#x2009;=&#x2009;0.0001; and -&#x2009;175.4 nL, p&#x2009;=&#x2009;0.0001, respectively). At Month 12, reductions in IRF and PED volumes were sustained. The maximal fluid-free interval increased from 4.4 weeks, prior to switching to faricimab, to 6.5 weeks (p&#x2009;=&#x2009;0.001) after switching, while mean last treatment interval improved from 5.0&#x2009;&#xb1;&#x2009;1.4 weeks at baseline to 7.3&#x2009;&#xb1;&#x2009;2.6 weeks at month 12 (p&#x2009;<&#x2009;0.0001).<br><br>CONCLUSION: Faricimab may offer a valuable alternative for patients with refractory nAMD. The use of four loading injections administered monthly, followed by a treat-and-extend regimen can result in maintenance of visual acuity and improve anatomical parameters and retinal fluid activity, allowing for longer treatment intervals.}, }
@article {pmid41258608, year = {2025}, author = {Sun, Y and Zhang, WY and Song, CL and Pan, ZQ and Du, GJ and Song, ZQ and Ren, J and Bo, LY and An, JJ and Wang, M}, title = {Effects of Plastein Reaction Mediated Corn Glutelin Hydrolysate on the Structure and Its Anti-Inflammatory Activity of ARPE-19 Cells in Vitro.}, journal = {Journal of food science}, volume = {90}, number = {11}, pages = {e70650}, doi = {10.1111/1750-3841.70650}, pmid = {41258608}, issn = {1750-3841}, support = {TSBICIP-KJGG-022//Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project/ ; 22HHSWSS00001//"Major Project" of Haihe Laboratory of Synthetic Biology/ ; 130212124135//Heilongjiang Education Department of Basic Business Project of China/ ; 145309403//Heilongjiang Education Department of Basic Business Project of China/ ; }, mesh = {*Anti-Inflammatory Agents/pharmacology/chemistry ; Humans ; *Protein Hydrolysates/chemistry/pharmacology ; Cell Line ; *Glutens/chemistry/pharmacology ; Antioxidants/pharmacology/chemistry ; *Zea mays/chemistry ; Amino Acids/chemistry ; Tumor Necrosis Factor-alpha/metabolism ; Retinal Pigment Epithelium/drug effects/cytology ; Interleukin-6/metabolism/immunology ; Interleukin-1beta/metabolism ; }, abstract = {Corn glutelin hydrolysate (CGH) has demonstrated potential diverse biological activities; however, its application in the food industry is often limited by physicochemical properties (e.g., peptide instability, solubility, or essential amino acid deficiency). The Plastein reaction, a very safe chemical reaction, involving exogenous amino acids (AAs), shows promise in altering the functionality of CGH. In this study, CGH was modified via the Plastein reaction using histidine, cysteine, or tryptophan to generate CGH-His, CGH-Cys, and CGH-Trp. These modified products with superior antioxidant activity and functional characteristics were screened out, and their anti-inflammatory activity was evaluated via an LPS-induced retinal inflammation ARPE-19 cell model. The results indicated that the free amino group contents of all three AA-modified CGHs were significantly lower than those of their corresponding mixtures (P < 0.05). Among the modifiers, CGH-Trp exhibited a significantly enhanced DPPH radical scavenging rate (78.66%), hydroxyl radical scavenging rate (58.35%), ABTS radical scavenging rate (83.29%), and average particle size (381.67 nm) (P < 0.05), compared to unmodified CGH. Structural characterization analysis revealed that the incorporation of tryptophan led to peptide condensation and improved thermal stability. Furthermore, pre-treatment with 10 µg/mL of CGH-Trp significantly reduced the secretion of TNF-α, IL-6, and IL-1β by 33.46%, 32.17%, and 44.49%, respectively, in ARPE-19 cells, compared to the LPS-induced group. This study confirms that the Plastein reaction promotes peptide condensation in CGH in the presence of exogenous amino acids and improves the characteristic, antioxidant, and anti-inflammatory activities, highlighting its potential as a preventive strategy for age-related macular degeneration (AMD).}, }
@article {pmid41262233, year = {2025}, author = {Abbas, A and Singaravelu, J and Fein, JG}, title = {Real-World Clinical Usage and Safety Profile of Intravitreal Pegcetacoplan in Age-Related Macular Degeneration-Associated Geographic Atrophy.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251387554}, pmid = {41262233}, issn = {2474-1272}, abstract = {Purpose: To examine the clinical usage and safety profile in real-world patients with age-related macular degeneration (AMD) receiving intravitreal pegcetacoplan (Syfovre) for the treatment of geographic atrophy, and to explore the effect of intravitreal pegcetacoplan on neovascular AMD (nAMD) disease activity. Methods: Information on patient demographics, AMD classification, treatment history, visual acuity, and ocular adverse events were extracted from the electronic medical records. Results: A total of 1069 patients (1451 eyes) initiated intravitreal pegcetacoplan treatment between February 2023 and October 2023 and were followed up until March 2024. Patients received a mean (±SD) 3.3 ± 2.1 injections, and the mean (±SD) follow-up after pegcetacoplan administration was 7.5 ± 2.3 months. The majority of this cohort displayed stable visual acuity throughout treatment, with logMAR values in 821 patients remaining within 0.20 of the initial value. Ocular hypertension occurred in 36 patients (2.5% of eyes). Seventy-six patients (5.2% of eyes) with non-neovascular AMD at treatment initiation subsequently developed nAMD. Five patients (0.34% of eyes) had intraocular inflammation, including 3 with anterior uveitis, 1 with nonocclusive retinal vasculitis, and 1 with hemorrhagic occlusive retinal vasculitis with subsequent poor outcomes. A rate of retinal vasculitis of 0.03% per injection and a rate of overall intraocular inflammation of 0.1% per injection were observed. In total, 460 patients with nAMD received intravitreal pegcetacoplan. Stability of the anti-vascular endothelial growth factor (anti-VEGF) treatment interval was observed in 289 of 396 patients (73%). Preserved or improved visual acuity while undergoing anti-VEGF therapy was noted in 384 of 396 patients (97%). Conclusions: Real-world data on intravitreal pegcetacoplan treatment identifies clinician practice patterns and demonstrates an acceptable safety profile, with complications leading to long-term vision loss following pegcetacoplan administration being rare in this cohort.}, }
@article {pmid41262993, year = {2025}, author = {Geetha, J and Govindhan, S and Kalifa, MRHM and Gaur, A and Varatharajan, S}, title = {Association of Visual Impairment and Falls in Elderly Individuals-A Cross-Sectional Study.}, journal = {Current health sciences journal}, volume = {51}, number = {2}, pages = {185-190}, pmid = {41262993}, issn = {2067-0656}, abstract = {BACKGROUND: Falls are considered to be the most frequent and significant cause of unintentional harm and mortality among the elderly. Impaired vision is a significant risk factor for falls.<br><br>AIM: To analyse the relationship between visual impairment and falls in the elderly.<br><br>METHODOLOGY: This hospital-based cross-sectional study included 270 participants after obtaining informed consent. Details of demographic profile, lifestyle, gait and balance deficits, ophthalmic and systemic condition were collected. The identification of independent risk variables for falls in the elderly was performed by logistic regression analysis.<br><br>RESULTS: Among 270 participants, 115 participants had falls. The mean age of fallers was 72.97 years. Females had significant falls. 87.8% of participants had visual impairment. Visual risk factors like cataract (80.9%), uncorrected refractive error (59.1%), glaucoma (24.3%), age-related macular degeneration (20.2%), and corneal opacity (13%) were very strongly associated with fall (P<0.001). On multivariate logistic regression analysis visual risk variables like Cataract, uncorrected refractive error and glaucoma had a significant association with falls (P<0.05) with an adjusted odds ratio (aOR) of less than 1. Diabetic retinopathy had strong association of fall (P<0.001) with aOR of 41.8 (95% CI 4.27-409.2).<br><br>CONCLUSION: Falls and visual impairment are public health concerns that require attention. Since many causes of visual impairment in the elderly are reversible, lowering the risk of falls in this population may be a controllable goal.}, }
@article {pmid41263219, year = {2026}, author = {Dang, TM and Invernizzi, A and Nguyen, V and Hashimoto, Y and Romano, F and Cozzi, M and Arnold, J and Wong, J and Mehta, H and Fraser-Bell, S and Barry, R and Barthelmes, D and Gillies, M and Luckie, A}, title = {Twelve-Month Outcomes of Brolucizumab in Routine Clinical Practice: Fight Retinal Blindness! Registry.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {54}, number = {2}, pages = {233-240}, doi = {10.1111/ceo.70033}, pmid = {41263219}, issn = {1442-9071}, support = {//Novartis/ ; }, mesh = {Humans ; Retrospective Studies ; Visual Acuity/physiology ; *Registries ; Male ; Female ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Follow-Up Studies ; Aged, 80 and over ; *Blindness/prevention &amp; control ; Tomography, Optical Coherence ; Fluorescein Angiography ; Middle Aged ; Australia ; Drug Substitution ; }, abstract = {BACKGROUND: We analysed 12-month real-world outcomes of treatment of eyes with neovascular age-related macular degeneration switched to brolucizumab from a first-generation VEGF inhibitor to determine whether switching chronically active eyes that required frequent treatment improved control of the disease safely with fewer injections.<br><br>METHODS: Retrospective analysis of Australian and Italian data from the prospectively designed observational Fight Retinal Blindness! registry. We studied eyes that switched to brolucizumab and received at least two injections with 12&#x2009;months of follow-up.<br><br>RESULTS: Of the 81 eligible eyes, the proportion of inactive lesions increased from 5% at baseline to 37% 12&#x2009;months after switching to brolucizumab (p&#x2009;<&#x2009;0.001). Mean (95% CI) visual acuity (VA) was stable (0.6 [-1.5, 2.8] letters, p&#x2009;=&#x2009;0.55), while median treatment intervals increased from 44 to 63&#x2009;days (p&#x2009;<&#x2009;0.001). Nearly a third (30%) of eyes switched back to another VEGF inhibitor within 12&#x2009;months. Eyes that stayed on brolucizumab had a significantly longer mean treatment interval at 12&#x2009;months than eyes that switched off it (66.1 [Q1, Q3: 56, 91] vs. 49 [28, 63.2] days, p&#x2009;&#x2264;&#x2009;0.001) while VA change and inactivation rates were similar. Intraocular inflammation (IOI) was recorded in 7 (9%) eyes receiving at least one injection of brolucizumab.<br><br>CONCLUSIONS: Eyes that switched from a first generation VEGF inhibitor to brolucizumab in routine clinical practice achieved a clinically significant extension of their treatment interval, with more than a third becoming inactive but with a relatively high rate of IOI.}, }
@article {pmid41264299, year = {2026}, author = {Yee, H and Wong, CMJ and Gupta, P and Thakur, S and Fenwick, E and Lamoureux, EL and Man, REK}, title = {Prevalence, Risk Determinants, and Burden of Undiagnosed Age-Related Eye Diseases Among Older Asian Adults.}, journal = {JAMA ophthalmology}, volume = {144}, number = {1}, pages = {23-32}, pmid = {41264299}, issn = {2168-6173}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Asian People/ethnology ; *Cataract/epidemiology/diagnosis/ethnology ; *Cost of Illness ; Cross-Sectional Studies ; *Diabetic Retinopathy/epidemiology/diagnosis/ethnology ; *Glaucoma/epidemiology/diagnosis/ethnology ; *Macular Degeneration/diagnosis/epidemiology/ethnology ; Prevalence ; Risk Factors ; Singapore/epidemiology ; *Undiagnosed Diseases/epidemiology ; }, abstract = {IMPORTANCE: While population-based surveys have identified a high prevalence of undiagnosed eye diseases among Asian adults, these studies were conducted more than a decade ago, and there is a paucity of contemporary data.<br><br>OBJECTIVES: To determine the contemporary prevalence of undiagnosed age-related macular degeneration (AMD), diabetic retinopathy (DR), cataracts, and glaucoma and their shared risk determinants and to evaluate these conditions' patient-centered and economic burden in a large multiethnic cohort of older Asian adults.<br><br>This cross-sectional cohort study was conducted among individuals from the Population Health and Eye Disease Profile in Elderly Singaporeans study (PIONEER-1, conducted from December 2017 to November 2022), a population-based cohort of community-dwelling individuals of Chinese, Malay, and Indian ethnicity aged 60 years or older living in Singapore. Data analysis was performed from April 2024 to December 2024.<br><br>EXPOSURES: The 4 eye diseases were diagnosed clinically by a study ophthalmologist; participants were considered undiagnosed if no prior physician diagnosis or related interventions were reported.<br><br>MAIN OUTCOMES AND MEASURES: One primary outcome, visual impairment (VI), was assessed clinically using the logMAR chart at 4 m by certified optometrists, while key patient-centered and economic outcomes were assessed using validated questionnaires.<br><br>RESULTS: This study was conducted among 1878 individuals from the PIONEER-1 study, among whom mean (SD) age was 72.7 (8.3) years and 1013 participants (53.9%) were female. A total of 742 participants (weighted prevalence: 35.8%) had at least 1 type of undiagnosed eye disease, with 650 participants (87.6%), 87 participants (11.7%), and 5 participants (0.7%) having 1, 2, and 3 conditions, respectively. Among individuals with AMD, DR, cataracts, or glaucoma, the weighted prevalences of undiagnosed disease were 89.8%, 89.8%, 40.8%, and 48.1%, respectively. Younger age (odds ratio [OR], 1.08 per year decrease; 95% CI, 1.06-1.10; P&#x2009;<&#x2009;.001), wearing multifocal glasses (OR, 1.75; 95% CI, 1.19-2.59; P&#x2009;=&#x2009;.005), and Malay (OR, 1.71; 95% CI, 1.21-2.43; P&#x2009;=&#x2009;.003) and Indian (OR, 1.43; 95% CI, 1.00-2.04; P&#x2009;=&#x2009;.05) ethnicities compared with Chinese individuals were associated with greater odds of having undiagnosed eye disease. Individuals with undiagnosed eye diseases reported -1.97% to -4.57% lower scores in health- and vision-related quality of life, as well as a greater likelihood of having VI (OR, 2.46; 95% CI, 1.68-3.61; P&#x2009;<&#x2009;.001). Additionally, undiagnosed individuals incurred 1.73-fold higher health care expenditures compared with those who were diagnosed (diagnosed: reference; undiagnosed: OR, 1.73; 95% CI, 1.06-2.84; P&#x2009;=&#x2009;.03).<br><br>CONCLUSIONS AND RELEVANCE: In this cross-sectional cohort study, the rates of undiagnosed age-related eye diseases were relatively high, and these conditions were associated with poorer patient-centered outcomes and greater health care expenditure. These results support the use of community eye screening services and health awareness campaigns targeted toward individuals at the lower end of the older than 60 years spectrum and those of Malay and Indian ethnicities to mitigate the detrimental effects of undiagnosed eye diseases in these individuals.}, }
@article {pmid41265309, year = {2026}, author = {Parra-Sánchez, &#xc1; and Román-Vallina, A and Fernández, E and Martínez-Navarrete, G}, title = {Computational modeling of anti-VEGFA drug interactions with VEGF-A: Insights into therapeutic strategies for neovascular AMD.}, journal = {Computational biology and chemistry}, volume = {120}, number = {Pt 1}, pages = {108788}, doi = {10.1016/j.compbiolchem.2025.108788}, pmid = {41265309}, issn = {1476-928X}, mesh = {*Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Humans ; *Macular Degeneration/drug therapy/metabolism ; Molecular Docking Simulation ; Ranibizumab/chemistry/pharmacology ; *Angiogenesis Inhibitors/chemistry/pharmacology ; Bevacizumab/chemistry/pharmacology ; Recombinant Fusion Proteins ; Receptors, Vascular Endothelial Growth Factor ; Antibodies, Monoclonal, Humanized ; }, abstract = {Vascular endothelial growth factor A (VEGF-A) is the main driver of pathological angiogenesis and represents the primary therapeutic target in neovascular age-related macular degeneration (nAMD). Several anti-VEGF agents are currently available, but systematic comparisons of their molecular interactions with VEGF-A remain limited. In this study, we performed the first integrated in silico evaluation of six clinically relevant anti-VEGF drugs: abicipar, aflibercept, bevacizumab, brolucizumab, faricimab, and ranibizumab. Structural modeling, residue conservation analysis, molecular docking (HADDOCK), and binding affinity prediction (PRODIGY) were employed to assess drug-VEGF-A interactions in terms of stability, energetic contributions, and key conserved residues. Our results showed that bevacizumab exhibited the most stable interaction profile, dominated by van der Waals forces and supported by highly conserved residues. Aflibercept displayed strong electrostatic stabilization, while ranibizumab and brolucizumab achieved robust interactions through mixed forces. Faricimab presented weaker binding stability but its dual-target mechanism, involving VEGF-A and angiopoietin-2, may extend its therapeutic efficacy beyond VEGF-A inhibition. Abicipar demonstrated favorable stability despite structural differences from conventional antibodies. Notably, hydrophobic interactions were consistently identified as a central determinant of complex stability across all drugs, whereas an excess of charged residues correlated with reduced affinity. This systematic analysis highlights the coexistence of evolutionary conservation and rational molecular engineering as complementary strategies shaping anti-VEGF drug performance. Overall, our findings demonstrate that computational modeling offers a cost-effective and predictive tool to guide the optimization of current therapies and the rational design of next-generation anti-VEGF agents for nAMD and other retinal vascular disorders.}, }
@article {pmid41267136, year = {2025}, author = {Choy, S and Chun, JM and Seok, JW and Park, SR and Kim, JD}, title = {Effectiveness of photobiomodulation therapy for ophthalmic diseases: protocol for a systematic review and meta-analysis of disease-specific and shared physiological outcomes.}, journal = {Systematic reviews}, volume = {14}, number = {1}, pages = {231}, pmid = {41267136}, issn = {2046-4053}, support = {KSN2511012//Korea Institute of Oriental Medicine/ ; }, mesh = {Humans ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; *Low-Level Light Therapy/methods ; *Eye Diseases/therapy/radiotherapy ; Research Design ; Treatment Outcome ; }, abstract = {BACKGROUND: Photobiomodulation therapy (PBMT)-a noninvasive therapeutic strategy-employs low-level red or near-infrared light to regulate cellular bioenergetics, reduce oxidative stress, and modulate inflammation. It has demonstrated therapeutic potential for several ophthalmic diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, retinitis pigmentosa, and dry eye disease. However, the clinical evidence remains fragmented due to heterogeneity in study designs, treatment parameters, and outcome measures. Moreover, existing reviews are largely confined to single diseases. Robust, prespecified assessments that standardize disease-specific endpoints and only explore shared physiological measures across conditions remain scarce.<br><br>METHODS: The protocol is registered in the PROSPERO database. This review will follow the PRISMA guidelines; randomized controlled trials and comparative nonrandomized clinical studies involving PBMT interventions for any clinically diagnosed ophthalmic disease will be included. Eligible comparators will include sham treatment, no treatment, or standard care, and outcomes will be primarily analyzed at the disease-specific level, with endpoints including best-corrected visual acuity, drusen volume, intraocular pressure, and diabetic retinopathy severity. Selected shared physiological or functional outcomes (e.g., electroretinogram amplitude, tear cytokine concentrations, and optical coherence tomography measurements of retinal structure) will be examined in a secondary exploratory framework to provide hypothesis-generating insights across conditions. Databases-including PubMed, Embase, Cochrane Library, Web of Science, and Scopus-will be searched for articles published up to July 31, 2025. Two reviewers will independently select studies, extract data, and assess risk of bias. Random-effects models will be used for the meta-analysis, and heterogeneity will be explored through prespecified subgroup (disease type, wavelength, irradiance, fluence, session duration, treatment frequency) and exploratory meta-regression analyses.<br><br>DISCUSSION: This review will provide pooled effect estimates for PBMT based on clinical outcomes across ophthalmic diseases. These will be stratified by intervention parameters and outcome types (disease-specific and shared physiological/biomarker-based). Rather than aiming to determine optimal treatment strategies, the findings are intended to provide exploratory insights and generate hypotheses for future clinical research. The study will synthesize clinical evidence regarding the effect of PBMT on ophthalmic diseases, highlighting methodological considerations to guide the design of future trials and serve as an exploratory framework for understanding potential multidisease and multioutcome perspectives.<br><br>PROSPERO CRD420251033569.}, }
@article {pmid41268217, year = {2025}, author = {Amer, M and Sonne, S and Piri, N}, title = {Hyperreflective Choroidal Foci: A Comprehensive Review.}, journal = {Journal of ophthalmic &amp; vision research}, volume = {20}, number = {}, pages = {}, pmid = {41268217}, issn = {2008-2010}, abstract = {Hyperreflective choroidal foci (HCF) are a finding on optical coherence tomography that may serve as a biomarker in various retinal and choroidal pathologies. These discrete hyperreflective spots, identified in various layers of the choroid, have been linked to inflammatory, vascular, and degenerative conditions. This review examines the clinical significance, histopathological correlation, and implications of HCF in various diseases, including diabetic retinopathy, age-related macular degeneration, Stargardt disease, choroideremia, Vogt-Koyanagi-Harada disease (VKH), idiopathic posterior uveitis, retinitis pigmentosa, and central serous chorioretinopathy (CSR), as well as non-pathological states. Although further studies are required to validate the findings in each pathology described herein, HCF may be used as a background prognostic marker of disease progression and therapeutic response, albeit with caution.}, }
@article {pmid41268988, year = {2025}, author = {Kozak, I and Sinclair, SH and Zhang, E and Murati, F and Lee, E and Stepura, A and Dey, A and Ribaric, N}, title = {Application of Deep Learning for Advanced Detection and Quantification of Drusen in Nonexudative AMD From Retinal Multispectral Imaging.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {11}, pages = {35}, pmid = {41268988}, issn = {2164-2591}, mesh = {*Deep Learning ; Humans ; *Retinal Drusen/diagnosis/diagnostic imaging ; *Macular Degeneration/diagnosis ; *Retina/diagnostic imaging/pathology ; Neural Networks, Computer ; Aged ; *Geographic Atrophy/diagnosis ; }, abstract = {PURPOSE: To propose a novel deep learning-based methodology for drusen detection and quantification in early age-related macular degeneration (AMD) using retinal multispectral images. The retinal multispectral images highlight features in several nonoverlapping spectral bands that the deep learning models leverage for automatic drusen detection and quantification in dry AMD.<br><br>METHODS: The proposed novel methodology comprises quality assessment of retinal images, region of interest extraction, drusen segmentation, and drusen quantification stages. Different deep learning models (such as UNet++ convolutional neural network with EfficientNetV2 encoder) have been implemented for these stages. A total of 170 drusen and 150 nondrusen retinal images (single eye) were split into four training and validation data sets to analyze the performance of a deep learning model for drusen segmentation.<br><br>RESULTS: The proposed methodology achieved an average score, recall, and precision of 0.691, 0.668, and 0.776, respectively, across all four validation sets. This work also analyzed the performance of the proposed deep learning model for discriminating drusen and drusen-like lesions, achieving a pixel-wise segmentation accuracy of 99.998%. The number and the diameter of the detected drusen were also computed. A Dice score distribution for drusen segmentation with different numbers and sizes of drusen per eye is also shown.<br><br>CONCLUSIONS: This work demonstrates that deep learning models applied to retinal multispectral images can provide accurate and clinically significant drusen segmentation and quantification, thereby facilitating early detection, longitudinal monitoring, and reduction of the risk of vision loss from AMD.<br><br>TRANSLATIONAL RELEVANCE: Deep learning-assisted detection of drusen from multispectral retinal images will refine and improve clinical diagnosis of early nonexudative age-related macular degeneration.}, }
@article {pmid41269403, year = {2025}, author = {Jin, J and Hand, R and Meltzer, M and Abate, C and Geva, M and Hayden, MR and Ross, CA}, title = {Sigma-2 Receptor Antagonism Enhances the Neuroprotective Effects of Pridopidine, a Sigma-1 Receptor Agonist, in Huntington's Disease.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {121}, pmid = {41269403}, issn = {1559-1182}, mesh = {*Receptors, sigma/antagonists &amp; inhibitors/agonists/metabolism ; *Huntington Disease/drug therapy/pathology/metabolism ; Animals ; *Neuroprotective Agents/pharmacology/therapeutic use ; Sigma-1 Receptor ; *Piperidines/pharmacology/therapeutic use ; Mice ; Humans ; Neurons/drug effects/metabolism/pathology ; Huntingtin Protein/metabolism ; }, abstract = {Pridopidine is a selective sigma-1 receptor (S1R) agonist in clinical development for Huntington's Disease (HD) and Amyotrophic Lateral Sclerosis (ALS). Activation of the S1R by pridopidine is neuroprotective in multiple preclinical models of neurodegenerative disease. The sigma-2 receptor (S2R) is evolutionarily and structurally unique from the S1R. Nevertheless, the S1R and S2R share an overlapping yet distinct ligand binding profile. Inhibition of the S2R is neuroprotective and S2R antagonists are in clinical development for Alzheimer's Disease (AD), ⍺-synucleinopathies, and dry age-related macular degeneration. In this study, we hypothesized that simultaneous activation of the S1R by pridopidine and inhibition of the S2R by the selective S2R antagonist FA10 might provide enhanced protection against mutant huntingtin (mHTT) expression in an in vitro model of neurodegeneration. Consistent with previous studies, pridopidine reduced neuronal cell death in a mouse primary neuron mHTT model. Similarly, we found that inhibition of the S2R by FA10 was also sufficient to protect against mHTT induced neurodegeneration in this model. The combination treatment of pridopidine and FA10 achieved greater efficacy than either compound alone, even at lower concentrations. The combination of these compounds may allow for lower efficacious doses leading to improved safety profiles and reduced off-target effects. This novel combinatorial approach, in which the S1R is activated while simultaneously inhibiting the S2R may prove to be a highly effective therapeutic strategy for HD and other neurodegenerative diseases.}, }
@article {pmid41269906, year = {2026}, author = {Korobelnik, JF and Chaudhary, V and Mitchell, P and Kang, SW and Allmeier, H and Lee, J and Zhang, X and Machewitz, T and Bailey, C}, title = {Aflibercept 2 mg for Neovascular Age-Related Macular Degeneration: XTEND at 3 Years.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {249}, number = {1}, pages = {17-29}, pmid = {41269906}, issn = {1423-0267}, mesh = {Humans ; Female ; Intravitreal Injections ; Aged ; Prospective Studies ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Male ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; Follow-Up Studies ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Time Factors ; Dose-Response Relationship, Drug ; Fluorescein Angiography ; Aged, 80 and over ; Fundus Oculi ; *Macula Lutea/pathology ; Angiogenesis Inhibitors/administration &amp; dosage ; }, abstract = {UNLABELLED: <p>Introduction: Long-term, global data evaluating intravitreal aflibercept (IVT-AFL) 2 mg for treatment of neovascular age-related macular degeneration (nAMD) in real-world practice are needed. This study investigated the long-term, real-world effectiveness and safety of IVT-AFL 2 mg in patients with nAMD.<br><br>METHODS: XTEND was a multicenter, observational, prospective study. Enrollment was conducted between May 2019 and May 2020; the patient follow-up period was 36 months. Treatment-na&#xef;ve patients were treated with IVT-AFL 2 mg (fixed dosing or treat-and-extend [T&amp;E]) according to the local label; for the T&amp;E regimen, treatment intervals could be extended according to the national label (either European Medicines Agency [EMA]-aligned or non-EMA-aligned).<br><br>RESULTS: Overall, 1,483 patients across 17 countries were treated with IVT-AFL 2 mg; mean &#xb1; standard deviation (SD) age was 78.8 &#xb1; 8.5 years; 60.4% were female. Overall, 62.6% of patients completed the 36-month follow-up visit. The mean (95% confidence interval [CI]) changes in best-corrected visual acuity from baseline were +4.6 (3.7, 5.4), +2.3 (1.3, 3.3), and +0.9 (-0.2, 1.9) at months 12, 24, and 36, respectively. The mean (95% CI) changes in central subfield thickness from baseline were -106 (-114, -99) &#x3bc;m, -109 (-117, -102) &#x3bc;m, and -110 (-118, -103) &#x3bc;m at months 12, 24, and 36, respectively. The mean &#xb1; SD numbers of injections from baseline to months 12, 24, and 36 were 7.7 &#xb1; 2.7, 11.3 &#xb1; 5.3, and 13.7 &#xb1; 7.5, respectively. No new safety concerns were identified.<br><br>CONCLUSION: This study demonstrates that improvements with IVT-AFL 2 mg were maintained through month 36, suggesting that long-term durability of vision is achievable in patients with treatment-na&#xef;ve nAMD in real-world practice. </p>.}, }
@article {pmid41270236, year = {2025}, author = {Shi, N and Li, J and Shang, M and Zhang, W and Xu, K and Li, Y and Liang, L}, title = {Detection and Management of Geographic Atrophy Secondary to Age-Related Macular Degeneration Using Noninvasive Retinal Images and Artificial Intelligence: Systematic Review.}, journal = {Journal of medical Internet research}, volume = {27}, number = {}, pages = {e81328}, pmid = {41270236}, issn = {1438-8871}, mesh = {Humans ; *Artificial Intelligence ; Deep Learning ; *Geographic Atrophy/diagnostic imaging/etiology/diagnosis/therapy ; *Macular Degeneration/complications/diagnostic imaging ; *Retina/diagnostic imaging ; Tomography, Optical Coherence ; }, abstract = {BACKGROUND: Geographic atrophy (GA), the endpoint of dry age-related macular degeneration (AMD), is irreversible. The recent approval by the Food and Drug Administration of a complement component 3 inhibitor marks a significant breakthrough, highlighting the critical importance of early detection and management of GA. Consequently, there is an urgent and unmet need for efficient, accurate, and accessible methods to identify and monitor GA. Artificial intelligence (AI), particularly deep learning (DL), applied to noninvasive retinal imaging, offers a promising solution for automating and enhancing GA management.<br><br>OBJECTIVE: This systematic review aimed to assess the performance of AI using noninvasive imaging modalities and compare it with clinical expert assessment as the ground truth.<br><br>METHODS: Two consecutive searches were conducted on PubMed, Embase, Web of Science, Scopus, Cochrane Library, and CINAHL. The last search was performed on October 5, 2025. Studies using AI for GA secondary to dry AMD via noninvasive retinal imaging were included. Two authors worked in pairs to extract the study characteristics independently. A third author adjudicated disagreements. Quality Assessment of Diagnostic Accuracy Studies-AI and Prediction Model Risk of Bias Assessment Tool (PROBAST) were applied to evaluate the risk of bias and application.<br><br>RESULTS: Of the 803 records initially identified, 176 were found through an updated search. Subsequently, 200 papers were assessed in full text, of which 41 were included in the final analysis, 10 for GA detection, 20 for GA assessment and progression, and 11 for GA lesion prediction. The reviewed studies collectively involved at least 24,592 participants (detection: n=7132, assessment and progression: n=14,064, and prediction: n=6706), with a wide age range of 50 to 94 years. The studies spanned a diverse array of countries, including the United States, the United Kingdom, China, Austria, Australia, France, Israel, Italy, Switzerland, and Germany, as well as a multicenter study encompassing 7 European nations. The studies used a variety of imaging modalities to assess GA, including color fundus photography, fundus autofluorescence, near-infrared reflectance, spectral domain-optical coherence tomography (OCT), swept-source (SS)-OCT, and 3D-OCT. DL algorithms (eg, U-Net, ResNet50, EfficientNetB4, Xception, Inception v3, and PSC-UNet) consistently showed remarkable performance in GA detection and management tasks, with several studies achieving performance comparable to clinical experts.<br><br>CONCLUSIONS: AI, particularly DL-based algorithms, holds considerable promise for the detection and management of GA secondary to dry AMD with performance comparable to ophthalmologists. This review innovatively consolidates evidence across GA management-from initial detection to progression prediction-using diverse noninvasive imaging. It has strong potential to augment clinical decision-making. However, to realize this potential in real-world settings, future research is needed to robustly enhance reporting specifications, ensure data diversity across populations and devices, and implement rigorous external validation in prospective, multicenter studies.}, }
@article {pmid41270813, year = {2026}, author = {Jiang, L and Xu, Z and Ma, J and Cai, W and Lin, R and Hu, C and Luo, Y and Liang, F and Wu, Y and Yu, J}, title = {siRASA1 in vascular endothelial cells alleviates subretinal fibrosis through inhibiting macrophage-myofibroblast transdifferentiation via SHH signaling pathway.}, journal = {Cellular signalling}, volume = {138}, number = {}, pages = {112261}, doi = {10.1016/j.cellsig.2025.112261}, pmid = {41270813}, issn = {1873-3913}, mesh = {*Hedgehog Proteins/metabolism ; Humans ; *Cell Transdifferentiation/drug effects ; Signal Transduction/drug effects ; Fibrosis ; *Macrophages/metabolism/drug effects ; Animals ; *Myofibroblasts/metabolism/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism ; Mice ; Vascular Endothelial Growth Factor A ; *Retina/pathology/metabolism ; }, abstract = {Subretinal fibrosis (SRF) is a vision-threatening complication of neovascular age-related macular degeneration (nAMD) driven by angiogenesis, inflammation, and collagen deposition，which is refractory to current anti-VEGF treatments. This study investigates the role of RASA1 in promoting SRF through Sonic Hedgehog (SHH) signaling. We found that VEGF stimulation upregulates RASA1 in human umbilical vein endothelial cells (HUVECs), potentiating the secretion of SHH. Secreted SHH then activates the SHH-SMO/PTCH1-GLI1 axis in macrophages, driving their transdifferentiation into myofibroblasts and promoting fibrogenesis. Furthermore, a positive feedback loop was identified: macrophage-derived EFNB2 activated EphB4-RASA1 in HUVECs, exacerbating fibrosis. To therapeutically disrupt this circuit, we engineered a multifunctional nanoparticle system, MGPDA@Eylea/siRASA1, for the co-delivery of siRASA1 and the anti-VEGF drug Eylea. This nanotherapeutic demonstrated excellent biocompatibility and effectively attenuated the fibrotic cascade by suppressing RASA1 expression, inhibiting SHH signaling, and mitigating macrophage-to-myofibroblast transition (MMT), thereby delaying SRF progression. Our work unveils a previously unrecognized intercellular circuit driving fibrosis and presents a promising nanomedicine-based strategy for managing fibrotic complications in nAMD.}, }
@article {pmid41271910, year = {2025}, author = {Tabuchi, H and Nagasato, D and Tanabe, M and Murata, K and Ishitobi, N and Kato, D and Kazunori, A}, title = {Evaluation of deep learning-based retinal pigment epithelium segmentation for a widely used optical coherence tomography device.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {41310}, pmid = {41271910}, issn = {2045-2322}, mesh = {Humans ; *Tomography, Optical Coherence/methods/instrumentation ; *Retinal Pigment Epithelium/diagnostic imaging/pathology ; *Deep Learning ; Algorithms ; Aged ; Macular Degeneration/diagnostic imaging ; Male ; Female ; Diabetic Retinopathy/diagnostic imaging ; Middle Aged ; *Image Processing, Computer-Assisted/methods ; }, abstract = {To develop our proposed technology method to improve retinal pigment epithelium (RPE) detection in optical coherence tomography (OCT) images and compare its efficacy with Topcon's automated segmentation algorithm across multiple retinal diseases and healthy eyes. OCT images from 88 patients with age-related macular degeneration (AMD) were used for our proposed technology model training and validation. For testing with separate images were obtained from patients with AMD (100), diabetic retinopathy (DR; 50), epiretinal membrane (ERM; 50), branch retinal vein occlusion (BRVO; 50), and healthy eyes (50). The proposed technology was used to identify RPE in OCT images using the Pyramid Scene Parsing Network on top of ResNet-50. The accuracy of the proposed technology method in RPE detection was measured using the mean absolute error (MAE) and compared with Topcon's automated segmentation algorithm for each retinal condition. As compared with Topcon's automated segmentation algorithm, the proposed technology showed significantly better MAEs across all conditions: AMD (2.18 vs. 4.79), DR (1.69 vs. 3.17), ERM (1.50 vs. 2.67), BRVO (1.86 vs. 2.98), and healthy eyes (1.59 vs. 2.28). Notably, the proposed technology's superiority was most evident in the AMD group. The proposed technology method outperformed Topcon's automated segmentation algorithm in accurately visualizing RPE in OCT images across all tested conditions, especially in AMD. Our results indicate the proposed technology's potential to elevate the RPE segmentation which can lead to enhancing ophthalmology care by providing more accurate OCT imaging analyses.}, }
@article {pmid41272236, year = {2025}, author = {Pidishetty, D and Damera, SK and Murugavel, M and Susaimanickam, PJ and Chittajallu, SNSH and Kushawah, G and Sarkar, P and Bharadwaj, SR and Mishra, R and Mariappan, I}, title = {Loss of retinal stem cell reserve and lipofuscin accumulation accelerates cone-rod degeneration and replicates Stargardt disease in abca4b null zebrafish.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {44988}, pmid = {41272236}, issn = {2045-2322}, mesh = {Animals ; Zebrafish/genetics ; *Lipofuscin/metabolism ; *Stargardt Disease/genetics/pathology/metabolism ; *ATP-Binding Cassette Transporters/genetics ; Disease Models, Animal ; *Stem Cells/metabolism/pathology ; *Zebrafish Proteins/genetics/metabolism ; *Retina/pathology/metabolism ; Retinal Cone Photoreceptor Cells/metabolism/pathology ; Retinal Rod Photoreceptor Cells/metabolism/pathology ; Retinal Pigment Epithelium/metabolism/pathology ; Gene Knockout Techniques ; *Cone-Rod Dystrophies/pathology/metabolism/genetics ; CRISPR-Cas Systems ; Mutation ; *Macular Degeneration/genetics/pathology/metabolism ; }, abstract = {Mutations in ABCA4 gene causes Stargardt macular degeneration, which manifests with toxic lipofuscin deposits in the outer retina, gradual atrophy of RPE cells, followed by photoreceptor cell loss. The cone-enriched retina, with macula-like 'area-temporalis' of zebrafish are better models than rodents for studying human macular dystrophies. Here, we generated abca4b knockout zebrafish model using CRISPR/Cas9 editing and evaluated the early and late-stage retinal changes. In adult abca4b[-/-] mutants, the RPE cells exhibited hyperpigmentation, altered retinomotor behaviour and lipofuscin accumulation, but they remained viable. However, the photoreceptors underwent progressive degeneration, with a sequential loss of blue and UV cones, followed by red and green cones and finally the rod cells. This triggered the chronic activation and early depletion of retinal stem cells at the ciliary marginal zone of mutants and resulted in accelerated outer-retinal degeneration and severe visual defects, despite them retaining the Müller glia-dependant retinal repair potential.}, }
@article {pmid41273407, year = {2026}, author = {Ferreira, AM and Vilares-Morgado, R and Martins, L and Marques-Couto, P and Rocha-Sousa, A and Carneiro, &#xc2; and Falcão, M}, title = {Non-exudative macular neovascularization: a 3-year follow-up study assessing the progression for exudative or atrophic stages.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {3}, pages = {689-699}, pmid = {41273407}, issn = {1435-702X}, mesh = {Humans ; Male ; Female ; Follow-Up Studies ; Disease Progression ; *Fluorescein Angiography/methods ; *Tomography, Optical Coherence/methods ; Aged ; Fundus Oculi ; *Visual Acuity ; *Macula Lutea/pathology ; *Geographic Atrophy/diagnosis ; Aged, 80 and over ; Time Factors ; *Wet Macular Degeneration/diagnosis ; Retrospective Studies ; *Retinal Pigment Epithelium/pathology ; Middle Aged ; }, abstract = {INTRODUCTION: Non-exudative macular neovascularization (NE-MNV) has been linked to smaller areas of geographic atrophy (GA), suggesting it may slow the progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA). This study aims to determine whether NE-MNV affects the prevalence and progression to later stages of age-related macular degeneration (AMD) over 3 years in the fellow eyes of patients with unilateral exudative AMD.<br><br>METHODS: Observational study including 61 patients with unilateral exudative AMD assessing 3-year cRORA progression and exudative conversion in the fellow eye. Patients were grouped based on the presence (NE-MNV) or absence of NE-MNV (no NE-MNV). The prevalence and progression of tomographic cRORA, GA on fundus autofluorescence (FAF) and exudative conversion rates were compared.<br><br>RESULTS: Sixty-one patients were included in our cohort. The prevalence of NE-MNV was 24.6%. We identified a 36.3% bilateral exudative conversion rate (n&#x2009;=&#x2009;4) in the NE-MNV group and a 15.2% conversion rate in the eyes without NE-MNV (n&#x2009;=&#x2009;7) at 3 years (p&#x2009;=&#x2009;0.036). There were no significant differences in cRORA or FAF GA prevalence between groups (2/15 (13.3%) with NE-MNV vs. 11/35 (31.4%) without NE-MNV, p&#x2009;=&#x2009;0.410). Eyes with NE-MNV presented a significantly smaller cRORA greatest linear diameter (GLD) than eyes without NE-MNV (1342.3&#x2009;&#xb1;&#x2009;1260 vs. 2897&#x2009;&#xb1;&#x2009;1925.3, p&#x2009;=&#x2009;0.023), and a smaller FAF GA area (4.5&#x2009;&#xb1;&#x2009;3.7 vs. 11.9&#x2009;&#xb1;&#x2009;10.6 mm2, p&#x2009;=&#x2009;0.042). The presence of reticular pseudodrusen and hypertransmission defects were significantly associated with the GA phenotype (p&#x2009;=&#x2009;0.002 and p&#x2009;<&#x2009;0.001, respectively) while the identification of concurrent large drusen was significantly associated with the presence of MNV, both exudative and non-exudative (p&#x2009;=&#x2009;0.023). The increase in OCTA NE-MNV area and the presence of anastomosis and loops pattern were associated with exudative conversion (p&#x2009;=&#x2009;0.046 and p&#x2009;=&#x2009;0.032, respectively).<br><br>CONCLUSION: The presence of NE-MNV was associated with smaller cRORA GLD and FAF GA area, corroborating that NE-MNV may prevent the progression of cRORA. One third of the eyes with NE-MNV converted to exudative AMD over 3-years. Reticular pseudodrusen, hypertransmission defects and concurrent large drusen were significant OCT biomarkers for late stages AMD. Extended monitoring is required to confirm these results at long term.}, }
@article {pmid41275318, year = {2025}, author = {Lim, J and Cho, H and Ramkumar, H and Adrean, SD}, title = {Neovascular age-related macular degeneration complicated by large submacular hemorrhage managed with faricimab monotherapy.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {142}, pmid = {41275318}, issn = {2056-9920}, abstract = {PURPOSE: To retrospectively evaluate the visual and anatomic outcomes of intravitreal faricimab monotherapy in treatment naïve neovascular age-related macular degeneration (nAMD) patients presenting with large submacular hemorrhage (SMH).<br><br>METHODS: Patients with neovascular age-related macular degeneration (nAMD) presenting with at least 50% subretinal hemorrhage (SRH) involving the fovea between March 2023 and June 2025 were identified. Patients with greater than 750 microns of total thickness of subfoveal hemorrhage were excluded. Patients were treated with faricimab as first line therapy utilizing a treat-extend-stop protocol for one year. Spectral domain optical coherence tomography (SD-OCT) and fluorescein angiogram (FA)/ indocyanine green angiography (ICG) were used to determine total CNV lesion size, SRH area size, and macular thickness. Visual acuity and SD-OCT were also obtained at each visit.<br><br>RESULTS: Six patients were identified that met the inclusion criteria. There were two males and four females. The average age of was 83.0 years. Prior to treatment, the average total CNV lesion size was 19.7mm[2] and the average hemorrhage area was 14.5 mm[2] for an average SRH percentage of 73.8%. The average central macular thickness (CMT) prior to treatment was 478.3 &#x3bc;m and the average CMT 6 months after beginning treatment was 306.8 &#x3bc;m (p = 0.0031). The average CMT 1 year after treatment was 259.0 &#x3bc;m (p = 0.0017). Average ETDRS letters before treatment was 48.8 letters {Snellen equivalent 20/138} with a range of 23&#x2013;70 letters. Average ETDRS letters after 6 months of treatment was 60.3 letters {Snellen equivalent 20/63} with a range of 42 to 76 letters (p = 0.017). Average ETDRS letters after 1 year of treatment was 64.7 letters {Snellen equivalent 20/50} with a range from 26 to 80 letters (p < 0.014). The average number of injections was 9.3 at 1 year.<br><br>CONCLUSION: In patients with nAMD complicated by at least 50% SRH, there was improved vision and decreased CMT. On average, vision improved by 16.4 ETDRS letters and improved on average from 20/138 to 20/50 on Snellen after 1 year of faricimab monotherapy. These patients may be successfully managed with faricimab monotherapy. While visual acuity overall improved, some patients had more improvement than others likely due to the location of the CNV.}, }
@article {pmid41276957, year = {2026}, author = {Yang, CC and Weng, CC and Chou, YB and Huang, YM and Lin, TC and Chen, SJ and Hwang, DK}, title = {Early anatomical outcomes of faricimab vs aflibercept 2 mg in treatment-naïve neovascular age-related macular degeneration and polypoidal choroidal vasculopathy: A head-to-head comparative study in Taiwan.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {89}, number = {1}, pages = {54-60}, pmid = {41276957}, issn = {1728-7731}, mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Female ; Male ; Aged ; Retrospective Studies ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Visual Acuity ; Aged, 80 and over ; Middle Aged ; *Choroidal Neovascularization/drug therapy ; Polypoidal Choroidal Vasculopathy ; Antibodies, Bispecific ; }, abstract = {BACKGROUND: While clinical trials have established the non-inferiority of faricimab compared to aflibercept regarding 1-year visual acuity, real-world evidence directly comparing their early effects on anatomical changes remains limited. This study aimed to compare the early effects of these treatments in treatment-naïve Asian patients with neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV).<br><br>METHODS: This retrospective study included treatment-na&#xef;ve nAMD patients who received three monthly intravitreal injections of 6.0&#x2009;mg/0.05&#x2009;ml faricimab or 2.0&#x2009;mg/0.05&#x2009;ml aflibercept. Best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), pigment epithelial detachment (PED), subretinal fluid (SRF), intraretinal fluid (IRF), hyperreflective foci (HRF), and subretinal hyperreflective material (SHRM) were assessed monthly for 4 months.<br><br>RESULTS: A total of 76 eyes of 76 patients (38 per group) were enrolled in this study. Baseline characteristics were comparable between the two groups, and there were no significant differences in BCVA, CMT, SFCT, SRF, and IRF at 4 months (p > 0.05). However, the faricimab group had significant improvements in BCVA at months 2, 3, and 4 (p < 0.05), while this was not seen in the aflibercept group. The decrease in mean logarithm of the minimum angle of resolution (logMAR) was from 0.78&#x2009;&#xb1;&#x2009;0.47 to 0.66&#x2009;&#xb1;&#x2009;0.65 in the faricimab group compared to 0.78&#x2009;&#xb1;&#x2009;0.41 to 0.72&#x2009;&#xb1;&#x2009;0.60 in the aflibercept group (p = 0.348) at 4 months. Moreover, significantly fewer faricimab-treated patients had PED (67.6% vs 91.9%, p = 0.016), SHRM (32.4% vs 59.5%, p = 0.022), and HRF (52.9% vs 89.2%, p = 0.001) at 4 months.<br><br>CONCLUSION: Faricimab and aflibercept demonstrated comparable effects on BCVA, CMT, and SFCT. However, faricimab was associated with better early control of PED, SHRM, and HRF. Further prospective trials are needed to validate our findings.}, }
@article {pmid41277047, year = {2026}, author = {Choe, S and Ye, J and Zhang, T and Gao, J}, title = {Advanced Drug Delivery Systems for Age-Related Macular Degeneration Treatment: Latest Trends and Future Prospects.}, journal = {Advanced healthcare materials}, volume = {15}, number = {9}, pages = {e03757}, doi = {10.1002/adhm.202503757}, pmid = {41277047}, issn = {2192-2659}, support = {W2442037//National Natural Science Foundation of China/ ; 2023GSP006851//Chinese Government Scholarship/ ; }, mesh = {Humans ; *Drug Delivery Systems/methods ; *Macular Degeneration/drug therapy ; Animals ; Hydrogels/chemistry ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly. While wet AMD is primarily characterized by choroidal neovascularization, dry AMD is characterized by dysfunction of the retinal pigment epithelium. One of the key challenges in AMD treatment is achieving efficient drug delivery to the posterior segment, a task complicated by the anatomical and physiological barriers, such as rapid clearance from the vitreous. Current therapeutic approaches, mainly constituted by frequent intravitreal injections of anti-vascular endothelial growth factor agents for wet AMD, place a heavy burden on patients, leading to complications such as retinal detachment and endophthalmitis. This review highlights recently developed drug delivery systems designed to overcome these challenges and the potential of these systems to transform AMD management. These systems include hydrogels, nanocarriers, and biologically derived vesicles, which enable sustained, localized drug release and improved targeting. Additionally, device-based delivery systems such as microneedles, ultrasound-mediated systems, magnetically guided systems, 3D bioprinting, and implantable sustained-release devices are explored for their potential to reduce injection frequency and improve therapeutic outcomes. Lastly, it outlines future efforts needed to accelerate the clinical adoption of these innovative therapies, with a focus on patient safety, efficacy, and quality of life in AMD treatment.}, }
@article {pmid41278702, year = {2025}, author = {Oshima, Y and Nagidi, Y and Moorthy, ME and Heier, J and Matsubara, JA and Hardin, J and Flajnik, M and Vogel, BE}, title = {TEP-1, a glial thioester protein is required for cilia organization and intraflagellar transport in ensheathed sensory neurons.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41278702}, issn = {2692-8205}, support = {P40 OD010440/OD/NIH HHS/United States ; R01 EY032868/EY/NEI NIH HHS/United States ; }, abstract = {Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by progressive degeneration of retinal photoreceptors. Traditional disease models suggest that defective repression of thioester protein C3 activity by complement factor H (CFH) is a major contributor to pathogenesis in AMD and a related disease, early-onset drusen maculopathy (EODM). Our previous study identified novel functions for human CFH and C. elegans CFH-1 in the maintenance of inversin compartment integrity in photoreceptors and mechanosensory neurons, indicating that CFH has a novel, evolutionarily conserved role in cilia compartment organization that is distinct from its established function in alternative complement pathway regulation. Here, we investigate the C. elegans thioester protein TEP-1, an ancestral relative of C3 and other members of the AMCOM family (C4, C5, CD109, and alpha-2-macroglobulin). TEP-1 localizes to select glial cell surfaces and regulates inversin compartment organization and intraflagellar transport (IFT) within the cilia of ensheathed sensory neurons. In addition to revealing a novel role for an AMCOM family member in sensory neuron structure and protein transport, the localization of C3 and CFH on human photoreceptors provides support for non-canonical models of AMD and EODM pathogenesis in which defects in cilia structure and protein transport contribute directly to the progressive photoreceptor dysfunction that characterizes these diseases.}, }
@article {pmid41278837, year = {2025}, author = {Oshima, Y and Hussey, KA and Hagen, J and Smit-McBride, Z and Moorthy, M and Matsubara, JA and Flajnik, M and Johnston, RJ and Vogel, BE}, title = {Complement Factor H and its C. elegans homolog regulate IFT52/OSM-6 and CNG channel localization in sensory neurons.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41278837}, issn = {2692-8205}, support = {P30 EY012576/EY/NEI NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; R01 EY032868/EY/NEI NIH HHS/United States ; }, abstract = {Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by progressive degeneration of retinal photoreceptors. Current disease models propose AMD pathogenesis is a consequence of cytolytic damage and tissue inflammation that result from defective repression of alternative complement pathway activity by complement factor H (CFH). However, recent studies demonstrate functions for CFH that are outside of its established role in the alternative complement pathway, suggesting that novel CFH-mediated mechanisms may influence AMD initiation and progression. Our previous demonstration that CFH and its nematode homolog, CFH-1, modulate inversin/NPHP-2 accumulation in vertebrate photoreceptor and C. elegans sensory neuron cilia during aging suggests that AMD patients with CFH loss-of-function mutations have cilia defects that may contribute to photoreceptor dysfunction. Here, we investigate the consequences of CFH and CFH-1 loss-of-function mutations on the dynamics and localization of intraflagellar transport (IFT) train and visual cycle components in these cells. In C. elegans sensory neurons, IFTB1 components IFT52/OSM-6 and IFT88/OSM-5 are transported at similar rates in WT animals but IFT52/OSM-6 transport slows significantly in cfh-1 mutant animals while IFT88/OSM-5 is unaffected. Defective localization of IFT52/OSM-6 in photoreceptors of CFH knockout mice and in human photoreceptors from AMD high-risk CFH Y402H homozygotes, suggest an evolutionarily conserved role for CFH in promoting IFT52/OSM-6 transport and localization in sensory neuron cilia. In addition, distribution of CNG channel subunits in C. elegans cfh-1 mutant sensory neurons and CFH Y402H high-risk human photoreceptors are distinct from their WT and Y402 low-risk counterparts. Together, the data indicate previously unappreciated functions for CFH in IFT train organization and cilia protein localization and suggest a novel mechanism for photoreceptor segment thinning, an early AMD biomarker that has been linked to CFH high-risk variants.}, }
@article {pmid41279129, year = {2025}, author = {Zhang, PW and Liu, S and Li, W and Fan, L and Li, S and Wan, ZH and Berlinicke, CA and Merbs, SL and Zack, DJ}, title = {Identification and functional characterization of an AMD associated c-ABL binding SNP streak within the ARMS2 gene promoter region.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41279129}, issn = {2692-8205}, support = {P30 EY001765/EY/NEI NIH HHS/United States ; }, abstract = {BACKGROUND: Large-scale genome-wide association studies (GWAS) have identified the human 10q26 locus as a major genetic risk factor for age-related macular degeneration (AMD). The AMD-associated interval has been refined to a 5,196 bp segment flanking the ARMS2-HTRA1 region, excluding HTRA1 and the ARMS2 3' indel (443del54ins) variant by risk haplotype analysis. Although the missense SNP rs10490924 has been proposed as a functional variant, its role in AMD remains controversial, and the causative variants and underlying mechanisms within this region remain unresolved.<br><br>METHODS: An unbiased bioinformatic screen identified a 5-SNP block within the 5,196 bp interval that potentially alters c-ABL protein binding. Protein-DNA interactions were validated using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. Genetic association with AMD (dry and wet subtypes) was assessed in patient cohorts using blood genomic DNA. The regulatory effect of the 5-SNP block was further examined using luciferase reporter assays.<br><br>FINDINGS: We identified a 5-SNP block located ~556 bp upstream of the ARMS2 start codon, representing a cluster of predicted c-ABL tyrosine kinase binding sites. This block, in complete linkage disequilibrium with rs10490924 (A69S), showed a strong association with both wet and dry AMD (136 controls, 179 dry AMD, 251 wet AMD). EMSA and ChIP confirmed direct c-ABL binding, while luciferase reporter assays demonstrated reduced transcriptional activity mediated by the 5-SNP block in the presence of c-ABL.<br><br>INTERPRETATION: Our results suggest that the c-ABL-responsive 5-SNP regulatory streak in the ARMS2 promoter region act as functional non-coding elements that may contribute to AMD pathogenesis through altered transcriptional regulation.}, }
@article {pmid41279388, year = {2025}, author = {Maniglia, M and Vice, J and Maxwell, E and Visscher, KM and Seitz, AR}, title = {Examining oculomotor behavior in central vision loss with a gaze-contingent display.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41279388}, issn = {2692-8205}, support = {R21 EY033623/EY/NEI NIH HHS/United States ; }, abstract = {Patients with central vision loss due to macular degeneration (MD) must rely on their peripheral vision for tasks normally performed by the fovea. Many patients develop a preferred retinal locus (PRL), an eccentric retinal location used as a substitute for the damaged fovea in tasks such as face recognition, navigation, and reading. However, the mechanisms underlying PRL development remain elusive, and no single hypothesis fully explains its characteristics. Investigations into PRL development are hindered by oculomotor assessments, which often focus on fixation ability while neglecting other eye movement characteristics and potentially conflating different behaviors over time. In previous work, we introduced a series of oculomotor metrics in cases of simulated central vision loss, demonstrating that complex profiles of eye movement behavior can be extracted from a simple visual task. Here we present longitudinal data from 10 patients with MD as evidence of the feasibility of using these metrics to characterize different profiles of eye movements following central vision loss. Consistent with findings in healthy individuals using artificial scotoma, the metrics reveal substantial individual differences in behavior, both at baseline and after visual training. Overall, patients exhibit significantly higher saccadic re-referencing than controls, despite larger inter-individual differences. These metrics provide a detailed evaluation of oculomotor behavior in patients with central vision loss and offer a valuable tool for assessing progress in training protocols.}, }
@article {pmid41280070, year = {2025}, author = {Shin, K and Brown, W and Tian, Y and Gopinath, T and Bobkov, AA and Marinelli, F and Marassi, FM}, title = {Structural basis for lipid binding by the blood protein vitronectin, a component of HDL.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41280070}, issn = {2692-8205}, support = {P01 AG081167/AG/NIA NIH HHS/United States ; P30 CA030199/CA/NCI NIH HHS/United States ; R35 GM118186/GM/NIGMS NIH HHS/United States ; }, abstract = {Vitronectin (Vn) is a multifunctional blood glycoprotein involved in cell adhesion and migration, blood coagulation, and inflammation. It is a component of the high-density lipoprotein (HDL) proteome, and often found associated with the calcified, lipid-rich, protein deposits that are a hallmark of age-related macular degeneration, Alzheimer's disease, atherosclerosis and other aging-related diseases. Here we explored the molecular basis for lipid binding by Vn using isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) and all-atom molecular dynamics (MD) simulations. The data reveal a hydrophobic groove on the surface of the hemopexin-like (HX) domain of Vn, that is capable of binding phosphatidylcholine (PC). Conformational landscape analyses of multiple, independent MD simulations identify key structural motifs and intermolecular contacts mediating the association of Vn with PC, and show that lipid binding is guided by interactions with positively charged and hydrophobic residues that organize the lipids in a tail-to-tail bilayer-like arrangement within the groove. Collectively, the data establish a comprehensive structural model for Vn association with HDL and provide mechanistic insight into its accumulation within lipid-rich deposits characteristic of age-related pathologies.}, }
@article {pmid41281747, year = {2025}, author = {Yang, B and Yang, K and Chen, Y and Xi, R and Han, J and Li, S and Chen, J and Wu, Y}, title = {Activation of GSDME by all-trans-retinal increases sensitivity to photoreceptor ferroptosis.}, journal = {International journal of biological sciences}, volume = {21}, number = {15}, pages = {7029-7042}, pmid = {41281747}, issn = {1449-2288}, mesh = {Animals ; *Ferroptosis/physiology/drug effects/genetics ; Mice ; Mice, Knockout ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; *Photoreceptor Cells, Vertebrate/metabolism ; *Retinaldehyde/metabolism/pharmacology ; Mice, Inbred C57BL ; Lipid Peroxidation ; Mitochondria/metabolism ; Retinal Degeneration/metabolism ; Macular Degeneration/metabolism ; ATP-Binding Cassette Transporters ; }, abstract = {Impaired clearance of all-trans-retinal (atRAL) due to visual cycle dysfunction contributes to photoreceptor atrophy, a key pathological hallmark of Stargardt disease type 1 (STGD1) and dry age-related macular degeneration (AMD). Prior studies have shown that light-induced atRAL accumulation promotes ferroptosis and activates gasdermin E (GSDME) in retinal photoreceptors of Abca4[-/-]Rdh8[-/-] mice, a model for STGD1 and dry AMD that exhibits visual cycle disorders. However, the role of GSDME in photoreceptor ferroptosis remains unclear. In this study, we revealed that GSDME activation by atRAL triggered photoreceptor ferroptosis and retinal atrophy via mitochondrial damage and oxidative stress. Knocking out GSDME significantly attenuated light-induced photoreceptor ferroptosis and retinal degeneration in Abca4[-/-]Rdh8[-/-] mice. Moreover, deleting the Gsdme gene in photoreceptor cells prevented atRAL-induced ferroptosis by inhibiting mitochondrial reactive oxygen species (mitoROS) production, iron overload, and lipid peroxidation. Notably, treatment with the mitoROS scavenger MitoTEMPO mitigated ferroptosis in atRAL-loaded photoreceptor cells and dramatically relieved photoreceptor ferroptosis and retinal degeneration in light-exposed Abca4[-/-]Rdh8[-/-] mice. We found that both GSDME elimination and MitoTEMPO treatment repressed atRAL-induced photoreceptor ferroptosis and retinal atrophy by inactivating the mitoROS-induced oxidative stress. In conclusion, GSDME-mediated photoreceptor ferroptosis is crucial for inducing structural and functional damage of the retina in retinopathies caused by atRAL accumulation, thereby providing new therapeutic insights for the prevention and treatment of STGD1 and dry AMD.}, }
@article {pmid41282061, year = {2025}, author = {Lizińczyk, AM and Pankiewicz, JE and Cullina, WL and Franco, LA and Sullivan, PM and Sadowski, MJ}, title = {APOE Genotype Differentially Modulates Prion Pathology in a Mouse Model.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {41282061}, issn = {2693-5015}, support = {R01 AG067478/AG/NIA NIH HHS/United States ; RF1 AG088226/AG/NIA NIH HHS/United States ; }, abstract = {APOE polymorphism affects the risk of occurrence and the rate of progression in several neurodegenerative diseases including Alzheimer's disease, primary tauopathies, α-synucleinopathy, and age-related macular degeneration, but its role in prionoses remains unestablished. Using APOE targeted replacement (TR) mice, we investigated how APOE genotype affects key neurodegenerative mechanisms involved in prion pathology. Male and female ε2/ε2, ε3/ε3, and ε4/ε4 APOE-TR mice were inoculated with 22L mouse-adapted scrapie strain or normal brain homogenate and monitored with behavioral testing from 10-week post inoculation (wpi.) onward. Mice were euthanized at 23 wpi. when all prion-infected animals were symptomatic, and their brains were analyzed for multiple neuropathological, biochemical, and transcriptomic metrics. ε4/ε4 22L mice featured the shortest disease latency time, the worst neurological score, and the highest load of spongiform lesions. ε2/ε2 22L mice performed significantly better than ε4/ε4 22L mice but significantly worse than ε3/ε3 22L animals. Numerous aspects of PrP proteinopathy were exacerbated in the presence of the ε4 allele including increased PrP[Sc] accumulation, reduced PrP solubility, and increased PrP oligomerization. These metrics were comparable between ε2/ε2 22L and ε3/ε3 22L mice. Prion pathology significantly increased brain apolipoprotein (apo) E levels, with the greatest increase in ε4/ε4 22L mice. All apoE isoforms formed complexes with conformationally altered PrP, but this interaction was the strongest in ε4/ε4 22L mice. ε4/ε4 22L mice had the highest load of reactive microglia and astrocytes and upregulation of transcriptomic markers typical of neurodegenerative microglia and astrocytes, followed by ε2/ε2 22L, with ε3/ε3 22L having the lowest. Thus, APOE polymorphism differentially regulates the progression of prion pathology attributable to two ε4-affected mechanisms: increased conversion and accumulation of PrP[Sc] and worsened prion-associated neuroinflammation. Though less severely than ε4, the ε2 allele also increased the inflammatory response, rendering disease outcome worse relative to the ε3 allele. Our findings suggest both ε4 and ε2 alleles are disadvantageous determinants in prion pathology.}, }
@article {pmid41282676, year = {2025}, author = {Banijamali, SMA and Versek, C and Lashkari, K and Bex, P and Sridhar, S}, title = {Mobile Objective Diagnostics of Macular Degeneration using Dark-Adapted Visual Evoked Potentials.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {41282676}, support = {R44 AG057250/AG/NIA NIH HHS/United States ; }, abstract = {PURPOSE: Delayed Dark-Adapted vision Recovery (DAR) is a known biomarker for Age-related Macular Degeneration (AMD); however, its measurement is often cumbersome for both patients and examiners. In this study, we developed NeuroVEP, a portable, wireless, and user-friendly system designed to objectively assess Dark-Adapted Visual Evoked Potentials (DAVEP).<br><br>METHODS: NeuroVEP consists of a headset with a smartphone that delivers controlled photo-bleach and monocular pattern reversal stimuli while utilizing custom electroencephalography (EEG) electrodes and electronics to measure DAVEP. The system allows for separate analysis of the near peripheral and macular visual field of each eye, completing the test in a comfortable, single-session format (<25 minutes) without requiring subjective patient feedback.The NeuroVEP test protocol included: (i) Mesopic luminance pattern reversal VEP for macular and peripheral regions (5 mins), (ii) Full-field photopic pattern reversal VEP (2.5 mins), (iii) Scotopic luminance DAVEP recovery post photo-bleach (up to 15 mins), measured simultaneously from both eyes.The data were analyzed for 66 participants, divided into four cohorts: (A) Age-matched healthy controls with no ophthalmic pathologies (n=10), (B) Early-stage AMD (AREDS1) (n=19), (C) Intermediate-stage AMD (AREDS3) (n=18), (D) Advanced-stage AMD (AREDS4/5) (n=19).Advanced signal processing and machine learning methodologies were applied to filter and process the VEP responses from the DAR segment of the experiment. 13 discriminating features were extracted from the processed signals and classified for each participant using a Bayesian statistical framework and Gaussian Mixture Model (GMM).<br><br>RESULTS: The algorithm demonstrated: 86% accuracy in early-stage AMD detection (Healthy vs. Early AMD) (Sensitivity: 97%, Specificity: 65%, AUC-ROC: 0.81 and AUC-PR: 0.92) and 93% accuracy in overall AMD detection (Healthy vs. All AMD stages) (Sensitivity: 98%, Specificity: 65%, AUC-ROC: 0.82 and AUC-PR: 0.97).<br><br>CONCLUSIONS: We successfully developed a portable, objective user-friendly VEP system and an advanced Bayesian-GMM statistical analysis framework capable of identifying DAR deficits in AMD patients. This novel technology shows high potential for early AMD detection and could serve as a non-invasive, objective diagnostic tool for AMD screening in clinical and remote settings.}, }
@article {pmid41282784, year = {2025}, author = {Zhang, PW and Wan, ZH and Liu, S and Wang, J and Sripathi, S and Li, W and Ahn, J and Li, S and Fan, L and Berlinicke, CA and Qian, J and Merbs, SL and Zack, DJ}, title = {HTRA1-AS1, an ARMS2-region long non-coding RNA, is downregulated in retinas of age-related macular degeneration patients.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {41282784}, support = {P30 EY001765/EY/NEI NIH HHS/United States ; R01 EY020406/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE: The human 10q26 locus is a major genetic risk factor for age-related macular degeneration (AMD). Fine mapping by linkage and large-scale genome-wide association studies (GWAS) has narrowed this region to a 30-kb interval encompassing the ARMS2 and HTRA1 genes. However, the causative gene(s), risk variants, and underlying pathogenic mechanisms remain unresolved.<br><br>METHODS: Long non-coding RNA (lncRNA) candidates within the ARMS2-HTRA1 region were identified using human postmortem retinal RNA-seq data and public databases (NCBI, Ensembl). Candidate transcripts were validated by RT-PCR and Sanger sequencing. Published single-cell RNA-seq datasets were analysed to define cell type-specific expression, and RNA levels were compared between AMD and non-AMD donor retinas. Additionally, expression changes were assessed in human iPSC-derived retinal pigment epithelium (RPE) cells exposed to cigarette smoke extract (CSE) and paraquat (PQT).<br><br>RESULTS: We identified and validated a lncRNA, HTRA1-AS1, and its transcript variants (ENST00000647969.1) within the ARMS2 locus. HTRA1-AS1 overlaps ARMS2 and is transcribed in the antisense orientation. It is predominantly expressed in rod photoreceptors, M&#xfc;ller glia and Choroid/RPE, and its retinal expression was significantly reduced in AMD compared with controls (43 AMD donors vs. 44 controls, p = 0.007). By contrast, HTRA1 mRNA showed no significant difference (p = 0.121). Furthermore, ENST00000647969.1, HTRA1-AS1 and ARMS2 expression increased dramatically, up to 101-fold, 8-fold and 75-fold, respectively, in induced pluripotent stem cells (iPSC)-derived RPE cells following cigarette smoke extract (CSE)-induced oxidative stress but showed no significant change after paraquat treatment.<br><br>CONCLUSION: These findings suggest that HTRA1-AS1, a dysregulated lncRNA within the ARMS2 locus, may act as a non-coding element contributing to transcriptional mis-regulation underlying AMD pathogenesis.}, }
@article {pmid41283408, year = {2025}, author = {Barranco Garcia, J and Ferrazzini, T and Coito, A and Brügger, D and Abegg, M}, title = {Recovery of the Pupillary Response After Light Adaptation Is Slowed in Patients with Age-Related Macular Degeneration.}, journal = {Journal of eye movement research}, volume = {18}, number = {6}, pages = {}, pmid = {41283408}, issn = {1995-8692}, abstract = {Purpose: This study evaluates a novel, non-invasive method using a virtual reality (VR) headset with integrated eye trackers to assess retinal function by measuring the recovery of the pupillary response after light adaptation in patients with age-related macular degeneration (AMD). Methods: In this pilot study, fourteen patients with clinically confirmed AMD and 14 age-matched healthy controls were exposed to alternating bright and dark stimuli using a VR headset. The dark stimulus duration increased incrementally by 100 milliseconds per trial, repeated over 50 cycles. The pupillary response to the re-onset of brightness was recorded. Data were analyzed using a linear mixed-effects model to compare recovery patterns between groups and a convolutional neural network to evaluate diagnostic accuracy. Results: The pupillary response amplitude increased with longer dark stimuli, i.e., the longer the eye was exposed to darkness the bigger was the subsequent pupillary amplitude. This pupillary recovery was significantly slowed by age and by the presence of macular degeneration. Test diagnostic accuracy for AMD was approximately 92%, with a sensitivity of 90% and a specificity of 70%. Conclusions: This proof-of-concept study demonstrates that consumer-grade VR headsets with integrated eye tracking can detect retinal dysfunction associated with AMD. The method offers a fast, accessible, and potentially scalable approach for retinal disease screening and monitoring. Further optimization and validation in larger cohorts are needed to confirm its clinical utility.}, }
@article {pmid41283579, year = {2025}, author = {Cao, JA and Zhou, AW and Teagle, GM and Baumann, LM and Sahraravand, RA and Wong, CW and De Zanet, S and Jovic, N and Steiner, P and Patel, SB and Minaker, SA and MacCumber, MW and Brown, DM and Al-Khersan, H and Wykoff, CC}, title = {Geographic Atrophy Progression in Clinical Practice Before and After Pegcetacoplan Treatment.}, journal = {Vision (Basel, Switzerland)}, volume = {9}, number = {4}, pages = {}, pmid = {41283579}, issn = {2411-5150}, support = {N/A//Texas Retina Research Foundation (TRRF), Houston, Texas/ ; }, abstract = {This retrospective study evaluated changes in ocular characteristics and retinal pigment epithelium (RPE) and photoreceptor ellipsoid zone (EZ) depletion rates before and after intravitreal pegcetacoplan initiation in clinical practice. A total of 168 eyes from 110 patients with GA secondary to age-related macular degeneration (AMD) who received at least 3 pegcetacoplan injections were included. Data was collected from 5 years before to 9 months after pegcetacoplan initiation. RPE and EZ depletion areas were measured using an automated artificial intelligence (AI) algorithm on optical coherence tomography (OCT) images. At baseline, 76 eyes (45.2%) had concurrent neovascular AMD (nAMD), with mean RPE and EZ depletion areas of 3.3 mm[2] and 4.9 mm[2], respectively. By pegcetacoplan initiation, these increased to 8.6 mm[2] and 11.2 mm[2], respectively, with 151 eyes (89.9%) having concurrent nAMD and 155 eyes (92.3%) having subfoveal GA. Pre-treatment to post-treatment RPE and EZ square root depletion rates decreased from 0.25 mm/year to 0.096 mm/year, and 0.26 mm/year to 0.049 mm/year, respectively. Mean best-recorded visual acuity (BRVA) worsened by 0.05 logMAR annually before and after treatment. These real-world findings align with data from the pegcetacoplan phase 3 trials, showing reduced RPE and EZ depletion rates without changes in rates of BRVA loss. Additional studies are warranted.}, }
@article {pmid41284475, year = {2025}, author = {Cui, Y and Song, Z and Wang, X}, title = {Bisphosphonate-related ocular adverse events: a pharmacovigilance study based on the FAERS database.}, journal = {Endocrine connections}, volume = {14}, number = {12}, pages = {}, pmid = {41284475}, issn = {2049-3614}, abstract = {This retrospective study aimed to identify and characterize signals of ocular adverse events (AEs) related to bisphosphonates (BPs) using FDA adverse event reporting system (FAERS) data (Q1 2004 to Q3 2024) to inform future safety investigations. Disproportionality analysis was conducted utilizing the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) methods to identify BP-related ocular AE signals. In addition, a modified ROR method was utilized to examine differences across gender and age. Among 6,965 ocular AE reports for five BPs (alendronate, zoledronate, pamidronate, risedronate, and ibandronate), 136 positive signals were identified, predominantly unlisted in drug labels. Notable risks included ocular inflammatory AEs (especially zoledronate) and novel risk signals such as cataract, glaucoma, and macular degeneration. Standardized MedDRA queries (SMQ) linked BPs to 11 eye disorders, with scleral disorders common to all five BPs and pamidronate involving the broadest SMQ categories. Ocular AEs for alendronate, zoledronate, and pamidronate exhibited age-related differences, while those for alendronate and zoledronate showed gender differences. This study identifies high-risk and novel ocular AEs related to BPs. These findings warrant further validation in future studies.}, }
@article {pmid41292308, year = {2026}, author = {Kim, TR and Kim, TG and Choi, J and Yu, SY and Kim, K}, title = {Quantitative Analysis of Drusen in South Korean Patients: A 36-Month Follow-Up Study.}, journal = {Korean journal of ophthalmology : KJO}, volume = {40}, number = {1}, pages = {87-98}, pmid = {41292308}, issn = {2092-9382}, mesh = {Humans ; Retrospective Studies ; Female ; Male ; Follow-Up Studies ; *Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnosis/epidemiology ; Republic of Korea/epidemiology ; Aged ; Middle Aged ; Disease Progression ; Time Factors ; Fundus Oculi ; *Macular Degeneration/diagnosis/epidemiology ; Fluorescein Angiography/methods ; Aged, 80 and over ; Incidence ; *Retinal Pigment Epithelium/pathology ; }, abstract = {PURPOSE: This study aimed to quantitatively evaluate longitudinal changes in drusen area and volume over 36 months in South Korean patients and to identify the factors associated with these changes and the development of advanced age-related macular degeneration (AMD).<br><br>METHODS: In this retrospective study, 38 eyes from 38 patients diagnosed with drusen were analyzed. The drusen area and volume were measured using spectral-domain optical coherence tomography (SD-OCT; Cirrus 5000, Carl Zeiss Meditec) with an automated retinal pigment epithelium elevation map algorithm. To minimize bias from variable follow-up intervals, an annualized classification framework was adopted. Based on percentage change in drusen area within the 5-mm circle, eyes were categorized as progressed (increase >20%), stable (change within &#xb1;20%), or regressing (decrease >20%).<br><br>RESULTS: Both drusen area and volume increased significantly up to 24 months (area, p = 0.003; volume, p = 0.028) and then showed a modest decline at 36 months, remaining above baseline levels. No significant difference in the proportions of progressed, stable, or regressing eyes was observed across 12-month intervals or compared with baseline (all p > 0.05). A larger baseline 5-mm drusen area was significantly associated with the development of advanced AMD (adjusted odds ratio, 2.818; 95% confidence interval, 1.022-7.767; p = 0.045). Eyes that exhibited at least one episode of drusen regression showed a higher incidence of advanced AMD (36.8% vs. 5.3%, p = 0.042).<br><br>CONCLUSIONS: Drusen in South Korean patients demonstrated dynamic morphological remodeling over time. Drusen regression was not a benign phenomenon but rather a potential high-risk marker for progression to advanced AMD. These findings highlight the importance of population-specific, quantitative SD-OCT monitoring for early risk stratification in East Asian eyes.}, }
@article {pmid41293061, year = {2025}, author = {Lorenzi, M and Ebohon, S and Kissner, J and Comiskey, J and Paap, M and Bouchet, C and Garnham, A and Wissinger, E}, title = {Network Meta-Analysis of Bevacizumab Gamma Versus Competing Interventions for Treating Neovascular Age-Related Macular Degeneration in the United Kingdom.}, journal = {Journal of market access &amp; health policy}, volume = {13}, number = {4}, pages = {58}, pmid = {41293061}, issn = {2001-6689}, abstract = {This study aimed to determine the relative efficacy of bevacizumab gamma (an ophthalmic formulation of bevacizumab) versus alternative interventions relevant to the treatment of neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) via a systematic literature review (SLR) and network meta-analysis (NMA). An SLR was conducted to identify randomized controlled trials (RCTs) of anti-vascular endothelial growth factor (anti-VEGF) therapies for the treatment of nAMD in adult patients relevant to the UK context. The included anti-VEGF treatments were ranibizumab, aflibercept, faricimab, and bevacizumab gamma. Bayesian NMA models were used to estimate relative efficacy in terms of change from baseline (CFB) in best-corrected visual acuity (BCVA) at 12 months, the proportion of patients gaining 15 or more letters at 12 months, and the proportion of patients losing less than 15 letters at 12 months. Twenty-two relevant RCTs were included in the NMA. At 12 months, all anti-VEGF treatments were similarly efficacious to ranibizumab 0.5 mg every four weeks (Q4W) in terms of CFB in BCVA, the proportion of patients gaining 15 or more letters, and the proportion of patients losing less than 15 letters (except for ranibizumab 0.5 mg every 12 weeks [Q12W] and ranibizumab 0.5 mg pro re nata [PRN]). Bevacizumab gamma provided similar improvements in visual acuity to other anti-VEGF treatments.}, }
@article {pmid41293704, year = {2025}, author = {Guo, Y and Hormel, TT and Wu, AL and Gao, M and Hwang, TS and Bailey, ST and Jia, Y}, title = {AI-aided segmentation of four types of drusen in volumetric OCT.}, journal = {Biomedical optics express}, volume = {16}, number = {11}, pages = {4380-4391}, pmid = {41293704}, issn = {2156-7085}, support = {P30 EY010572/EY/NEI NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; R01 EY036429/EY/NEI NIH HHS/United States ; R01 EY024544/EY/NEI NIH HHS/United States ; R01 EY031394/EY/NEI NIH HHS/United States ; R01 EY027833/EY/NEI NIH HHS/United States ; T32 EY023211/EY/NEI NIH HHS/United States ; R01 EY035410/EY/NEI NIH HHS/United States ; R43 EY036781/EY/NEI NIH HHS/United States ; }, abstract = {Drusen are a hallmark biomarker of age-related macular degeneration (AMD), with their size, number, and morphology (type) closely linked to disease severity and progression. Accurate segmentation and classification of drusen from optical coherence tomography (OCT) images are essential for objective AMD assessment and monitoring. In this work, we present a deep learning framework that combines a convolutional neural network for automated drusen segmentation with a dedicated classification module to distinguish four clinically relevant, distinct drusen types based on segmentation output. We evaluated our approach on a comprehensive dataset and achieved a mean Dice score of 0.74 ± 0.21 for voxel-wise segmentation accuracy and a critical success index of 0.69 ± 0.24 for drusen count accuracy. This method demonstrates substantial improvements in the quantitative drusen analysis and offers a promising tool for enhanced AMD diagnosis and tracking of disease progression.}, }
@article {pmid41293996, year = {2025}, author = {Xin, X and Zhao, X and Han, X and Pu, W}, title = {ASNS Regulates H2O2-Induced Senescence, Oxidative Stress, and Glucose Metabolism in ARPE-19 Cells by Modulating USP13 Expression.}, journal = {BioFactors (Oxford, England)}, volume = {51}, number = {6}, pages = {e70057}, pmid = {41293996}, issn = {1872-8081}, support = {2023GLLH0239//Science and Technology Program of the Joint Fund of Scientific Research for the Public Hospitals of InnerMongolia Academyof Medical Sciences/ ; 2023YK17//Scientific Research Program of Aerospace Medical and Healthcare Technology Group Co./ ; }, mesh = {Oxidative Stress/drug effects ; Humans ; Hydrogen Peroxide/pharmacology ; *Glucose/metabolism ; Cellular Senescence/drug effects ; Animals ; Cell Line ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Macular Degeneration/genetics/metabolism/pathology ; Cell Survival/drug effects ; Reactive Oxygen Species/metabolism ; Disease Models, Animal ; }, abstract = {Age-related macular degeneration (AMD) is a common degenerative disease of the eye that ultimately leads to irreversible vision loss. Asparagine synthase (ASNS) is an aminotransferase, and its low expression is associated with retinal damage. The present study centered on the protective effect of ASNS on retinal epithelial cells. We found that in the AMD cell model, overexpression of ASNS reduced SA-β-gal staining and ROS production, and increased cell viability in H2O2-treated ARPE-19 cells. In addition, overexpression of ASNS increased glucose consumption, lactate production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR) and enhanced the expression of glycolytic markers. Molecular mechanistic studies revealed that ASNS was highly bound to USP13 protein and increased USP13 expression. Furthermore, ASNS protected the retinal epithelium from oxidative stress damage in an animal model of AMD. Taken together, these findings suggest that the ASNS/USP13 axis plays an important regulatory role in AMD development. Our findings not only emphasized the understanding of the role of glucose metabolism in AMD, but also identified a promising target for future AMD therapy.}, }
@article {pmid41294302, year = {2025}, author = {Quarta, A and Corradetti, G and Romano, F and Trinco, A and Feo, A and Corvi, F and Nardi, C and Alhelaly, M and Abbasgholizadeh, R and Chujo, S and Popovic, M and Soylu, C and Chung, YC and Kwak, HD and Rattu, R and Nittala, MG and Staurenghi, G and Sadda, SR}, title = {Distinct Profiles of Choriocapillaris Involvement in Extensive Macular Atrophy With Pseudodrusen-Like Appearance and Geographic Atrophy.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {14}, pages = {64}, pmid = {41294302}, issn = {1552-5783}, mesh = {Humans ; *Geographic Atrophy/physiopathology/diagnosis/etiology ; Retrospective Studies ; Female ; *Choroid/blood supply ; Cross-Sectional Studies ; Male ; Tomography, Optical Coherence/methods ; Aged ; Fluorescein Angiography/methods ; Aged, 80 and over ; *Retinal Drusen/diagnosis/physiopathology ; Capillaries/pathology/physiopathology ; *Macular Degeneration/complications/diagnosis/physiopathology ; Visual Acuity ; Fundus Oculi ; Middle Aged ; Regional Blood Flow/physiology ; }, abstract = {PURPOSE: To quantitatively compare choriocapillaris flow deficit percentages (CCFD%) between eyes with extensive macular atrophy with pseudodrusen-like appearance (EMAP) and geographic atrophy (GA) secondary to age-related macular degeneration (AMD), and to identify predictive factors for CCFD% at the atrophy margin.<br><br>METHODS: This retrospective cross-sectional study included 53 eyes (27 with GA and 26 with EMAP). CCFD% were computed within a 500-&#xb5;m-wide marginal zone (CCFD%_M) and beyond the margin (CCFD%_BM) using compensated en face optical coherence tomography angiography (OCTA) images. Atrophy-to-fovea distance (AFD) was quantified by pixel-wise Euclidean analysis.<br><br>RESULTS: Eyes with EMAP demonstrated significantly higher CCFD% compared to GA both at the atrophy margin (CCFD%_M, P < 0.05) and beyond (CCFD%_BM, P < 0.01). In univariable analysis, belonging to the GA group was associated with a 5.9-unit reduction in CCFD%_M, reflecting a substantial preservation of choriocapillaris (CC) perfusion in GA relative to EMAP. AFD was greater in EMAP (2.35 &#xb1; 0.56 mm) than GA (1.74 &#xb1; 0.55 mm; P = 0.014) suggesting more eccentric positioning of the lesions in the former. A multivariable mixed-effects model confirmed disease subtype (EMAP vs. GA) as an independent determinant of CC impairment with EMAP associated with a significantly higher CCFD%_M (P < 0.01).<br><br>CONCLUSIONS: CC impairment is more pronounced in EMAP than in GA, with EMAP exhibiting more extensive and diffuse CCFD, particularly at the atrophy margins. This pattern may reflect a more aggressive vascular compromise in EMAP. These findings underscore a distinct CC pathoanatomy between the two conditions, with implications for disease progression and therapeutic targeting.}, }
@article {pmid41294847, year = {2025}, author = {Alam, J and Ponnam, A and Souvangini, A and Gopi, S and Ildefonso, CJ and Biswal, MR}, title = {EPO-R76E Enhances Retinal Pigment Epithelium Viability Under Mitochondrial Oxidative Stress Induced by Paraquat.}, journal = {Cells}, volume = {14}, number = {22}, pages = {}, pmid = {41294847}, issn = {2073-4409}, support = {R01 EY033415/EY/NEI NIH HHS/United States ; R01EY033415/EY/NEI NIH HHS/United States ; }, mesh = {*Oxidative Stress/drug effects ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Humans ; *Mitochondria/metabolism/drug effects ; *Paraquat/toxicity/pharmacology ; *Erythropoietin/genetics/metabolism ; Cell Survival/drug effects ; Reactive Oxygen Species/metabolism ; Cell Line ; NF-E2-Related Factor 2/metabolism ; Apoptosis/drug effects ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, primarily driven by oxidative stress-induced degeneration of retinal pigment epithelium (RPE). Erythropoietin (EPO), a hematopoietic cytokine with neuroprotective properties, has been shown to reduce apoptosis and retinal degeneration. In this study, we examined the cytoprotective role of a non-erythropoietic EPO variant, EPO-R76E, in suppressing oxidative stress and mitochondrial dysfunction related to oxidative stress in RPE cells. Stable ARPE-19 cell lines expressing EPO-R76E were generated via lentiviral transduction and exposed to paraquat to induce oxidative stress. Oxidative stress was induced using paraquat. EPO-R76E expression conferred increased cell viability and resistance to mitochondrial damage, as assessed by cytotoxicity assays. Western blot analysis revealed reduced expression of ferritin and p62/SQSTM1, diminished activation of p-AMPK and NRF2, and restoration of GPX4 levels, indicating enhanced antioxidant defenses. Moreover, intracellular iron accumulation and reactive oxygen species were significantly reduced in EPO-R76E-expressing cells exposed to paraquat. These findings suggest that EPO-R76E promotes mitochondrial homeostasis and modulates oxidative stress pathways. Our study positions EPO-R76E as a promising therapeutic candidate for halting RPE degeneration in AMD.}, }
@article {pmid41297424, year = {2025}, author = {Zhou, L and Ma, Y and Li, X and Cao, G}, title = {Gut-eye axis in ophthalmic diseases: Focus on ocular neurodegeneration.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {193}, number = {}, pages = {118800}, doi = {10.1016/j.biopha.2025.118800}, pmid = {41297424}, issn = {1950-6007}, mesh = {*Gastrointestinal Microbiome ; Humans ; Animals ; *Eye Diseases/microbiology ; Brain-Gut Axis ; *Neurodegenerative Diseases/microbiology ; Eye/metabolism ; }, abstract = {Ocular neurodegeneration comprises a group of complex processes that severely affect visual function and is recognized as a key pathogenetic process in a variety of blinding ocular diseases, including glaucoma, diabetic retinopathy, age-related macular degeneration and retinitis pigmentosa. Although these diseases have different etiologies and mechanisms, apoptosis, metabolic disorders and oxidative damage are common features shared by all of them. Increasing evidence indicates that gut microbiota regulates distant organs by engaging in the host's neural, endocrine, immune regulation and even intercellular information. However，in ocular degenerative diseases, specific gut microbiota and their metabolites play an important role in ocular degenerative diseases. Therefore, in this review, we summarize the pathways through which the "gut-eye axis" functions and the mechanisms by which it interacts with ocular degenerative diseases, as well as the alterations in gut microbiota profiles observed in several common ocular degenerative diseases. Additionally, we provide an outlook on the clinical application of the "gut-eye axis", including its potential diagnostic, therapeutic, and adjunctive therapies.}, }
@article {pmid41297526, year = {2025}, author = {Paneerselvam, GS and Wai, NJ and Sheng, LJ and Kenneth, LKC}, title = {Cost-Effectiveness of Vascular Endothelial Growth Factor Inhibitors in the Management of Wet Age-Related Macular Degeneration: A Systematic Review.}, journal = {Value in health regional issues}, volume = {53}, number = {}, pages = {101542}, doi = {10.1016/j.vhri.2025.101542}, pmid = {41297526}, issn = {2212-1102}, abstract = {OBJECTIVES: To evaluate the cost-effectiveness of VEGF inhibitors, ranibizumab, aflibercept, bevacizumab, brolucizumab, pegaptanib, and conbercept for wAMD treatment.<br><br>METHODS: A systematic search was conducted in PubMed, Cochrane, and SpringerLink databases to identify cost-effectiveness analyses and cost-utility analyses related to wAMD treatment. Eligible studies were assessed using Drummond's 10-point checklist to evaluate methodological quality. The extracted data included intervention costs, quality-adjusted life-years, and incremental cost-effectiveness ratios.<br><br>RESULTS: Twenty-two studies met the inclusion criteria. Bevacizumab and brolucizumab were frequently reported as cost-effective alternatives, offering comparable or superior visual outcomes at lower costs than ranibizumab or aflibercept. Pegaptanib was consistently less cost-effective. Findings for ranibizumab versus aflibercept varied by treatment regimen and analytic assumptions. Across studies, cost-effectiveness estimates were influenced by model perspective, time horizon, exclusion of adverse events, and single-eye modeling. A further limitation is that in contexts of non-inferior efficacy, small incremental quality-adjusted life-years differences may artificially inflate incremental cost-effectiveness ratios, potentially overstating the costs relative to benefits.<br><br>CONCLUSIONS: Decision making in wAMD treatment requires more thorough economic evaluations that incorporate standardized methodologies and lengthy cost assessments.}, }
@article {pmid41300254, year = {2025}, author = {Shi, C and Lee, J and Shi, D and Wang, G and Yuan, F and Lai, TYY and Liu, J and Lu, Y and Liu, D and Qin, B and Zee, BC}, title = {AI-Based Retinal Image Analysis for the Detection of Choroidal Neovascular Age-Related Macular Degeneration (AMD) and Its Association with Brain Health.}, journal = {Brain sciences}, volume = {15}, number = {11}, pages = {}, pmid = {41300254}, issn = {2076-3425}, abstract = {Purpose: This study aims to develop a method for detecting referable (intermediate and advanced) age-related macular degeneration (AMD) and neovascular AMD, as well as providing an automatic segmentation of choroidal neovascularisation (CNV) on colour fundus retinal images. We also demonstrated that brain health risk scores estimated by AI-based Retinal Image Analysis (ARIA), such as white matter hyperintensities and depression, are significantly associated with AMD and neovascular AMD. Methods: A primary dataset of 1480 retinal images was collected from Zhongshan Hospital of Fudan University for training and 10-fold cross-validation. Additionally, two validation subdataset comprising 238 images (retinal images and wide-field images) were used. Using fluorescein angiography-based labels, we applied the InceptionResNetV2 deep network with the ARIA method to detect AMD, and a transfer ResNet50_Unet was used to segment CNV. The risks of cerebral white matter hyperintensities and depression were estimated using an AI-based Retinal Image Analysis approach. Results: In a 10-fold cross-validation, we achieved sensitivities of 97.4% and 98.1%, specificities of 96.8% and 96.1%, and accuracies of 97.0% and 96.4% in detecting referable AMD and neovascular AMD, respectively. In the external validation, we achieved accuracies of 92.9% and 93.7% and AUCs of 0.967 and 0.967, respectively. The performances on two validation sub-datasets show no statistically significant difference in detecting referable AMD (p = 0.704) and neovascular AMD (p = 0.213). In the segmentation of CNV, we achieved a global accuracy of 93.03%, a mean accuracy of 91.83%, a mean intersection over union (IoU) of 68.7%, a weighted IoU of 89.63%, and a mean boundary F1 (BF) of 67.77%. Conclusions: The proposed method shows promising results as a highly efficient and cost-effective screening tool for detecting neovascular and referable AMD on both retinal and wide-field images, and providing critical insights into CNV. Its implementation could be particularly valuable in resource-limited settings, enabling timely referrals, enhancing patient care, and supporting decision-making across AMD classifications. In addition, we demonstrated that AMD and neovascular AMD are significantly associated with increased risks of WMH and depression.}, }
@article {pmid41300437, year = {2025}, author = {Hong, SJ and Lee, DH and Choi, JW and Lee, H and Sung, Y and Kim, GJ}, title = {Nrf2 Activated by PD-MSCs Attenuates Oxidative Stress in a Hydrogen Peroxide-Injured Retinal Pigment Epithelial Cell Line.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, pmid = {41300437}, issn = {2076-3921}, support = {RS - 2025 - 431 02313877//Industry - Academia - Research Institute (IAR) Collabo R&amp;D Fund Grant funded by the Korean Government/ ; }, abstract = {Age-related macular degeneration (AMD) is a retinal degenerative disease caused by oxidative stress. Thus, we aimed to reduce oxidative stress through the use of placenta-derived mesenchymal stem cells (PD-MSCs). To induce oxidative stress in ARPE-19 cells, we treated them with 200 µM hydrogen peroxide (H2O2) for 2 h and then cocultured them with PD-MSCs. The dissociation of the KEAP1/Nrf2 complex, along with the expression of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), increased in the coculture group compared with the H2O2 treatment group (* p < 0.05). The expression levels of antioxidant genes increased in the cocultured group compared with those in the H2O2 treatment group (* p < 0.05), whereas the ROS levels decreased in the cocultured group (* p < 0.05). Additionally, both the expression of mitochondrial dynamics markers and the mitochondrial membrane potential increased when the cells were cocultured with PD-MSCs (* p < 0.05). PD-MSC cocultivation decreased the expression levels of lipoproteins (* p < 0.05). Finally, we confirmed that PD-MSCs promoted the expression of RPE-specific genes in H2O2-injured ARPE-19 cells (* p < 0.05). These findings suggest a new aspect of stem cell treatment for AMD induced by oxidative stress.}, }
@article {pmid41301489, year = {2025}, author = {Intonti, S and Olivieri, C and Reibaldi, M and Borrelli, E and Curcio, C and Conedera, FM}, title = {Translational Molecular and Fluid Biomarkers for Age-Related Macular Degeneration: Practical Insights from Animal Models and Humans.}, journal = {Biomolecules}, volume = {15}, number = {11}, pages = {}, pmid = {41301489}, issn = {2218-273X}, support = {PZ00P3_223803/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {Humans ; *Biomarkers/metabolism ; Animals ; *Macular Degeneration/metabolism/diagnosis/pathology/genetics ; Disease Models, Animal ; Oxidative Stress ; Mice ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss. Its pathogenesis is complex and multifactorial, involving genetic predisposition, inflammation, oxidative stress, and environmental influences, which underscores the need to better understand biomarkers associated with the disease. This review provides a comprehensive translational overview of biomarkers linked to both dry and wet forms of AMD by integrating findings from human studies and preclinical mouse models, including chemical, genetic, and laser-induced paradigms. It outlines key tissue, fluid, and systemic biomarkers related to oxidative stress, inflammation, complement activation, extracellular matrix remodeling, angiogenesis, and gut microbiota alterations. The main findings highlight similarities and differences between human AMD and animal models, identify challenges in biomarker validation, and emphasize the potential of combining biomarker profiles from ocular tissues, blood, tear fluid, aqueous and vitreous humor, and gut microbiome samples to improve early diagnosis, therapeutic monitoring, and personalized treatment strategies. These insights suggest that integrating experimental and clinical biomarker data could advance precision medicine in AMD, facilitating better early detection and individualized therapies. Future research should aim to bridge these datasets to optimize biomarker-driven approaches for AMD management.}, }
@article {pmid41301509, year = {2025}, author = {Nardella, M and Pellegrini, M and Yu, AC and Adamo, GG and Mura, M and Busin, M}, title = {Nanotechnology-Based Delivery Systems and Retinal Pigment Epithelium: Advances, Targeting Approaches, and Translational Challenges.}, journal = {Biomolecules}, volume = {15}, number = {11}, pages = {}, pmid = {41301509}, issn = {2218-273X}, mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Drug Delivery Systems/methods ; Animals ; *Nanotechnology/methods ; Translational Research, Biomedical ; Nanomedicine/methods ; Macular Degeneration/drug therapy ; Retinal Diseases/drug therapy ; Nanoparticles/chemistry ; }, abstract = {The retinal pigment epithelium (RPE) is essential for maintaining retinal integrity, and its dysfunction underlies several progressive ocular diseases, including age-related macular degeneration, choroidal neovascularization (CNV), inherited retinal disorders (IRDs), and proliferative vitreoretinopathy (PVR). Although current therapies have improved disease management, they mainly target secondary pathological mechanisms and do not directly preserve or restore RPE function. Moreover, the delivery of therapeutic molecules or genes to the RPE remains a major challenge due to the presence of multiple ocular barriers and the need for sustained, localized action. Nanomedicine offers innovative solutions to these limitations by enabling precise, controlled, and cell-specific delivery of drugs and genetic materials. Engineered nanocarriers can be optimized to traverse ocular barriers, enhance bioavailability, and modulate the retinal microenvironment. This review summarizes recent advances in nanoscale delivery systems for RPE-targeted therapies, focusing on design principles, targeting strategies, and therapeutic applications, and discusses the translational challenges that must be addressed to bring nanotechnology-based treatments closer to clinical application.}, }
@article {pmid41301918, year = {2025}, author = {Lee, Y and Seo, JH}, title = {Potential Causal Effects of Cystatin C on Age-Related Macular Degeneration: A Two-Sample Mendelian Randomization Study.}, journal = {Biomedicines}, volume = {13}, number = {11}, pages = {}, pmid = {41301918}, issn = {2227-9059}, support = {VHSMC24002//Veterans Health Service Medical Center Research Grant/ ; }, abstract = {Background/Objectives: Previous studies have shown an association between kidney function and age-related macular degeneration (AMD). This study aims to assess whether the kidney function-related parameters of serum cystatin C and creatinine levels are associated with increased risk of AMD and its subtypes. Methods: Genetic instruments for variants associated with serum cystatin C and creatinine levels as exposure at genome-wide significance (p < 5.0 × 10[-8]) were obtained from the UK Biobank. Genetic data for AMD and its subtypes were obtained from the FinnGen project. A two-sample Mendelian randomization analysis was performed to evaluate the causal effects of serum cystatin C and creatinine levels on AMD and its subtypes. Results: Using an inverse-variance weighted approach, higher cystatin C levels are associated with an increased risk of AMD [odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.04 to 1.22, p = 0.004 for overall AMD; OR = 1.14, 95% CI: 1.04 to 1.25, p = 0.007 for dry AMD; OR = 1.14, 95% CI: 1.03 to 1.26, p = 0.011 for wet AMD]. However, serum creatinine levels did not significantly impact the risk of AMD or its subtypes. Conclusions: This study provides genetic evidence that higher cystatin C levels may be a causal risk factor for AMD and its subtypes, whereas serum creatinine was not. This result implies the need to investigate the effect of cystatin C on AMD potentially independent of kidney function.}, }
@article {pmid41302082, year = {2025}, author = {Liesenhoff, C and Meyrl, C and Krause, D and Eckardt, F and Lorger, A and Deiters, V and Schiefelbein, J and Klaas, JE and Schworm, B and Priglinger, SG and Siedlecki, J}, title = {High-Dose 8 mg Aflibercept for Neovascular Age-Related Macular Degeneration: Who Is Being Treated with This New Agent?.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {11}, pages = {}, pmid = {41302082}, issn = {2075-1729}, abstract = {Purpose: To describe the indication spectrum for high-dose 8 mg aflibercept for neovascular age-related macular degeneration (nAMD) in a real-world cohort in a tertiary referral center. Methods: The database of the University Eye Hospital Munich, Ludwig Maximilians-University was screened for eyes with nAMD treated with 8 mg aflibercept. Demographic data, multimodal imaging and treatment parameters were recorded. Reasons for treatment with 8 mg aflibercept were analyzed. Results: Thirty-four consecutive eyes of 31 patients (mean age 78.6 ± 8.9 years) were identified. There were 22 women (70.1%) and 9 men (29.9%). In all eyes (100%), 8 mg Aflibercept was applied as switching therapy. Prior to switching, the mean anti-vascular endothelial growth factor (VEGF) treatment duration for nAMD was 3.9 ± 2.9 years, pretreatment amounted to a mean of 34.5 ± 26.3 injections, equaling 9.2 ± 2.4 injections/year, and the mean visual acuity (VA) was 0.4 ± 0.4 logMAR. The last treatment before switching was 2 mg aflibercept in 76%, faricimab in 18%, ranibizumab in 3% and bevacizumab in 3% of cases. Reasons for switching included (A) recalcitrant nAMD with persistent fluid despite q4w dosing (17 eyes, 50%), (B) the wish for interval extension (15 eyes, 44%) and (C) macular hemorrhage (2 eyes, 6%). In group B, two-thirds of eyes (10/15, 66.7%) were maintained at ≤q6w prior to switching. Conclusions: In this study, high-dose 8 mg aflibercept was exclusively used as a switch therapy. Most eyes (76%) switched were from pretreatment with 2 mg aflibercept. The main reasons for switching were recalcitrant nAMD with persistent fluid despite q4w dosing (50%) or the wish for treatment extension beyond 6 weeks (32%). In the future, these data will aid in the design of prospective real-world studies comparing the efficacy of high-dose 8 mg aflibercept with older generation treatment options, especially 2 mg aflibercept.}, }
@article {pmid41302976, year = {2025}, author = {Molin, C and Midena, E and Convento, E and Midena, G and Pilotto, E}, title = {Fixation Stability as a Surrogate for Reading Abilities in Age-Related Macular Degeneration: A Perspective.}, journal = {Journal of clinical medicine}, volume = {14}, number = {22}, pages = {}, pmid = {41302976}, issn = {2077-0383}, abstract = {Age-related macular degeneration (AMD) significantly impacts central vision, fixation site and stability and reading abilities. This work aims to analyze the relationship between retinal fixation parameters measured using microperimetry and reading performance in patients with AMD. We identified the role of fixation stability measurement in the evaluation of reading abilities and discussed its implications both in clinical practice and in clinical trials. Our analysis highlights the importance of retinal fixation assessment as a precise surrogate for evaluating reading ability outcomes in AMD patients and as new clinical endpoint to demonstrate the functional effects of present and emerging target therapies.}, }
@article {pmid41303214, year = {2025}, author = {Wu, KY and Qian, SY and Camiré, A and Kim, DT and Giunta, M}, title = {Aflibercept for Wet Age-Related Macular Degeneration: A Prospective, Randomized Trial Comparing Treat-And-Extend and Fixed Bimonthly Dosing.}, journal = {Journal of clinical medicine}, volume = {14}, number = {22}, pages = {}, pmid = {41303214}, issn = {2077-0383}, support = {Unknown//Bayer (Canada)/ ; }, abstract = {Background/Objectives: Currently, treatments for age-related macular degeneration (AMD) consist of regular intravitreal injections that exert significant pressure on healthcare systems via their high labor costs and economic burden. To address this, our study's goal is to propose new treatment protocols by comparing the efficacy of bimonthly fixed dosing aflibercept injections versus the treat-and-extend (T&amp;E) approach for wet AMD. Secondary objectives included categorical best-corrected visual acuity (BCVA) changes, anatomical outcomes, treatment intervals, and adverse events. Methods: This study is a 1-year randomized, open-label, prospective trial that included 44 eyes from 44 patients, 32 in the T&amp;E arm and 12 in the bimonthly arm. Treatment-naïve AMD patients with neovascularization were randomized to a bimonthly fixed dosing group or a T&amp;E group after receiving 3 consecutive monthly aflibercept injections. Following the induction doses, retreatment intervals for patients in the T&amp;E arm were adjusted based on a predetermined algorithm. Results: Over 12 months, mean BCVA improvements were 5.0 letters in the bimonthly group and 4.1 in the T&amp;E group (p = 0.096 for non-inferiority test). On average, T&amp;E patients received 9.6 injections compared to 7.7 for those in the fixed dosing group (p < 0.001). Anatomical outcomes were comparable in both treatment arms. Conclusions: In our trial, the T&amp;E approach provided significant visual improvements, but did not meet the threshold for non-inferiority when compared to fixed bimonthly dosing. It was also unable to minimize treatment burden over the course of the first year of injections. Further research is required to optimize the T&amp;E algorithm with aflibercept.}, }
@article {pmid41303260, year = {2025}, author = {Lee, SY and Hwang, DD}, title = {Short-Term Effects of Intravitreal Ranibizumab Biosimilar Injections in Patients with Neovascular Age-Related Macular Degeneration on Retinal Nerve Fiber Layer Thickness.}, journal = {Journal of clinical medicine}, volume = {14}, number = {22}, pages = {}, pmid = {41303260}, issn = {2077-0383}, abstract = {Background/Objectives: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the standard treatment for neovascular age-related macular degeneration (nAMD), but concerns remain regarding its potential effects on optic nerve structure. Evidence on the structural safety of ranibizumab biosimilars, including LucenBS[®], is still limited. This study aimed to investigate the short-term effects of intravitreal LucenBS[®] injections on peripapillary retinal nerve fiber layer (RNFL) thickness in previously treated nAMD patients using optical coherence tomography (OCT). Methods: This retrospective, observational case series included 24 eyes from 24 nAMD patients who had previously received anti-VEGF agents other than ranibizumab biosimilar. In bilateral cases, the eye that developed nAMD earlier was selected. Patients received between one and three LucenBS[®] injections, and the mean follow-up period after the final injection was 11.92 ± 4.81 weeks. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), and peripapillary RNFL thickness were assessed before and after each injection using spectral-domain OCT. Sectoral and global RNFL values were compared using the Wilcoxon signed-rank test. Results: The mean age of participants was 74.6 ± 9.0 years, and baseline BCVA and IOP were 0.83 ± 0.66 logMAR and 14.88 ± 2.80 mmHg, respectively. RNFL thickness showed no significant changes in either global or sectoral regions after any injection (all p > 0.05). CMT significantly decreased after the first injection (p = 0.007), but remained stable with subsequent treatments. BCVA remained stable after the first and second injections, but slightly worsened after the third injection (p = 0.012). IOP showed no significant changes at any time point. Conclusions: Short-term intravitreal LucenBS[®] injections did not induce structural alterations in the peripapillary RNFL, supporting their short-term ocular safety in previously treated nAMD patients. Although CMT improved after the first injection, functional and anatomical responses varied with repeated dosing. Larger, long-term studies are required to further validate the structural and functional safety of ranibizumab biosimilars in nAMD management.}, }
@article {pmid41303405, year = {2025}, author = {Noreen, S and Lim, SS and Lee, D}, title = {Preventive and Protective Effects of Nicotinamide Adenine Dinucleotide Boosters in Aging and Retinal Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {22}, pages = {}, pmid = {41303405}, issn = {1422-0067}, support = {RS-2021-NR060133//NRF/ ; }, mesh = {Humans ; *NAD/metabolism ; Animals ; *Aging/metabolism/drug effects ; *Retinal Diseases/metabolism/prevention &amp; control/drug therapy ; Niacinamide/analogs &amp; derivatives/pharmacology/therapeutic use ; Diabetic Retinopathy/metabolism/drug therapy/prevention &amp; control ; Macular Degeneration/metabolism/drug therapy ; Mitochondria/metabolism/drug effects ; Retina/metabolism/drug effects ; Oxidative Stress/drug effects ; *Protective Agents/pharmacology ; Nicotinamide Mononucleotide/pharmacology/therapeutic use ; Pyridinium Compounds ; }, abstract = {Nicotinamide adenine dinucleotide (NAD[+]) boosting can sustain energy metabolism and neurovascular stability in the retinal tissue. Depletion of NAD[+] is linked to the development of pathological retinal conditions, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Mitochondrial dysfunction, oxidative stress, and inflammation occur in these diseases. This review summarizes substantial evidence of therapeutic NAD[+] boosters, including nicotinamide, nicotinamide mononucleotide, or nicotinamide riboside. They help improve mitochondrial function and lessen neurovascular injury. We also emphasize the importance of natural products and sirtuins in facilitating cytoprotective effects through the regulation of mitochondrial balance and inflammation. Developments in drug delivery methods, such as nanoparticle encapsulation and targeted eye treatments, are promising for enhancing the bioavailability and effectiveness of NAD[+] boosters. The novelty of this work is its combination of mechanistic insights regarding NAD[+] metabolism with efficacy data from preclinical studies. Furthermore, natural products may work together to boost their therapeutic effects against retinal damage. Together, our review article highlights NAD[+] metabolism as a potential therapeutic target for addressing retinal degeneration and maintaining vision in aging, neurologic disorders, and various metabolic diseases, including diabetes.}, }
@article {pmid41303406, year = {2025}, author = {Chao, WW and Chao, HW and Peng, PH and Lee, YT and Chao, HM}, title = {Retinal Ischemia: Therapeutic Effects and Mechanisms of Paeoniflorin.}, journal = {International journal of molecular sciences}, volume = {26}, number = {22}, pages = {}, pmid = {41303406}, issn = {1422-0067}, mesh = {Animals ; *Glucosides/pharmacology/therapeutic use ; *Monoterpenes/pharmacology/therapeutic use ; Rats ; Rats, Wistar ; Male ; Vascular Endothelial Growth Factor A/metabolism ; *Ischemia/drug therapy/metabolism/pathology ; Disease Models, Animal ; Retinal Pigment Epithelium/drug effects/metabolism/pathology ; *Retinal Diseases/drug therapy/metabolism/pathology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Cell Survival/drug effects ; Reperfusion Injury/drug therapy/metabolism/pathology ; Apoptosis/drug effects ; Neuroprotective Agents/pharmacology ; Glycosides ; }, abstract = {Retinal ischemia is a key factor in the progression of vision-threatening ocular diseases, including central retinal artery/vein occlusion, exudative age-related macular degeneration (eAMD), and proliferative diabetic retinopathy. This study investigates the effects of paeoniflorin along with its related neuroprotective molecular pathways in the treatment of retinal ischemia. Free radical or ischemic-like damage was induced by incubating retinal pigment epithelium (RPE) cells for 24 h with 1 mM hydrogen peroxide (H2O2) or by subjecting retinal neuronal cells to 8 h of oxygen-glucose deprivation (OGD). Both treatments caused significant cell loss. Treatment with paeoniflorin significantly increased cell viability at 0.5 mM in both cell types. In a Wistar rat model of retinal ischemia and reperfusion (I/R) elicited by sustained high intraocular pressure (HIOP), pre-treatment with 0.5 mM paeoniflorin mitigated the ischemia-induced decline in ERG b-wave amplitude, reduction in whole and inner retinal thickness, loss of fluorogold-labeled retinal ganglion cells, and formation of apoptotic cells. Meanwhile, paeoniflorin effectively downregulated pro-neovascular mediators β-catenin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and the pro-inflammatory/angiogenic biomarker angiopoietin-2 (Ang-2), producing effects similar to the Wnt/β-catenin inhibitor (dickkopf-related protein 1), anti-angiogenic pigment epithelium-derived factor (PEDF), and anti-VEGF Avastin (bevacizumab). These findings suggest that paeoniflorin may protect against retinal ischemia through its anti-inflammatory, anti-neovascular/angiogenic, antioxidative, and neuroprotective properties.}, }
@article {pmid41303411, year = {2025}, author = {Gyenes, A and István, L and Papp, A and Resch, M and Récsán, Z and Ecsedy, M and Szepessy, Z and Szabó, A and Lesch, B and Barcsay, G and Borbándy, &#xc1; and Sándor, GL and Nagy, ZZ and Kovács, I}, title = {Evaluation of the Duration of Good Visual Acuity During Anti-VEGF Therapy for Age-Related Macular Degeneration in Routine Clinical Practice.}, journal = {International journal of molecular sciences}, volume = {26}, number = {22}, pages = {}, pmid = {41303411}, issn = {1422-0067}, mesh = {Humans ; *Visual Acuity/drug effects ; *Ranibizumab/therapeutic use/administration &amp; dosage ; Male ; Female ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Macular Degeneration/drug therapy/physiopathology ; Retrospective Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Aged, 80 and over ; Treatment Outcome ; Middle Aged ; }, abstract = {The aim of this study was to analyse data from a clinical database using a novel visual acuity parameter to determine whether anti-VEGF molecules that target multiple domains involved in neovascularisation are more likely to achieve good visual acuity than agents that solely inhibit VEGF. This retrospective study analysed data from patients treated with anti-VEGF injections between 2015 and 2023. We set an ETDRS score threshold of 70 (equivalent to 20/40 Snellen acuity) to calculate 'time in range' (TIR). TIR is defined as 'time spent with best-corrected visual acuity (BCVA) better than 20/40' and can highlight significant variations in the time individuals spend above the threshold during their AMD treatment. Over nine years, 30,209 aflibercept and 10,876 ranibizumab injections were administered to 6043 patients. Patients received an average of 6.8 injections. The mean BCVA at the first injection was 57.00 ± 16.15 ETDRS letters for ranibizumab patients and 58.75 ± 15.82 for aflibercept patients, with a statistically significant difference (p < 0.001). Both groups showed significant improvement in visual acuity at follow-up (aflibercept: 60.21 ± 15.53; ranibizumab: 59.43 ± 15.81; both p < 0.001). The mean time between the two consecutive injections, including both the initial loading phase and the subsequent maintenance phase, was 67.22 ± 34.08 days for ranibizumab and 72.15 ± 31.00 days for aflibercept; the difference was statistically significant (p < 0.001). After controlling for the effect of initial BCVA and time between injections, patients who received aflibercept had a significantly higher average TIR (60.90 ± 36.27 days vs. 56.55 ± 38.78 days, p < 0.001), and significantly more likely to achieve >70 letters at the next visit (OR: 1.10; 95% CI: 1.05-1.15; p < 0.001) compared to patients receiving ranibizumab. Aflibercept treatment improves the likelihood of maintaining good BCVA by 10% compared to ranibizumab in patients receiving intravitreal anti-VEGF treatment for nAMD. Furthermore, the beneficial effects of aflibercept treatment are observed with less frequent dosing. Our results suggest that using anti-VEGF compounds that target multiple domains provides a detectable advantage in treating age-related macular degeneration, particularly when these agents have a longer duration of action.}, }
@article {pmid41303866, year = {2025}, author = {Kang, SG and Singh, M and Lee, G and Lee, KE and Vinayagam, R}, title = {Formulation of α-Linolenic Acid-Based Microemulsions for Age-Related Macular Degeneration: Physicochemical Tests and HET-CAM Assays for Anti-Angiogenic Activities.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {11}, pages = {}, pmid = {41303866}, issn = {1648-9144}, support = {1345370673, LINC3.0-2023-54//Ministry of Education and National Research Foundation of Korea/ ; }, mesh = {Emulsions/therapeutic use ; *alpha-Linolenic Acid/therapeutic use/pharmacology ; Animals ; *Angiogenesis Inhibitors/therapeutic use/pharmacology ; *Macular Degeneration/drug therapy ; Chorioallantoic Membrane/drug effects ; Humans ; Chick Embryo ; Drug Delivery Systems/methods ; Chickens ; Mice ; Intravitreal Injections/methods ; }, abstract = {Background and Objectives: Age-related macular degeneration (AMD) is an age-associated retinal disorder characterized by blood-retinal barrier (BRB) breakdown and pathological angiogenesis, leading to vascular leakage. The intravitreal administration of anti-VEGF agents remains the most effective treatment for neovascular AMD. However, repetitive intravitreal injections have risks, causing side effects such as cataracts, bleeding, retina damage, and, in severe cases, post-injection endophthalmitis. Hence, the development of innovative drug delivery systems is essential to minimize the risks and discomfort associated with intravitreal injections. Materials and Methods: We developed a microemulsion (ME)-based topical drug delivery system incorporating α-linolenic acid (ALA). In brief, pseudo-ternary phase diagrams were constructed by the water titration method using different combinations of surfactants and cosurfactants (Smix-Cremophor RH 40: Span 80: Transcutol P in ratios of 1:1.05, 1:1:1, 1:1:1.5) containing ALA as the oil phase. Three blank microemulsions (ME1, ME2, and ME3) were prepared and characterized based on the optimized pseudo-ternary phase equilibrium with a Smix ratio of 1:1:1. Results: ME3, with an average particle size of 38.59 nm, was selected as the optimized formulation for developing drug-loaded ME containing Fenofibrate, Axitinib, and Sirolimus. The drug-loaded ME showed particle size (46.94-56.39 nm) and in vitro release displayed sustained and longer time drug release for 240 h. The irritation and antiangiogenic activities were evaluated using the hen's egg chorioallantoic membrane (HET-CAM) assay employing the optimized ME loaded with each drug. Among the three drug-loaded ME, the Sirolimus ME showed a reduction in blood vessel sprouting in the HET-CAM assay, indicating strong antiangiogenic activity. Treatment with the optimized blank ME and Sirolimus ME significantly (p < 0.05) reduced COX-2 protein expression in LPS-stimulated RAW 264.7 cells, suggesting their potential anti-inflammatory effects. Conclusions: Overall, we suggest that the α-linolenic acid-based Sirolimus microemulsion may serve as a promising topical therapeutic approach for managing AMD and offering a potential alternative to invasive intravitreal injections.}, }
@article {pmid41304869, year = {2025}, author = {Alali, NM and Aljahdali, A and AlBalawi, HB and Al Jarallah, OJ and Al Zaid, SM and Abuallut, I and ALMarek, F and Shajry, I and Alotaibi, YA and Hazzazi, MA and Magliyah, MS}, title = {Effectiveness, Safety, and Real-World Experience of Brolucizumab: A Systematic Review.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {11}, pages = {}, pmid = {41304869}, issn = {1424-8247}, abstract = {Background/Objectives: Brolucizumab is a humanized single-chain antibody fragment with a molecular weight of approximately 26 kilodaltons (scFv, ~26 kDa) targeting all VEGF-A isoforms. Intravitreal brolucizumab (6 mg) is FDA-approved for neovascular age-related macular degeneration (nAMD) (2019) and diabetic macular edema (DME) (2022). We systematically review the literature on brolucizumab for nAMD and DME, focusing on efficacy, safety, pharmacokinetics, real-world outcomes, and cost-effectiveness in adult and pediatric patients. Methods: Our method involves a comprehensive literature search of PubMed, Embase, Scopus, Cochrane, and related databases (through late 2024) using terms including "brolucizumab," "Beovu," "neovascular AMD," "diabetic macular edema," "safety," "pharmacokinetics," and "pediatric." High-quality clinical trials, meta-analyses, regulatory documents, and real-world studies were prioritized. Results: In pivotal Phase III trials (HAWK/HARRIER for nAMD), brolucizumab 6 mg demonstrated non-inferior visual acuity (VA) gains to aflibercept, with >50% of eyes maintained on 12-week dosing and greater retinal fluid reduction. In DME trials (KESTREL/KITE), brolucizumab was similarly non-inferior to aflibercept for VA and showed superior anatomic drying, with 33-48% of eyes maintained on ≥12-week intervals. However, brolucizumab use has been associated with intraocular inflammation (IOI), retinal vasculitis, and vascular occlusion: clinical trials and post hoc analyses reported higher rates of these events than comparator agents. Real-world cohorts found IOI in ~4-10% of treated eyes, often occurring early (within 3 months) after initiation. Conclusions: In conclusion, Brolucizumab is an effective anti-VEGF option for nAMD and DME, providing durable anatomic control with fewer injections. Non-inferior vision outcomes and superior fluid resolution have been demonstrated. However, it carries a distinct risk of IOI and occlusive vasculitis, necessitating careful patient selection, dosing, and monitoring.}, }
@article {pmid41305085, year = {2025}, author = {Wang, MH}, title = {Explainable Artificial Intelligence Framework for Predicting Treatment Outcomes in Age-Related Macular Degeneration.}, journal = {Sensors (Basel, Switzerland)}, volume = {25}, number = {22}, pages = {}, pmid = {41305085}, issn = {1424-8220}, support = {82501368//National Natural Science Foundation of China/ ; }, mesh = {Treatment Outcome ; *Macular Degeneration/diagnosis/therapy ; Humans ; Male ; Female ; Middle Aged ; Aged ; Prognosis ; *Large Language Models ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness, yet current tools for forecasting treatment outcomes remain limited by either the opacity of deep learning or the rigidity of rule-based systems. To address this gap, we propose a hybrid neuro-symbolic and large language model (LLM) framework that combines mechanistic disease knowledge with multimodal ophthalmic data for explainable AMD treatment prognosis. In a pilot cohort of ten surgically managed AMD patients (six men, four women; mean age 67.8 ± 6.3 years), we collected 30 structured clinical documents and 100 paired imaging series (optical coherence tomography, fundus fluorescein angiography, scanning laser ophthalmoscopy, and ocular/superficial B-scan ultrasonography). Texts were semantically annotated and mapped to standardized ontologies, while images underwent rigorous DICOM-based quality control, lesion segmentation, and quantitative biomarker extraction. A domain-specific ophthalmic knowledge graph encoded causal disease and treatment relationships, enabling neuro-symbolic reasoning to constrain and guide neural feature learning. An LLM fine-tuned on ophthalmology literature and electronic health records ingested structured biomarkers and longitudinal clinical narratives through multimodal clinical-profile prompts, producing natural-language risk explanations with explicit evidence citations. On an independent test set, the hybrid model achieved AUROC 0.94 ± 0.03, AUPRC 0.92 ± 0.04, and a Brier score of 0.07, significantly outperforming purely neural and classical Cox regression baselines (p ≤ 0.01). Explainability metrics showed that >85% of predictions were supported by high-confidence knowledge-graph rules, and >90% of generated narratives accurately cited key biomarkers. A detailed case study demonstrated real-time, individualized risk stratification-for example, predicting an >70% probability of requiring three or more anti-VEGF injections within 12 months and a ~45% risk of chronic macular edema if therapy lapsed-with predictions matching the observed clinical course. These results highlight the framework's ability to integrate multimodal evidence, provide transparent causal reasoning, and support personalized treatment planning. While limited by single-center scope and short-term follow-up, this work establishes a scalable, privacy-aware, and regulator-ready template for explainable, next-generation decision support in AMD management, with potential for expansion to larger, device-diverse cohorts and other complex retinal diseases.}, }
@article {pmid41307029, year = {2024}, author = {Araki, T and Shimazawa, M and Nakamura, S and Otsu, W and Numata, Y and Sakata, M and Kabayama, K and Tsusaki, H and Hara, H}, title = {Macular white dot lesions with hyperreflective optical coherence tomography findings in cynomolgus and rhesus monkeys.}, journal = {Molecular vision}, volume = {30}, number = {}, pages = {219-233}, pmid = {41307029}, issn = {1090-0535}, mesh = {Animals ; *Tomography, Optical Coherence ; Macaca mulatta ; Female ; Macaca fascicularis ; Electroretinography ; *Macula Lutea/pathology/ultrastructure/physiopathology ; Retinal Pigment Epithelium/pathology/ultrastructure ; *Macular Degeneration/pathology/physiopathology ; }, abstract = {PURPOSE: We screened 28 female cynomolgus monkeys (CMs) and 25 female rhesus monkeys (RMs) for white dots (WDs) in the macula and detected several animals with WDs in colonies at the Shin Nippon Biomedical Laboratories, Ltd., Drug Safety Research Laboratories (SNBL) facility. To determine the functional and morphological characteristics of WDs, we conducted ophthalmological and pathological examinations on these animals.<br><br>METHODS: Fundus examination, optical coherence tomography (OCT), and focal electroretinogram (f-ERG) were conducted for all animals. Histopathology and transmission electron microscopy were conducted for one representative adult CM with WDs.<br><br>RESULTS: In both CMs and RMs, individual differences were observed in the number of WDs in the macula (ranging from approximately 10 to 500 per eye). Hyperreflective granules were observed between the ellipsoid zone (EZ) and the retinal pigment epithelium (RPE) in OCT. Both CMs and RMs exhibited a significant increase in the thicknesses of the RPE and choroid in WD animals compared to their normal counterparts. In the f-ERG, significant decreases and/or tendencies toward decreases in amplitudes and increases in implicit times of both a- and b-waves were observed in animals with WDs. In pathology, diffuse vacuolization of the RPE cells with tiny granules was observed in the macula.<br><br>CONCLUSIONS: Based on the results of OCT and pathological examinations, it was suggested that animals with WDs can develop macular degeneration in the future. To assess their suitability as a model for precursor lesions of age-related macular degeneration, it is imperative to continue monitoring the animals used in the present study until they reach a more advanced age of approximately another 5-10 years.}, }
@article {pmid41307906, year = {2025}, author = {Liem, Y and Vemula, V and Lim, CC and Chong, CCY and Choo, JCJ and Cheng, CY and Sabanayagam, C}, title = {Impact of chronic kidney disease on the incidence of visual impairment and age-related eye diseases in a multi-ethnic Asian population.}, journal = {Journal of global health}, volume = {15}, number = {}, pages = {04316}, pmid = {41307906}, issn = {2047-2986}, mesh = {Humans ; Middle Aged ; Aged ; Male ; Female ; *Renal Insufficiency, Chronic/complications/ethnology/epidemiology ; Singapore/epidemiology ; Incidence ; Adult ; Aged, 80 and over ; *Vision Disorders/epidemiology/ethnology ; *Eye Diseases/epidemiology/ethnology ; *Asian People/statistics &amp; numerical data ; Risk Factors ; Cataract/epidemiology ; }, abstract = {BACKGROUND: The kidney and eye share common metabolic and vascular risk factors, and chronic kidney disease (CKD) has been associated with the prevalence of visual impairment (VI). In this study, we examined the association of CKD with incident VI and major age-related eye diseases, including cataract, age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma, in a multi-ethnic Asian population.<br><br>METHODS: We analysed data from 6486 Chinese, Malay, and Indian adults aged 40-80 years who participated in the Singapore Epidemiology of Eye Diseases study at baseline (2004-11) and six-year follow-up visit (2011-17) and were free of VI and the respective eye diseases at baseline. We defined CKD (n&#x2009;=&#x2009;564; 8.7%) as an estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m[2], and categorised the severity of CKD into stages G1-G5. Eye examinations included refraction, slit-lamp examinations, and retinal imaging. We defined incident VI as best-corrected visual acuity <20/40 in the better eye. Eye diseases examined included cataract, AMD, retinopathy, including DR in those with diabetes and glaucoma. We examined associations between CKD, VI, and eye diseases using multivariable logistic regression models adjusted for age, gender, ethnicity, diabetes, and hypertension status, presenting the results as odds ratios (ORs) and 95% confidence intervals (CIs).<br><br>RESULTS: CKD participants had a higher incidence of any VI (14.3% vs. 3.3%; P&#x2009;<&#x2009;0.001), any AMD (8.0% vs. 5.4%; P&#x2009;<&#x2009;0.001), and cataracts (65.1% vs. 40.8%; P&#x2009;<&#x2009;0.001) than non-CKD participants. VI incidence increased with CKD severity in G1-G2 (3.3%), G3a (13.5%), and G3b-G5 (16.3%) (P&#x2009;<&#x2009;0.001). In multivariable models, CKD was associated with incident VI (OR&#x2009;=&#x2009;1.47; 95% CI&#x2009;=&#x2009;1.03-2.10) and moderate/worse DR (OR&#x2009;=&#x2009;2.62; 95% CI&#x2009;=&#x2009;1.35-5.10).<br><br>CONCLUSIONS: Our results suggest that the presence of CKD increases the risk and severity of VI and eye diseases in Asian adults. Our findings highlight the importance of regular eye exams for CKD patients to reduce the risk of VI.}, }
@article {pmid41308839, year = {2026}, author = {Wang, W and Wazny, VK and Mahadzir, MDA and Maier, AB}, title = {Multivitamin and mineral use: A rapid review of meta-analyses on health outcomes.}, journal = {Ageing research reviews}, volume = {114}, number = {}, pages = {102965}, doi = {10.1016/j.arr.2025.102965}, pmid = {41308839}, issn = {1872-9649}, mesh = {Female ; Humans ; Pregnancy ; Cognition/drug effects ; COVID-19 ; *Dietary Supplements ; *Minerals/administration &amp; dosage/therapeutic use ; *Vitamins/administration &amp; dosage/therapeutic use ; Meta-Analysis as Topic ; }, abstract = {Multivitamin and mineral (MVM) supplements are among the most widely used dietary supplements globally, however, their role in promoting healthspan and longevity remains unclear. This review evaluated comprehensive findings from meta-analyses to clarify their health effects. A rapid review of MEDLINE and EMBASE identified 19 eligible meta-analyses published from 2000 to 2025, encompassing 5535,426 participants, including over 333,943 pregnancies and 904,947 children exposed to maternal MVM supplementation. Randomized controlled trials indicated that MVM use improved global cognition, episodic memory, and immediate recall in older or cognitively intact adults, reduced psychological symptoms in healthy individuals, and lowered systolic blood pressure in at-risk populations. However, no benefits were found for all-cause mortality, COVID-19 outcomes, visual acuity, or multiple cognitive domains, and a higher risk of age-related macular degeneration progression was reported. Observational studies found associations between MVM use and a reduced risk of colorectal cancer, coronary heart disease, cataracts, and fragility hip fractures, but not breast or prostate cancer, stroke, or overall mortality. During pregnancy, MVM supplementation was linked to reduced risks of small-for-gestational-age births and pediatric cancers, but not to preterm birth, stillbirth, or low birth weight. Overall, the findings revealed a lack of consistency in the definition of MVM supplementation, and substantial variability in MVM effectiveness depending on population, age, and health status. These results highlighted the importance of shifting from generalized supplementation approaches to more targeted, personalized nutritional strategies to support healthspan and longevity.}, }
@article {pmid41308856, year = {2026}, author = {Chuang, CC and Chen, YS and Lu, WY and Su, SC and Liao, TY and Yang, SF and Hsieh, YH}, title = {Protective role of Oxyresveratrol against NaIO3-induced oxidative stress in RPE cells via targeting NRF2-mediated ferroptosis in vitro and in vivo.}, journal = {European journal of pharmacology}, volume = {1010}, number = {}, pages = {178402}, doi = {10.1016/j.ejphar.2025.178402}, pmid = {41308856}, issn = {1879-0712}, mesh = {*Oxidative Stress/drug effects ; *NF-E2-Related Factor 2/metabolism/genetics ; Animals ; Humans ; *Retinal Pigment Epithelium/drug effects/pathology/metabolism/cytology ; *Ferroptosis/drug effects ; *Iodates/toxicity ; Mice ; Cell Line ; *Stilbenes/pharmacology/therapeutic use ; *Macular Degeneration/pathology/chemically induced/metabolism/drug therapy ; Mice, Inbred C57BL ; *Plant Extracts/pharmacology ; Male ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; Disease Models, Animal ; Kelch-Like ECH-Associated Protein 1/metabolism ; Apoptosis/drug effects ; }, abstract = {Age-related macular degeneration (AMD) is a chronic retinal disorder that occurs when oxidative damages are gradually accumulated to the center of retina. Oxyresveratrol (OxyR), a naturally occurring stilbene found in many plants, has been reported to exhibit anti-inflammatory and anti-oxidative activities. To fill this gap, we explored the effect of OxyR on retinal pigment epithelial cells in response to oxidative stress and on a mouse model of AMD and further dissected the molecular mechanism underlying OxyR's actions. In this study, we demonstrated that OxyR efficiently impeded both apoptosis and ferroptosis of a human ARPE-19 cells induced by sodium iodate (NaIO3). Such protective effect of OxyR on NaIO3-induced ARPE-19 cells was accompanied with altered expression levels of NRF2, KEAP1, and several ferroptosis-related proteins. Moreover, OxyR treatment, coupled with silencing of NRF2, ferroptosis inhibitor (ferrostatin-1) or depletion of ROS, enhanced the protection of ARPE-19 cells from NaIO3-induced damages. Consistently, oral gavage of OxyR restored the reduction of retinal thickness and attenuated the upregulation of NRF2 in retinal pigment epithelium layers of NaIO3-treated mice. These results demonstrated that OxyR mitigates NaIO3-induced ARPE19 cell death via targeting NRF2-ferroptosis signaling. Our findings provided potential avenues for the use of OxyR in controlling AMD.}, }
@article {pmid41308857, year = {2026}, author = {Cen, S and Liu, S and Zhao, M and Tang, L}, title = {Comparative efficacy and safety of faricimab, aflibercept, conbercept, and ranibizumab for neovascular age-related macular degeneration: A systematic review and network meta-analysis.}, journal = {European journal of pharmacology}, volume = {1010}, number = {}, pages = {178406}, doi = {10.1016/j.ejphar.2025.178406}, pmid = {41308857}, issn = {1879-0712}, mesh = {Humans ; *Angiogenesis Inhibitors/adverse effects/therapeutic use ; *Choroidal Neovascularization/drug therapy ; *Macular Degeneration/drug therapy ; Randomized Controlled Trials as Topic ; *Ranibizumab/therapeutic use/adverse effects ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Recombinant Fusion Proteins/therapeutic use/adverse effects ; Treatment Outcome ; Visual Acuity/drug effects ; Antibodies, Bispecific ; }, abstract = {BACKGROUND: Existing meta-analyses of anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration focus mainly on ranibizumab and aflibercept, with limited data on newer agents (faricimab, conbercept). This network meta-analysis (NMA) comprehensively compares all four key agents.<br><br>METHODS: We systematically searched multiple databases for randomized controlled trials. Bayesian random-effects network meta-analysis was conducted, with evidence certainty assessed using CINeMA (Confidence in Network Meta-Analysis).<br><br>RESULTS: Thirty-nine randomized controlled trials involving 11,548 participants were included. For best-corrected visual acuity, agents showed comparable efficacy (high to moderate evidence); differences were neither statistically nor clinically significant. Choroidal neovascularization regression showed no important differences (mostly low certainty evidence). For retinal thickness, superior reductions versus ranibizumab 0.5&#xa0;mg were observed with aflibercept 2&#xa0;mg (MD: -14.27, 95&#xa0;% CrI: -27.25, -1.75; high certainty), aflibercept 8&#xa0;mg (MD: -32.43, 95&#xa0;% CrI: -57.40, -7.75; high certainty), and conbercept 0.5&#xa0;mg (MD: -10.26, 95&#xa0;% CrI: -19.43, -0.98; moderate certainty). Faricimab required significantly fewer injections (high certainty evidence). Aflibercept 2&#xa0;mg showed better ocular safety than faricimab 6&#xa0;mg (OR: 0.58, 95&#xa0;% CrI: 0.37, 0.90) and ranibizumab 0.5&#xa0;mg (OR: 0.72, 95&#xa0;% CrI: 0.53, 0.97; high certainty).<br><br>CONCLUSION: Aflibercept and conbercept may be preferred when anatomical outcomes are prioritized, whereas faricimab's extended dosing interval could benefit treatment-adherent populations. The superior safety profile of aflibercept 2&#xa0;mg warrants consideration in risk averse patients. These differential effects support personalized therapeutic decision-making.}, }
@article {pmid41308944, year = {2026}, author = {Wang, L and Wang, Z}, title = {Therapeutic targeting of lncRNAs in age-related ocular disease.}, journal = {Experimental eye research}, volume = {263}, number = {}, pages = {110771}, doi = {10.1016/j.exer.2025.110771}, pmid = {41308944}, issn = {1096-0007}, mesh = {Humans ; *RNA, Long Noncoding/genetics ; *Aging/genetics ; *Eye Diseases/genetics/therapy ; *Macular Degeneration/genetics ; *Gene Expression Regulation/physiology ; Animals ; Oxidative Stress ; *Glaucoma/genetics ; *Cataract/genetics ; }, abstract = {Age-related ocular diseases, including age-related macular degeneration, cataract, and glaucoma, are significant causes of visual loss and blindness worldwide. Long non-coding RNAs (lncRNAs) participate in gene regulation, epigenetic control, and cellular homeostasis, and increasing evidence implicates them in age-related ocular disorders by modulating oxidative stress, inflammation, angiogenesis, apoptosis, and extracellular matrix remodeling within ocular tissues. LncRNAs are linked to retinal degeneration, lens opacity, and optic nerve damage, supporting their promise as biomarkers and targets for treatment approaches. This review summarizes current understanding of lncRNA-related processes in age-related ocular disease and emphasizes their potential roles in diagnosis, prognosis, and treatment. An integrated view of lncRNA function in aging ocular tissues may guide precision medicine strategies to prevent or slow vision loss in older individuals.}, }
@article {pmid41310732, year = {2025}, author = {Yoo, HS and Chakravarthy, H and Xi, J and Cui, J and Ai, Z and Hosseini, A and Song, J and Tan, N and Ma, N and Zhou, C and Li, B and Bell, R and Haegert, A and Le Bihan, S and Ju, MJ and Granville, DJ and Matsubara, JA}, title = {Granzyme B contributes to subretinal fibrosis in neovascular age-related macular degeneration by modulating inflammation and epithelial-mesenchymal transition.}, journal = {Journal of neuroinflammation}, volume = {23}, number = {1}, pages = {1}, pmid = {41310732}, issn = {1742-2094}, abstract = {BACKGROUND: More than half of patients with neovascular age-related macular degeneration (nAMD) develop subretinal fibrosis, regardless of anti-vascular endothelial growth factor (VEGF) therapy. No treatment exists for subretinal fibrosis, as its pathophysiology remains elusive. Granzyme B (GzmB) is a serine protease elevated in human eyes with nAMD and contributes to choroidal neovascularization (CNV). Although GzmB is involved in dermal and cardiac fibrosis, its role in subretinal fibrosis has yet to be elucidated.<br><br>METHODS: Using the two-stage laser-induced mouse model of subretinal fibrosis, fibrotic lesions were induced in younger (3&#x2013;6 months old) and older (7&#x2013;14 months old) C57BL/6J and GzmB deficient mice. Seven days after the second laser, in vivo imaging of fibrotic lesions was performed using custom-built polarization diversity-optical coherence tomography (PD-OCT) system. Eyes were collected and used for either retina wholemounts or cross-sections. Wholemounts were immunostained to assess pathological features of fibrosis and determine the size of fibrotic lesions and mast cell counts within fibrotic lesions. Cross-sections were processed to quantify the levels of GzmB substrates within fibrotic lesions, namely pro-fibrotic thrombospondin-1 (TSP-1) and anti-fibrotic decorin (DCN), the extent of macrophage-to-myofibroblast transition (MMT), activation of astrocytes/M&#xfc;ller cells and finally photoreceptor cell death. ARPE-19 wound healing assay was performed to study the direct role of GzmB in RPE wound healing in vitro. GzmB-mediated transcriptional changes in ARPE-19 were determined by performing bulk RNA sequencing. Immunocytochemistry was performed to assess epithelial-mesenchymal transition (EMT).<br><br>RESULTS: GzmB deficiency resulted in smaller fibrotic lesions in older mice and was associated with decreased levels of TSP-1 and increased levels of DCN within fibrotic lesions. It also led to increased MMT but reduced mast cell counts within fibrotic lesions, which was correlated with reduced photoreceptor cell death. In ARPE-19, exogenous application of GzmB impaired wound closure and promoted partial EMT by selectively modulating genes involved in transforming growth factor-&#x3b2; signaling, EMT, inflammation, angiogenesis and cell-cell interaction.<br><br>CONCLUSIONS: Our study reveals that extracellular GzmB is a key contributor to subretinal fibrosis in nAMD, modulating inflammation, EMT and photoreceptor degeneration. These findings suggest GzmB as a promising therapeutic target for mitigating the development of subretinal fibrosis in nAMD.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-025-03619-9.}, }
@article {pmid41311657, year = {2025}, author = {Hanson, J and Yamamoto, M and Tsui, E and Tsui, I}, title = {Efficacy of faricimab for recalcitrant multifactorial cystoid macular edema.}, journal = {American journal of ophthalmology case reports}, volume = {40}, number = {}, pages = {102475}, pmid = {41311657}, issn = {2451-9936}, abstract = {PURPOSE: More information is emerging on faricimab-svoa (faricimab) used for etiologies beyond wet age-related macular degeneration (AMD) and diabetic macular edema (DME), including ongoing trials for use in macular edema following retinal vein occlusion (RVO). This manuscript describes a case of recalcitrant postoperative cystoid macular edema (CME), confounded by a history of branch retinal vein occlusion (BRVO), in which faricimab resulted in resolution of CME after incomplete response to topical anti-inflammation drops, intravitreal aflibercept and bevacizumab, a corticosteroid intravitreal implant, grid laser therapy, and suprachoroidal triamcinolone acetonide (SCS-TA).<br><br>OBSERVATIONS: An 83-year-old pseudophakic male with history of steroid-induced ocular hypertension and BRVO with mild preoperative CME and visual acuity (VA) of 20/160 presented with significant worsening CME following a pars plana vitrectomy (PPV) and internal limiting membrane (ILM) peel for an epiretinal membrane (ERM) in the right eye. CME persisted for eight years despite treatment with topical anti-inflammatories, anti-VEGF injections, a dexamethasone intravitreal implant, grid laser therapy, and a SCS-TA injection. However, after 3 faricimab injections, CME resolved with a CST change from 748 &#x3bc;m to 339 &#x3bc;m and VA improved from 20/50 to 20/40.<br><br>CONCLUSIONS AND IMPORTANCE: This case demonstrates the effectiveness of faricimab in treatment of CME resistant to other therapies and the importance of continued attempts at using new agents for chronic, recurrent CME. The unique benefits of new agents like faricimab, with both VEGF and Ang-2 inhibition, may be particularly helpful in mixed or inflammatory CME when other proven therapies have failed.}, }
@article {pmid41312453, year = {2025}, author = {Wei, L and Yan, W and Zhang, K and Gao, F and Li, Z and Pan, R and Zhang, Z and Wang, X}, title = {Allogeneic whole-eye transplantation: advancements, challenges, and future directions in vision restoration.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1691259}, pmid = {41312453}, issn = {2296-858X}, abstract = {Vision loss remains a significant global health burden, primarily driven by irreversible ocular conditions such as age-related macular degeneration (AMD), glaucoma, severe ocular trauma, and intraocular malignancies. Despite advances in retinal prosthetics and stem cell-based therapies, current treatment options are still limited in their ability to fully restore visual function. Allogeneic whole-eye transplantation (WET) has recently gained attention as a novel and potentially transformative strategy for vision restoration. This review synthesizes recent progress in the field, including advancements in microsurgical techniques, immunosuppressive protocols, and neural integration strategies, drawing on evidence from both preclinical animal models and emerging human studies. Key components, including optic nerve (ON) regeneration, vascular anastomosis, immune tolerance, and donor-recipient matching, are critically examined. Furthermore, we address ongoing barriers, including graft viability, chronic rejection, central visual pathway rewiring, and ethical considerations surrounding the procurement of donor eyes. While substantial milestones have been achieved, particularly in experimental settings, clinical translation remains in its early stages. This review highlights current limitations and proposes future directions for multidisciplinary research aimed at overcoming these challenges and advancing WET toward clinical reality.}, }
@article {pmid41312773, year = {2025}, author = {Ju, X and Ramke, J and Turnbull, PR}, title = {Emerging research on non-neovascular age-related macular degeneration treatments.}, journal = {Clinical &amp; experimental optometry}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/08164622.2025.2579872}, pmid = {41312773}, issn = {1444-0938}, abstract = {Age-related macular degeneration (AMD) is a common condition that causes vision impairment in the elderly, significantly impacting their physical and psychosocial well-being. Historically, treatment options to slow or prevent atrophic AMD progression have been limited but are recently increasing in number. This scoping review aims to provide an overview of the research (both preclinical and clinical) on non-neovascular AMD (including early, intermediate, and geographic atrophy) treatments published in the past decade. Our study protocol was prospectively registered on the Open Science Framework.Searches were conducted on MEDLINE, Embase, ProQuest, and CINAHL for studies investigating treatments for atrophic AMD (including early, intermediate, and geographic atrophy stages) published between 1 January 2014 and 14 July 2024, the search date. Data screening, full-text review, and extraction were independently performed by two researchers. Study characteristics and outcomes were summarised, and the results were synthesised narratively. The search identified 1,211 studies, of which 132 were included in this review. Studies were most often conducted in the United States (n = 92, 68.7%) or Europe (n = 25, 18.5%) and most frequently investigated antioxidant or anti-inflammatory treatments (n = 30, 22.7%) or complement pathway inhibitors (n = 25, 18.9%) as potential therapies. Over three quarters (n = 101, 76.5%) of the included studies reported positive outcomes. Across the decade, the number of studies published increased at an annual rate of 24.0%.This review highlights the growing body of research on atrophic AMD treatments over the past decade, with antioxidant and anti-inflammatory treatments emerging as prominent, promising avenues. However, more phase III human clinical trials are needed to ensure that future therapies effectively serve the global AMD population.}, }
@article {pmid41313467, year = {2025}, author = {Cheng, X and Lohmann, T and Johnen, S and Walter, P and Baumgarten, S}, title = {Relationship between monocyte-to-lymphocyte ratio and age-related macular degeneration: Findings from a national cross-sectional study.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721251402991}, doi = {10.1177/11206721251402991}, pmid = {41313467}, issn = {1724-6016}, abstract = {BackgroundRecent advances have revealed the important role of the immune system in the progression of age-related macular degeneration (AMD). Monocyte-to-lymphocyte ratio (MLR) is a combined marker reflecting inflammation status. However, research on the correlation between MLR and AMD is limited.MethodsIn this cross-sectional analysis, weighted multivariable logistic regression, multinomial logistic regression, subgroup analysis, smoothed curve fitting and threshold effect analysis were used to investigate the relationship between MLR and AMD based on data from the 2005-2008 National Health and Nutrition Examination Survey (NHANES).ResultsThis study included data of 4,655 participants. The proportions of no AMD, early AMD and late AMD were 92.27%, 6.79% and 0.95%, respectively. After adjusting for covariates, weighted multivariable logistic regression analysis revealed that MLR was positively associated with AMD (OR = 3.22, 95%CI 1.32-7.82). Threshold effect analysis revealed that higher MLR associated with prevalence of AMD after MLR was greater than 0.37 (OR = 8.93, 95%CI 2.53-31.60). The diagnostic performance of MLR > 0.37 for AMD was assessed using ROC curve analysis. In addition, MLR was proven to have a significant positive correlation with early AMD (OR = 1.20, 95%CI 1.19-1.21) and late AMD (OR = 9.21, 95%CI 9.10-9.31) through weighted multinomial logistic regression.ConclusionsOur study demonstrates that an elevated MLR is independently associated with the prevalence of AMD.}, }
@article {pmid41314477, year = {2026}, author = {Poirot, M and Buñay, J and Ayadi, S and Silvente-Poirot, S and de Medina, P}, title = {Liver X receptors and the hallmarks of aging: From molecular mechanisms to therapeutic opportunities.}, journal = {Ageing research reviews}, volume = {114}, number = {}, pages = {102967}, doi = {10.1016/j.arr.2025.102967}, pmid = {41314477}, issn = {1872-9649}, mesh = {Humans ; *Liver X Receptors/metabolism/agonists ; *Aging/metabolism ; Animals ; Signal Transduction ; }, abstract = {Aging is the primary risk factor for cardiovascular disease, cancer, neurodegeneration, and other chronic disorders. Therefore, targeting the hallmarks of aging has emerged as a promising strategy to extend healthspan. Liver X receptors (LXRs) are ligand-dependent nuclear receptors that are activated by specific oxysterols and cholesterol derivatives. They are traditionally known as key regulators of cholesterol homeostasis. However, recent evidence reveals that LXRs also influence autophagy, mitochondrial function, epigenetics, senescence, stem cell dynamics, and intercellular communication. This positions LXRs at the crossroads of multiple hallmarks of aging. This review synthesizes current knowledge on endogenous and synthetic LXR ligands, their transcriptional mechanisms, and their effects on the aforementioned hallmarks and age-related pathophysiology. The clinical development of pan-LXR agonists for atherosclerosis has been hindered by side effects, notably hepatic steatosis. Emerging strategies, including LXRβ-selective ligands, selective LXR modulators (SLiMs), and biased agonists such as dendrogenin A, offer ways to separate the protective vascular, metabolic, and neuroprotective effects from adverse outcomes. Additionally, we explore how LXR signaling intersects with the hallmarks of aging and how it can be leveraged to intervene in atherosclerosis, diabetes, cancer, osteoporosis, age-related macular degeneration, and neurodegenerative diseases. Positioning LXRs within the geroscience framework suggests that LXRs may serve as pharmacological hubs to delay aging and its comorbidities. Future work should prioritize isoform- and tissue-selective approaches, metabolite-inspired ligand design, and integration with the hallmarks of aging to unlock the full therapeutic potential of LXRs.}, }
@article {pmid41316066, year = {2025}, author = {Pei, Y and Meng, J and He, W and Zhang, K and Guo, D and Lu, Y and Zhu, X}, title = {Unique liver function in high myopia: associations with myopic macular degeneration.}, journal = {BMC ophthalmology}, volume = {25}, number = {1}, pages = {677}, pmid = {41316066}, issn = {1471-2415}, support = {82301188//National Natural Science Foundation of China/ ; 82122017//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Male ; Cross-Sectional Studies ; Female ; Middle Aged ; *Myopia, Degenerative/physiopathology/blood/complications ; *Macular Degeneration/blood/physiopathology/etiology ; Adult ; Liver Function Tests ; *Liver/physiopathology ; ROC Curve ; gamma-Glutamyltransferase/blood ; Lipids/blood ; }, abstract = {PURPOSE: To investigate liver function and lipid indexes in patients with high myopia and their association with myopic macular degeneration (MMD).<br><br>METHODS: This cross-sectional comparative study included 995 emmetropic patients and 805 highly myopic patients. Serum levels of liver function and lipid indexes were measured using a Roche C702 biochemical analyzer. Ultra-widefield fundus photographs of eyes were classified according to the International META-PM Classification: Category 0: No myopic retinal degeneration, Category 1: tessellated fundus, Category 2: diffuse choroidal retinal atrophy, Category 3: patchy choroidal retinal atrophy, Category 4: macular atrophy. A machine learning model based on liver function indexes was employed to predict the presence of MMD in patients with high myopia.<br><br>RESULTS: Serum levels of albumin (Alb), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) and triglyceride (TG) were significantly lower, whereas high-density lipoprotein cholesterol (HDL) and apolipoprotein-A (Apo-A) were higher in patients with high myopia than those in emmetropic patients (all P&#x2009;<&#x2009;0.05). Significant differences in serum ALT and GGT were found among MMD categories (both P&#x2009;<&#x2009;0.05). Multivariate logistic regression showed that MMD4 was associated with lower serum GGT than MMD1 (P&#x2009;<&#x2009;0.05). The decision tree model to predict MMD achieved an area under the curve (AUC) of 0.735 using serum GGT (sensitivity&#x2009;=&#x2009;53.12%; specificity&#x2009;=&#x2009;82.09%; P&#x2009;<&#x2009;0.001). When using multiple liver function indexes, the AUC of the model reached 0.803 (sensitivity&#x2009;=&#x2009;73.4%; specificity&#x2009;=&#x2009;76.1%; P&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: We identified close associations between liver function and MMD, suggesting serum GGT serve as a potential diagnostic indicator for MMD among highly myopic patients.}, }
@article {pmid41316395, year = {2025}, author = {Dundar, A and Cetik Yildiz, S}, title = {Kynurenine pathway metabolites as potential biomarkers in age-related macular degeneration: an ELISA-based prospective study.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {131}, pmid = {41316395}, issn = {2056-9920}, abstract = {OBJECTIVES: Age-related macular degeneration (AMD), in which oxidative stress, inflammation and metabolic imbalances play a role in its pathogenesis, is one of the leading causes of irreversible vision loss. The kynurenine (KYN) pathway, one of the principal routes of tryptophan (TRP) metabolism, constitutes an important mechanism in retinal neurodegeneration. Based on this information, our study aimed to compare the serum TRP, KYN, kynurenic acid (KYNA), 3-hydroxykynurenine (3HK), 3-hydroxyanthranilic acid (3HAA) and, quinolinic acid (QA) levels of AMD patients and to investigate the diagnostic values of these biomarkers.<br><br>METHODS: Serum samples were collected from AMD patients and control groups. TRP, KYN, KYNA, 3HK, 3HAA, and QA levels were measured using a commercial ELISA method. KYN pathway activity, KYN/TRP and, KYNA/3HK ratios were also assessed. Mann-Whitney U test, ROC analysis, Spearman correlation were applied for statistical comparisons.<br><br>RESULTS: According to our results, 3HK was significantly higher in the AMD group, while TRP, KYN, QA, and KYNA/3HK ratio were higher in the control. ROC analysis revealed 3HK to be the strongest discriminatory marker. The KYNA/3HK ratio also provided significant diagnostic value. Correlation analysis revealed strong negative correlations between 3HK and KYN, QA, and especially KYNA/3HK. Conversely, strong positive correlations were found between KYN and KYNA/3HK, and between TRP, KYN, QA, and KYNA.<br><br>CONCLUSION: KYN pathway metabolites exhibit significant alterations in patients with AMD. 3HK levels and the reduction of the KYNA/3HK ratio suggest a disruption of the neurotoxic-neuroprotective balance and imply that KYN pathway dysfunction may play a role in the pathogenesis of AMD. Among the biomarkers examined, 3HK displayed the highest diagnostic performance, while the KYNA/3HK ratio emerged as an additional biological indicator. These findings indicate that 3HK and the KYNA/3HK ratio may serve as potential biomarker candidates for the early diagnosis and monitoring of AMD.}, }
@article {pmid41316464, year = {2025}, author = {Zhang, Z and Yang, H and Tan, L and Li, Y and Ren, X and Li, X}, title = {Associations between the monocyte‑lymphocyte ratio and age‑related macular degeneration among US adults: evidence from NHANES 2005-2008.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {2}, pmid = {41316464}, issn = {2056-9920}, support = {TJYXZDXK-037A//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; }, abstract = {BACKGROUND: Previous studies have established an association between age-related macular degeneration (AMD) and chronic systemic inflammation. However, the relationship between AMD and the monocyte-to-lymphocyte ratio (MLR), a novel inflammatory biomarker, remains unclear. In this study, we aimed to investigate the association between MLR and AMD using data from the 2005-2008 National Health and Nutrition Examination Survey (NHANES).<br><br>METHODS: Data from three NHANES cycles (2005-2008) were analyzed to preliminarily assess the association between MLR and AMD, excluding participants with incomplete data. We utilized weighted logistic regression models, restricted cubic spline functions (RCS) and constructed receiver operating characteristic (ROC) curves to evaluate the association between MLR and AMD.<br><br>RESULTS: A total of 4,894 participants were deemed eligible for our analysis, with 379 individuals diagnosed with AMD. The Monocyte to Lymphocyte Ratio (MLR) was significantly elevated in the AMD group compared to the non-AMD group. After adjusting for potential confounding factors, we found that elevated MLR levels were significantly associated with an increased risk of AMD, with an OR of 2.56, 95% CI: (1.17,5.58), P&#x2009;=&#x2009;0.022. The restricted cubic spline (RCS) analysis revealed a significant nonlinear relationship between MLR and AMD, with an inflection point at 0.26 (nonlinear P&#x2009;<&#x2009;0.05). Furthermore, the receiver operating characteristic (ROC) curve analysis demonstrated that MLR exhibited acceptable discrimination for AMD.<br><br>CONCLUSIONS: Elevated MLR is associated with an increased risk of AMD, suggesting that MLR may serve as a simple and effective clinical biomarker of AMD.}, }
@article {pmid41317302, year = {2026}, author = {Hashimoto, Y and Arai, Y and Takahashi, H and Tampo, H and Kondo, R and Takahashi, H and Yoshida, H and Takahashi, R and Inoda, S and Kaburaki, T and Yanagi, Y}, title = {Increased aqueous flare after intravitreal brolucizumab injections compared to aflibercept in neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {3}, pages = {701-709}, pmid = {41317302}, issn = {1435-702X}, support = {21K09751//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; Intravitreal Injections ; Retrospective Studies ; Male ; Female ; *Aqueous Humor/diagnostic imaging/metabolism ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Recombinant Fusion Proteins/administration &amp; dosage ; Aged ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Tomography, Optical Coherence ; *Visual Acuity ; Aged, 80 and over ; Angiogenesis Inhibitors/administration &amp; dosage ; Fluorescein Angiography ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Fundus Oculi ; Follow-Up Studies ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; }, abstract = {PURPOSE: To evaluate aqueous flare values in patients with neovascular age-related macular degeneration (nAMD) receiving anti-vascular endothelial growth factor (VEGF) therapy, including brolucizumab.<br><br>METHODS: This retrospective study included 101 patients treated with intravitreal anti-VEGF injections at Jichi Medical University Hospital from March to July 2021. Aqueous flare values were measured in both affected and fellow eyes. The number of treated eyes was 28 for aflibercept and 73 for brolucizumab. Flare values were compared between affected and fellow eyes, and associations with age, gender, drug type, number of injections, disease duration, and time since last injection were analyzed. We also measured flare values from pre-filled syringes.<br><br>RESULTS: In unilateral treatment cases, brolucizumab-treated eyes had significantly higher aqueous flare values than fellow eyes (6.7 vs. 6.2 photon counts/ms, P&#x2009;=&#x2009;0.0032), while no significant difference was observed with aflibercept (6.9 vs. 6.7 pc/ms, P&#x2009;=&#x2009;0.55). Flare values increased significantly with age in the brolucizumab group (P&#x2009;=&#x2009;0.0076) but not in the aflibercept group (P&#x2009;=&#x2009;0.56). The number of brolucizumab injections did not alter flare values. Multivariate analysis identified age as the only significant factor associated with increased aqueous flare. The mean (standard deviation) flare values measured from pre-filled syringes were 430 (15.6) pc/ms for Beovu[&#xae;] (brolucizumab) and 161.8 (31) pc/ms for Eylea[&#xae;] (aflibercept).<br><br>CONCLUSION: In nAMD, aqueous flare values were higher in brolucizumab-treated eyes and increased with age but were unaffected by the number of injections. Different flare values of each drug might affect the aqueous flare values within hours after injection.}, }
@article {pmid41317829, year = {2026}, author = {Kerwin, AF and Perlman, EM and Browning, DJ}, title = {Atrophy Advisor: A Clinical Tool for Dry Macular Degeneration With Geographic Atrophy.}, journal = {American journal of ophthalmology}, volume = {283}, number = {}, pages = {81-90}, doi = {10.1016/j.ajo.2025.11.037}, pmid = {41317829}, issn = {1879-1891}, mesh = {Humans ; *Geographic Atrophy/diagnosis/drug therapy/physiopathology ; Female ; Retrospective Studies ; Male ; Aged ; Visual Acuity/physiology ; Aged, 80 and over ; Disease Progression ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis/drug therapy ; Follow-Up Studies ; Intravitreal Injections ; }, abstract = {OBJECTIVE: To develop and evaluate Atrophy Advisor, a clinical decision tool integrating geographic atrophy (GA) progression and personalized lifespan estimates to help clinicians considering complement factor inhibitor injections for dry macular degeneration with GA.<br><br>DESIGN: Retrospective cohort study.<br><br>SUBJECTS: Fifty consecutive patients with GA secondary to nonexudative age-related macular degeneration, seen at Wake Forest-affiliated retina clinics from May 2013 to June 2025.<br><br>METHODS: Fundus images at two or more time points were analyzed using ImageJ to measure the distance from the fovea to the nearest GA edge. Pixel-to-micron conversion was made using an assumed vertical disk diameter of 1800 microns. Demographics, comorbidities, and corrected visual acuities were extracted from records. Lifespan estimates were calculated using University of Connecticut and Social Security Administration algorithms and compared to observed outcomes.<br><br>MAIN OUTCOME MEASURES: GA edge-to-fovea distance, GA progression rate, corrected visual acuity, and predicted vs observed lifespan.<br><br>RESULTS: Median age was 78 years (IQR: 74-82); 64% were female. Baseline median GA-to-fovea distance was 792 &#xb5;m (IQR: 508-1213 &#xb5;m), declining to 395 &#xb5;m (IQR: 194-702 &#xb5;m) at last follow-up. Median GA progression was 122 &#xb5;m/y (range 2-626 &#xb5;m/y), with a direct relationship between initial distance and progression rate (P = .006, R&#xb2; = 0.146). Lifespan calculators (University of Connecticut and Atrophy Advisor) yielded median estimates of 11.9 and 11.0 years, respectively, influencing treatment guidance in 4% of cases.<br><br>CONCLUSIONS: Atrophy Advisor is feasible for combining GA progression kinetics and lifespan estimates to inform treatment decisions. Variability in progression rates and lifespan predictions highlights the need for personalized approaches. Limitations include measurement variability and retrospective design; future studies should validate the tool in larger, prospective cohorts.}, }
@article {pmid41318054, year = {2026}, author = {Zhang, Z and Shan, X and Liang, F and Fang, L}, title = {Integrative single-cell transcriptomic and experimental analyses unveil Qihuang granule's protection against retinal photodamage via PI3K/AKT/mTOR-mediated autophagy.}, journal = {The international journal of biochemistry &amp; cell biology}, volume = {190}, number = {}, pages = {106881}, doi = {10.1016/j.biocel.2025.106881}, pmid = {41318054}, issn = {1878-5875}, mesh = {Animals ; *TOR Serine-Threonine Kinases/metabolism/genetics ; *Autophagy/drug effects/radiation effects ; *Proto-Oncogene Proteins c-akt/metabolism ; *Drugs, Chinese Herbal/pharmacology ; Rats ; *Phosphatidylinositol 3-Kinases/metabolism/genetics ; Humans ; Signal Transduction/drug effects ; Rats, Sprague-Dawley ; *Retina/drug effects/metabolism/pathology/radiation effects ; Single-Cell Analysis ; Light/adverse effects ; Male ; *Transcriptome/drug effects ; }, abstract = {Light-induced retinal damage is a significant contributor to age-related macular degeneration (AMD). Qihuang granule (QHG), a traditional Chinese herbal formulation, has been clinically employed in the treatment of retinal diseases, including AMD; however, the precise protective mechanisms remain unclear. This study investigated the protective effects and underlying mechanisms of QHG using a rat model of blue light-induced retinal injury and a human retinal pigment epithelial (ARPE-19) cell model. The results demonstrated that QHG significantly alleviated retinal morphological abnormalities, ultrastructural damage, and apoptosis induced by light exposure. Single-cell RNA sequencing further revealed that specific cell clusters were notably enriched in the PI3K-AKT-mTOR and autophagy-related signaling pathways after QHG treatment, characterized by increased MAP1LC3B (LC3B) expression and decreased SQSTM1 (P62) expression. Validation at the protein and gene levels in vivo confirmed that QHG activated the autophagy pathway by downregulating PI3K, AKT, mTOR, and P62 expression while upregulating LC3B expression. Collectively, this study demonstrates that QHG protects against retinal photodamage by modulating autophagy via the PI3K/AKT/mTOR signaling pathway, providing theoretical support for its clinical application in the treatment of AMD.}, }
@article {pmid41321555, year = {2025}, author = {Gregori, G and Mangoni, L and Muzi, A and Mariotti, C and Lupidi, M}, title = {Neovascular Maculopathy after Laser Retinal Rejuvenation Therapy in a Young Myopic Patient: A Case Report.}, journal = {Case reports in ophthalmology}, volume = {16}, number = {1}, pages = {841-846}, pmid = {41321555}, issn = {1663-2699}, abstract = {INTRODUCTION: Laser photobiomodulation, including retinal rejuvenation therapy (2RT), is a system which selectively targets the retinal pigment epithelium by a concise 3 ns pulse duration. The advantage of this laser system over the traditional thermal laser is that the pulsed, very short duration laser effects can be titrated as spatially confined photodisruptors without resultant conductive thermal spread and therefore collateral damage. It has been investigated primarily in age-related macular degeneration (AMD), particularly in decreasing drusen and slowing the rate of AMD progression. In this case, we have described a case of neovascular maculopathy occurring shortly after 2RT in a young myopic patient.<br><br>CASE PRESENTATION: We report the case of a 28-year-old male who presented with unilateral visual impairment following laser 2RT. Two months before, he was subjected to photorefractive keratectomy for moderate myopia (-3.00 D). The baseline optical coherence tomography (OCT) imaging revealed "sharp-peaked" pigment epithelium detachment (PED) in the subfoveal area. Fluorescein angiography indicated a focal area of irregular foveal hyperfluorescence. Observation was advised, and laser 2RT was performed. However, 1 month later, the patient developed a neovascular lesion in the same eye, confirmed by OCT-angiography, requiring urgent intravitreal anti-VEGF therapy.<br><br>CONCLUSIONS: In summary, this case illustrates a progressive maculopathy culminating in choroidal neovascularization triggered by laser 2RT in a young myopic patient.}, }
@article {pmid41323371, year = {2025}, author = {Iwama, Y and Masuda, T and Maeyama, A and Eade, KT and Friedlander, M and Nishida, K and Mandai, M}, title = {Cell-based regenerative therapy for retinal diseases: challenges and emerging bioengineering strategies.}, journal = {Regenerative therapy}, volume = {30}, number = {}, pages = {1101-1112}, pmid = {41323371}, issn = {2352-3204}, abstract = {Cell-based regenerative therapy holds promise for a broad spectrum of retinal diseases characterized by irreversible photoreceptor cell (PRC) loss, including retinitis pigmentosa (RP) and age-related macular degeneration. While gene therapy has delivered landmark successes for selected indications, it does not directly replace lost PRCs and is not well suited for advanced-stages of diseases. In this context, cell-based regenerative approaches-either PRC suspensions or retinal sheets-aim to rebuild the outer retinal circuitry and restore light responses across different retinal diseases. In addition to its relatively high prevalence (1 in 3000-5000 individuals), the PRC-specific degeneration pattern in RP has motivated numerous preclinical studies aimed at clinical application. In this review, we first outline the two major graft modalities-cell suspensions and retinal sheet transplantation-from the perspective of their respective advantages and limitations. Here, we summarize preclinical and clinical evidence for both modalities, highlighting the first-in-human trial of transplantation of human iPSC-derived retinal organoid sheets in late-stage RP, which demonstrated a favorable safety profile and two-year graft survival. We then analyze the challenges that emerged from this first-in-human trial and discuss potential bioengineering and biological solutions. Finally, we consider the prospects of extending these transplantation strategies beyond RP to macular diseases, where PRC replacement may also provide therapeutic benefit. Collectively, the field is transitioning from proof-of-concept to diversified clinical exploration; converging advances in developmental biology, genome engineering, and high-throughput cell analytics are poised to accelerate functional vision restoration in retinal diseases.}, }
@article {pmid41324896, year = {2026}, author = {Kojima, H and Yamashita, A and Nakano, Y and Booka, A and Tatara, Y and Yamada, T and Akimitsu, J and Miyoshi, Y and Osaka, R and Suzuma, K}, title = {Significant Correlation Between Choroidal Thickness and Decrease in Choroidal Blood Flow After Switching to Brolucizumab for Refractory Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {1}, pages = {393-402}, pmid = {41324896}, issn = {2193-8245}, abstract = {INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) therapy suppresses neovascularization in neovascular age-related macular degeneration (nAMD) but may reduce ocular blood flow. However, its relationship with choroidal thickness remains unclear. This study evaluated 1-month outcomes after switching from intravitreal aflibercept or ranibizumab to intravitreal brolucizumab (IVBr) in patients with refractory nAMD.<br><br>METHODS: This prospective, single-center study included 50 eyes of 50 patients with nAMD. Changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), choroidal stromal area (SA), choroidal luminal area (LA), optic nerve head (ONH) mean blur rate (MBR), and choroidal (CHOR) MBR were evaluated before and 1&#xa0;month after switching to IVBr, with blood flow measured using laser speckle flowgraphy. Univariate analyses were performed to identify potential predictors of changes in CHOR-MBR, and variables with P&#x2009;<&#x2009;0.1 were entered into a multiple regression model.<br><br>RESULTS: BCVA was maintained. CRT decreased from 371.6&#x2009;&#xb1;&#x2009;118.7 to 288.8&#x2009;&#xb1;&#x2009;89.7&#xa0;&#xb5;m (P&#x2009;<&#x2009;0.001). SFCT decreased from 231.9&#x2009;&#xb1;&#x2009;118.7 to 196.0&#x2009;&#xb1;&#x2009;117.4&#xa0;&#xb5;m (P&#x2009;<&#x2009;0.001). CVI showed no significant changes, while SA and LA exhibited significant reductions. ONH-MBR and CHOR-MBR decreased (P&#x2009;=&#x2009;0.004 and P&#x2009;<&#x2009;0.001, respectively). The baseline SFCT was the only significant predictor of change in CHOR-MBR. Older age correlated with thinner baseline SFCT and a greater decrease in CHOR-MBR.<br><br>CONCLUSIONS: IVBr is associated with significant reductions in CRT and SFCT and may decrease choroidal blood flow, particularly in older patients and those with thinner SFCTs.<br><br>TRIAL REGISTRATION: UMIN-CTR Registration ID, UMIN000041382.}, }
@article {pmid41325920, year = {2026}, author = {Wang, Z and Zhang, Q and Li, B and Chen, J and Yoshida, S and Sun, B and Zhou, Y}, title = {tRNA-derived small RNAs-Biogenesis, functions, and potential applications in ocular diseases: A review.}, journal = {International journal of biological macromolecules}, volume = {337}, number = {Pt 2}, pages = {149334}, doi = {10.1016/j.ijbiomac.2025.149334}, pmid = {41325920}, issn = {1879-0003}, mesh = {Humans ; *Eye Diseases/genetics/metabolism ; *RNA, Transfer/genetics/metabolism ; Animals ; *RNA, Small Untranslated/genetics ; Gene Expression Regulation ; }, abstract = {tRNA-derived small RNAs (tsRNAs), a burgeoning class of small non-coding RNAs, are emerging as pivotal regulators in gene expression and cellular signaling networks. Derived from specific cleavage of precursor or mature tRNAs, these molecules exhibit diverse functionalities, including epigenetic remodeling, transcriptional regulation, and translational modulation. Growing evidence underscores their significant roles in the pathogenesis of various ocular diseases, such as age-related macular degeneration, diabetic retinopathy, myopia, and cataract, where they influence critical processes like angiogenesis, inflammation, and neuronal homeostasis. Their dynamic expression profiles in ocular tissues and biofluids position tsRNAs as promising diagnostic biomarkers and therapeutic targets. This review systematically delineates the biogenesis and classification of tsRNAs, elaborates their multifaceted molecular mechanisms, and comprehensively examines their implications in ocular diseases. We further discuss the translational potential of tsRNAs in early detection and precision treatment of ocular diseases, while highlighting current challenges and future directions in this rapidly evolving field.}, }
@article {pmid41326361, year = {2025}, author = {Sarkar, S and Kannan, R and Panigrahi, T and Veeramani, K and Mb, T and Shanker Bhattacharya, S and Ghosh, A}, title = {Comparative transcriptomic analysis of retinal response to diverse cellular stresses reveals relative contributions of different cell death processes and signalling networks.}, journal = {Cell death &amp; disease}, volume = {16}, number = {1}, pages = {876}, pmid = {41326361}, issn = {2041-4889}, support = {/WT_/Wellcome Trust/United Kingdom ; IA/TSG/20/1/600029//DBT India Alliance (Wellcome Trust/DBT India Alliance)/ ; }, mesh = {Animals ; Oxidative Stress/genetics ; *Gene Expression Profiling ; Mice ; Mice, Inbred C57BL ; Cell Death/genetics ; *Signal Transduction/genetics ; Endoplasmic Reticulum Stress/genetics ; *Retina/metabolism/pathology ; *Transcriptome ; Retinal Pigment Epithelium/metabolism/pathology ; Apoptosis/genetics ; *Retinal Degeneration/genetics/pathology/metabolism ; }, abstract = {Retinal degeneration comprises a diverse group of progressive disorders leading to visual impairment and ultimately blindness. These include inherited retinal dystrophies (IRDs), diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma, affecting millions worldwide. The underlying pathology involves dysfunction and death of photoreceptor cells and the retinal pigment epithelium (RPE), driven by various stress-induced cell death mechanisms. Although multiple pathways have been reported, the relative contribution of each remains incompletely understood, highlighting the need for further investigation. Therefore, we studied how different stress types that induce retinal degeneration alter the global gene expression profile in vivo (C57BL/6 mice), aiming to identify predominant cell death mechanisms as well as key genes and networks. Retinal toxicity was induced using established models of oxidative stress, hypoxia, endoplasmic reticulum (ER) stress, and chronic inflammation. Transcriptomic profiling revealed both unique and convergent gene expression changes associated with each stressor. In total, 170, 328, 146, and 151 genes were significantly altered under oxidative stress, inflammation, ER stress, and hypoxia, respectively (Log2 fold change >2 or <-2; p < 0.05). Genes such as Arhgap26, Ccdc9, Ube2e2, and Fndc3b were commonly dysregulated across ER stress, inflammation, and oxidative stress, whereas Nfix, Elp6, Naca, and Plcd3 were selectively altered in oxidative stress, inflammation, ER stress, and hypoxia, respectively. Analysis of cell death-related gene subsets revealed that pyroptosis was commonly activated across different stress types. Additionally, autophagy-mediated cell death, ferroptosis, and extrinsic apoptosis were preferentially associated with oxidative stress, chronic inflammation, and hypoxia, respectively. Both ER and oxidative stress models showed strong activation of autophagy-associated cell death. Together, these findings delineate distinct molecular signatures and predominant cell death mechanisms triggered by specific stressors, providing important insights that could aid in developing targeted therapies to prevent or slow retinal degeneration.}, }
@article {pmid41327637, year = {2025}, author = {Jian, L and Huang, Z and Qi, J and Meng, J and Zhang, K and Zhu, X}, title = {Associations between estimated glucose disposal rate and age-related ocular diseases in cardiovascular-kidney-metabolic syndrome stages 0-3: a large prospective cohort study.}, journal = {BMJ open ophthalmology}, volume = {10}, number = {1}, pages = {}, pmid = {41327637}, issn = {2397-3269}, mesh = {Humans ; Prospective Studies ; Female ; Male ; *Metabolic Syndrome/complications/metabolism ; Middle Aged ; *Eye Diseases/epidemiology/etiology/metabolism ; Aged ; Risk Factors ; *Blood Glucose/metabolism ; *Cardiovascular Diseases/complications/metabolism ; Incidence ; United Kingdom/epidemiology ; Follow-Up Studies ; }, abstract = {OBJECTIVE: This study investigated the relationship between estimated glucose disposal rate (eGDR) and the risk of age-related ocular diseases, including macular degeneration, glaucoma, cataracts, diabetic retinopathy (DR) and retinal detachment (RD), in individuals with stages 0-3 of cardiovascular-kidney-metabolic (CKM) syndrome.<br><br>METHODS AND ANALYSIS: This prospective cohort study included 223&#x2009;120 participants from the UK Biobank. The CKM stages were defined based on adiposity, metabolic risk factors and subclinical cardiovascular disease. Lower eGDR values indicate greater insulin resistance. Outcomes were incidences of macular degeneration, glaucoma, cataract, DR and RD. HRs and 95% CIs were estimated using Cox proportional hazards models. Non-linear relationships were explored using restricted cubic splines.<br><br>RESULTS: The study showed that macular degeneration (HR 0.92, 95%&#x2009;CI 0.87 to 0.97, p=0.001) and glaucoma (HR 0.91, 95%&#x2009;CI 0.87 to 0.95, p<0.001) were linearly associated with eGDR. Cataracts exhibited a U-shaped association with eGDR (P non-linear=0.001) and DR exhibited an L-shaped association (P non-linear=0.018). Quartile stratification of eGDR significantly differentiated risk in DR (Q4 vs Q1: HR 0.15, 95%&#x2009;CI 0.04 to 0.52, p=0.003) and RD (Q4 vs Q1: HR 0.65, 95%&#x2009;CI 0.47 to 0.89, p=0.007). Stratified effects analysis revealed that these associations were more significant in advanced CKM syndrome stages.<br><br>CONCLUSIONS: eGDR is associated with ocular diseases risk in CKM syndrome, especially in advanced stages. This finding suggests the potential use of eGDR for guiding ophthalmic screening in CKM management.}, }
@article {pmid41328469, year = {2025}, author = {Ermilov, VV and Nesterova, AA}, title = {[Amyloidogenesis and neurotrophic dysfunction in age-related macular degeneration in correlation with Alzheimer's disease].}, journal = {Arkhiv patologii}, volume = {87}, number = {6}, pages = {61-68}, doi = {10.17116/patol20258706161}, pmid = {41328469}, issn = {0004-1955}, mesh = {Humans ; *Alzheimer Disease/pathology/metabolism/genetics/complications ; *Macular Degeneration/pathology/metabolism/genetics/complications ; *Amyloidosis/pathology/metabolism/genetics ; *Amyloid/metabolism/genetics ; Aged ; Glaucoma, Open-Angle/pathology/metabolism/genetics ; }, abstract = {The pathogenesis of diseases associated with amyloid deposition in various organs and tissues has been a concern for researchers and clinicians since their discovery. Particular attention is paid to the relationship between amyloidogenesis and neurotrophic disorders in age-related neurodegenerative pathology. In this context, the amyloid cascade theory and the neurotrophic dysfunction theory remain relevant, as evidenced by the results of numerous studies conducted in recent years. Meanwhile, it has been shown that amyloidosis, being a systemic pathological process, affects ocular tissues and extraocular structures in various forms with diverse clinical and morphological manifestations. This highlights the need for improved diagnostics of ocular amyloidosis and the study of its association with geriatric ophthalmic diseases such as age-related macular degeneration (AMD), senile cataract, primary open-angle glaucoma, and pseudoexfoliation syndrome. Accumulating evidence suggests that both amyloidogenesis and neurotrophic disturbances share common triggers and mutually contribute to the development of neurodegenerative pathology in both AMD and Alzheimer's disease (AD). Therapeutic strategies aimed not only at suppressing amyloidogenesis and correcting neurotrophic dysfunction but also at the overall regulation of these two pathogenic mechanisms may have a positive effect on geriatric ophthalmic diseases and AD, significantly improving the quality of life of elderly patients. This article summarizes current concepts on the role of neurotrophic dysfunction and amyloidogenic processes in the development of AMD.}, }
@article {pmid41328785, year = {2025}, author = {Jonas, JB and Panda-Jonas, S and Wang, YX and Jonas, RA}, title = {Associations of macular drusen in an East Asian population. The Beijing Eye Study.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70043}, pmid = {41328785}, issn = {1755-3768}, support = {82271086//National Natural Science Foundation of China/ ; }, abstract = {PURPOSE: To assess associations of macular drusen in a general population, affected by age-related macular degeneration (AMD) or free of any retinal disease.<br><br>METHODS: Participants of the population-based cross-sectional Beijing Eye Study underwent optical coherence tomography. Macular volume scans were assessed for macular drusen.<br><br>RESULTS: The study included 870 eyes (870 participants) (age: 64.7&#x2009;&#xb1;&#x2009;9.9&#x2009;years; range: 50-91&#x2009;years), randomly selected within the groups of early AMD (n&#x2009;=&#x2009;356 (40.9%) eyes), intermediate AMD (n&#x2009;=&#x2009;201; 23.1%), late AMD (n&#x2009;=&#x2009;6; 0.7%) and within eyes without AMD (n&#x2009;=&#x2009;307; 35.3%). In multivariable analysis, higher drusen count was associated (r[2]&#x2009;=&#x2009;25) with older age (beta: 0.08; p&#x2009;=&#x2009;0.048), higher serum concentration of cholesterol (beta: 0.10; p&#x2009;=&#x2009;0.008), shorter axial length (beta: -0.09; p&#x2009;=&#x2009;0.03), thicker subfoveal choroidal thickness (beta: 0.08; p&#x2009;=&#x2009;0.04), higher prevalences of macular hyperpigmentations (beta: 0.13; p&#x2009;<&#x2009;0.001), hyperreflective foci (HRFs) (beta: 0.12; p&#x2009;=&#x2009;0.004) and reticular pseudodrusen (beta: 0.27; p&#x2009;<&#x2009;0.001), and a lower prevalence of a visible Henle's layer (beta: -0.15; p&#x2009;<&#x2009;0.001). Larger drusen size was associated with shorter axial length (beta: -0.08; p&#x2009;=&#x2009;0.03), thicker subfoveal choroidal thickness (beta: 0.18; p&#x2009;<&#x2009;0.001), higher prevalences of macular hypopigmentations (beta: 0.14; p&#x2009;<&#x2009;0.001) and HRFs (beta: 0.31; p&#x2009;<&#x2009;0.001), and lower prevalences of a visible Henle's layer (beta: -0.19; p&#x2009;<&#x2009;0.001) and of reticular pseudodrusen (beta: -0.09; p&#x2009;=&#x2009;0.02).<br><br>CONCLUSIONS: In this population-based study on Chinese, higher macular drusen count was associated with shorter axial length, thicker subfoveal choroidal thickness, higher prevalences of macular hyperpigmentations, HRFs and reticular pseudodrusen and lower prevalence of a visible Henle's layer. These findings may be clinically helpful and etiologically interesting.}, }
@article {pmid41329005, year = {2025}, author = {Trinh, M and Duong, A and Cheung, R and Chen, S and Ng, D and Friedrich, J and Hodge, C and Nivison-Smith, L and Ly, A}, title = {Determinants of Intergrader Agreement for Key Retinal Photography and OCT Biomarkers in AMD.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {12}, pages = {4}, pmid = {41329005}, issn = {2164-2591}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; Biomarkers ; *Macular Degeneration/diagnosis/diagnostic imaging ; *Photography/methods ; Middle Aged ; Aged, 80 and over ; Retinal Drusen ; *Retina/pathology/diagnostic imaging ; Retinal Pigment Epithelium/pathology ; }, abstract = {PURPOSE: To quantify determinants of intergrader agreement for key retinal photography and optical coherence tomography (OCT) biomarkers in early to intermediate age-related macular degeneration (AMD) and to inform future consensus definitions and grading protocol.<br><br>METHODS: Single eyes from 269 participants with early to intermediate AMD were consecutively sampled. Retinal photographs were evaluated for the presence of large drusen and pigmentary abnormalities. OCT B-scans were graded for reticular pseudodrusen (RPD), outer retinal band abnormality (external limiting membrane [ELM], ellipsoid zone [EZ], and retinal pigment epithelium [RPE]), nascent geographic atrophy (nGA), intraretinal hyperreflective foci (IHRFs), hyporeflective drusen cores (hDCs), shallow irregular RPE elevations (SIREs), and drusenoid pigment epithelial detachment (DPED). Biomarkers were classified using a trinary certainty system: "definitely present" (&#x2265;90%), "questionably present" (50%-90%), or "absent" (<50%). The main outcome was odds of intergrader agreement from generalized estimating equations adjusting for intraparticipant correlations, biomarker type, and eye- and participant-level factors.<br><br>RESULTS: Odds of agreement were comparable for large drusen, nGA, RPE abnormality, IHRF, and ELM abnormality; higher for RPD (odds ratio [95% confidence interval], 3.17 [1.56-6.45], P < 0.01); and lower for SIRE, EZ abnormality, pigmentary abnormalities, hDC, and DPED (up to 0.5 [0.32-0.78], P < 0.01). Agreement improved with higher grading certainty (1.4 [1.22-1.6], P < 0.0001) but declined with age (per decade, 0.8 [0.7-0.93], P < 0.01).<br><br>CONCLUSIONS: Biomarker type, grading certainty, and participant age influence OCT agreement. Consensus definitions and grading protocols, including the use of high certainty thresholds (&#x2265;90%), may improve consistency.<br><br>TRANSLATIONAL RELEVANCE: Implementing consensus definitions and protocols can improve agreement and strengthen the clinical utility of OCT biomarkers in AMD.}, }
@article {pmid41331277, year = {2025}, author = {Moon, S and Park, S and Kim, CG and Kim, J and Yoon, YS and Kim, JH}, title = {Predicting visual acuity using optical coherence tomography in patients with neovascular age-related macular degeneration.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {90}, pmid = {41331277}, issn = {2045-2322}, support = {25ZK1100//Electronics and Telecommunications Research Institute/ ; }, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; Aged ; *Visual Acuity ; Retrospective Studies ; Aged, 80 and over ; *Macular Degeneration/diagnostic imaging/physiopathology/drug therapy ; Middle Aged ; Artificial Intelligence ; }, abstract = {This study aimed to assess the feasibility of an artificial intelligence(AI) model to predict visual acuity(VA) using optical coherence tomography(OCT) in treatment-naïve patients with neovascular age-related macular degeneration (AMD). This retrospective study enrolled 240 patients(240 eyes) with pseudophakic neovascular AMD who received antivascular endothelial growth factor therapy. Each patient underwent 10 visits where they underwent best-corrected visual acuity(BCVA) testing and horizontal OCT scans, yielding 2,400 images. The images were cropped, resized to 224 × 224 pixels, and partitioned at the patient level to avoid data leakage. A pretrained VGG16 CNN was modified for five-class VA classification (< 0.1, 0.1-0.3, 0.3-0.5, 0.5-0.8, ≥ 0.8). The performance was assessed by five-fold cross-validation using the macro-averaged AUC, accuracy, Top-2 accuracy, and binary accuracy (threshold VA = 0.5). The average performance showed a macro-averaged AUC of 0.772, accuracy of 50.3%, Top-2 accuracy of 71.0%, and binary accuracy of 79.6%. For high-confidence predictions (29.2% of the samples), the accuracy improved to 74.1%, with a binary accuracy of 94.2%. ROC analyses demonstrated AUCs of 0.73-0.83 across VA categories, with the strongest discrimination for VA < 0.1 (AUC 0.83). The confusion matrix showed that the VA 0.5-0.8 and ≥ 0.8 categories achieved relatively higher accuracies; however, misclassifications mainly occurred between these adjacent ranges, with frequent bidirectional errors observed. Our pretrained VGG16 showed moderate ability at predicting VA from OCT images in patients with neovascular AMD. While the overall classification was limited, high binary accuracy highlights the potential clinical value of distinguishing good from poor vision.}, }
@article {pmid41332270, year = {2025}, author = {Li, KV and Pan, A and Liu, YV and Antonio-Aguirre, B and Wang, J and Adams, M and McNerney, C and Tun, SBB and Jimenez, K and Lu, Y and Li, Z and McNally, M and Barathi, VA and Johnston, RJ and Singh, MS}, title = {Application of Machine Learning to Discriminate Photoreceptor Cell Species in Xenotransplanted Chimeric Retinas.}, journal = {Clinical and translational science}, volume = {18}, number = {12}, pages = {e70420}, pmid = {41332270}, issn = {1752-8062}, support = {EY001765//Johns Hopkins University/ ; R01 EY030872/EY/NEI NIH HHS/United States ; //Juliette RP Vision Foundation/ ; //Maryland Technology Development Corporation/ ; /FFB/Foundation Fighting Blindness/United States ; //Joseph Albert Hekimian Fund/ ; R01EY033103/EY/NEI NIH HHS/United States ; R01EY030872/EY/NEI NIH HHS/United States ; //Shulsky Foundation/ ; F31EY033187/EY/NEI NIH HHS/United States ; G2019300//BrightFocus Foundation/ ; //Wilmer Pooled Professor Fund (PPF) Lutty Grant/ ; 147042//Knights Templar Eye Foundation/ ; }, mesh = {*Machine Learning ; Animals ; Humans ; Mice ; Swine ; *Transplantation, Heterologous/methods ; *Retina/cytology/transplantation ; *Retinal Degeneration/pathology/therapy ; *Photoreceptor Cells, Vertebrate/transplantation ; Disease Models, Animal ; Species Specificity ; Organoids/transplantation/cytology ; Heterografts ; Human Embryonic Stem Cells/transplantation/cytology ; }, abstract = {Photoreceptor transplantation is being studied to restore visual function in retinal diseases causing blindness, including age-related macular degeneration, hereditary eye diseases, and traumatic retinopathy. Preclinical studies often involve delivering exogenous human photoreceptor cells into animal models' retinas. A key readout in such experiments is distinguishing donor cell integration from artificial labeling secondary to material transfer of cytosolic or nuclear labels. Recognizing donor (human) versus animal photoreceptor nuclei is key, but purely immunohistology discrimination is challenging due to antigenic species overlap or intercellular antigen transfer. To address this, we sought to develop and validate a computational technique to discriminate between photoreceptor cells of different animal species based on machine learning of nuclear morphology. We aim to evaluate the feasibility of computer-assisted nuclear detection combined with random forest classification to automate species differentiation in DAPI-stained photoreceptors after xenotransplantation into mouse and pig retinas. Our models were trained on single-species samples and validated with mixed-species samples. We then transplanted human embryonic stem cell-derived retinal organoid cells into rodent and pig retinal degeneration models. The random forest model accurately determined cell identity post-xenotransplantation, validated by histological assessment using an antihuman nuclear antibody. Our results support the potential efficacy of employing machine learning image analysis and classification techniques that may promote experimental rigor, minimize observer bias, and enable high throughput semiautomated workflows for transplantation outcomes analysis. The methodological framework reported here may enable a more nuanced and precise analysis of the behavior of transplanted photoreceptors for the purposes of human retinal regeneration.}, }
@article {pmid41334300, year = {2025}, author = {Sarkar, AD and Kannan, NB and Thakur, S and Balakrishnan, TN and Ramasamy, K}, title = {Long-Term Outcome of Intravitreal Expansile Gas and Bevacizumab Injection for Macular Neovascularization-Induced Subfoveal Hemorrhage: A Retrospective Study.}, journal = {Journal of current ophthalmology}, volume = {37}, number = {1}, pages = {86-92}, pmid = {41334300}, issn = {2452-2325}, abstract = {PURPOSE: To analyze the results of the long-term outcome of pneumatic displacement (PD) with intravitreal bevacizumab (IVB) for subfoveal hemorrhage (SFH) secondary to polypoidal choroidal vasculopathy (PCV)/macular neovascularization secondary to neovascular age-related macular degeneration (n-AMD).<br><br>METHODS: This is a retrospective and interventional study executed in the population of southern part of India who attended a tertiary care ophthalmic hospital over a decade. Patients who presented with a complaint of diminution of vision following SFH secondary to PCV or n-AMD who were treated with PD using sulphur hexafluoride (SF6) along with IVB were included in the study. The patients were followed up for at least 24 months posttreatment. Finally, a dataset of 54 patients was chosen who fulfilled all the criteria and a thorough analysis on their long-term outcome was done.<br><br>RESULTS: The mean age at baseline was 57.55 &#xb1; 13.02 years. Average treatment delay was measured 9.43 &#xb1; 5.22 days. Best-corrected visual acuity (BCVA) on presentation was 1.07 &#xb1; 0.46 in logMAR. The average size of the SFH was measured 4.46 &#xb1; 1.17-disc diameter area. The average long-term follow-up was measured 29.33 &#xb1; 4.53 months. Final BCVA improved to 0.74 &#xb1; 0.62 in logMAR (P < 0.001). Overall improvement in BCVA was significantly better, although only a minority of patients (n = 24, 44.44%) improved BCVA &#x2265; 0.3 in logMAR. Subgroup analysis reveals smaller SFH (&#x2264;2 disc diameter) and presentation earlier than 1 week shows comparatively better visual outcome.<br><br>CONCLUSIONS: The study shows encouraging results on the long-term follow-up with respect to anatomical and visual acuity outcome. This serves as the second largest dataset on PD with IVB for SFH secondary to PCV/n-AMD in ophthalmic literature.}, }
@article {pmid41334307, year = {2025}, author = {Sadeghi, E and Mahmoudinezhad, G and Valsecchi, N and Vupparaboina, SC and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Eller, AW and Chhablani, J}, title = {Long-Term Follow-Up of Dry Age-Related Macular Degeneration Patients.}, journal = {Journal of current ophthalmology}, volume = {37}, number = {1}, pages = {78-85}, pmid = {41334307}, issn = {2452-2325}, abstract = {PURPOSE: To assess the progression rate from dry age-related macular degeneration (dAMD) to advanced AMD and possible risk factors.<br><br>METHODS: Demographics, medical and ocular conditions, baseline eye examinations, optical coherence tomography features, and progression rates to advanced AMD were collected.<br><br>RESULTS: We included 74 eyes from 47 dAMD patients, with a mean age of 74.58 &#xb1; 8.29 years and 38.30% males. During a follow-up period of 8.9 &#xb1; 0.4 years, 40 eyes (54.05%) progressed to advanced AMD, with 25 eyes (33.78%) developing neovascular AMD (nAMD) and 22 eyes (29.72%) progressing to geographic atrophy (GA). Patients progressing to advanced AMD were older (77.8 &#xb1; 6.5 vs. 73.8 &#xb1; 9.5, P = 0.03). A higher incidence of open-angle glaucoma (OAG) was noted in progressing eyes (32.5% vs. 8.8%, P = 0.01), along with thinner baseline central macular thickness (CMT) (247.93 &#xb1; 32.55 vs. 268.67 &#xb1; 16.75, P = 0.007). Smokers with OAG had a higher tendency to develop nAMD (P < 0.05). Females with lower best-corrected visual acuity (BCVA) were more likely to develop GA (P < 0.001).<br><br>CONCLUSIONS: The progression rate to advanced AMD was 54.05% over 8.9 &#xb1; 0.4 years. Advanced age, reduced baseline CMT, and lower BCVA were linked to progression. OAG and smoking were associated with higher nAMD, while females had a higher risk of GA.}, }
@article {pmid41335183, year = {2026}, author = {Borrelli, E and Coco, G and Scorcia, V and Carnevali, A and Reibaldi, M and Giannaccare, G}, title = {A Response to: Letter to the Editor Regarding "Safety, Tolerability, and Short-Term Efficacy of Low-Level Light Therapy for Dry Age-Related Macular Degeneration".}, journal = {Ophthalmology and therapy}, volume = {15}, number = {1}, pages = {499-501}, pmid = {41335183}, issn = {2193-8245}, }
@article {pmid41335184, year = {2026}, author = {Augustin, AJ and Koss, M}, title = {Letter to the Editor Regarding "Safety, Tolerability, and Short-Term Efficacy of Low-Level Light Therapy for Dry Age-Related Macular Degeneration".}, journal = {Ophthalmology and therapy}, volume = {15}, number = {1}, pages = {495-497}, pmid = {41335184}, issn = {2193-8245}, }
@article {pmid41335185, year = {2026}, author = {de Angelis, L and Galasso, M and Di Simplicio, S and Raimondi, R and Vidal-Aroca, F and Romano, MR and Toro, MD and Rizzo, S and Barca, F}, title = {Correction: In Vivo Evaluation of SING IMT™ Alignment for Late-Stage Age-Related Macular Degeneration Using Anterior Segment OCT.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {1}, pages = {251-252}, doi = {10.1007/s40123-025-01294-w}, pmid = {41335185}, issn = {2193-8245}, }
@article {pmid41335372, year = {2026}, author = {Shirley, M}, title = {Elamipretide: First Approval.}, journal = {Drugs}, volume = {86}, number = {3}, pages = {377-383}, pmid = {41335372}, issn = {1179-1950}, mesh = {Humans ; Drug Approval ; *Oligopeptides/therapeutic use/pharmacology/adverse effects ; *Barth Syndrome/drug therapy ; United States ; United States Food and Drug Administration ; }, abstract = {Elamipretide (Forzinity™) is a mitochondrial cardiolipin binder being developed by Stealth BioTherapeutics for the treatment of a range of disorders featuring mitochondrial dysfunction. In September 2025, elamipretide was granted accelerated approval in the USA for use to improve muscle strength in adult and pediatric patients with Barth syndrome weighing ≥ 30 kg. With this accelerated approval, elamipretide became the first disease-specific treatment approved for Barth syndrome, an ultra-rare X-linked recessive genetic disorder. Elamipretide is also under phase III clinical development for use in the treatment of dry age-related macular degeneration and mitochondrial myopathies. This article summarizes the milestones in the development of elamipretide leading to this first approval for Barth syndrome.}, }
@article {pmid41335529, year = {2025}, author = {Machna, B and Jastrzebska-Miazga, I and Pacwa, A and Liu, X and Oseka, M and Smedowski, A}, title = {Experimental models of myopia development: A review of literature.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {76}, number = {4}, pages = {335-367}, doi = {10.26402/jpp.2025.4.01}, pmid = {41335529}, issn = {1899-1505}, mesh = {*Myopia/physiopathology/etiology/epidemiology/pathology ; Humans ; Animals ; *Disease Models, Animal ; Refraction, Ocular ; }, abstract = {Myopia is one of the most prevalent refractive errors and one of the leading causes of visual impairment and blindness worldwide. It results from a mismatch between the axial length and optical power of the eye, resulting in a focal plane that lies in front of the retina. In children and young adults, myopia is most commonly caused by excessive elongation of the eyeball during development - a hallmark of school-age and some early-onset genetic forms of myopia. However, myopic refractive error can also result from other mechanisms, such as increased lens power in age-related nuclear cataracts or corneal steepening in keratoconus, which are not associated with axial elongation. The prevalence of myopia in young Asian adults has increased from 20-30% to 80-85% over the last 50 years. In contrast, recent meta-analytic data for European young adults, emphasizing studies with cycloplegic refraction essential for accuracy, indicate myopia prevalence rates of approximately 19-24%. The prevalence of high myopia (greater than or equal to-6.0 diopters) has increased disproportionately to myopia in the last 50 years, from 1-5% to 10-20% and became a global problem. The reason for this state of affairs is believed to be lifestyle and prolonged near vision activities. Although refractive error can be corrected, sight-threatening pathologies such as retinal detachment, macular degeneration, glaucoma, and cataracts are more challenging to control. Owing to years of research, the biological mechanisms of eye growth and refractive development are increasingly elucidated. The signaling cascade mechanisms that link the retinal image processing and alterations in choroidal thickness and scleral development have also been studied. While the retina can detect defocus and changes in defocus, decades of research have led to a growing understanding of the fundamental pathways in visually guided eye growth, yet the precise initial mechanisms by which the retina senses and transduces these optical signals continue to be an active and important area of investigation. Animal studies have demonstrated that the retina can locally regulate visually guided eye growth through intrinsic mechanisms, even in the absence of direct input from the brain. The precise molecular mechanisms underlying common forms of myopia, particularly those involving axial elongation, are yet to be fully elucidated. This reflects the complexity and multifactorial influences inherent even in these prevalent forms, alongside the challenges posed by experimental models in completely recapitulating all aspects of the human condition.}, }
@article {pmid41335743, year = {2025}, author = {Herrero-Tudela, M and Romero-Oraa, R and Hornero, R and Gutierrez-Tobal, GC and Lopez, MI and Romero-Aroca, P and Garcia, M}, title = {Explainable Artificial Intelligence for Early Detection and Diagnosis of Age-Related Macular Degeneration.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2025}, number = {}, pages = {1-4}, doi = {10.1109/EMBC58623.2025.11254905}, pmid = {41335743}, issn = {2694-0604}, mesh = {*Artificial Intelligence ; *Macular Degeneration/diagnosis ; Early Diagnosis ; Humans ; Datasets as Topic ; Neural Networks, Computer ; Deep Learning ; *Diagnosis, Computer-Assisted/methods ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Early identification of individuals at risk of progressing from an asymptomatic stage to advanced AMD is critical for preventing severe vision loss. Automated image assessment systems for AMD can enhance screening efficiency by reducing time, cost, and effort. Despite the success of convolutional neural networks in AMD detection, their limited interpretability restricts their use in clinical practice. To address this issue, we present an explainable deep-learning approach based on ResNetRS-200, incorporating Kernel SHAP for model interpretability. Our approach achieved a quadratic kappa of 0.6927 and an accuracy of 60.95% on the publicly available Age-Related Eye Disease Study dataset, while achieving a quadratic kappa of 0.7784 and an accuracy of 77.95% on a private dataset. Kernel SHAP analysis highlighted specific retinal regions close to the macula influencing the predictions of the model, providing a clinically interpretable framework, and enhancing diagnostic confidence. Our findings demonstrate the effectiveness of the proposed framework for automated AMD grading. Therefore, the proposed method could be an explainable diagnostic aid for the early detection and grading of AMD.Clinical relevanceThis research establishes the useful- ness of an eXplainable Artificial Intelligence approach using ResNetRS-200 architecture and Kernel SHAP for automated AMD grading.}, }
@article {pmid41337039, year = {2025}, author = {Abay, SG and Asmare, MH and Geurts, L}, title = {An Affordable Smartphone-based Fundus Imaging Device for Retinal Examination.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2025}, number = {}, pages = {1-6}, doi = {10.1109/EMBC58623.2025.11254224}, pmid = {41337039}, issn = {2694-0604}, mesh = {*Smartphone ; Humans ; *Fundus Oculi ; *Retina/pathology/diagnostic imaging ; Glaucoma/diagnosis ; Equipment Design ; Optic Disk/pathology ; }, abstract = {Fundus imaging is widely used for diagnosing and monitoring ocular diseases such as diabetic retinopathy, glaucoma, and age-related macular degeneration. However, the high cost and limited availability of conventional fundus cameras pose significant barriers, particularly in resource-constrained settings. This study introduces the Glaucoma Screening on Phone (GSoP), an affordable and portable smartphone-based fundus imaging adapter designed to address these challenges. The adapter is developed using accessible and cost-effective components. We recorded retinal videos from dilated pupil with a focus on the optic disc region, which provides critical information on the degeneration of the optic nerve. While field testing revealed artifacts such as glare that reduced overall image quality, the GSoP demonstrated its ability to capture diagnostically relevant images of the optic disc region. A subjective qualitative comparison with the commercially available ophthalmoscope called oDocs-nun showed that although the GSoP's field of view is smaller, it effectively highlights the optic nerve head, a critical area for glaucoma screening. Our approach is well-suited for mydriatic video-based screening due to its limited field of view. With a production cost of under C10, the GSoP offers a practical and accessible solution for primary healthcare and educational purposes. Future improvements, including glare reduction mechanisms, AI-driven automation, and modular design options, have the potential to enhance its diagnostic capabilities and broaden its impact.}, }
@article {pmid41340913, year = {2025}, author = {Sun, M and Wang, J and Fan, W and Wang, K and Wang, Y and Zhang, J and Ding, S and Zhang, C and Feng, Z and Wang, YG and Song, Z and Tao, Y}, title = {From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics.}, journal = {Materials today. Bio}, volume = {35}, number = {}, pages = {102537}, pmid = {41340913}, issn = {2590-0064}, abstract = {Delivering medications to targeted lesions poses significant challenges due to the unique anatomical structure and physical barriers of the eyeball. Polymer nanomicelles are spontaneously assembled from surfactants and amphiphilic polymers, encapsulating insoluble drugs within their cores to augment their hydrosolubility. Nanomicelles have demonstrated potential to surmount these biological hurdles and convey encapsulated therapeutic agents to intended sites. Nanomicelle can prolong the drug half-life and promote molecule permeation through ocular epithelium. Notably, they can be formulated at concentrations marginally exceeding the critical micelle concentration while maintaining a stable conformation, thereby boosting therapeutic effectiveness. Moreover, the physicochemical attributes of polymeric micelles can be precisely adjusted by integrating diverse hydrophilic or hydrophobic moieties. Surface modifications can further impart specific charges or facilitate targeted organ delivery enhancing adhesion to ocular tissues and mitigating systemic toxicity. This review delves into the utilization of polymer nanomicelles in ophthalmological practice, encompassing block copolymer design, the pharmacokinetics of encapsulated drugs within nanomicelles, and the molecule pathways governing nanomedicines. This review also explores their applications in treating ocular disorders including infectious keratitis, DED, glaucoma, corneal graft rejection, neovascular age-related macular degeneration (nAMD), and DR, while introducing progress in clinical deployment and potentials in ocular diagnosis. We also discuss the key challenges in clinical translation and scalable manufacturing. With continued optimization, polymer nanomicelles are poised to become a versatile, non-invasive platform for personalized ophthalmologic therapies.}, }
@article {pmid41341962, year = {2025}, author = {Ly, A and Harnick, E and Jowsey, T and Bannatyne, AJ}, title = {Qualitative Factors Impacting Patients and Clinicians Regarding Intravitreal Injections for Retinal Disorders: A Scoping Review.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {4349-4365}, pmid = {41341962}, issn = {1177-5467}, abstract = {BACKGROUND: Intravitreal injections are among the most frequently performed eye procedures worldwide. They are vital in managing vision-related retinal conditions such as neovascular age-related macular degeneration, diabetic macular edema and retinal vein occlusion. This review scopes qualitative research concerning people's beliefs, perspectives, experiences and behaviors towards intravitreal injections.<br><br>METHODS: Academic databases (PubMed, Embase, CINAHL and Web of Science) were searched for studies focused on qualitative research of intravitreal injections in adult patients, published between January 2000 and May 2024. We extracted data regarding publication and participants' characteristics, main study objectives, and methodological approaches.<br><br>RESULTS: Of the 795 identified citations, 28 met the inclusion criteria. Most studies reported on patients' emotional experiences of undergoing intravitreal injections, with the fear of vision loss compounded with ongoing injections prompting significant anxiety and uncertainty for patients. Other studies also reported on the physical component as the invasiveness of the procedure caused pain and discomfort, which varied with the clinician's delivery of the injection. One study reported on clinician experiences of performing intravitreal injections, stating that the treatment decisions are dependent on patient-related factors such as their adherence to regular injections. Overall, qualitative research in ophthalmology is increasing, with most studies employing semi-structured interviews with thematic analysis.<br><br>CONCLUSION: Qualitative research offers valuable insights into both patient and clinician experiences of intravitreal injections, which can shape person-centered and sustainable models of intravitreal treatment. Understanding qualitative factors such as personal experiences and barriers to treatment can refine the delivery of intravitreal injections and ultimately improve patient adherence.}, }
@article {pmid41342587, year = {2025}, author = {Zhao, S and Voegele, F and Tang, J and Clark, SJ and Tschulakow, AV and Julien, S}, title = {Time Course of Structural, Functional, Complement Changes and Inflammatory Processes in a Sodium Iodate Rat Model of Geographic Atrophy.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {23}, pages = {e71307}, pmid = {41342587}, issn = {1530-6860}, support = {//Dr. Werner Jackstaedt Stiftung, Germany/ ; //Guangzhou Elites Scholarship Council, China/ ; //Open access Publishing Fund of University of Tuebingen/ ; }, mesh = {Animals ; *Geographic Atrophy/chemically induced/pathology/metabolism ; *Iodates/toxicity ; Rats ; Disease Models, Animal ; Rats, Long-Evans ; Retinal Pigment Epithelium/pathology/metabolism ; *Inflammation/pathology/metabolism/chemically induced ; Tomography, Optical Coherence ; Electroretinography ; Male ; }, abstract = {Geographic atrophy (GA) is characterized by the loss of choriocapillaris, retinal pigment epithelium (RPE) and photoreceptors and is an advanced form of age-related macular degeneration (AMD)-a leading cause of central vision loss in the elderly. The development of effective treatments has been hindered by the lack of reliable animal models that recapitulate the structural, functional, and molecular hallmarks of GA. In this study, we established and extensively characterized a sodium iodate (NaIO3)-induced model of GA in pigmented Long Evans rats using a comprehensive set of in vivo and histological techniques. NaIO3 was administered intraperitoneally at 80 mg/kg to induce bilateral retinal degeneration. Morphological, functional, and ultrastructural changes were evaluated using scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), electroretinography (ERG), light and electron microscopy, and immunohistochemistry at pre-dose and 3, 7, and 14 days post-injection. The model exhibited typical GA features including choriocapillaris loss, RPE degeneration, photoreceptor death, Bruch's membrane remodeling, and mitochondrial damage. Complement activation (C3, C5b-9) and immune cell infiltration (Iba1, CD68) were observed, along with gliosis and RPE65 loss. ERG analysis revealed profound and persistent functional deficits. These findings demonstrate that the NaIO3 rat model robustly mimics the key pathological events in GA, particularly at 7 days post-injection, making it a suitable model for preclinical evaluation of therapeutic interventions targeting choriocapillaris and RPE protection.}, }
@article {pmid41342623, year = {2025}, author = {Peter, VG and Hayoz, M and Scandella, D and Sznitman, R and Escher, P and Zinkernagel, MS}, title = {AI-Assisted Optical Coherence Tomography Segmentation for Enhanced Diagnosis of Inherited Retinal Diseases.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {12}, pages = {8}, pmid = {41342623}, issn = {2164-2591}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Diseases/diagnosis/diagnostic imaging/genetics ; *Artificial Intelligence ; Male ; Female ; Middle Aged ; Aged ; Algorithms ; Adult ; Macular Degeneration/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Retina/diagnostic imaging ; }, abstract = {PURPOSE: Inherited retinal diseases (IRDs) are rare and diverse, posing a diagnostic challenge in ophthalmology. This study aimed to determine whether artificial intelligence (AI)-assisted image processing can improve IRD diagnosis and provide insights into disease characteristics. We used an optical coherence tomography (OCT) segmentation algorithm to characterize retinal features in IRDs. Two control groups were included to enhance the contextual understanding of these features: healthy eyes and eyes with age-related macular degeneration (AMD). An AI-driven classification model was then used to classify the data into disease and control groups.<br><br>METHODS: We analyzed 327 images from 181 patients with IRD and 146 control individuals, including healthy subjects and patients with AMD. IRD cases were stratified into macular and retinal dystrophies. Automated segmentation of six retinal layers and detection of nine biomarkers were performed on retinal OCT images using the AI-based RetinAI Discovery tool. A random forest classifier differentiated macular IRD, retinal IRD, and controls.<br><br>RESULTS: The model detected IRD with 91% accuracy and achieved 91% accuracy in differentiating macular from retinal IRD. Key OCT features for differentiation included reduced perifoveal photoreceptor and outer nuclear layer thicknesses and increased retinal nerve fiber layer thickness in retinal IRD. Macular IRD featured significant foveal photoreceptor and outer nuclear layer thinning.<br><br>CONCLUSIONS: This study shows that standardized OCT image analysis combined with AI-based classification can accurately detect and stratify IRDs. The model's high accuracy highlights its potential as a reliable diagnostic tool in ophthalmology.<br><br>TRANSLATIONAL RELEVANCE: This AI-assisted OCT evaluation approach enhances ophthalmic diagnostics by improving IRD detection and classification.}, }
@article {pmid41342744, year = {2025}, author = {Cakici, O and Yilmaz, OF and Karaca, S and Sarmis, A and Mutlu, MA and Sahin, ZB and Borucu, B and Oguz, H}, title = {Conjunctival Microbiota in retinal diseases requiring anti-VEGF therapy: Age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721251393397}, doi = {10.1177/11206721251393397}, pmid = {41342744}, issn = {1724-6016}, abstract = {PurposeThis study aimed to investigate the conjunctival microbiota of patients requiring intravitreal injections due to diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO).MethodsA total of 182 participants (46 DR, 71 AMD, 16 RVO, and 49 controls) were enrolled between August and November 2024. Conjunctival swabs were collected from both eyes under sterile conditions prior to injection and cultured on 5% sheep blood and chocolate agar. Microorganisms were identified using Vitek MS.ResultsNo significant differences were observed among the groups in overall microbial growth frequency (all p > 0.05). Gram-negative bacteria, fungi, and polymicrobial growth were more frequently detected in DR and AMD patients, suggesting a trend toward greater microbial diversity, although these differences were not statistically significant.ConclusionDR and AMD patients exhibited higher prevalence of gram-negative, fungal, and polymicrobial colonization. These findings underscore the importance of strict aseptic preparation, povidone-iodine disinfection, and targeted prophylactic strategies to minimize post-injection infection risk in high-risk populations.}, }
@article {pmid41343426, year = {2025}, author = {DeLucia, PR and Oberfeld, D and Kearney, JK and Cloutier, M and Jilla, AM and Zhou, A and Corona, ST and Cormier, J and Taylor, A and Wykoff, CC and Baurès, R}, title = {Visual, auditory, and audiovisual time-to-collision estimation among participants with age-related macular degeneration compared to a normal-vision group: The TTC-AMD study.}, journal = {PloS one}, volume = {20}, number = {12}, pages = {e0337549}, pmid = {41343426}, issn = {1932-6203}, mesh = {Humans ; *Macular Degeneration/physiopathology ; Male ; Female ; Aged ; *Visual Perception/physiology ; *Auditory Perception/physiology ; Aged, 80 and over ; Middle Aged ; Cues ; *Vision, Ocular ; }, abstract = {Little is known about whether and to what degree people with different amounts of visual impairment rely on hearing instead of vision for mobility, particularly in judgments of collision. We measured how much importance was assigned to visual and auditory cues during time-to-collision judgments made by people with age-related macular degeneration (Impaired Vision Group; IV) compared to a control group without age-related macular degeneration (Normal Vision Group; NV). A virtual reality system simulated a roadway with an approaching vehicle viewed from the perspective of a pedestrian. Participants pressed a button to indicate the time the vehicle would reach them. The vehicle was presented visually only, aurally only, or both simultaneously. Standardized regression coefficients and general dominance weights indicated that time-to-collision (TTC) judgments were determined by both auditory and visual cues in both groups. In the vision-only modality condition, the relative importance of distance and optical size compared to TTC was higher in the IV group compared to the NV group, but with a relatively small effect size. In all modality conditions, the mean absolute error of TTC estimates was comparable between groups, and a multimodal advantage was not observed. Intraindividual variability was greater in the IV group only in the AV condition. The implication is that similar performance can be achieved through the use of different sources of information. Importantly, people with and without IV achieved similar performance but showed differences in the relative importance of different sensory sources of information. A comparison of two IV subgroups differing in severity suggested that simply having IV in both eyes is not sufficient to predict TTC estimation differences between people with IV and people without IV who have normal vision. Rather it appears to be the degree of bilateral visual impairment of the IV that matters.}, }
@article {pmid41344859, year = {2026}, author = {Schmidt, I and Volkmer, P and Müskens, RPHM and van der Waaij, AM and van Dam, GM and Huiskamp, EA and Nagengast, WB}, title = {Targeted Fluorescence Imaging of Bevacizumab-800CW in Patients with Neovascular Age-Related Macular Degeneration.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {67}, number = {1}, pages = {119-125}, pmid = {41344859}, issn = {1535-5667}, mesh = {Humans ; *Bevacizumab/administration &amp; dosage/pharmacokinetics/adverse effects ; Male ; Female ; Aged ; *Macular Degeneration/diagnostic imaging/drug therapy/metabolism ; Middle Aged ; *Optical Imaging/methods ; Aged, 80 and over ; Angiogenesis Inhibitors ; }, abstract = {The purpose of this study was to determine the safety and feasibility of fluorescence molecular imaging using a commercially available system and intravenous injection of fluorescently labeled bevacizumab (bevacizumab-800CW) to visualize bevacizumab distribution in patients with neovascular age-related macular degeneration (nAMD)s. Methods: Twelve patients with active nAMD aged 60 y or older, who were either on anti-vascular endothelial growth factor (VEGF) therapy or were anti-VEGF therapy naïve, received an intravenous injection of 4.5 mg (n = 3) or 15 mg (n = 9) of bevacizumab-800CW. This clinical trial was divided into 2 parts. An interim analysis was performed after the inclusion of 3 patients per dose group (study part 1) to determine the more optimal dose. Then 6 additional patients were included with the optimal dose in study part 2. All patients underwent standard clinical imaging, including fundus photography, optical coherence tomography, optical coherence tomography angiography, and fluorescein angiography. Fluorescence imaging was performed 1 min, 60 min, and 3-4 d after bevacizumab-800CW injection. Results: Bevacizumab-800CW injections were safe and well tolerated. One minute after injection, only the 15-mg group demonstrated a significantly higher contrast-to-noise ratio (median, 6.32) in vessels compared with baseline (median, -4.44; P = 0.0342). This, combined with the clear visual uptake after 3-4 d, supported 15 mg as the preferred dose. Contrast-to-noise ratio values inside the macula of patients receiving 15 mg of bevacizumab-800CW (n = 8) were significantly higher after 3-4 d (median, 4.45) compared with baseline (median, 0.19; P = 0.0078). Conclusion: Targeted fluorescent tracers such as bevacizumab-800CW can visualize VEGF expression, providing important insights into nAMD, and can pave the way toward personalized treatments and targeted drug development.}, }
@article {pmid41345313, year = {2026}, author = {Niknahad, A and Zielińska, A and Auffarth, GU and Son, HS and Lee, H and Khoramnia, R and Łabuz, G}, title = {[Emerging technology for retinal function testing: two-photon microperimetry].}, journal = {Die Ophthalmologie}, volume = {123}, number = {1}, pages = {12-21}, pmid = {41345313}, issn = {2731-7218}, mesh = {Humans ; *Visual Field Tests/methods/trends/instrumentation ; *Retina/physiopathology ; *Retinal Diseases/diagnosis/physiopathology ; Photons ; }, abstract = {The technique of 2‑photon microperimetry is an emerging procedure that combines measurement of retinal sensitivity with retinal imaging and offers substantial improvements compared to conventional microperimetry. Conventional microperimetry relies on 1‑photon linear absorption while 2‑photon microperimetry relies on the simultaneous absorption of two photons, leading to enough energy for photoisomerization of visual pigments and perception of colors, such as green. This 2‑photon absorption process has shown a lower spread of measurements at one retinal location, leading to more reproducible data compared to conventional microperimetry. The current literature also suggests that 2‑photon microperimetry provides more reliable measurements in the presence of lens opacities, a common issue in an aging eye. Furthermore, it has been successfully utilized to assess retinal function in patients with diabetic retinopathy, age-related macular degeneration and glaucomatous neuropathy. These advantages highlight the very promising application in clinical settings. Future adjustments focusing on implementing this technology in the clinical practice could improve outcomes in the early detection and monitoring of retinal diseases.}, }
@article {pmid41346473, year = {2025}, author = {Buscaglia, M and Gouriou, B and Asquoët, Y and Le Goïc, N and Le Grand, F and Hachem, M and Soudant, P}, title = {Production of [13]C-labeled docosahexaenoic acid from heterotrophic marine microorganisms Aurantiochytrium mangrovei and Crypthecodinium cohnii enabling fluxomic applications.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {13}, number = {}, pages = {1690863}, pmid = {41346473}, issn = {2296-4185}, abstract = {Docosahexaenoic acid (DHA, 22:6n-3) is the predominant polyunsaturated fatty acid in the human brain and eyes, playing a crucial role in vision and cognitive development. DHA deficiency has been associated with ocular diseases, such as macular degeneration and glaucoma, as well as neurodegenerative disorders. Since the human body has a limited ability to synthesize DHA from its precursor, alpha-linolenic acid (ALA, 18:3n-3), targeted DHA supplementation is essential for these patients. To investigate DHA metabolism and integration, researchers commonly use stable ([2]H,[13]C) or radioactive ([3]H,[14]C) isotopes, which are expensive and not widely accessible, restricting the scope and duration of studies. This study aimed to develop a sustainable method for biosynthesizing uniformly labeled [13]C-DHA by culturing the heterotrophic protists Aurantiochytrium mangrovei and Crypthecodinium cohnii with [13]C-glucose. The major fatty acids (FA) of A. mangrovei included 16:0, 22:5n-6 (DPA), and DHA, with DHA accounting for 50.5% ± 4.9% of the total FA. Gas Chromatography-Mass Spectrometry (GC-MS) analysis revealed a[13]C-enrichment of DHA at 96.7% ± 0.4% after the effective High Performance Liquid Chromatography (HPLC) purification. The predominant FA of C. cohnii were 12:0, 14:0, 16:0, and DHA, with DHA representing around 27% of the total FA and exhibiting a[13]C-enrichment of 86.3% ± 1.6%. Based on FA content, A. mangrovei showed a balanced distribution of neutral and polar lipids, with DHA predominantly in the polar fraction (57.8% ± 3.1%), whereas C. cohnii exhibited a predominance of neutral lipids (82.4% ± 0.3%), which contained the majority of its DHA (57.5% ± 1.0%).}, }
@article {pmid41347874, year = {2025}, author = {Trivizki, O and Wykoff, CC and Smoor, MA and Rabinovitch, D and Zhou, A and Cao, JA and Lechanteur, YTE and van den Heuvel, L and van Gool, AJ and Gloerich, J and Vergroesen, JE and Klaver, CCW}, title = {Effect of Pegcetacoplan on Aqueous Humor Proteome in Geographic Atrophy: A Prospective Exploration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {24}, pmid = {41347874}, issn = {1552-5783}, mesh = {Humans ; *Aqueous Humor/metabolism ; *Geographic Atrophy/drug therapy/metabolism ; Prospective Studies ; Male ; Aged ; Female ; *Proteome/metabolism/drug effects ; Tandem Mass Spectrometry ; Chromatography, Liquid ; Complement C3/antagonists &amp; inhibitors ; Proteomics/methods ; Aged, 80 and over ; Middle Aged ; }, abstract = {PURPOSE: Pegcetacoplan, a complement component 3 (C3) inhibitor, has recently received U.S. Food and Drug Administration approval for treating geographic atrophy (GA), an advanced stage of age-related macular degeneration (AMD). However, the limited treatment response prompts further investigations into its molecular effects.<br><br>METHODS: We prospectively collected aqueous humor (AH) samples from 11 patients with GA before and at 2 months during pegcetacoplan treatment. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to analyze the proteome, and global normalization was applied to account for differences in protein concentration. To assess global proteomic shifts over time, principal component analysis (PCA) was performed. The Friedman test was used to assess differences in protein intensities across time points while adjusting for multiple testing using Benjamini-Hochberg false discovery rate (FDR) correction.<br><br>RESULTS: A total of 283 proteins were analyzed. PCA revealed temporal changes in global protein expression profiles, with a significant shift between baseline and month 2 (P = 0.01). The levels of complement components C3 (P = 0.12) and C5 (P = 0.27) remained stable after initiation of treatment, but the levels of C1qB, C1RL, C2, C6, C7, C8, C9, factor D, factor H, and factor I increased significantly (all P < 0.05). Most non-complement proteins showed no significant changes; however, beta-2-glycoprotein 1 (FDR = 0.09), kininogen 1 (FDR < 0.05), and prothrombin (FDR < 0.05) increased significantly, and kallistatin (FDR < 0.05) and plasma serine protease inhibitor (FDR < 0.05) decreased.<br><br>CONCLUSIONS: This exploratory study suggests that pegcetacoplan modulates the AH proteome in GA. Although no changes in the target protein C3 were detected following treatment, significant changes in proteins tightly connected to complement, inflammation, and coagulation were observed. These findings underscore the need for further investigation into the biological and clinical relevance of the observed molecular shifts.}, }
@article {pmid41348248, year = {2025}, author = {Bartol-Puyal, FA and Sánchez Monroy, J and Puzo Bayod, M and Mallén, V and Méndez-Martínez, S and Calvo, P and Pablo, L}, title = {Choroidal changes after antiVEGF in neovascular age-related macular degeneration with type 1 and 3 macular neovascularization.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {8}, pmid = {41348248}, issn = {1573-2630}, mesh = {*Wet Macular Degeneration/drug therapy/pathology ; *Choroid/diagnostic imaging/drug effects/pathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/administration &amp; dosage ; Retrospective Studies ; Intravitreal Injections ; Follow-Up Studies ; *Ranibizumab/administration &amp; dosage ; Tomography, Optical Coherence ; *Choroidal Neovascularization/drug therapy/pathology ; Humans ; Male ; Female ; Aged ; Aged, 80 and over ; }, abstract = {PURPOSE: To analyze choroidal thickness (CT) in patients with neovascular age-related macular degeneration (nAMD) with type 1 macular neovascularization (MNV) and type 3 (or retinal angiomatous proliferation) after antiVEGF treatment for two years.<br><br>METHODS: Retrospective study enrolling Caucasian na&#xef;ve patients with nAMD (type 1 MNV), and patients with type 3 MNV with no other ophthalmological disorders, and without switching treatment. Nine manual CT measurements were performed on optical coherence tomography (OCT) Spectralis (Heidelberg Engineering). Demographic data, smoking, disease activity, and number of injections, among others were recorded. Three visits were analyzed: pretreatment baseline visit, first and last visits with no disease activity.<br><br>RESULTS: 53 eyes of 53 patients with type 1 MNV, and 41 eyes of 41patients with type 3 MNV were analyzed. Both groups received the same number of injections (p&#x2009;=&#x2009;0.282). Type 3 MNV patients showed lower CT (between 143.29 and 174.17&#x3bc;m) than type 1 MNV patients (between 169.91 and 220.17&#x3bc;m) in the baseline visit, but differences disappeared in first and last visits. Choroidal thinning was only observed in type 1 MNV patients between baseline and first visit (p&#x2009;<&#x2009;0.05). In the las visit, they had a CT between 87 and 96% of baseline measurement. No other influencing factor was detected.<br><br>CONCLUSIONS: Patients with nAMD (type 1 MNV) have higher CT than patients with type 3. However, patients with type 1 MNV experience significant choroidal thinning, and CT is similar in both groups after antiVEGF treatment. Smoking, type of drusen or other OCT features have no influence in this reduction.}, }
@article {pmid41348378, year = {2025}, author = {Wang, S and Hong, Y and Qu, Y and Zheng, K and Luo, H and Chen, R and Jia, H and Liu, X and Sun, X}, title = {Association between low handgrip strength and the increased risk of age-related macular degeneration: results from UK biobank cohort study.}, journal = {Aging clinical and experimental research}, volume = {38}, number = {1}, pages = {16}, pmid = {41348378}, issn = {1720-8319}, mesh = {Humans ; *Hand Strength/physiology ; Male ; Female ; *Macular Degeneration/epidemiology/physiopathology ; Middle Aged ; Aged ; United Kingdom/epidemiology ; Prospective Studies ; Risk Factors ; Adult ; Incidence ; Biological Specimen Banks ; Biomarkers/blood ; Cohort Studies ; Proportional Hazards Models ; UK Biobank ; }, abstract = {OBJECTIVES: To determine whether handgrip strength is associated with the incidence of age-related macular degeneration.<br><br>METHODS: A prospective cohort study of over 500 thousand UK Biobank participants aged 40-69 years. Individuals&#x2009;&#x2265;&#x2009;50 years and without age-related macular degeneration at baseline were included. Exposure was the handgrip strength measured by dynamometer. Primary outcome was the incidence of age-related macular degeneration during 13 years of follow-up. Cox proportional-hazard models were fitted to estimate the risk effect for handgrip strength on age-related macular degeneration, and stratified for sociodemographic and lifestyle factors. Mediation models were regressed to explore underlying mechanisms driven by inflammatory and erythrocyte-related biomarkers.<br><br>RESULTS: 382174 eligible participants in the UK Biobank were included. After 4680431 person-year, 7987 individuals (2.09%) developed age-related macular degeneration. Individuals in the lowest quintile of handgrip strength had higher risk of age-related macular degeneration incidence (Hazard Ratio, 1.25; 95% CI, 1.16-1.35) compared with those in the highest quintile. Per 5&#xa0;kg decrement in handgrip strength was associated with increased risk of age-related macular degeneration incidence (Hazard Ratio, 1.06; 95% CI, 1.04-1.08) with similar trend among all subgroups except for sex. Specific inflammatory and erythrocyte-related biomarkers partially (37.5%) mediated the incidence of age-related macular degeneration as substantial biological mechanisms following handgrip strength decrease.<br><br>CONCLUSIONS: Our findings suggest that handgrip strength is associated with the incidence of age-related macular degeneration under the mediation of systemic proinflammatory factors. The current study holds an outlook for improved visual health over the evaluation and intervention of muscle strength in old-age population.}, }
@article {pmid41348407, year = {2025}, author = {Hang, Z and Li, Y and Ren, W and Du, H}, title = {The blood-retinal barrier in ocular pathologies: an updated narrative review.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {10}, pmid = {41348407}, issn = {1573-2630}, mesh = {Humans ; *Blood-Retinal Barrier/physiopathology/pathology ; *Retinal Diseases/physiopathology ; *Eye Diseases/physiopathology ; }, abstract = {PURPOSE: To provide a comprehensive overview of the structural and functional characteristics of the blood-retinal barrier (BRB), examine its critical role in the pathogenesis of major ocular diseases, and summarize current and emerging therapeutic strategies aimed at restoring BRB integrity.<br><br>METHODS: A literature search was conducted in PubMed, Scopus, and Web of Science databases, focusing primarily on publications from the past 10 years supplemented by seminal earlier works. This narrative review synthesizes evidence on BRB molecular anatomy, pathological mechanisms, disease-specific roles, and therapeutic interventions.<br><br>RESULTS: The BRB comprises inner (iBRB) and outer (oBRB) compartments with distinct cellular and molecular architectures. BRB dysfunction is driven by convergent mechanisms including aging, hyperglycemia, oxidative stress, inflammation, and hypoxia, which disrupt tight junction proteins and promote aberrant angiogenesis. This barrier breakdown constitutes a pivotal pathogenic driver in major blinding diseases: age-related macular degeneration, diabetic retinopathy and retinal vein occlusion, glaucoma, and uveitis. Current standard treatments include anti-VEGF agents and corticosteroids. Emerging strategies target Wnt/&#x3b2;-catenin signaling, employ senolytic therapies, utilize biomaterial-based drug delivery, and develop organ-on-a-chip models for personalized medicine.<br><br>CONCLUSIONS: BRB disruption represents a critical inflection point in ocular disease progression, triggering self-perpetuating cycles of neuroinflammation and degeneration. Effective restoration requires multi-faceted approaches combining anti-angiogenic, antiinflammatory, and barrier-strengthening mechanisms. Future research should focus on dynamic functional assessment, single-cell multi-omics integration, and adaptive therapeutic strategies to prevent irreversible vision loss.}, }
@article {pmid41349782, year = {2026}, author = {Horrigan, WF and Caron, Q and Rodriguez, A and Singh, R and Anand-Apte, B}, title = {The effect of age on wound healing in the laser induced choroidal neovascularization model.}, journal = {Experimental eye research}, volume = {263}, number = {}, pages = {110790}, pmid = {41349782}, issn = {1096-0007}, support = {R01 EY027083/EY/NEI NIH HHS/United States ; R01 EY020861/EY/NEI NIH HHS/United States ; T32 EY024236/EY/NEI NIH HHS/United States ; T32 GM137868/GM/NIGMS NIH HHS/United States ; R01 EY016490/EY/NEI NIH HHS/United States ; P30 EY025585/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Choroidal Neovascularization/physiopathology/metabolism/etiology/pathology ; Mice, Inbred C57BL ; *Disease Models, Animal ; Mice ; *Wound Healing/physiology ; Fluorescein Angiography ; Tomography, Optical Coherence ; *Aging/physiology ; Tomography, X-Ray Computed ; Laser Coagulation ; Epithelial-Mesenchymal Transition ; Indocyanine Green ; Choroid/pathology ; Gliosis ; Fibrosis ; }, abstract = {The laser induced model of choroidal neovascularization (LiCNV) is a commonly used in vivo rodent model to study neovascular age-related macular degeneration (nAMD), although progression of this model is not well understood. In this study we characterize and compare the longitudinal progression of wound healing of laser induced choroidal neovascular (CNV) lesions in young and old mice. Using 2-month and 12-month-old C57BL/6J mice and ocular computerized tomography (OCT), fluorescein and indocyanine green angiography we performed a longitudinal imaging analysis at 3-, 7-, 14- and 28-days following laser injury. This was compared with immunohistochemical analysis of the lesions at similar timepoints for markers of angiogenesis, fibrosis, epithelial-to-mesenchymal transition (EMT), and gliosis. OCT analysis determined an increased lesion volume in older mice. In contrast younger mice demonstrated earlier vascularization and fibrosis with no difference in neovascularization or leakage. Reactive gliosis occurs directly above the laser-induced CNV lesion in both ages. The RPE in this model encloses the lesion area by day 14 in both young and old mice. This study concludes that age is an important variable in some but not all aspects of laser-induced CNV.}, }
@article {pmid41350718, year = {2025}, author = {Ruiz-Medrano, J and Pana, I and García-Zamora, M and Flores-Moreno, I and Puertas, M and Ruiz-Moreno, JM}, title = {Faricimab treat-and-extend approach for neovascular age-related macular degeneration: insights from real-world clinical practice.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {5}, pmid = {41350718}, issn = {2056-9920}, abstract = {PURPOSE: To evaluate the clinical outcomes of the switch to faricimab in a treat-and-extend (T&amp;E) regimen patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective cohort study included consecutive patients with nAMD who had previously been treated with anti-VEGF agents in a T&amp;E regimen, with treatment intervals (TI) that could not be extended beyond 12 weeks, and a minimum follow-up of 24 weeks. These patients were switched to faricimab therapy in a T&amp;E regimen for at least 6 months. The primary endpoint was the TI between intravitreal injections (IVIs), and the secondary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to the last follow-up visit (LFUV).<br><br>RESULTS: A total of 225 eyes from 188 patients were included, with a mean age of 79.6&#x2009;&#xb1;&#x2009;7.4 years. Previous anti-VEGF treatments included ranibizumab (n&#x2009;=&#x2009;34), aflibercept (n&#x2009;=&#x2009;144), brolucizumab (n&#x2009;=&#x2009;6), and bevacizumab (n&#x2009;=&#x2009;41). TI1 (5.9&#x2009;&#xb1;&#x2009;2.0 weeks) matched the prior treatment interval. Significant increases in treatment intervals were observed at subsequent time points (TI2: 8.2&#x2009;&#xb1;&#x2009;3.2 weeks, TI3: 10.1&#x2009;&#xb1;&#x2009;3.9 weeks, TI4: 10.7&#x2009;&#xb1;&#x2009;4.3 weeks, TI5: 9.9&#x2009;&#xb1;&#x2009;4.0 weeks, and TI6: 8.5&#x2009;&#xb1;&#x2009;4.4 weeks; p&#x2009;<&#x2009;0.001). BCVA remained stable, going from 0.41&#x2009;&#xb1;&#x2009;0.23 to 0.43&#x2009;&#xb1;&#x2009;0.24 (p&#x2009;=&#x2009;0.0112). The mean number of injections was 5.9&#x2009;&#xb1;&#x2009;1.9, with a mean follow-up duration of 51.4&#x2009;&#xb1;&#x2009;11.8 weeks.<br><br>CONCLUSIONS: The switch to faricimab in a T&amp;E regimen significantly increased treatment intervals maintaining BCVA in patients with nAMD under other anti-VEGF treatments. No serious adverse events were reported. Longer follow-up is needed to confirm these results.}, }
@article {pmid41350762, year = {2025}, author = {Ma, Y and Zan, H and Li, L and Li, S and Yu, X and Li, J and Cai, J and Zhang, H and Yang, J and Zhang, R and Salvi, R and Li, W and Wang, H and Yin, S}, title = {Global burden and geospatial drivers of sensory impairment with sense organ disease projections to 2050.}, journal = {Communications medicine}, volume = {6}, number = {1}, pages = {8}, pmid = {41350762}, issn = {2730-664X}, support = {82271161//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82330034//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {BACKGROUND: Sense organ diseases represent the leading causes of years lived with disability. Despite its major impact, a comprehensive understanding of sense organ diseases burden remains limited.<br><br>METHODS: Based on the data from the Global Burden of Disease Study 2021 and nighttime light exposure data from remote-sensing satellites, we did secondary analysis and described the epidemiological characteristics of sense organ diseases globally and nationally. The relationship between the specific causes of blindness and vision loss and nighttime light exposure was further explored. We assessed the trends, causes and cross-country inequalities related to sense organ diseases and forecasted the burden of disease until 2050.<br><br>RESULTS: Here we show that in 2021, there are more than 2 billion prevalent cases and more than 77 million years lived with disability cases of sense organ diseases globally. Both age-related macular degeneration and near vision loss show positive correlations with nighttime light exposure. The global burden of sense organ diseases continues to rise from 1990 to 2021, primarily driven by population growth and ageing. Health inequalities exist between different countries and increase over time. Projections of years lived with disability for sense organ diseases from 2022 to 2050 show that although the age-standardized rate remains stable, the number increases significantly.<br><br>CONCLUSIONS: Over the past 32 years, the global burden of sense organ diseases has increased, and cross-country inequalities have intensified due to the trends of population growth and aging. Therefore, it is urgently necessary to formulate more targeted and effective prevention and management strategies.}, }
@article {pmid41352547, year = {2026}, author = {Wang, N and Liu, X and Wu, J and Xiang, X and Gao, Y and Yao, L and Zhang, S}, title = {Multimodal and 3D imaging presentation of the evolution of pressure-related CNV.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {57}, number = {}, pages = {105305}, doi = {10.1016/j.pdpdt.2025.105305}, pmid = {41352547}, issn = {1873-1597}, mesh = {Humans ; Female ; Aged ; *Choroidal Neovascularization/diagnostic imaging/etiology/drug therapy ; *Multimodal Imaging/methods ; *Imaging, Three-Dimensional/methods ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Macular Degeneration/drug therapy ; Indocyanine Green ; }, abstract = {This study reports a unique case that visually demonstrates the six-year evolution of a pressure-related choroidal neovascularization (CNV) using multimodal image registration and three-dimensional (3D) reconstruction. A 65-year-old female with neovascular age-related macular degeneration received 33 anti-VEGF injections over six years but experienced continued vision decline. Through precise registration of indocyanine green angiography, and optical coherence tomography angiography images, combined with 3D modeling of swept-source OCTA volume data. We found that the main trunk of this large, tree-like type II CNV originated from an abnormally dilated great vein, which exhibited an anastomosis with an accompanying great vein. Furthermore, the 3D reconstruction viewed from the scleral side revealed that this vein was closely opposed to and shared a shunt branch with an underlying choroidal great artery. The CNV appeared to function as a "pressure-relief valve," sprouting from the venous trunk to alleviate pressure. This case underscores the critical role of deep multimodal imaging integration in tracing CNV origins and reveals that some anti-VEGF-resistant CNVs may represent hemodynamic compensatory disorders secondary to pre-existing large vessel structural abnormalities, rather than purely neovascular diseases.}, }
@article {pmid41352549, year = {2026}, author = {Wang, N and Liu, X and Wu, J and Xiang, X and Gao, Y and Yao, L and Wang, X}, title = {SS-OCTA versus ICGA: a comparison of detection efficiency for large choroidal vein patterns in AMD patients.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {57}, number = {}, pages = {105303}, doi = {10.1016/j.pdpdt.2025.105303}, pmid = {41352549}, issn = {1873-1597}, mesh = {Humans ; Female ; Male ; Cross-Sectional Studies ; Retrospective Studies ; Aged ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/diagnostic imaging ; *Fluorescein Angiography/methods ; *Indocyanine Green ; Aged, 80 and over ; *Macular Degeneration/diagnostic imaging ; *Choroidal Neovascularization/diagnostic imaging ; Middle Aged ; *Wet Macular Degeneration/diagnostic imaging ; }, abstract = {PURPOSE: To compare the efficacy of swept-source optical coherence tomography angiography (SS-OCTA) and indocyanine green angiography (ICGA) in visualizing and classifying large choroidal vein topography, and to evaluate the association between specific venous patterns and pachychoroid spectrum disease (PSD)-associated macular neovascularization (MNV).<br><br>METHODS: This retrospective cross-sectional study included 222 eyes from 160 patients with neovascular age-related macular degeneration (nAMD). All participants underwent both SS-OCTA and ICGA imaging. Choroidal venous patterns were classified into four types based on ICGA venous phase images: watershed, anastomotic, upper thicker, and lower thicker. SS-OCTA images were processed and analyzed using Fiji software. Diagnostic agreement between modalities was assessed using Cohen's Kappa. Logistic regression was used to evaluate the association between venous patterns and disease subtypes.<br><br>RESULTS: SS-OCTA and ICGA showed almost perfect agreement in classifying choroidal venous patterns in discernible cases (unweighted Kappa = 0.978). Among 77 eyes where ICGA failed to provide a clear classification, SS-OCTA achieved a definitive diagnosis in 87.0 % (P < 0.001), with the anastomotic type being the most common. Furthermore, the watershed pattern was significantly more prevalent in non-PCV nAMD compared to PCV (29.8 % vs. 12.1 %, p = 0.002), suggesting distinct choroidal venous backgrounds between these subtypes.<br><br>CONCLUSION: SS-OCTA provides a reliable, non-invasive alternative to ICGA for visualizing and classifying large choroidal veins, with superior performance in cases obscured by hemorrhage or leakage. The distinct distribution of venous patterns across nAMD subtypes highlights the potential role of choroidal venous architecture in disease phenotyping and pathogenesis.}, }
@article {pmid41352581, year = {2026}, author = {Dinah, C and Esmaeelpour, M and Rachitskaya, AV and De Salvo, G and Munk, MR}, title = {Functional endpoints in patients with geographic atrophy: What to consider when designing a clinical trial.}, journal = {Progress in retinal and eye research}, volume = {110}, number = {}, pages = {101421}, doi = {10.1016/j.preteyeres.2025.101421}, pmid = {41352581}, issn = {1873-1635}, mesh = {Humans ; *Geographic Atrophy/physiopathology/diagnosis/therapy ; *Clinical Trials as Topic/methods ; *Visual Acuity/physiology ; Quality of Life ; *Research Design ; Endpoint Determination ; }, abstract = {There is an unmet need in patients with geographic atrophy (GA) for treatments that preserve and improve functional vision to maintain their independence and quality of life. The limited number of available treatments for GA have demonstrated structural benefits, but none have consistently shown significant functional outcomes in clinical trials. Currently, best-corrected visual acuity (BCVA) is considered the gold standard functional endpoint in clinical trials; however, in the case of GA, it cannot fully evaluate visual impairment or treatment response, particularly in fovea-sparing GA lesions. In addition, BCVA may not fully capture the functional impact of foveal and parafoveal scotomas. There is emerging evidence for the utility of other functional assessments that may provide a more robust representation of the functional impact of GA; however, the current utilization of these tests in GA clinical trials varies widely. This review aims to evaluate current functional endpoints in GA and their strengths and limitations based on characteristics such as strength of structure-function correlation, practicality and feasibility, and patient perspective. There are many factors to consider when choosing a functional vision assessment when designing a GA clinical trial, and each functional vision assessment has several advantages and disadvantages, which are summarized in this review article.}, }
@article {pmid41353311, year = {2025}, author = {Willmington, C and Kirby, A and Murphy, A}, title = {The economic impact of retinal diseases for which gene therapy is emerging: a systematic literature review.}, journal = {Health economics review}, volume = {16}, number = {1}, pages = {21}, pmid = {41353311}, issn = {2191-1991}, support = {101073316//European Union's Horizon Europe/ ; }, abstract = {BACKGROUND: Retinal disease is one of the leading causes of blindness and vision impairment worldwide, including Europe. With the advent of gene therapy, the treatment landscape for retinal disease is changing and clinical trials are underway investigating the therapeutic potential of gene therapy in both acquired and inherited retinal diseases. Given the high price of innovative medicines, it is essential to consider the current costs associated with retinal diseases to inform economic evaluations early in the life cycle of these forthcoming treatments. These could inform future reimbursement decisions, health budgets and service delivery plans.<br><br>AIM: This systematic literature review sought to examine the economic burden of retinal diseases, for which gene therapy is emerging for patients in Europe.<br><br>METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline, a systematic search was performed using the Medline, CINAHL, EconLit and Embase databases. The searches were restricted to English language articles published after 1st January 2000. Following article selection, data were extracted in a tabular form and a narrative synthesis was performed.<br><br>RESULTS: A total of 28 research studies were identified and included in the review that varied in terms of disease of interest, size, country setting, methodology, as well as how costs were reported and valued. While many retinal diseases were considered, almost half of the articles related to the costs of neovascular age-related macular degeneration (nAMD). Significant cost variations were observed across the studies as costs ranged from 45 USD to almost 30,000 USD per patient per annum, across all conditions combined.<br><br>CONCLUSION: This systematic literature review evidences the heterogeneity among studies analysing the economics of retinal diseases underlying vision impairment. The paucity in the literature, signals the need for further research investigating the costs associated with retinal diseases, for which innovative therapies are expected to enter the market and will be subject to evaluation by decision-makers, whose decisions will have a significant impact on the delivery of these technologies to patients.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13561-025-00707-7.}, }
@article {pmid41353467, year = {2025}, author = {E de Carlo Forest, T and Marin, AI and Gill, Z and Gnanaraj, R and Patnaik, JL and Poppelaars, F and Lynch, AM and Palestine, AG and Mathias, MT and Manoharan, N and Frazer-Abel, AA and Holers, VM and Mandava, N}, title = {Association between systemic complement levels and choroidal thickness in advanced non-neovascular age-related macular degeneration.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {1442}, pmid = {41353467}, issn = {2045-2322}, support = {R01 EY032456/EY/NEI NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; R01EY032456//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; }, mesh = {Humans ; Female ; Male ; *Macular Degeneration/pathology/blood/diagnostic imaging/immunology ; *Choroid/pathology/diagnostic imaging ; Aged, 80 and over ; Aged ; Cross-Sectional Studies ; Tomography, Optical Coherence ; *Complement System Proteins/metabolism ; Complement Activation ; }, abstract = {To investigate associations between systemic complement activation and choroidal thickness (CT) in advanced non-neovascular age-related macular degeneration (nnAMD). Cross-sectional study of 96 patients (187 eyes) with advanced nnAMD enrolled in the University of Colorado AMD Registry (August 2014-June 2021). Medical histories, multimodal imaging, and plasma samples were collected. Plasma was analyzed via enzyme-linked immunosorbent assay and multiplex Luminex assays for complement factors C1q, monoclonal B-cell lymphocytosis, C2, C4, C4b, C3, C3a, Factor B, Bb, Factor D, Factor H, Factor I, C5 and soluble C5b-9. CT was measured subfoveally and at 1000 μm intervals superiorly, inferiorly, nasally, and temporally using Spectralis OCT. Linear modeling with generalized estimating equations assessed log-transformed OCT and complement factors. The mean age was 82.2 years (± 7.1 SD); 54.2% were female. Average CT was negatively associated with Bb (β=-0.47, SE: 0.12, p = 0.0001) and the Bb/Factor B ratio (β=-0.28, SE: 0.12, p = 0.02), but not other complement markers. Bb levels correlated with alternative pathway components but not with classical or lectin pathway markers. We found a key association between systemic complement activation of Factor B and choroidal thickness in patients with advanced nnAMD, implying the potential involvement of the systemic alternative pathway in nnAMD patients.}, }
@article {pmid41353670, year = {2026}, author = {Poteet, J and Koetting, C and Vakharia, PS}, title = {Role of B Vitamins in Preventing the Development and Progression of Age-Related Macular Degeneration.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {1}, pages = {1-19}, pmid = {41353670}, issn = {2193-8245}, support = {Editorial/writing assistance//Bausch + Lomb/ ; Funding for rapid service fee//Bausch + Lomb/ ; }, abstract = {No current treatments are curative for age-related macular degeneration (AMD), and preventing disease progression is challenging. Dietary factors play a role in the course of macular degeneration, and management of AMD commonly includes nutraceuticals (e.g., supplementation with a combination of antioxidant vitamins and minerals). This commentary summarizes the existing literature, emerging evidence, and upcoming research on the role of B vitamins in both preventing the development of AMD and slowing its progression.}, }
@article {pmid41354182, year = {2026}, author = {Xu, L and Chen, ZA and Wu, CH and Chen, YP and Wu, SH and Mou, CY and Tseng, CL and Chien, Y and Chan, HW and Yang, TC and Chiou, SH}, title = {Dual-functionalized mesoporous silica nanoparticles for topical axitinib delivery to the posterior eye segment.}, journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences}, volume = {217}, number = {}, pages = {107398}, doi = {10.1016/j.ejps.2025.107398}, pmid = {41354182}, issn = {1879-0720}, mesh = {Animals ; *Silicon Dioxide/chemistry/administration &amp; dosage ; *Axitinib/administration &amp; dosage/pharmacokinetics/chemistry ; *Nanoparticles/chemistry/administration &amp; dosage ; Choroidal Neovascularization/drug therapy/metabolism ; Mice ; Porosity ; Mice, Inbred C57BL ; *Posterior Eye Segment/metabolism/drug effects ; Ophthalmic Solutions/administration &amp; dosage ; Administration, Topical ; *Angiogenesis Inhibitors/administration &amp; dosage/pharmacokinetics/chemistry ; Drug Delivery Systems ; Male ; Drug Carriers/chemistry ; }, abstract = {Topical drug delivery to the posterior eye segment remains a significant challenge due to ocular anatomical barriers, particularly in diseases such as wet age-related macular degeneration (AMD), where treatment typically relies on frequent intravitreal (IVT) injections of anti-angiogenic agents. In this study, we present a non-invasive eye drop formulation of axitinib (AXT), a potent vascular endothelial growth factor receptor (VEGFR) inhibitor, encapsulated within 25-nm dual-functionalized mesoporous silica nanoparticles (AXT@dual-MSNs) engineered for efficient retinal delivery. The nanoparticles feature sulfonate-functionalized mesopores that enhanced AXT loading and solubilization, along with a PEGylated/quaternary ammonium-modified surface that improved colloidal stability and favored intramesopore drug confinement. Following topical administration, AXT@dual-MSNs achieved retinal accumulation via the conjunctiva-sclera-choroid pathway, effectively bypassing the corneal route. A pharmacokinetic analysis confirmed rapid, transscleral delivery of AXT with therapeutically relevant concentrations in the retina. In a laser-induced choroidal neovascularization (CNV) mouse model, a well-established surrogate for wet AMD, AXT@dual-MSN eyedrops significantly suppressed neovascular lesion formation, outperforming free-drug eyedrops and IVT AXT injection. Notably, the formulation exhibited excellent ocular tolerance, with no evidence of local toxicity or contralateral eye exposure. This work introduces a novel nanocarrier system capable of overcoming the longstanding delivery barrier to the posterior eye segment via eyedrops, offering a safe, effective, and clinically translatable alternative to IVT injections. The modular design of AXT@dual-MSNs also holds promise for expanding topical access to other hydrophobic or labile therapeutics targeting retinal diseases.}, }
@article {pmid41354398, year = {2026}, author = {Fernández, Y and Subirada, PV and Vaglienti, MV and Tovo, A and Paz, MC and Barcelona, PF and Sánchez, MC}, title = {Glial fibrillary acidic protein, an early and sustained indicator of retinopathy progression.}, journal = {Experimental eye research}, volume = {263}, number = {}, pages = {110796}, doi = {10.1016/j.exer.2025.110796}, pmid = {41354398}, issn = {1096-0007}, mesh = {*Glial Fibrillary Acidic Protein/metabolism ; Humans ; Disease Progression ; Biomarkers/metabolism ; *Retinal Diseases/metabolism/diagnosis ; Astrocytes/metabolism ; Ependymoglial Cells/metabolism ; Gliosis/metabolism ; Animals ; Retina/metabolism ; Neuroglia/metabolism ; }, abstract = {Macroglial cells, particularly astrocytes and Müller glial cells (MGCs), are crucial for maintaining retinal health and function. Both cell types express glial fibrillary acidic protein (GFAP), although their expression levels and patterns differ. In a healthy retina, astrocytes constitutively express GFAP, whereas MGCs typically show low or undetectable levels. In response to retinal insults, macroglial cells are activated through a process known as gliosis to preserve retinal homeostasis. The gliotic response includes cellular hypertrophy and the upregulation of intermediate filaments -primarily GFAP- as a protective mechanism. However, when harmful stimuli persist, both astrocytes and MGCs may contribute to pathology, becoming associated with ongoing damage and loss of retinal function. Changes in GFAP expression have been described in conditions like diabetic retinopathy, sickle-cell retinopathy, and age-related macular degeneration, indicating retinal stress and dysfunction. A deeper understanding of GFAP's dual role in retinal diseases is critical for developing effective treatments for these conditions and for identifying its potential as a biofluid-based biomarker.}, }
@article {pmid41354925, year = {2025}, author = {Nafar, H and Mahdavi Sharif, P and Rezaei, N}, title = {Advances in nanomedicine-based retinal drug delivery: mechanisms and translational applications.}, journal = {Journal of nanobiotechnology}, volume = {24}, number = {1}, pages = {33}, pmid = {41354925}, issn = {1477-3155}, mesh = {Humans ; *Nanomedicine/methods ; Animals ; *Drug Delivery Systems/methods ; *Retinal Diseases/drug therapy ; Nanoparticles/chemistry ; *Retina/drug effects/metabolism ; Blood-Retinal Barrier ; Intravitreal Injections ; Translational Research, Biomedical ; Biological Availability ; }, abstract = {Retinal diseases like age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME), alongside optic neuropathies such as glaucoma, are primary contributors to irreversible visual impairment and blindness, and not only impact the quality of life but also place considerable socioeconomic pressures on healthcare systems worldwide. Despite the availability of several therapeutic modalities, the clinical management of these conditions remains challenging due to the unique anatomical and physiological barriers of the eye (i.e., tear film, cornea, blood-aqueous barrier, and the blood-retinal barrier), which impede achieving therapeutic drug concentrations in the posterior segment. Topical administration exhibits low bioavailability, while systemic delivery is generally inefficient and associated with adverse effects. Intravitreal injections (IVIs) deliver drugs directly to the vitreous but necessitate frequent administration, hence increasing risks of endophthalmitis, retinal detachment, and patient non-compliance. Nanomedicine has revolutionized drug delivery science across various medical fields, offering significant advantages for therapeutic interventions. Nanoparticle (NP)-based systems enhance drug solubility and stability, improve pharmacokinetic profiles, facilitate passage across biological barriers, and enable targeted delivery to specific cells or tissues with surface modifications, thereby potentially increasing bioavailability while minimizing systemic toxicity. This review aims to illustrate recent advancements in the design principles, preclinical applications, and translational potential of NP-based drug delivery systems aimed at addressing the challenges inherent in treating posterior segment eye diseases. NPs (ranging from polymeric and lipid-based systems to inorganic and hybrid forms) have been able to effectively carry various formulations of antiangiogenic, anti-inflammatory, anti-neoplastic, and antioxidant compounds, as well as genetic materials, to counteract such disorders. NP's size, surface charge, and composition can be modulated to optimize interaction with ocular tissues and overcome barriers. With their controlled and sustained drug release, NPs decrease the required frequency of IVIs. In addition, NPs can encapsulate a wide range of therapeutic agents (including hydrophobic molecules, proteins, and nucleic acids) and are amenable to the functionalization of their surfaces with ligands for specific receptors on retinal cells, thereby enhancing therapeutic efficacy and minimizing local toxicities. The findings of this review will establish a research agenda for translating NP-based interventions into clinical practice.}, }
@article {pmid41356440, year = {2025}, author = {Mimura, T and Noma, H}, title = {Metabolites of traffic-related volatile organic compounds in age-related macular degeneration.}, journal = {PeerJ}, volume = {13}, number = {}, pages = {e20405}, pmid = {41356440}, issn = {2167-8359}, mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; *Macular Degeneration/urine/metabolism ; Aged ; *Volatile Organic Compounds/urine/metabolism ; *Vehicle Emissions/analysis/toxicity ; Middle Aged ; *Air Pollutants/adverse effects ; Gas Chromatography-Mass Spectrometry ; Aged, 80 and over ; Case-Control Studies ; }, abstract = {BACKGROUND: Volatile organic compounds (VOCs), commonly emitted from vehicle exhaust and industrial activities, are prevalent air pollutants in urban environments. These compounds have been reported to cause various health effects through mechanisms such as oxidative stress and neurotoxicity. Recently, air pollution has attracted attention as a potential risk factor for age-related macular degeneration (AMD); however, the association between VOC exposure and AMD remains unclear.<br><br>OBJECTIVE: This study aimed to assess VOC exposure levels among urban-dwelling AMD patients by quantifying urinary metabolites and investigating the association between VOCs and AMD.<br><br>METHODS: This cross-sectional study included 40 untreated AMD patients (AMD group), 10 cataract patients (Cataract group), and 10 healthy controls (Healthy group). Representative urinary metabolites of VOCs-2-methylhippuric acid, 3-methylhippuric acid, mandelic acid, phenylglyoxylic acid, and trans,trans-muconic acid-were measured using gas chromatography-mass spectrometry (GC/MS), with concentrations corrected for urinary creatinine. Group comparisons were performed based on creatinine-adjusted metabolite levels.<br><br>RESULTS: The AMD group exhibited elevated urinary VOC metabolite levels compared to both control groups. The ratios of mean concentrations in the AMD group versus the Healthy and Cataract groups, respectively, were: 2-methylhippuric acid (201% and 181%), 3-methylhippuric acid (190% and 139%), mandelic acid (304% and 198%), phenylglyoxylic acid (118% and 90%), and trans,trans-muconic acid (214% and 92%). Among these, 2-methylhippuric acid and mandelic acid were significantly higher in the AMD group than in both controls (p&#xa0;<&#xa0;0.001 and p&#xa0;=&#xa0;0.042; p&#xa0;<&#xa0;0.001, respectively). Trans,trans-muconic acid also showed a significant increase compared to the Healthy group (p&#xa0;<&#xa0;0.001). Correlation analysis within the AMD group revealed moderate but significant associations for 2-methylhippuric acid (r&#xa0;=&#xa0;0.29, p&#xa0;=&#xa0;0.011), mandelic acid (r&#xa0;=&#xa0;0.47, p&#xa0;<&#xa0;0.001), and trans,trans-muconic acid (r&#xa0;=&#xa0;0.27, p&#xa0;=&#xa0;0.020). Multivariate logistic regression identified mandelic acid as an independent factor significantly associated with AMD (odds ratio = 17.20, p&#xa0;<&#xa0;0.001). Subgroup analysis categorized the AMD group into drusenoid AMD, typical AMD (t-AMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). No significant differences in urinary VOC metabolite levels were observed among the four subtypes after multiple comparison adjustment.<br><br>CONCLUSIONS: These findings indicate that AMD patients are exposed to higher levels of traffic-related VOCs. While mandelic acid-a styrene metabolite-was independently associated with AMD, its role should be interpreted as a potential exposure marker rather than a definitive disease biomarker. Further longitudinal studies are warranted to clarify causal relationships between VOC exposure and AMD development.}, }
@article {pmid41356765, year = {2025}, author = {Warner, JD and Tuli, A and Zhang, DD and Singireddy, R and Ebrahimiadib, N and Chen, J}, title = {Full-Spectrum Pachychoroid Manifestation in One Eye: A Case Report.}, journal = {Case reports in ophthalmology}, volume = {16}, number = {1}, pages = {896-902}, pmid = {41356765}, issn = {1663-2699}, abstract = {INTRODUCTION: The pachychoroid spectrum refers to a group of chorioretinal disorders including pachychoroid pigment epitheliopathy (PPE), pachychoroid neovasculopathy (PNV), polypoidal choroidal vasculopathy (PCV), and central serous chorioretinopathy (CSC). These conditions are thought to represent progressive stages, beginning with subclinical retinal pigment epithelium (RPE) changes in PPE, advancing to serous retinal detachment in CSC, followed by choroidal neovascularization in PNV, and culminating in aneurysmal dilation of vessels in PCV. We present a rare case of the pachychoroid spectrum in which lesions in all four stages were simultaneously observed in a single, fovea-sparing eye.<br><br>CASE PRESENTATION: An 85-year-old man presented with a 1-month history of a visual disturbance in his left eye. Examination revealed all four stages of pachychoroid disease in the same eye: choroidal neovascular membrane (CNV) with subretinal hemorrhage (pachychoroid neovascularization, PNV), multiple RPE defects (PPE), and findings consistent with CSC and PCV. He was treated with a combination of anti-VEGF injections and focal laser therapy with the lesions stabilizing after 2 years.<br><br>CONCLUSION: Although it has features similar to age-related macular degeneration, pachychoroid spectrum is a distinct disease entity, with a slower onset and greater response to initial therapy. It may necessitate therapies otherwise not used for other causes of neovascularization like focal laser treatment and verteporforin photodynamic therapy. It is a unique pathologic process presenting with varying stages/lesions that have distinct morphological features but are thought to be a part of the same spectrum.}, }
@article {pmid41358132, year = {2025}, author = {Pashandi, Z and Liu, M and Azam, M and Das, S and Sheves, M and Jastrzebska, B}, title = {Therapeutic Potential of Partial Retinoid Agonists against Vertebrate Rhodopsin Misfolding Disorders.}, journal = {ACS omega}, volume = {10}, number = {47}, pages = {57487-57502}, pmid = {41358132}, issn = {2470-1343}, support = {P30 EY011373/EY/NEI NIH HHS/United States ; R01 EY032874/EY/NEI NIH HHS/United States ; T32 EY024236/EY/NEI NIH HHS/United States ; T32 GM158814/GM/NIGMS NIH HHS/United States ; }, abstract = {Mutations in rod opsin are a leading cause of inherited retinal degenerative diseases such as retinitis pigmentosa (RP). Pharmacological compounds that stabilize rhodopsin (Rho) and mitigate cellular stress pathways hold promise for therapeutic intervention. Among these, retinoid analogs have shown efficacy in models of autosomal dominant RP (adRP) and age-related macular degeneration (AMD). In this study, we evaluated the pharmacological potential of two partial retinoid agonists, acyclic-retinal and 9-cis-9-demethyl-retinal, as well as newly synthesized retinol and amine derivatives of 9-cis-9-demethyl-retinal. A photoreceptor-derived 661W cell line stably expressing two RP-linked misfolding rod opsin mutants, P23H and T289P, was used to assess the compound activity. We investigated the effects on opsin folding, glycosylation, membrane localization, and pigment regeneration. Both acyclic-retinal and 9-cis-9-demethyl-retinal promoted mature glycosylation and enhanced cell surface trafficking of P23H and T289P rod opsins. Spectroscopic analysis confirmed that these compounds regenerated functional, photosensitive pigments and stabilized the receptor in the Meta-I conformation upon light exposure. Notably, 9-cis-9-demethyl-retinal exhibited higher binding affinity than 9-cis-retinal, without impairing visual signaling postphotoisomerization. Among the derivatives, the amine form of 9-cis-9-demethyl-retinal was most effective in promoting proper folding and localization of misfolded rod opsin, outperforming the corresponding retinol analog. These findings support the therapeutic potential of acyclic-retinal, 9-cis-9-demethyl-retinal, and its derivatives for rescuing misfolded rod opsin and delaying photoreceptor degeneration in RP.}, }
@article {pmid41361163, year = {2025}, author = {Farashi, S and Abbott, CJ and Ansell, BRE and Wu, Z and Altay, L and Arnon, E and Arnould, L and Bagdasarova, Y and Balaskas, K and Chen, FK and Chew, E and Chowers, I and Clarke, S and Cukras, C and Delcourt, C and Delyfer, MN and den Hollander, AI and Fauser, S and Finger, RP and Gabrielle, PH and Han, J and Hodgson, LAB and Hogg, R and Holz, FG and Hoyng, C and Kumar, H and Lad, EM and Lee, A and Luhmann, UFO and Mauschitz, MM and McKnight, AJ and McLenachan, S and Mishra, A and Moghul, I and Orozco, LD and Sampson, DM and Scott, LW and Sitnilska, V and Song, S and Stockwell, A and Swaroop, A and Terheyden, JH and Tiosano, L and Tufail, A and Yaspan, BL and ,  and ,  and Pébay, A and Fletcher, EL and Guymer, RH and Bahlo, M and , }, title = {HTRA1/lncRNA HTRA1-AS1 dominates in age-related macular degeneration reticular pseudodrusen genetic risk with no complement involvement.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {10854}, pmid = {41361163}, issn = {2041-1723}, support = {K23 EY026988/EY/NEI NIH HHS/United States ; GNT1195236//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1157776//Department of Health | National Health and Medical Research Council (NHMRC)/ ; Independent Research Institute Infrastructure Support Scheme//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT2008382//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1181010//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1154389//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1194667//Department of Health | National Health and Medical Research Council (NHMRC)/ ; Z01EY000546//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; Operational Infrastructure Support//Department of Health, State Government of Victoria (Victorian Department of Health)/ ; }, mesh = {Humans ; *High-Temperature Requirement A Serine Peptidase 1/genetics ; *Macular Degeneration/genetics/pathology ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Aged ; Male ; Female ; *RNA, Long Noncoding/genetics ; Polymorphism, Single Nucleotide ; Retina/pathology/metabolism ; *Retinal Drusen/genetics ; Chromosomes, Human, Pair 10/genetics ; Chromosomes, Human, Pair 1/genetics ; Quantitative Trait Loci ; Middle Aged ; Aged, 80 and over ; Proteins/genetics ; }, abstract = {Age-related macular degeneration (AMD) is a multifactorial retinal disease with a large genetic risk contribution. Reticular pseudodrusen (RPD) is a sub-phenotype of AMD with a high risk of progression to late vision threatening AMD. In a genome-wide association study of 2165 AMD+/RPD+ and 4181 AMD+/RPD- compared to 7639 control participants, both chromosomes 1 (CFH) and 10 (ARMS2/HTRA1) major AMD risk loci are reidentified. However association is only detected for the chromosome 10 locus when comparing AMD+/RPD+ to AMD+/RPD- cases. The chromosome 1 locus is notably absent. The chromosome 10 RPD risk region contains a long non-coding RNA HTRA1-AS1 (ENSG00000285955/BX842242.1) which colocalizes with genetic markers of retinal thickness. HTRA1-AS1 has a strong retinal eQTL signal, pinpointing the parafoveal photoreceptor outer segment layer. Whole genome sequencing of phenotypically extreme RPD cases identifies even stronger enrichment for the chromosome 10 risk genotype.}, }
@article {pmid41361469, year = {2025}, author = {Wang, X and Gui, S and Liu, X and Tao, Y and Gao, J and Liu, H}, title = {Eriocitrin inhibits sodium iodate-induced cuproptosis and barrier function impairment in retinal pigment epithelium via SIRT7/YAP/ATP7A pathway.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {86}, pmid = {41361469}, issn = {1479-5876}, support = {2023zhyx-C72//the Research Fund Project of Anhui Institute of Translational Medicine/ ; }, mesh = {*Retinal Pigment Epithelium/drug effects/pathology/metabolism ; *Iodates ; Animals ; Humans ; *Signal Transduction/drug effects ; Cell Line ; Mice, Inbred C57BL ; Mice ; Macular Degeneration/pathology/drug therapy ; YAP-Signaling Proteins ; Oxidative Stress/drug effects ; Cell Survival/drug effects ; Apoptosis/drug effects ; *Adaptor Proteins, Signal Transducing/metabolism ; *Flavones/pharmacology ; Reactive Oxygen Species/metabolism ; }, abstract = {BACKGROUND: Dry age-related macular degeneration (AMD) is characterized by retinal pigment epithelium (RPE) barrier dysfunction, and currently lacks effective treatment options. Eriocitrin is a natural flavonoid with antioxidant and anti-inflammatory properties, and its potential role in inhibiting cuproptosis and improving RPE barrier function remains unclear.<br><br>METHODS: ARPE-19 cells treated with sodium iodate (NaIO&#x2083;) were used to establish an in vitro AMD model. The effects of eriocitrin at various concentrations (0-100 &#xb5;M) and treatment durations on cell viability were assessed using the CCK-8 assay. ELISA and ROS fluorescence were used to assess inflammation and oxidative stress levels. Western blotting and qPCR analysis were employed to evaluate the expression of copper-dependent programmed cell death (cuproptosis)-related markers. RPE barrier function was analyzed by transepithelial electrical resistance (TEER), FITC-dextran permeability assays, and the expression of tight junction proteins. We further utilized siRNA to knockdown SIRT7 and ATP7A gene, and pharmacological inhibition of YAP using verteporfin. In vivo, a NaIO&#x2083;-induced AMD model was established in both C57BL/6J and SIRT7 silencing mice, followed by administration of eriocitrin (25 or 50&#xa0;mg/kg). Retinal histology and protein expression were subsequently analyzed.<br><br>RESULTS: Eriocitrin significantly ameliorated NaIO&#x2083;-induced reductions in cell viability, decreased ROS levels, and suppressed inflammatory cytokine expression. It also restored RPE barrier function in a dose-dependent manner. Mechanistically, eriocitrin modulated SIRT7 expression, inhibited YAP activity, and enhanced ATP7A expression. Genetic silencing or knockdown of SIRT7 markedly weakened the protective effects of eriocitrin, including its antioxidant and barrier-restoring functions. YAP inhibition by verteporfin partially mimicked the actions of eriocitrin, while ATP7A silencing completely abrogated its effects, indicating that the SIRT7/YAP/ATP7A axis plays a crucial role in the therapeutic mechanism of eriocitrin against AMD.<br><br>CONCLUSION: This study demonstrated that eriocitrin alleviates NaIO&#x2083;-induced oxidative stress and RPE barrier dysfunction by modulating the SIRT7/YAP/ATP7A signaling pathway and inhibiting cuproptosis. Our findings indicated eriocitrin as a promising natural therapeutic candidate for dry AMD and lay the foundation for developing flavonoid-based anti-cuproptosis strategies.}, }
@article {pmid41362358, year = {2026}, author = {Hinterhuber, L and Birner, K and Schrittwieser, J and Coulibaly, LM and Fuchs, P and Schürer-Waldheim, S and Gumpinger, M and Bogunovic, H and Schmidt-Erfurth, U and Reiter, GS}, title = {Biomarker-Specific Test-Retest Repeatabilities of Microperimetry in Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100978}, pmid = {41362358}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the biomarker-specific intradevice and interdevice repeatability of microperimetry (MP) examinations in patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Cross-sectional study.<br><br>SUBJECTS: Twenty eyes of 20 individuals with nAMD.<br><br>METHODS: Patients underwent 2 consecutive MP assessments on the MP-3 (photopic) and Macular Integrity Assessment ([MAIA], mesopic), each in a randomized sequence. The pointwise sensitivity values were obtained using a 45-stimuli grid and were coregistered with the OCT volumes. Intraretinal fluid (IRF), subretinal fluid, and pigment epithelium detachment (PED) were quantified with deep learning, whereas subretinal hyperreflective material (SHRM) and ellipsoid zone (EZ) loss were manually annotated. Intradevice repeatability was assessed using Bland-Altman plots, coefficient of repeatability (CoR) and intraclass correlation coefficient. Differences in fixation stability and examination time were calculated using mixed-effect models.<br><br>MAIN OUTCOME MEASURES: Intradevice and interdevice repeatability and impact of OCT biomarkers on repeatability.<br><br>RESULTS: Analysis of a total of 3600 stimuli points revealed a CoR of &#xb1;6.37 decibel and &#xb1;5.68 for MP-3 and MAIA, respectively. Presence of OCT biomarkers had a significant impact on repeatability in the MP-3 for IRF (P < 0.0001), SHRM (P = 0.015), and EZ loss (P < 0.0001). Statistically significant results were obtained in the MAIA for IRF (P < 0.0001), PED (P < 0.0001), SHRM (P = 0.0005), and EZ loss (P < 0.0001). Intraclass correlation coefficients revealed excellent intradevice repeatability and good interdevice repeatability, ranging from 0.83 [95% confidence interval [CI]: 0.60-0.91] to 0.94 [95% CI: 0.93-0.94].<br><br>CONCLUSIONS: OCT biomarkers IRF, SHRM, and EZ loss significantly impacted repeatability under photopic and mesopic testing conditions with the MAIA also revealing a statistically significant association for PED. These findings demonstrate the viability of the MP devices to detect functional variability associated with nAMD biomarkers. Repeatability between consecutive MP tests in 2 commonly used MP devices showed good-to-excellent metrics in nAMD, which further supports the use of MP as a viable outcome measure in clinical trials and practice.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41366440, year = {2025}, author = {Soni, T and Gupta, S and Bharany, S and Rehman, AU and Ghoniem, RM and Taye, BM}, title = {Retinal vessel segmentation using multi scale feature attention with MobileNetV2 encoder.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {43369}, pmid = {41366440}, issn = {2045-2322}, mesh = {Humans ; *Retinal Vessels/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Diabetic Retinopathy/diagnostic imaging ; Algorithms ; Macular Degeneration/diagnostic imaging ; Glaucoma/diagnostic imaging ; *Retinal Diseases/diagnostic imaging ; }, abstract = {This work introduces the MSFAUMobileNet model, a complex U-Net structure tailored for retinal blood vessel segmentation, which is a critical process for detecting and monitoring retinal diseases such as diabetic retinopathy, glaucoma, and age-related macular degeneration (AMD). The model uses Multi-Scale Feature Aggregation (MSFA), Residual Connections, and Attention Mechanisms to enhance its segmentation accuracy. Utilizing MobileNetV2 as the encoder, the model is capable of effectively generating 13 bottleneck layers' worth of hierarchical features. Although residual connections and attention mechanisms are useful in improving the segmentation process and guaranteeing the precise outlining of intricate vascular networks, MSFA extracts spatial information at various resolutions. The model was tested on the DRIVE dataset and produced exceptionally high scores with accuracy at 99.99%, Dice coefficient at 99.95%, and Intersection over Union (IoU) at 99.94%. These scores show how efficiently the model separates the complex retinal network, enabling early treatment and detection of retinal disease. MSFAUMobileNet is a good medical image analysis software for real clinical practice owing to its computational speed and precision, particularly in the management of retinal disease.}, }
@article {pmid41369339, year = {2025}, author = {Boey, E and Zaidi, H and Tang, T and Yazdanyar, A}, title = {Role of Angiogenesis in Retinal Diseases and New Advances in Drug Development.}, journal = {Cells}, volume = {14}, number = {23}, pages = {}, pmid = {41369339}, issn = {2073-4409}, mesh = {Humans ; Animals ; *Drug Development/methods ; *Neovascularization, Pathologic/drug therapy ; *Angiogenesis Inhibitors/therapeutic use ; *Retinal Diseases/drug therapy/etiology/pathology ; Macular Degeneration/complications ; Diabetes Complications ; }, abstract = {Dysregulation of angiogenesis can cause a disruption in oxygen and nutrient delivery, resulting in impaired neural retinal function. Understanding the underlying components involved in its pathophysiology is essential to develop new treatments for preserving and restoring vision. The aim of this review is to describe the role of angiogenesis in different retinal and choroidal pathologies and evaluate current and emerging anti-angiogenic therapies for retinopathies. Current research articles, focusing on the latest clinical trials from the last two decades, were used to write this review. We discuss normal angiogenesis, in contrast to pathological angiogenesis, in four diseases: retinal vein occlusion (RVO), age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinopathy of prematurity (ROP). Alongside these diseases, this review discusses relevant anti-angiogenic therapies that have been approved for use and are under active investigation through clinical trials for their safety and efficacy.}, }
@article {pmid41371587, year = {2025}, author = {Chan, KS and Congivaram, HTS and Cuamatzi-Castelan, AS and Lavine, JA and , }, title = {Levodopa and Dopamine Agonists in Neovascular Age-Related Macular Degeneration in the Sight Outcomes Research Collaborative Database.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, pmid = {41371587}, issn = {2468-6530}, support = {K08 EY030923/EY/NEI NIH HHS/United States ; R01 EY034486/EY/NEI NIH HHS/United States ; R01 EY036341/EY/NEI NIH HHS/United States ; R01 EY036826/EY/NEI NIH HHS/United States ; }, abstract = {OBJECTIVE: There is a need for therapies that delay neovascular age-related macular degeneration (AMD) progression. Levodopa (L-DOPA) and dopamine receptor D2 (DRD2) agonists have been proposed as potential agents. We investigated the association between dopamine agonist (DA) exposure and conversion to neovascular AMD using the Sight Outcomes Research Collaborative (SOURCE) database.<br><br>DESIGN: Retrospective cohort analysis from SOURCE.<br><br>PARTICIPANTS: Eyes with nonneovascular AMD at the early or intermediate stage.<br><br>METHODS: We included eyes with a diagnosis of early- or intermediate-stage AMD in 1 eye. We excluded eyes with new exposure to L-DOPA or DRD2 agonist after the time of nonneovascular AMD diagnosis or when a variable of interest was unknown. Propensity score matching was performed, and survival analysis with Cox proportional hazard models was conducted in 3 separate analyses: (1) eyes with no DA exposure versus eyes exposed to any DA; (2) eyes with no DA exposure versus eyes with exposure to DRD2 agonist; and (3) eyes with no DA exposure versus eyes with exposure to L-DOPA.<br><br>MAIN OUTCOME MEASURES: Adjusted hazard ratios of any (1) DA exposure, (2) DRD2 agonist exposure, and (3) L-DOPA exposure in association with conversion to new-onset neovascular AMD.<br><br>RESULTS: There was a 47% reduced likelihood of conversion to neovascular AMD in eyes exposed to L-DOPA compared with those without DA exposure over 5 years (P = 0.028). There was no association between exposure to any DA or exposure to DRD2 agonist and conversion to neovascular AMD.<br><br>CONCLUSIONS: Levodopa exposure was associated with reduced conversion from nonneovascular AMD to new-onset neovascular AMD. A randomized clinical trial to study whether L-DOPA decreases the development of neovascular AMD should be considered.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41372725, year = {2025}, author = {Chang, CP and Hwang, YS and Chou, HD and Yeung, L and Kang, EY and Wu, WC and Lai, CC and Liu, L and Wu, JS and Chen, KJ and Chao, AN and Lin, JY and Chen, YT and Tsai, TH and Ho, MC and Chen, YH}, title = {Use of brolucizumab in refractory neovascular age-related macular degeneration: characteristics and biomarkers of intraocular inflammation from an Asian real-world study.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {41372725}, issn = {1613-2246}, abstract = {PURPOSE: To investigate the clinical features and biomarkers associated with intraocular inflammation (IOI) following brolucizumab treatment in Asian switched neovascular age-related macular degeneration (nAMD) patients.<br><br>STUDY DESIGN: Multi-center, retrospective cohort study.<br><br>METHODS: This study included 109 eyes from 93 nAMD patients switched from other anti-vascular endothelial growth factor (VEGF) agents to brolucizumab (Beovu) without loading. Baseline characteristics, IOI timing, initial symptoms, and risk factors were assessed.<br><br>RESULTS: IOI was observed in 17 eyes from 14 patients, including anterior uveitis (AU, n = 7), intermediate uveitis (IU, n = 5), and panuveitis with or without retinal vasculitis (RV, n = 5). Two eyes were asymptomatic. The median duration for IOI onset was 26 days, with 11 of 17 eyes (82.4%) developing IOI before the third brolucizumab injection. Firth-penalized multivariate Cox regression analysis depicted that the total number of anti-VEGF injections within one year prior to brolucizumab initiation (HR = 1.4, p = 0.009) and retinal angiomatous proliferation (RAP) (HR = 10.9, p = 0.009), may be associated with IOI development. In contrast, baseline macular neovascularization (MNV) size and the presence of retinal pigment epithelial and outer retinal atrophy were not associated with IOI occurrence.<br><br>CONCLUSION: Vigilant examination after the initial brolucizumab injections is critical. Patients with identified risk factors may need meticulous monitor following brolucizumab injections.}, }
@article {pmid41373306, year = {2025}, author = {Virk, A and Qin, H and Shahid, MM and Liu, H and Feng, C and Allison, K}, title = {The Impact of Social Determinants of Health on Ocular Diseases in Western New York: A Comparative Ecological Study of Two U.S. Counties.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {23}, pages = {}, pmid = {41373306}, issn = {2227-9032}, abstract = {Background/Objectives: As the world becomes more connected, it is becoming critical for clinicians to understand other cultures, races, and ethnicities to provide the most effective therapy. A comprehensive understanding of all communities necessitates an examination of the social determinants of health (SDH). Eye diseases and many other conditions are influenced by SDH. To elucidate the impact of SDH on eye health, a comparative ecological analysis of Monroe and Erie Counties in New York State was conducted to identify any differences in SDH and glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy prevalence. Methods: The CDC Vision and Eye Health Surveillance System (VEHSS) was utilized to collect glaucoma, AMD, and diabetic retinopathy data in Monroe and Erie Counties, New York State, and the USA for 2019. The American Community Survey, County Health Rankings, and Neighborhood Atlas data portals were used to collect the county socioeconomic demographics, along with other health statistics. Results: Overall, Erie County had a higher prevalence of AMD (9.56% vs. 6.61%, p < 0.0001) and glaucoma (13.05% vs. 11.71%, p < 0.0001) compared to Monroe County. Erie County also had a higher prevalence of AMD and glaucoma across all races, aside from North American Natives. Erie County also had a greater primary care shortage, with only 1 primary care physician for every 1230 individuals. Although income inequality and poverty were similar between Erie and Monroe Counties, Erie County also has more racial segregation regarding the residential layout (ranked 74 on a scale of 0 to 100, with 100 being the most segregated). Conclusions: The results indicate that Erie County had an increased prevalence of AMD and glaucoma compared to Monroe County in 2019, along with a greater primary care shortage. Although this analysis targeted Western New York, disparities such as lack of primary care access and segregation are prevalent across the US, necessitating widespread action to address these problems.}, }
@article {pmid41373488, year = {2025}, author = {Yang, JY and Kim, Y and An, S and Han, JW and Choi, JS and Park, TK}, title = {Retinal Organoid-Derived Exosomes Reduce CNV Lesion and Restore RPE Integrity in Mouse Laser-Induced Choroidal Neovascularization (CNV) Model.}, journal = {International journal of molecular sciences}, volume = {26}, number = {23}, pages = {}, pmid = {41373488}, issn = {1422-0067}, support = {RS-2025-02217948//National Research Foundation of Korea (NRF)/ ; RS-2024-00452984//National Research Foundation of Korea (NRF)/ ; Soonchunhyang University Research fund//Soonchunhyang University Research fund/ ; }, mesh = {Animals ; *Choroidal Neovascularization/therapy/metabolism/pathology/etiology ; *Retinal Pigment Epithelium/metabolism/pathology ; *Exosomes/metabolism/transplantation ; Mice ; Disease Models, Animal ; Humans ; Mice, Inbred C57BL ; *Organoids/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; *Retina/metabolism ; Induced Pluripotent Stem Cells/metabolism/cytology ; Lasers/adverse effects ; }, abstract = {To address the shortcomings of existing anti-VEGF monotherapy in neovascular age-related macular degeneration (nAMD), we investigated the therapeutic capabilities of exosomes obtained from human induced pluripotent stem cell (hiPSC)-derived retinal organoids in a mouse model of laser-induced choroidal neovascularization (CNV). To evaluate Retinal Organoid-derived exosome (RO-Exo) distribution after intravitreal (IVT) injection, calcein-labeled RO-Exo was observed using confocal microscopy. CNV was induced in C57BL/6 J mice by laser photocoagulation. RO-Exo was isolated from retinal organoids (differentiation days 55-65) and injected 5 days post-laser. Therapeutic efficacy was evaluated on day 12. Vascular leakage and CNV size were assessed by angiography and CD31 immunostaining. We also examined HIF-1α/VEGF-A expression (Western blotting), Retinal Pigment Epithelium (RPE) integrity markers (immunofluorescence staining for α-SMA, fibronectin, and ZO-1), and the activation of the Mitogen-Activated Protein Kinase (MAPK) pathway (phospho-ERK, -p38, -JNK) in CNV lesions. After IVT injection, RO-Exo migrated to the RPE layer, showing high retinotropic distribution. In the CNV model, RO-Exo significantly reduced vascular leakage and CNV size, with greater suppression of HIF-1α and VEGFA expression than aflibercept, the standard-of-care anti-VEGF drug. CD31-positive vasculature was decreased, accompanied by downregulation of fibronectin (a fibrotic marker) and restoration of RPE hexagonality and integrity. Furthermore, RO-Exo inhibited the activation of ERK, P38, and JNK in CNV lesions. Our study results demonstrate that RO-Exo exhibits multi-target therapeutic effects-including anti-angiogenic, anti-fibrotic, and neuroprotective actions-offering a promising alternative to conventional anti-VEGF therapy for nAMD.}, }
@article {pmid41373629, year = {2025}, author = {Mahmud, NM and Paraoan, L and Kamalden, TA}, title = {Thymoquinone Attenuates NF-κβ Signalling Activation in Retinal Pigment Epithelium Cells Under AMD-Mimicking Conditions.}, journal = {International journal of molecular sciences}, volume = {26}, number = {23}, pages = {}, pmid = {41373629}, issn = {1422-0067}, support = {RP033-14HTM//University of Malaya/ ; H-20001-00-E000059//Ministry of Higher Education/ ; }, mesh = {*Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Benzoquinones/pharmacology ; Humans ; *Signal Transduction/drug effects ; *NF-kappa B/metabolism ; *Macular Degeneration/metabolism/pathology/drug therapy ; Tumor Necrosis Factor-alpha/pharmacology ; Oxidative Stress/drug effects ; Cell Line ; Antioxidants/pharmacology ; }, abstract = {Oxidative stress in retinal pigment epithelium (RPE) cells plays a key role in the development of age-related macular degeneration (AMD), a leading cause of vision loss in the elderly. Thymoquinone, a bioactive antioxidant from Nigella sativa, has shown promise in reducing cellular oxidative stress. In AMD, prolonged exposure to oxidative stress may activate the NF-κβ signalling pathway in RPE cells, contributing to chronic inflammation, and its regulation by thymoquinone remains understudied. This study investigates the effects of thymoquinone in TNFα-induced RPE cells exposed to AGEs to mimic ageing conditions relevant for AMD. Gene and protein expression levels of NF-κβ pathway markers (P65, pP65 and Iκβα) were measured using qPCR and Western blotting, and statistical analysis was performed using Student's t-test and one-way ANOVA. Thymoquinone pretreatment at 0.1 µM and 10 µM significantly reduced the expression of these markers in TNFα-stimulated RPE cells. Notably, AGE-exposed cells demonstrated a heightened response to thymoquinone compared to non-AGE-exposed controls. These findings suggest that thymoquinone modulates NF-κβ signalling and may serve as a potential adjuvant therapeutic agent for AMD.}, }
@article {pmid41373691, year = {2025}, author = {Huo, W and Yin, J and Ghose, P and Schafer, JC and Chaum, E and Bhattacharya, S}, title = {Prominin-1 Regulates Retinal Pigment Epithelium Homeostasis: Transcriptomic Insights into Degenerative Mechanisms.}, journal = {International journal of molecular sciences}, volume = {26}, number = {23}, pages = {}, pmid = {41373691}, issn = {1422-0067}, support = {P30 DK058404/DK/NIDDK NIH HHS/United States ; S10 OD021630/OD/NIH HHS/United States ; Unrestricted Departmental Research Grant//Research to Prevent Blindness/ ; Gift//Potocsnak Family/ ; P30 EY008126/EY/NEI NIH HHS/United States ; GF02527//International Retinal Research Foundation/ ; P30 CA068485/CA/NCI NIH HHS/United States ; P30EY08126/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/pathology ; Mice ; *Homeostasis ; *Transcriptome ; *AC133 Antigen/genetics/metabolism ; Mice, Knockout ; Mice, Inbred C57BL ; *Retinal Degeneration/genetics/metabolism/pathology ; Signal Transduction ; Glycoproteins ; }, abstract = {Inherited retinal degenerations (IRDs), driven by pathogenic mutations, often involve primary dysfunction of the retinal pigment epithelium (RPE)-a pathogenic feature shared with atrophic age-related macular degeneration (aAMD), despite aAMD's multifactorial etiology. Prominin-1 (Prom1), traditionally linked to photoreceptor pathology, has an unclear role in RPE homeostasis. We assessed Prom1 expression in C57BL/6J mouse retina sections and RPE flat mounts using immunohistochemistry and generated Prom1-knockout (KO) mouse RPE cells via CRISPR/Cas9. Bulk RNA sequencing with DESeq2 and gene set enrichment analysis (GSEA) revealed Prom1-regulated pathways. Prom1-KO cells exhibited upregulation of Grem1, Slc7a11, Serpine2, Il1r1, and IL33 and downregulation of Ablim1, Cldn2, IGFBP-2, BMP3, and OGN. Hallmark pathway interrogation identified reduced expression of PINK1 (mitophagy) and MerTK (phagocytosis), implicating defects in mitochondrial quality control and outer segment clearance. Enrichment analysis revealed activation of E2F/MYC targets, mTORC1 signaling, oxidative phosphorylation, and TNFα/NF-κB signaling, alongside suppression of apical junctions, bile acid metabolism, and Epithelial-Mesenchymal Transition (EMT) pathways. These findings suggest Prom1 safeguards RPE integrity by modulating stress responses, mitochondrial turnover, phagocytosis, metabolism, and junctional stability. Our study uncovers Prom1-dependent signaling networks, providing mechanistic insights into RPE degeneration relevant to both IRD and aAMD, and highlights potential therapeutic targets for preserving retinal health.}, }
@article {pmid41374087, year = {2025}, author = {Bogdănici, CG and Bogdănici, CM and Pavel, IA and Ganea, CV and Donica, VC and Cărăușu, EM}, title = {Associations Between Nutritional Factors, Obesity and Ocular Diseases: A Narrative Literature Review.}, journal = {Nutrients}, volume = {17}, number = {23}, pages = {}, pmid = {41374087}, issn = {2072-6643}, mesh = {Humans ; *Obesity/complications ; *Eye Diseases/etiology/epidemiology ; *Nutritional Status ; Micronutrients/deficiency ; Risk Factors ; Oxidative Stress ; Macular Degeneration/etiology ; Diet ; }, abstract = {Background: Nutritional imbalances significantly affect ocular physiology, contributing to dry eye disease, cataracts, age-related macular degeneration (AMD), and optic neuropathies. This review summarizes recent evidence on how micronutrient deficiencies and obesity influence eye health. Methods: A narrative search was performed in PubMed, Scopus, and ScienceDirect (last 10 years). Human studies evaluating associations between micronutrients, dietary patterns, obesity, and ocular diseases were included. Out of 843 records, 50 studies met the eligibility criteria. Results: Deficiencies in vitamins A, D, E, C, and B-complex were consistently linked to ocular surface inflammation, retinal oxidative stress, cataracts, AMD, and nutritional optic neuropathies. Altered levels of zinc, copper, selenium, and magnesium were associated with impaired photoreceptor function, glaucoma risk, and retinal degeneration. Obesity emerged as an independent risk factor for AMD, diabetic retinopathy, and glaucoma through mechanisms involving oxidative stress and vascular dysfunction. Evidence from AREDS/AREDS2 supports targeted antioxidant supplementation in intermediate AMD. Conclusions: Adequate nutritional status and metabolic balance play a critical role in preserving ocular health. Early detection and correction of deficiencies may prevent or slow the progression of several eye diseases. Further high-quality trials are needed to define optimal nutritional recommendations.}, }
@article {pmid41374757, year = {2025}, author = {Takahashi, H and Tsuge, T and Kondo, Y and Yanagi, Y and Inoda, S and Morikawa, S and Senoo, Y and Kaburaki, T and Oshika, T and Yamasaki, T}, title = {Intraocular Cytokine Level Prediction from Fundus Images and Optical Coherence Tomography.}, journal = {Sensors (Basel, Switzerland)}, volume = {25}, number = {23}, pages = {}, pmid = {41374757}, issn = {1424-8220}, support = {21K09751//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Aged ; Female ; *Cytokines/metabolism ; Fundus Oculi ; Deep Learning ; Middle Aged ; Retina/diagnostic imaging/metabolism ; Aged, 80 and over ; Aqueous Humor/metabolism ; Neural Networks, Computer ; Macular Degeneration/diagnostic imaging ; Image Processing, Computer-Assisted ; }, abstract = {The relationship between retinal images and intraocular cytokine profiles remains largely unexplored, and no prior work has systematically compared fundus- and OCT-based deep learning models for cytokine prediction. We aimed to predict intraocular cytokine concentrations using color fundus photographs (CFP) and retinal optical coherence tomography (OCT) with deep learning. Our pipeline consisted of image preprocessing, convolutional neural network-based feature extraction, and regression modeling for each cytokine. Deep learning was implemented using AutoGluon, which automatically explored multiple architectures and converged on ResNet18, reflecting the small dataset size. Four approaches were tested: (1) CFP alone, (2) CFP plus demographic/clinical features, (3) OCT alone, and (4) OCT plus these features. Prediction performance was defined as the mean coefficient of determination (R[2]) across 34 cytokines, and differences were evaluated using paired two-tailed t-tests. We used data from 139 patients (152 eyes) and 176 aqueous humor samples. The cohort consisted of 85 males (61%) with a mean age of 73 (SD 9.8). Diseases included 64 exudative age-related macular degeneration, 29 brolucizumab-associated endophthalmitis, 19 cataract surgeries, 15 retinal vein occlusion, and 8 diabetic macular edema. Prediction performance was generally poor, with mean R[2] values below zero across all approaches. The CFP-only model (-0.19) outperformed CFP plus demographics (-24.1; p = 0.0373), and the OCT-only model (-0.18) outperformed OCT plus demographics (-14.7; p = 0.0080). No significant difference was observed between CFP and OCT (p = 0.9281). Notably, VEGF showed low predictability (31st with CFP, 12th with OCT).}, }
@article {pmid41375896, year = {2025}, author = {Kamao, H and Goto, K and Mizukawa, K and Hiraki, R and Miki, A and Kimura, S}, title = {Clinical Characteristics of Patients with Neovascular Age-Related Macular Degeneration and Responses to Anti-VEGF Therapy: Four-Group Stratification Based on Drusen and Punctate Hyperfluorescence.}, journal = {Journal of clinical medicine}, volume = {14}, number = {23}, pages = {}, pmid = {41375896}, issn = {2077-0383}, abstract = {Background/Objectives: Different disease subtypes in neovascular age-related macular degeneration (nAMD) influence treatment burden, yet existing classifications such as the pachychoroid neovasculopathy (PNV)/non-PNV dichotomy may not fully capture clinical heterogeneity. This study aimed to compare the 12-month outcomes of intravitreal aflibercept (IVA) in treatment-naïve patients with unilateral nAMD stratified by the presence or absence of drusen and punctate hyperfluorescence (PH). Methods: This retrospective study included 130 eyes of 130 patients categorized into the Drusen-/PH-, Drusen+/PH-, Drusen-/PH+, and Drusen+/PH+ groups. Their best-corrected visual acuity, retinal thickness, choroidal thickness, number of injections, no-retinal fluid rate during the loading dose regimen, and 12-month retreatment rate following treatment initiation were determined. The primary outcome was 12-month retreatment rate for the four groups, which was determined using Kaplan-Meier curves and log-rank tests. Exploratory metric multidimensional scaling (MDS) was used to visualize the baseline profiles. Results: The 12-month retreatment rates of the groups were significantly different. The Drusen+/PH- group had a higher retreatment rate and required more injections than the Drusen-/PH+ and Drusen+/PH+ groups. The Drusen+/PH- group was older than the Drusen-/PH+ and Drusen-/PH- groups. The Drusen-/PH+ group had a thicker choroid than the Drusen+/PH- group. The MDS results clear separation of the groups, consistent with the older age of the Drusen+/PH- group and the thicker choroid of the Drusen-/PH+ group. Conclusions: nAMD stratified based on drusen and PH differed in age, choroidal thickness, and IVA outcomes. The four-category framework provides greater pathophysiologic and therapeutic resolution than the simple PNV/non-PNV dichotomy and may help anticipate injection demand to guide individualized dosing strategies.}, }
@article {pmid41377064, year = {2026}, author = {Rathi, S and Didangelos, A and Pisarenka, S and Green, R and Zafeiri, S and Emery-Billcliff, P and Patel, N and Whalley, P and Zamiri, P and Tilakaratna, V and Szula, E and Hasan, R and Munye, MM and Unwin, RD and Bishop, PN and Keefe, D and Clark, SJ}, title = {CTx001 for Geographic Atrophy: A Gene Therapy Expressing Soluble, Truncated Complement Receptor 1 (Mini-CR1).}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100980}, pmid = {41377064}, issn = {2666-9145}, abstract = {PURPOSE: Preclinical evaluation of a novel gene therapy called CTx001 for treating geographic atrophy (GA). CTx001 encodes a protein called mini-CR1, which is a soluble fragment of complement receptor 1.<br><br>DESIGN: CTx001 was used in vitro and in vivo to analyze expression and complement-modulating activity. Mini-CR1 was used in vitro to analyze complement-modulating activity, and its ability to cross human Bruch's membrane was evaluated ex vivo.<br><br>PARTICIPANTS: CTx001, which is a self-complementary rAAV2 gene therapy vector expressing mini-CR1. Recombinant mini-CR1 protein, retinal pigment epithelium (RPE) cell lines, serum, human donor Bruch's membrane, and a rat model.<br><br>METHODS: Recombinant mini-CR1 protein was produced in mammalian cells and purified. C3b and C4b breakdown assays were performed. Wieslab assays measured complement regulatory activity in serum. Mini-CR1 binding to C3b was measured using biolayer interferometry. The diffusion of mini-CR1 across human Bruch's membrane was assessed using an Ussing chamber. Retinal pigment epithelium cell lines were transduced with CTx001 to assess expression, including directionality and complement modulatory activity. In vivo efficacy of CTx001 was tested using a rat laser-induced choroidal neovascularization (CNV) model.<br><br>MAIN OUTCOME MEASURES: C3b/iC3b/C4b degradation, inhibition of membrane attack complex (MAC) formation in human serum, mini-CR1 binding to C3b, vector transduction efficiency, protein secretion and localization, and complement inhibition in vivo.<br><br>RESULTS: Mini-CR1 demonstrated potent cofactor activity for factor I-mediated cleavage of C3b, iC3b, and C4b; therefore, it inhibits both the alternative and classical complement pathways. It inhibited complement activation with an IC50 of 125 nM in human serum. Mini-CR1 demonstrated high-affinity binding to C3b. The mini-CR1 protein diffused across human Bruch's membrane and retained activity postdiffusion. CTx001-transduced RPE cells secreted mini-CR1 apically and basolaterally, leading to reduced C3 activation and MAC deposition. In rats, subretinal administration of CTx001 resulted in a 75.4% reduction in MAC deposition in CNV lesions (P < 0.01).<br><br>CONCLUSIONS: CTx001 is a potent inhibitor of complement. It efficiently transduces RPE cells, resulting in apical and basolateral secretion and crosses Bruch's membrane, so it is expected to deliver mini-CR1 to the retina and choroid. These findings support its further development as a 1-time gene therapy for addressing complement overactivation in GA.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41377065, year = {2026}, author = {Fragiotta, S and Querques, G and Polito, MS and Costanzo, E and Rossi, T and Varano, M and Pannarale, FM and Sakurada, Y and Parravano, M}, title = {Structural Biomarkers Influencing Drusenoid Pigment Epithelial Detachment Lifecycle and the Development of Late Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100977}, pmid = {41377065}, issn = {2666-9145}, abstract = {PURPOSE: Drusenoid pigment epithelial detachment (dPED) is a notable phenotype in age-related macular degeneration (AMD), often evolving into macular complications such as macular neovascularization (MNV) and geographic atrophy (GA). The aim of this study was to identify potential prognostic biomarkers associated with the development of both MNV and GA.<br><br>DESIGN: A retrospective cohort study.<br><br>PARTICIPANTS: Patients with dPED in the setting of AMD.<br><br>METHODS: This observational study analyzed OCT biomarkers to assess the dPED lifecycle and identify features predictive of macular complications. Seventy-one eyes with dPED from 51 patients were reviewed over an average follow-up of 37.5 &#xb1; 17.6 months (range: 24-104), examining structural alterations via multimodal imaging, which included color fundus photography, fundus autofluorescence, and OCT, while fluorescein angiography, indocyanine green angiography, or both were performed as needed. Associations between baseline biomarkers and macular complications were assessed using Cox proportional hazard models with a frailty term to account for intereye correlation. The Fine-Gray model was used to account for competing risk analysis.<br><br>MAIN OUTCOME MEASURES: Incidence and time to development of macular complications (MNV and GA) and their associations with baseline OCT biomarkers (cuticular drusen, hyperreflective foci, external limiting membrane/ellipsoid zone integrity, and retinal pigment epithelium [RPE] hypertransmission), modeled with frailty-adjusted Cox proportional hazards and Fine-Gray competing risks; secondary measures included dPED lifecycle features (collapse, timing) and morphometrics (height, width, volume).<br><br>RESULTS: Key findings included a 39.4% incidence of dPED collapse, with 60.7% of cases progressing to complications postcollapse. In the multivariable Cox proportional model, cuticular drusen (hazard ratio [HR]: 3.8, 95% confidence interval [CI]: 1.62-9.2, P = 0.002) and the presence of hyperreflective foci (HRF) at baseline (HR: 6.6, 95% CI: 1.97-22, P = 0.02) represented the main prognostic indicators of macular complications. In the Fine-Gray competing risks analysis, cuticular drusen remained a significant independent predictor (subdistribution hazard ratio [sHR] = 18.1, 95% CI: 1.89-174, P = 0.01) of MNV development, while HRF (sHR = 6.69, 95% CI: 1.98-22.61, P = 0.002) and external limiting membrane disruption at baseline (sHR = 3.69, 95% CI: 1.03-13.14, P = 0.044) were factors significantly associated with increased GA risk.<br><br>CONCLUSIONS: These results underscore the prognostic relevance of specific imaging biomarkers in dPED. Recognizing these features early may support timely treatment and help prevent irreversible photoreceptor and RPE damage.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41377141, year = {2025}, author = {Zhang, LL and Yu, JM and Fan, ZX and Xie, WQ and Zou, L and Sheng, F}, title = {Regulated cell death in age-related macular degeneration: Regulatory mechanisms and therapeutic potential.}, journal = {Journal of pharmaceutical analysis}, volume = {15}, number = {11}, pages = {101285}, pmid = {41377141}, issn = {2214-0883}, abstract = {Age-related macular degeneration (AMD) represents a predominant cause of blindness among older adults, with limited therapeutic options currently available. Oxidative stress, inflammation, and retinal pigment epithelium injury are recognized as key contributors to the pathogenesis of AMD. Regulated cell death plays a pivotal role in mediating cellular responses to stress, maintaining tissue homeostasis, and contributing to disease progression. Recent research has elucidated several regulated cell death pathways-such as apoptosis, ferroptosis, pyroptosis, necroptosis, and autophagy-that may contribute to the progression of AMD owing to cell death in the retinal pigment epithelium. These discoveries open new avenues for therapeutic interventions in patients with AMD. In this review, we provide a comprehensive summary and analysis of the latest advancements regarding the relationship between regulated cell death and AMD. Moreover, we examined the therapeutic potential of targeting regulated cell death pathways for the treatment and prevention of AMD, highlighting their roles as promising targets for future therapeutic strategies.}, }
@article {pmid41378371, year = {2025}, author = {Meng, N and Xia, L and Gong, Y and Shi, C and Lu, P}, title = {A Bibliometric Analysis of Research Progress on Age-Related Macular Degeneration and Autophagy From 2010 to 2024.}, journal = {Journal of ophthalmology}, volume = {2025}, number = {}, pages = {6670966}, pmid = {41378371}, issn = {2090-004X}, abstract = {BACKGROUND: Autophagy regulates intracellular metabolism and is crucial in the development of age-related macular degeneration (AMD). Despite the growing number of studies on AMD and autophagy in recent years, bibliometric analyses in this field remain scarce. Therefore, a bibliometric analysis was applied to explore the research trends and hot spots of this field in this study.<br><br>METHODS: We collected publications on autophagy in AMD from the MEDLINE database, covering the period from January 2010 to October 2024. The "bibliometrix" R package (Version R 4.2.3) was utilized for bibliometric analysis, and WPS Excel, PowerPoint, and Word (12.1.0.18276) were used to manage data and create related tables.<br><br>RESULTS: A total of 349 articles were included. The amount of literature was on the rise from 2010 to 2024. China leads in article quantity, whereas the United States holds the most influence. Although Finland ranks the third position in publication volume, followed by China and the United States, Finland led research in this field, with the University of Eastern Finland being the most active and prolific institution and Kaarniranta Kai as the most productive and influential author. International Journal of Molecular Sciences and Autophagy is the journal with the most volume. The three most referenced studies primarily examine the interplay between inflammation, oxidative stress, and autophagy in retinal pigment epithelial cells. The analysis for keywords found that mitophagy has also received increasing attention in this field.<br><br>CONCLUSIONS: This bibliometric analysis identifies current research hotspots in autophagy related to AMD and informs future research directions. Future trends in this field may involve identifying and developing novel autophagy-targeted therapies for the prevention and treatment of AMD.}, }
@article {pmid41381091, year = {2025}, author = {Shi, Q and Zhan, D and Wang, W and Wu, X and Sheng, S and Wang, Y}, title = {Causal associations between cognitive impairments and retinal diseases: A two-sample Mendelian randomization study.}, journal = {The Journal of international medical research}, volume = {53}, number = {12}, pages = {3000605251404265}, pmid = {41381091}, issn = {1473-2300}, mesh = {Humans ; *Mendelian Randomization Analysis ; Genome-Wide Association Study ; *Retinal Diseases/genetics/complications ; *Alzheimer Disease/genetics ; *Cognitive Dysfunction/genetics ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Macular Degeneration/genetics ; Dementia, Vascular/genetics ; *Lewy Body Disease/genetics ; }, abstract = {ObjectiveThis study employed a bidirectional two-sample Mendelian randomization approach to investigate the causal links between Alzheimer's disease, Lewy body dementia, vascular dementia, and various retinal diseases.MethodsSummary data from large-scale genome-wide association studies of European ancestry were used to select genetic variants as instrumental variables. Causal estimates were derived using the inverse variance-weighted method, complemented by Mendelian randomization-Egger, weighted median, and weighted mode analyses to ensure robustness.ResultsGenetically predicted Alzheimer's disease was associated with a reduced risk of disorders of the choroid and retina (odds ratio = 0.93, 95% confidence interval: 0.88-0.98), retinal detachments and breaks (odds ratio = 0.90, 95% confidence interval: 0.84-0.97), and retinal detachment with retinal break (odds ratio = 0.84, 95% confidence interval: 0.74-0.95). Lewy body dementia was negatively associated with age-related macular degeneration (odds ratio = 0.88, 95% confidence interval: 0.79-0.98), disorders of the choroid and retina (odds ratio = 0.96, 95% confidence interval: 0.93-0.99), and degeneration of the macula (odds ratio = 0.93, 95% confidence interval: 0.88-0.98). Vascular dementia showed negative associations with age-related macular degeneration (odds ratio = 0.93, 95% confidence interval: 0.87-0.99) and degeneration of the macula (odds ratio = 0.96, 95% confidence interval: 0.93-0.99). Conversely, reverse Mendelian randomization indicated that genetic liability to macular degeneration and choroidal/retinal disorders was causally associated with cognitive performance and a reduced risk of Alzheimer's disease.ConclusionsFindings support inverse causal relationships in which specific dementias may reduce retinal disease risk and vice versa, suggesting complex shared biological mechanisms.}, }
@article {pmid41383281, year = {2025}, author = {Cheng, S and Ma, Y and Huang, F and Luo, R and Han, L and He, L and Yuan, ZX}, title = {Mesenchymal Stem Cell-Derived Exosomes for Ocular Diseases: Therapeutic Mechanisms and Clinical Perspectives.}, journal = {International journal of nanomedicine}, volume = {20}, number = {}, pages = {14521-14550}, pmid = {41383281}, issn = {1178-2013}, mesh = {*Exosomes/chemistry/transplantation ; Humans ; *Mesenchymal Stem Cells/cytology/metabolism ; *Eye Diseases/therapy ; Animals ; Drug Delivery Systems/methods ; }, abstract = {Ocular diseases represent a major and increasing public health concern. Although current treatment options are available, the management of complex cases, such as corneal diseases, diabetic retinopathy, glaucoma, age-related macular degeneration, and uveitis, remains inadequate. Recent studies have demonstrated that mesenchymal stem cell-derived exosomes (MSC-Exos), obtained from bone marrow, adipose tissue, and umbilical cord, have emerged as a promising cell-free therapeutic platform for various ocular diseases. These nanovesicles can be delivered via systems such as topical eye drops and intravitreal injection, targeting ocular tissues to exert anti-inflammatory, anti-apoptotic, and tissue-repairing effects. This review systematically synthesizes recent advances and the molecular mechanisms underlying the use of MSC-Exos in treating ocular diseases. Moreover, it provides an in-depth discussion of the challenges in the clinical application of MSC-Exos in ophthalmology, including standardized production, dosage optimization, delivery system improvement, and targeting enhancement, and proposes engineered targeting strategies based on surface modification and carrier optimization. Overall, this work establishes a rigorous framework for advancing MSC-Exos from experimental models to clinical implementation, offering novel therapeutic strategies through these innovative biopharmaceuticals for previously untreatable ocular conditions.}, }
@article {pmid41383834, year = {2025}, author = {Li, MM and Zhang, H and Cen, ZM and Su, DW}, title = {Management of submacular hemorrhage secondary to age-related macular degeneration with vitrectomy and subretinal tissue plasminogen activator injection: Outcomes and prognostic factors.}, journal = {SAGE open medicine}, volume = {13}, number = {}, pages = {20503121251403361}, pmid = {41383834}, issn = {2050-3121}, abstract = {PURPOSE: To evaluate the efficacy of pars plana vitrectomy combined with subretinal tissue plasminogen activator injection, pneumatic displacement, and intraoperative intravitreal antivascular endothelial growth factor therapy for treating submacular hemorrhage secondary to polypoidal choroidal vasculopathy or neovascular age-related macular degeneration.<br><br>METHODS: This retrospective study enrolled 28 patients who were diagnosed with submacular hemorrhage secondary to polypoidal choroidal vasculopathy or neovascular age-related macular degeneration, all of whom received a minimum follow-up period of 6&#x2009;months. Key preoperative parameters, such as submacular hemorrhage height and diameter, tissue plasminogen activator dosage, and hemorrhage duration, were documented. Postoperative outcomes evaluated included the degree of submacular hemorrhage displacement, visual acuity changes, incidence of complications, and the requirement for additional intravitreal antivascular endothelial growth factor injections during the follow-up period.<br><br>RESULTS: The mean patient age was 66.71&#x2009;&#xb1;&#x2009;10.62&#x2009;years. The mean visual acuity progressively improved from a preoperative logMAR of 1.57&#x2009;&#xb1;&#x2009;0.64 to 1.26&#x2009;&#xb1;&#x2009;0.67, 1.15&#x2009;&#xb1;&#x2009;0.59, 1.14&#x2009;&#xb1;&#x2009;0.55, and 1.12&#x2009;&#xb1;&#x2009;0.56 at postoperative months 1, 3, and 6, respectively. Complete hemorrhage displacement was achieved in 85.71% (24/28) of cases. Preoperative hemorrhage duration was significantly negatively correlated with postoperative best-corrected visual acuity at 1&#x2009;month (r&#x2009;=&#x2009;0.46; p&#x2009;=&#x2009;0.013), 3&#x2009;months (r&#x2009;=&#x2009;0.42; p&#x2009;=&#x2009;0.028), 6&#x2009;months (r&#x2009;=&#x2009;0.41; p&#x2009;=&#x2009;0.032), and final follow-up (r&#x2009;=&#x2009;0.38; p&#x2009;=&#x2009;0.047).<br><br>CONCLUSIONS: Pars plana vitrectomy with tissue plasminogen activator subretinal injection, pneumatic displacement, and intraoperative vitreous antivascular endothelial growth factor injection represents a safe and effective approach for managing submacular hemorrhage secondary to polypoidal choroidal vasculopathy and neovascular age-related macular degeneration. The duration of submacular hemorrhage emerges as the most critical prognostic factor for final visual outcomes. Patients with hemorrhage duration exceeding 14&#x2009;days demonstrate a significantly reduced likelihood of achieving favorable visual outcomes.}, }
@article {pmid41384795, year = {2025}, author = {Jonas, JB and Panda-Jonas, S and Xu, J and Jonas, RA and Wang, YX}, title = {Changes of the Optic Nerve Head and Macula in High Myopia in a 10-Year Follow-Up: The Beijing Eye Study.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {39}, pmid = {41384795}, issn = {1552-5783}, mesh = {Humans ; *Optic Disk/pathology ; Male ; Female ; Follow-Up Studies ; Aged ; Tomography, Optical Coherence/methods ; *Macula Lutea/pathology ; Middle Aged ; *Myopia, Degenerative/epidemiology/diagnosis ; Beijing/epidemiology ; Incidence ; Disease Progression ; China/epidemiology ; *Myopia ; }, abstract = {PURPOSE: To assess the incidence of myopic changes of the optic nerve head and macula in highly myopic eyes.<br><br>METHODS: All highly myopic eyes (axial length >26.0 mm or refractive error &#x2264;-6.0 diopters) examined in the longitudinal population-based Beijing Eye Study 2001/2011 underwent fundus photography (2001/2011) and optic coherence tomography (2011).<br><br>RESULTS: The study included 89 highly myopic eyes (patient age, 65.0 &#xb1; 9.8 years). Progressive macula changes were detected in 63 of 89 eyes (71%), including increases in fundus tessellation (n = 61 [69%]), diffuse chorioretinal atrophy (n = 15 [17%]), lacquer cracks (n = 12 [14%]), patchy atrophies (n = 8 [9%]), macular atrophy (n = 6 [7%]), and overall myopic macular degeneration stage (n = 23 [26%]). Without considering fundus tessellation changes, any macular change was detected in 31 of 80 eyes (35%). Progressive optic nerve head changes were found in 69 of 89 eyes (78%), including optic disc diminution (n = 28 [32%]), disc enlargement (n = 13 [15%]), change in disc shape (n = 36 [40%]), enlargement in beta/gamma zone (n = 68 [76%]) or delta zone (n = 22 [25%]), and lengthening of parapapillary retinal vessels (n = 47 [53%]). Any type of progression of the macula and/or optic nerve head was detected in 74 of 89 eyes (83%), and without considering fundus tessellation changes in 70 of 89 eyes (79%). Higher incidence of any macular change (fundus tessellation change not considered) and of optic nerve head changes correlated with longer axial length (odds ratio [OR], 2.15 [P < 0.001] and OR, 2.20 [P = 0.02], respectively) and older age (OR, 1.11 [P = 0.001] and OR, 1.08 [P = 0.02], respectively). Optic disc diminution correlated with disc shape change from a more circular to an elliptical shape (OR, 37.9; 95% confidence interval, 9.7-148.0; P < 0.001) and in all eyes with beta/gamma zone enlargement.<br><br>CONCLUSIONS: Over the 10-year follow-up, >75% of highly myopic eyes showed progressive myopic changes of the optic nerve head and macula.}, }
@article {pmid41385093, year = {2026}, author = {Lingardo, S and Sacconi, R and Balduzzi, E and Beretta, F and Menean, M and Querques, G}, title = {The spectrum of pachychoroid neovasculopathy.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {3}, pages = {617-632}, pmid = {41385093}, issn = {1435-702X}, mesh = {Humans ; *Choroidal Neovascularization/diagnosis ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Choroid/blood supply/pathology ; *Central Serous Chorioretinopathy/diagnosis ; Fundus Oculi ; Multimodal Imaging/methods ; *Retinal Pigment Epithelium/pathology ; }, abstract = {PURPOSE: To provide a comprehensive overview of pachychoroid neovasculopathy (PNV), focusing on its current understanding in terms of clinical behavior, multimodal retinal imaging characteristics, and treatment.<br><br>METHODS: A narrative review of the literature on PNV was conducted using the following keywords: pachychoroid neovasculopathy, pachychoroid, pachychoroid disease spectrum, pachychoroid pigment epitheliopathy, central serous chorioretinopathy, polypoidal choroidal vasculopathy.<br><br>RESULTS: PNV is a clinical entity within the pachychoroid disease spectrum, typically presenting as type 1 choroidal neovascularization (CNV). It may arise either directly from pachychoroid pigment epitheliopathy (PPE) without prior central serous chorioretinopathy (CSC) or from chronic CSC. PNV is frequently misdiagnosed as neovascular age-related macular degeneration (nAMD), particularly in patients older than 50 years, making multimodal retinal imaging essential for distinguishing its characteristic features from CNV secondary to AMD. The therapeutic management of PNV depends on its underlying initial condition and differs from the treatment strategy for CNV secondary to AMD.<br><br>CONCLUSIONS: Recognizing PNV as a distinct entity is crucial for optimizing diagnosis and treatment. Multimodal retinal imaging is essential to ensure appropriate therapeutic management.<br><br>KEY MESSAGES: What is known? Pachychoroid neovasculopathy (PNV) is a distinct clinical entity within the pachychoroid disease spectrum, frequently misdiagnosed as neovascular age-related macular degeneration (nAMD). What is new? PNV includes subtypes arising from pachychoroid pigment epitheliopathy or chronic central serous chorioretinopathy, which differ in treatment responses and strategies. Multimodal retinal imaging plays an essential role in differentiating PNV from nAMD. The lack of standardized diagnostic criteria for PNV highlights the need for shared definitions to improve PNV classification, patient stratification, and treatment selection.}, }
@article {pmid41385282, year = {2025}, author = {Sagiv, RG and Rosenblatt, HN and Zamir, E and Altarescu, A and Ben-Zaken, SG and Rotfogel, Z}, title = {Efficiency of anti-vascular endothelial growth factor drug switch in patients who did not respond to a series of bevacizumab injections.}, journal = {Indian journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.4103/IJO.IJO_1740_25}, pmid = {41385282}, issn = {1998-3689}, abstract = {PURPOSE: To assess the effectiveness of switching anti-vascular endothelial growth factor (VEGF) agents in eyes with retinal pathologies that poorly respond to intravitreal bevacizumab injections.<br><br>METHODS: We compared central macular thickness (CMT) and VA between eyes with suboptimal responses to at least three bevacizumab injections that either continued with bevacizumab or switched to aflibercept or ranibizumab. Eyes were categorized into group D (DME), group N (neovascular age-related macular degeneration [nAMD]), and group A - all eyes (D and N plus eyes with retinal vein occlusion (RVO) or pseudophakic central macular edema [PCME]). Each group was further divided into those continuing bevacizumab (D1, N1, A1) or switching to aflibercept or ranibizumab (D2, N2, A2).<br><br>RESULTS: A total of 21 eyes were included in group D (8 in D1 and 13 in D2), 28 in group N (14 in N1 and 14 in N2), and 59 eyes in group A (25 in A1 and 34 in A2). In all eyes with treatment shift, CMT decreased: 38.5 (SD: 46.2), 92.6 (SD: 106.8), and 82.1 (SD: 115.6) microns in D2, N2, and A2, respectively. CMT difference was statistically significant between N1 versus N2 and between A1 versus A2 (P = 0.025 and 0.004, respectively). No significant difference in VA was observed.<br><br>CONCLUSION: Switching anti-VEGF agents appears anatomically beneficial in nonresponding eyes. Notably, the inclusion of a control group continuing bevacizumab despite poor response allows for a more reliable evaluation of treatment efficacy, addressing a key limitation of prior studies and contributing to the evidence-based rationale for agent switching.}, }
@article {pmid41388185, year = {2026}, author = {Rinaldi, M and Cennamo, G and Concilio, M and Corvino, G and Riccardo, A and Nubi, R and Costagliola, C}, title = {Aflibercept 8 mg in Neovascular AMD-A Fast-Drying Anti-VEGF Drug: A Prospective Morpho-Functional Pilot Study.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {2}, pages = {677-687}, pmid = {41388185}, issn = {2193-8245}, abstract = {INTRODUCTION: This study investigated early anatomical and functional outcomes in patients with treatment-naïve neovascular age-related macular degeneration (nAMD) treated with 8 mg aflibercept compared to patients treated with the standard dose of 2 mg aflibercept using spectral domain optical coherence tomography (SD-OCT), microperimetry, and macular pigment optical density (MPOD) after loading phase administration.<br><br>METHODS: This prospective, observational study included 30 eyes of 30 patients (mean age 70&#x2009;&#xb1;&#x2009;5&#xa0;years; 15 male, 15 female) recruited between January and June 2025 at the Eye Clinic of the University of Naples "Federico II". Patients were assigned to one of two age- and gender-matched groups receiving intravitreal injections of aflibercept at the dose of 2&#xa0;mg (group&#xa0;A) or 8&#xa0;mg (group&#xa0;B). All patients underwent complete ophthalmological examination, SD-OCT, OCT angiography, microperimetry, fixation stability, and measurement of MPOD at baseline, month&#xa0;2, and month&#xa0;4.<br><br>RESULTS: Group&#xa0;B showed an improvement in all parameters, compared to group&#xa0;A, in particular: a greater reduction in central macular thickness (CMT) (p&#x2009;=&#x2009;0.008), an improvement in best-corrected visual acuity (BCVA) (p&#x2009;=&#x2009;0.012), increased retinal sensitivity (p&#x2009;=&#x2009;0.015), increased MPOD (p&#x2009;=&#x2009;0.027), and reduced bivariate contour ellipse area (BCEA) (p&#x2009;=&#x2009;0.039). Group&#xa0;B showed a faster drying rate during the first 2&#xa0;months (70 vs. 40&#xa0;&#x3bc;m/month) and overall at month&#xa0;4.<br><br>CONCLUSIONS: Intravitreal injections of aflibercept 8&#xa0;mg resulted in significant short-term anatomical and functional improvement compared to standard dose and thus appear to be an effective option to achieve faster results in nAMD. MPOD can be considered as a potential new biomarker of macular health to study retinal functional response.<br><br>TRIAL REGISTRATION: The research protocol was registered on ClinicalTrials.gov (NCT07074054).}, }
@article {pmid41388211, year = {2025}, author = {Srivastava, V and Yadav, P and Yadav, A and Parashar, P}, title = {Artificial Intelligence in Ocular Drug Delivery: Precision Drug Delivery's New Horizon.}, journal = {AAPS PharmSciTech}, volume = {27}, number = {1}, pages = {55}, pmid = {41388211}, issn = {1530-9932}, mesh = {Humans ; *Artificial Intelligence/trends ; *Drug Delivery Systems/methods ; *Eye Diseases/drug therapy ; Precision Medicine/methods ; Administration, Ophthalmic ; Animals ; Machine Learning ; Eye/drug effects/metabolism ; }, abstract = {BACKGROUND: Artificial intelligence is emerging as a transformative force in pharmaceutical sciences by enabling data-driven decision-making, automation, and predictive modeling. In ocular drug delivery, where therapeutic efficacy is hindered by complex anatomical and physiological barriers, AI presents significant opportunities to overcome these challenges. Its ability to optimize drug combinations, design smart delivery systems, and personalize therapies underscores its relevance in advancing ophthalmic care.<br><br>AREA COVERED: This review explores the intersection of AI and ophthalmic therapeutics, highlighting its role in formulation design, disease prediction, patient-specific treatment strategies, and smart delivery platforms, and outlines future research directions to bridge current gaps. Machine learning is advancing ocular drug delivery by optimizing nano-formulations, predicting release kinetics, and modeling pharmacokinetics. Alongside AI-powered diagnostics and integration with biosensors, contact lenses, and implants, these innovations are driving real-time monitoring and truly personalized ocular therapy and early detection and monitoring ocular diseases such as glaucoma, diabetic retinopathy, and macular degeneration. Challenges including limited clinical validation, model interpretability, data security, and regulatory complexities are highlighted. Furthermore, current gaps such as the lack of comprehensive studies on AI-assisted stimuli-responsive carriers and integration with patient-specific data are identified. Future directions emphasize explainable AI, smart biomaterials, and robust ethical-regulatory frameworks for clinical translation.<br><br>EXPERT OPINION: AI integration in ocular therapeutics marks a paradigm shift toward precision drug delivery and personalized care. Despite progress, challenges in explainability, regulation, and validation remain, yet innovations in AI-driven nanocarriers, smart systems, and real-time monitoring hold the potential to revolutionize ocular pharmacology overcoming limitations of conventional therapies.}, }
@article {pmid41389973, year = {2026}, author = {Xiong, X and Li, Q and Zhang, Y and Liu, P and Pan, Y and Song, Q}, title = {Exploring copper metabolism and cuproptosis, and their implications in ocular diseases.}, journal = {European journal of pharmacology}, volume = {1011}, number = {}, pages = {178472}, doi = {10.1016/j.ejphar.2025.178472}, pmid = {41389973}, issn = {1879-0712}, mesh = {Humans ; *Copper/metabolism ; Animals ; *Eye Diseases/metabolism/pathology ; Mitochondria/metabolism/pathology/drug effects ; Oxidative Stress ; }, abstract = {Copper is a vital trace element for all living organisms and plays an important role in numerous physiological functions, including the formation of mitochondrial respiratory chain complexes, antioxidant defense, and signal transduction. However, excess copper can cause cellular toxicity and initiate a form of cell death that is characterized by the aggregation of lipoylated proteins and a reduction in Fe-S cluster proteins. This series of events can culminate in mitochondrial process of respiratory dysfunction known as cuproptosis. Excessive copper can also inhibit the ubiquitin-proteasome system, which results in the accumulation of harmful proteins and a vicious cycle of Fenton and Haber-Weiss reactions that trigger oxidative stress and cellular damage. The eye, particularly the retina, is one of the most energy-dependent tissues in the body and has an extraordinary dependence on mitochondrial function. Dysregulated copper-ion levels can lead to mitochondrial dysfunction, which can cause various ocular diseases, including uveal melanoma, age-related macular degeneration, and diabetic retinopathy. Therefore, the relationship between copper and ocular diseases provides promising research opportunities. This review summarizes recent research findings on copper metabolism, cuproptosis, and their implications in ocular diseases. It also introduces potential therapeutic approaches for related diseases, including copper chelation therapy, copper ionophores and nanomedicine, and genetic treatment strategies.}, }
@article {pmid41390041, year = {2026}, author = {Lin, Z and Deng, H and Wang, S and Wang, Z and Yang, G and Huang, K}, title = {Apoferritin-conjugated melanin nanoparticles rescue photoreceptor degeneration via dual iron chelation and ROS scavenging in dry AMD therapy.}, journal = {International journal of biological macromolecules}, volume = {337}, number = {Pt 2}, pages = {149586}, doi = {10.1016/j.ijbiomac.2025.149586}, pmid = {41390041}, issn = {1879-0003}, mesh = {Animals ; *Nanoparticles/chemistry ; Mice ; *Reactive Oxygen Species/metabolism ; *Apoferritins/chemistry/pharmacology ; *Iron Chelating Agents/pharmacology/chemistry ; *Macular Degeneration/drug therapy/metabolism/pathology ; *Melanins/chemistry/pharmacology ; Oxidative Stress/drug effects ; Disease Models, Animal ; Humans ; Ferroptosis/drug effects ; Antioxidants/pharmacology ; Iron/metabolism ; Iodates ; *Free Radical Scavengers/pharmacology/chemistry ; Mice, Inbred C57BL ; }, abstract = {Oxidative stress in the retina and dysregulation of iron homeostasis are established as central pathogenic mechanisms in dry age-related macular degeneration (dAMD). Nonetheless, effective clinical treatments to counteract retinal degeneration in this condition are still absent. Our research began with developing a single-cell transcriptome profile of retinal tissue subjected to sodium iodate (NaIO3)-induced oxidative injury. This analysis identified ferroptosis in photoreceptor cells as a key driver of disease progression. Apoferritin (AFn) is a hollow, spherical protein nanocage formed by 24 self-assembled subunits, enabling supramolecular iron storage through ferroxidase-mediated mineralization while providing dynamic iron buffering and antioxidant protection in biological systems. We then engineered a biomimetic nanoparticle, AFn-MNP, by combining Afn with melanin nanoparticles (MNP). AFn-MNP displayed significant ferrous ion-chelating ability and antioxidant activity, effectively mitigating NaIO3-triggered photoreceptor ferroptosis in vitro and in vivo. Significantly, a single intravitreal injection of 10 μg AFn-MNP effectively counteracted visual impairment in NaIO3-induced dAMD model mice, reversed damage to photoreceptor synaptic terminals, and significantly alleviated photoreceptor degeneration and retinal oxidative injury. In summary, our results indicate that AFn-MNP holds significant promise as a novel therapy for dAMD and other retinal degenerative diseases linked to oxidative damage and impaired iron metabolism.}, }
@article {pmid41390091, year = {2026}, author = {Tao, L and He, D and Chen, Y and Cai, P and Yang, K and Wu, J and Liao, C and Chen, J and Wu, Y}, title = {Gene editing of JNK alleviates sodium iodate-induced retinal degeneration in mice.}, journal = {Life sciences}, volume = {385}, number = {}, pages = {124145}, doi = {10.1016/j.lfs.2025.124145}, pmid = {41390091}, issn = {1879-0631}, mesh = {Animals ; *Iodates/toxicity ; Mice ; *Retinal Degeneration/chemically induced/genetics/therapy ; Mice, Inbred C57BL ; *Gene Editing/methods ; Electroretinography ; Disease Models, Animal ; Retinal Pigment Epithelium/pathology/metabolism ; Tomography, Optical Coherence ; Mice, Knockout ; Male ; Retina/pathology ; Macular Degeneration/genetics/chemically induced ; *Mitogen-Activated Protein Kinase 9/genetics ; }, abstract = {PURPOSE: Dry age-related macular degeneration (dry AMD) still lacks effective treatment strategies due to its complex mechanisms. Although c-Jun N-terminal kinase (JNK) signaling has been reported to be associated with retinal degeneration in dry AMD, the efficacy of JNK gene editing in treating dry AMD remains unclear. This study aims to investigate the protective potential of JNK genetic inhibition in a sodium iodate (SI)-induced retinal degeneration model that recapitulates the key features of human dry AMD.<br><br>METHODS: A retinal degeneration model was constructed from a single intraperitoneal injection of 50&#xa0;mg/kg body weight SI into C57BL/6&#xa0;J mice. The retina was examined by electroretinography (ERG), fundus imaging, optical coherence tomography (OCT), hematoxylin and eosin (H&amp;E) staining, and whole-mount ZO-1 immunofluorescence staining. Protein levels were determined using Western blotting. Jnk1[+/-]Jnk2[-/-] mice were obtained by crossbreeding Jnk2[-/-] mice with Jnk1[+/-] mice.<br><br>RESULTS: In C57BL/6&#xa0;J mice, SI robustly activated JNK signaling in the retinal pigment epithelium (RPE)/choroid, triggering a parallel loss of retinal function and structural integrity. By contrast, Jnk1[+/-]Jnk2[-/-] mice were largely protected: both the SI-evoked JNK response in the RPE/choroid and the ensuing retinal degeneration were markedly attenuated.<br><br>CONCLUSIONS: Gene editing of JNK is effective in ameliorating SI-driven retinal injury and may serve as a promising therapeutic avenue for dry AMD.}, }
@article {pmid41390463, year = {2025}, author = {Dastgheib, KA}, title = {Histopathologic evidence of VEGF in early neovascular AMD: from a 1992 hypothesis to a 1994 discovery - a historical perspective.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {137}, pmid = {41390463}, issn = {2056-9920}, abstract = {BACKGROUND: In the early1990s, neovascular age-related macular degeneration (nAMD) was the leading cause of irreversible vision loss in older adults, yet its molecular basis remained unknown. In 1992, a hypothesis was proposed in which localized hypoxia could trigger vascular endothelial growth factor (VEGF)-mediated choroidal neovascularization in nAMD. Although hypoxia was recognized in ischemic retinopathies, nAMD was not considered a hypoxia-mediated retinal vascular disease.<br><br>MAIN BODY: In 1994, this hypothesis was tested using antigen retrieval immunohistochemistry on paraffin-embedded whole human eye sections with early nAMD. The study demonstrated strong VEGF immunoreactivity in the retinal pigment epithelium in the macular area but not in normal control eyes, providing the first direct histopathologic evidence of VEGF expression at the site of disease in intact human eyes with early nAMD. Until that point, the role of VEGF in ischemic retinopathies was being uncovered, but its involvement in early-stage nAMD had not yet been demonstrated.<br><br>CONCLUSION: The 1992-1994 work established both the hypothesis and the first direct tissue evidence linking VEGF to early nAMD. This discovery, made just over a decade before the advent of anti-VEGF therapy, anticipated one of ophthalmology's most transformative achievements, preserving vision for millions worldwide.}, }
@article {pmid41392555, year = {2026}, author = {Andreev, V and Yakovleva, M and Kostyukov, A and Sokolova, V and Shcheslavskiy, V and Goltsman, G and Feldman, T and Kuzmin, V and Ostrovsky, M and Morozov, P}, title = {Interrogation of Retinal Lipofuscin by Fluorescence Lifetime Imaging Microscopy.}, journal = {Journal of biophotonics}, volume = {19}, number = {3}, pages = {e202500418}, doi = {10.1002/jbio.202500418}, pmid = {41392555}, issn = {1864-0648}, support = {23-65-10005//Russian Science Foundation/ ; 122041400102-9//Ministry of Science and Higher Education of the Russian Federation/ ; 23-SCH06-20//Moscow State University Program of Development/ ; }, mesh = {*Lipofuscin/metabolism ; Retinal Pigment Epithelium/metabolism/pathology ; Microscopy, Fluorescence/methods ; Humans ; *Retina/metabolism ; Animals ; Macular Degeneration/metabolism/pathology ; Time Factors ; }, abstract = {Age-related macular degeneration is a disease that affects the middle part of the vision and involves pathological alterations in the retinal pigment epithelium. Accurate and timely evaluation of the retinal pigment epithelium is a cornerstone of effective treatment planning. In this study, we present the development of a preclinical method for early diagnostics of age-related macular degeneration using time and spectral characteristics of fluorescence of lipofuscin granules from the retinal pigment epithelium. Using the unique system based on a superconducting single-photon detector and time-correlated single-photon counting electronics integrated in the confocal laser scanning microscope we determined the parameters of fluorescence (distribution long and short fluorescence lifetime components and their contribution to the total fluorescence signal as well as fluorescence spectral shift) that have a diagnostic value for differentiation of the normal and pathological states in the degenerative diseases of the retina and retinal pigment epithelium.}, }
@article {pmid41393074, year = {2025}, author = {Nagaoka, K and Makino, S and Inoda, S and Kaburaki, T}, title = {Secondary Angle Closure Glaucoma due to Massive Subretinal and Suprachoroidal Hemorrhage in Neovascular Age-Related Macular Degeneration: Clinical Case and Literature Review.}, journal = {Case reports in ophthalmological medicine}, volume = {2025}, number = {}, pages = {2230622}, pmid = {41393074}, issn = {2090-6722}, abstract = {Massive subretinal hemorrhage secondary to neovascular age-related macular degeneration (nAMD) is relatively uncommon, and reports of secondary angle closure glaucoma associated with such hemorrhage are even rarer. We report a case of a 93-year-old woman with a history of nAMD who developed this condition, along with a review of the relevant literature.}, }
@article {pmid41393127, year = {2025}, author = {Lin, TH and Lin, YY and Huang, YT and Huang, YC and Tien, PT and Wan, L and Lin, HJ}, title = {Chronic kidney disease increases the risks of age-related macular degeneration: a systematic review and meta-analysis.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1635766}, pmid = {41393127}, issn = {2296-858X}, abstract = {IMPORTANCE: Age-related macular degeneration (AMD) and chronic kidney disease (CKD) are common causes of morbidity, with systemic risk factors shared. Clarifying the association between the two is crucial to guiding comprehensive management.<br><br>OBJECTIVE: This study aimed to systematically review current and latest evidence on the influence of CKD on AMD prevalence. An investigation was performed into various AMD stages and how different CKD severities exert their effects.<br><br>DATA SOURCES: Databases of PubMed and Embase were searched from their inception to 11 November 2024. Reference lists of studies were reviewed, and relevant researchers were contacted. The study was accepted and registered with PROSPERO (CRD420250612669).<br><br>STUDY SELECTION: Eligible studies of the current review are observational, peer-reviewed, and include quantitative comparisons of AMD prevalence between populations with and without CKD. Studies with overlapping data or investigating AMD incidence were excluded. Twenty studies met the inclusion criteria from the 3,218 initially identified.<br><br>DATA EXTRACTION AND SYNTHESIS: We extracted data and assessed study quality using the Appraisal tool for Cross-Sectional Studies (AXIS) tool for cross-sectional studies. Our meta-analyses followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and were conducted with Review Manager 5.4.1. Risk of bias was evaluated using the AXIS quality appraisal tool, and the overall certainty of evidence was qualitatively assessed following the GRADE approach.<br><br>MAIN OUTCOMES AND MEASURES: Primary outcomes are the prevalence of all-stage, early-stage, and late-stage AMD among CKD and non-CKD patients. Secondary outcomes investigated AMD prevalence among patients with different CKD stages. We reported in our analyses the risk ratios (RRs) with 95% confidence intervals (CIs).<br><br>RESULTS: All-stage AMD prevalence was found to be higher among CKD patients (RR: 1.65; 95% CI: 1.49-1.83). Similarly, early-stage AMD was more prevalent among CKD patients (RR: 1.47; 95% CI: 1.26-1.71). In late-stage AMD, an even stronger association was shown (RR: 3.72; 95% CI: 2.14-6.45). Meanwhile, there was no significant difference in AMD prevalence between moderate and advanced CKD stages (RR: 1.08; 95% CI: 0.48-2.46).<br><br>CONCLUSION AND RELEVANCE: Our findings indicate that CKD is significantly associated with higher AMD prevalence. These findings suggest the effects of shared systemic mechanisms and underscore the need for ophthalmic screening in CKD patients. Further studies are needed to strengthen causality and expand generalizability beyond the Asian population.<br><br>The systematic review was registered in PROSPERO (CRD420250612669).}, }
@article {pmid41394258, year = {2025}, author = {Blehm, C and Hall, B}, title = {Comparison of Visual Field Assessments Between the Humphrey Field Analyzer, Tempo, and Virtual Eye Elite Perimeters.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {4535-4542}, pmid = {41394258}, issn = {1177-5467}, abstract = {PURPOSE: To compare test duration and the agreement of summary metrics between the TEMPO, Virtual Eye ELITE (VEE), and Humphrey Field Analyzer (HFA) perimeters.<br><br>METHODS: This was a prospective, randomized, comparative study. Subjects were excluded if they were unable to tolerate ophthalmic imaging or had any ocular or systemic conditions that could affect visual field test results, such as age-related macular degeneration, peripheral retinal disease, or severe glaucoma. Eligible subjects were assessed at 1 visit with all perimeters for total bilateral acquisition time, mean deviation (MD), pattern standard deviation (PSD), foveal threshold (FT), visual field index (VFI), false positives and false negatives, and administered a questionnaire.<br><br>RESULTS: A total of 54 subjects completed the study. Mean bilateral visual field acquisition time differences were significant between TEMPO and HFA (p < 0.001) and TEMPO and VEE (p < 0.001), and not significant between HFA and VEE (p = 0.34). Mean MD differences were not significant between TEMPO and HFA (p = 0.96) and were significant for TEMPO and VEE (p = 0.01) and HFA and VEE (p = 0.02). Mean PSD differences were not significant between TEMPO and HFA (p = 0.27), TEMPO and VEE (p = 0.72), or HFA and VEE (p = 0.72). Mean foveal threshold differences were significant between TEMPO and HFA (p < 0.001), TEMPO and VEE (p < 0.001), and HFA and VEE (p < 0.001). A significantly higher percentage of subjects reported agreement that the testing was "Easy" to perform with the TEMPO compared to HFA (p < 0.001), TEMPO compared to VEE (p = 0.006), and with VEE compared to HFA (p = 0.002).<br><br>CONCLUSION: The results suggest similar summary metrics between the HFA, TEMPO, and VEE perimeters. There was faster acquisition time with the TEMPO. These results also indicate the potential for streamlined clinical workflow.}, }
@article {pmid41394857, year = {2025}, author = {Fan, Q and Li, Z}, title = {Breach and restoration of retinal immune privilege: barrier failure, innate dysregulation, and adaptive autoimmunity.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1703382}, pmid = {41394857}, issn = {1664-3224}, mesh = {Humans ; *Blood-Retinal Barrier/immunology ; *Autoimmunity ; *Immunity, Innate ; Animals ; *Immune Privilege/immunology ; *Adaptive Immunity ; *Retina/immunology/pathology ; *Retinal Diseases/immunology ; Uveitis/immunology ; }, abstract = {The retina preserves vision by tightly regulating inflammation ("immune privilege") via blood-retinal barriers, neuroglial checkpoints, and tolerogenic cues. This actively maintained-and potentially restorable-state is breached in major retinal diseases through three recurrent archetypes. We synthesize 2015-2025 advances into a framework of barrier failure, innate dysregulation, and adaptive autoimmunity. Across age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), and non-infectious uveitis (NIU): AMD exhibits complement-microglia para-inflammation with later outer-barrier compromise; DR exemplifies inner-BRB failure with inflammatory amplification; RP begins with degeneration-triggered innate activation and progresses to combined innate-adaptive injury; NIU represents T-cell-driven breach of the blood-retinal barrier. Interventional human evidence supports immunity as a therapeutic target: complement inhibition slows geographic atrophy; anti-VEGF reduces leak; intravitreal corticosteroids suppress inflammatory edema; and anti-TNF/IL-6R improve refractory NIU. Emerging strategies aim at privilege restoration-reinforcing myeloid checkpoints, tempering inflammasomes, and exploring tolerance-oriented approaches to re-educate adaptive immunity. Evidence from preclinical and early translational studies indicates that ocular tissues can imprint regulatory/anergic programs on pathogenic T cells, supporting mechanism-aligned, patient-tailored immunotherapy as a testable route to restore regulation, mitigate inflammation, and slow degeneration.}, }
@article {pmid41394869, year = {2025}, author = {Wei, Y and Lin, Y and Li, Y and Liu, J and Yang, Y and Chen, H and Han, Z and Wang, K and Qian, T and Ju, Y and Zheng, W}, title = {Redefining cell death: ferroptosis as a game-changer in ophthalmology.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1709354}, pmid = {41394869}, issn = {1664-3224}, mesh = {*Ferroptosis ; Humans ; Animals ; *Eye Diseases/metabolism/pathology/etiology ; Reactive Oxygen Species/metabolism ; *Ophthalmology ; Cell Death ; }, abstract = {Ferroptosis, recently proposed as a novel type of cell death, is characterized by unique characteristics and recognition functions. It is involved in diverse physiological processes and in the onset and progression of various diseases and is characterized by reactions between reactive oxygen species (ROS) and iron-dependent lipid peroxidation. This process is finely regulated by a variety of metabolic pathways. Ferroptosis fundamentally differs from conventional cell death mechanisms such as apoptosis, necrosis, and autophagy. In recent years, research on ferroptosis in the field of ophthalmology has gradually emerged, and a large amount of evidence has shown that it is closely related to the occurrence and development of ophthalmic diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal ischemia-reperfusion injury (RIRI), retinitis pigmentosa, dry eye disease, cataracts, and glaucoma. This paper provides a comprehensive review of the latest advancements in ferroptosis within ophthalmological research and systematically describes the molecular mechanisms and pathophysiological significance of ferroptosis in the pathogenesis and progression of ophthalmic diseases. Exploring the mechanisms of ferroptosis holds promise for the delivery of novel molecular targets and therapeutic approaches to prevent and treat ophthalmic diseases. Additionally, its clinical translational and application are anticipated to surmount current therapeutic limitations and emerge as a significant direction for breakthroughs in the precision medicine era.}, }
@article {pmid41395976, year = {2025}, author = {Shekho, N and Vergmann, AS and Pedersen, FN and Stokholm, L and Thinggaard, BS}, title = {Characterizing and assessing vision-related quality of life among patients discontinued treatment for neovascular age-related macular degeneration.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70044}, pmid = {41395976}, issn = {1755-3768}, support = {//The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark/ ; 167-A6477//The Chief Physicians' Council Research Foundation (Overl&#xe6;ger&#xe5;dets Forskningsfond), Odense University Hospital/ ; }, abstract = {PURPOSE: This study characterized and assessed vision-related quality of life (VRQoL) in patients with neovascular age-related macular degeneration (nAMD) who discontinued treatment with intravitreal anti-vascular endothelial growth factor (anti-VEGF), comparing them to those undergoing treatment. Secondarily, it explored reasons for treatment discontinuation against medical advice.<br><br>METHODS: This survey-based cross-sectional study used data collected for the Danish study, "Identification of Patient-Reported Barriers in Treatment for nAMD" (I-OPTA) at Odense University Hospital, Denmark. I-OPTA included a self-developed questionnaire and the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25). Main outcomes were demographics, treatment details, NEI-VFQ-25 scores, and reasons for treatment discontinuation against medical advice. Linear regression models investigated the impact of variables on the composite NEI-VFQ-25 score.<br><br>RESULTS: The study included 172 (32.6%) patients who had discontinued treatment and 356 (67.4%) patients who were undergoing treatment; 10 (5.8%) discontinued against medical advice. Discontinued patients were older (median 81.0&#x2009;years, p-value&#x2009;=&#x2009;0.004), had lower best-corrected visual acuity (BCVA) in the worse-seeing eye (p-value<0.001), had a shorter treatment duration (p-value&#x2009;=&#x2009;0.001) and lived alone (p-value&#x2009;=&#x2009;0.044). Discontinued patients showed lower scores in all NEI-VFQ-25 domains except ocular pain. Higher BCVA correlated with a higher composite score of NEI-VFQ-25. Reasons for discontinuation against medical advice included treatment burden and perceived inefficacy.<br><br>CONCLUSION: Patients who discontinued treatment for nAMD report lower VRQoL, with lower BCVA in the worse-seeing eye, older age, living alone, and unilateral treatment possibly contributing to treatment discontinuation. Future studies on visual acuity and retinal fluid in this group could guide decisions on treatment discontinuation, emphasizing patients' quality of life.}, }
@article {pmid41396384, year = {2025}, author = {Li, Z and Jin, S and Xu, W and Zhang, M and Liu, X}, title = {Advances in the treatment of blinding retinal diseases.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {21}, pmid = {41396384}, issn = {1573-2630}, support = {No. 82371043//National Natural Science Foundation of China/ ; No.20240601014RC//the Project of Outstanding Talents in Scientific and Technological Innovation and Entrepreneurship for Middle-aged and Young Scientists of Jilin Provincial Science and Technology Department/ ; }, mesh = {Humans ; *Genetic Therapy/methods ; *Retinal Diseases/therapy/complications ; *Blindness/etiology/therapy ; *Retinal Pigment Epithelium/transplantation ; *Stem Cell Transplantation/methods ; }, abstract = {Blinding retinal diseases, including inherited and degenerative conditions, rank globally among the primary causes of permanent vision loss. While certain degenerative retinal diseases like age-related macular degeneration and diabetic retinopathy can be partially managed through intravitreal anti-VEGF injections or the use of complement inhibitors, most patients still lack effective treatment options. Recently, several promising therapeutic avenues have surfaced, such as stem cell-derived retinal pigment epithelium cell transplantation, gene therapy, and the implantation of retinal prostheses. This review summarizes recent clinical trials and advances in gene therapy for inherited retinal diseases, outlines techniques for retinal pigment epithelium cell transplantation, and discusses methods to improve graft survival. It also examines strategies for enhancing the resolution of retinal prostheses and explores their future clinical potential, providing new perspectives on the management of degenerative retinal conditions.}, }
@article {pmid41396449, year = {2025}, author = {Karaca, I and Wei, Y and Nelson, R and Sassen, SH and Daynes, K and Clark, F and Brown, T and Messina, A and Pfau, M and Zhang, Y and Schmitz-Valckenberg, S and Fleckenstein, M}, title = {Association of Mesopic and Dark-Adapted Retinal Sensitivity With Type 1 Macular Neovascularization in Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {45}, pmid = {41396449}, issn = {1552-5783}, support = {P30 EY014800/EY/NEI NIH HHS/United States ; R01 EY033365/EY/NEI NIH HHS/United States ; UM1 TR004409/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Female ; Male ; Aged ; *Dark Adaptation/physiology ; Visual Field Tests ; *Mesopic Vision/physiology ; Visual Fields/physiology ; Aged, 80 and over ; Visual Acuity/physiology ; Tomography, Optical Coherence ; *Retina/physiopathology ; *Macular Degeneration/physiopathology/complications ; }, abstract = {PURPOSE: To assess the impact of type 1 macular neovascularization (MNV) on mesopic and dark-adapted (DA) cyan retinal sensitivity using fundus-controlled perimetry (FCP [microperimetry]) in patients with age-related macular degeneration (AMD).<br><br>METHODS: This index study includes baseline data from AMD patients with type 1 MNV without complete retinal pigment epithelium and outer retinal atrophy (cRORA). Mesopic and DA-cyan sensitivity were measured using FCP with standardized and MNV-lesion-tailored test grids. We applied linear mixed-effects models to compare retinal sensitivity in regions with versus without co-localized type 1 MNV. Age-specific hill-of-vision data that served as reference were estimated using Bayesian quantile regressions.<br><br>RESULTS: Of the 55 eyes with baseline data, 27 eyes without cRORA (27 patients; mean age, 76.8 &#xb1; 6.7 years; 74.1% female) were included in this detailed analysis. In regions co-localizing with type 1 MNV, unadjusted mesopic sensitivity was significantly increased by a mean of 2.10 dB (95% confidence interval [CI], 1.58-2.63; P < 0.001), whereas unadjusted DA-cyan sensitivity was significantly reduced by 3.12 dB (95% CI, 2.38-3.86; P < 0.001) compared to regions without evidence of MNV. When adjusting for age-specific hill-of-vision reference data, mesopic sensitivity remained significantly higher by 0.78 dB (95% CI, 0.29-1.28; P = 0.002) and DA-cyan sensitivity remained significantly lower by 2.07 dB (95% CI, 1.33-2.80; P < 0.001) in regions co-localizing with type 1 MNV versus those without MNV.<br><br>CONCLUSIONS: In AMD, areas overlying type 1 MNV showed higher mesopic but reduced DA-cyan sensitivity, suggesting localized preservation yet subtype-specific vulnerability. These findings will be further examined through structural analyses and prospective validation in our ongoing study.}, }
@article {pmid41396593, year = {2025}, author = {Zhong, Y and Qin, Y}, title = {Frailty-Driven Risk Stratification in Age-Related Ophthalmic Diseases: Thresholds, Precision Screening, and Mendelian Randomization Insights.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {12}, pages = {17}, pmid = {41396593}, issn = {2164-2591}, mesh = {Humans ; *Mendelian Randomization Analysis/methods ; Male ; Aged ; *Frailty/diagnosis ; Middle Aged ; Female ; *Eye Diseases/diagnosis/epidemiology ; Macular Degeneration/epidemiology ; Risk Assessment/methods ; Adult ; Nutrition Surveys ; Cataract ; Risk Factors ; Aged, 80 and over ; Glaucoma ; Disease Progression ; }, abstract = {PURPOSE: To define frailty thresholds for accelerated progression of age-related ophthalmic diseases and inform precision intervention.<br><br>METHODS: Using NHANES 2005-2008 (n = 7081 adults &#x2265; 40 years), we constructed a 49-item frailty index (FI) via the deficit accumulation model. Missing data were addressed with complete-case analysis (n = 4120) and multiple imputation. Two analytic cohorts were defined: (1) objective diagnosis group and (2) composite diagnosis group. Multivariable logistic regression with restricted cubic splines (RCS) assessed associations between the FI and age-related macular degeneration (AMD), cataract, glaucoma, and diabetic retinopathy (DR). Bidirectional Mendelian randomization (MR) tested causality.<br><br>RESULTS: Findings were consistent across complete-case and imputed datasets. In continuous analyses, the FI was associated with AMD (composite odds ratio [OR] = 1.17; objective OR = 1.16), cataract (OR = 1.30), DR (OR = 1.33), and glaucoma (OR = 1.12). In categorical analyses, extreme frailty (FI > 0.45) conferred the highest risks: cataract (OR = 2.51), DR (OR = 2.04), AMD (OR = 1.77), and glaucoma (OR = 1.45). RCS analyses identified nonlinear thresholds at FI = 0.20 (AMD) and FI = 0.19 (cataract), whereas DR and glaucoma showed linear trends. MR supported a causal effect of frailty on four diseases, with no evidence for reverse causation.<br><br>CONCLUSIONS: Frailty was shown to accelerate ophthalmic disease progression. Three clinical implications are proposed here: (1) prioritized screening for individuals with FI > 0.45, (2) recognizing FI thresholds around 0.19 to 0.20 as potential early warning signals for accelerated AMD and cataract, and (3) integrating geriatric and ophthalmic care.<br><br>TRANSLATIONAL RELEVANCE: This study provides actionable FI thresholds to identify high-risk aging populations and reinforces frailty as a modifiable upstream driver of ocular aging.}, }
@article {pmid41397442, year = {2026}, author = {Li, N and Hong, R and You, H and Xu, F and Zhang, Q and Lin, Y and Su, Y and Lan, D and Jin, L and She, J}, title = {DELP Treatment on Vision and Retinal Microcirculation in Patients With Acute Ischemic Stroke: Report of Five Cases and Literature Review.}, journal = {Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy}, volume = {30}, number = {2}, pages = {168-175}, pmid = {41397442}, issn = {1744-9987}, support = {2023YFC3604500//National Key Research and Development Program of China/ ; 2023YFC3604505//National Key Research and Development Program of China/ ; 22Y31900200//Science and Technology Innovation Plan Of Shanghai Science and Technology Commission/ ; 22Y31900203//Science and Technology Innovation Plan Of Shanghai Science and Technology Commission/ ; Z155080000004//National Clinical Key Specialty Project Foundation/ ; SHDC22023304//Shanghai Municipal Hospital Development Center/ ; 82230084//National Natural Science Foundation of China/ ; 82172545//National Natural Science Foundation of China/ ; 82201404//National Natural Science Foundation of China/ ; //Shanghai Blue Cross Hospital Co., Ltd. and Shanghai Tongji University Educationg Development Foundation/ ; 2024QN05//Shanghai Jing'an District Science and Technology Commission and Jing'an District Health Commission/ ; }, mesh = {Humans ; Microcirculation ; Aged ; Male ; Female ; *Ischemic Stroke/therapy/complications/physiopathology ; Visual Acuity ; Middle Aged ; Retinal Vessels/diagnostic imaging ; Tomography, Optical Coherence/methods ; Aged, 80 and over ; }, abstract = {BACKGROUND: The delipid extracorporeal lipoprotein filter from plasma (DELP) treatment can effectively reduce blood lipid, increase blood flow, and improve neurological deficits in patients with acute ischemic stroke (AIS). However, its effect on vision and retinal microcirculation in stroke patients has never been reported.<br><br>METHODS: Between November 2023 and June 2024, five patients underwent DELP treatment as a routine adjuvant therapy for AIS. Detailed ophthalmological examinations, including best corrected visual acuity (BCVA) and optical coherence tomography angiography (OCTA), were performed on them one day prior to and 1-3&#x2009;days following the DELP treatment.<br><br>RESULTS: Among the ten eyes examined, six had diabetic retinopathy (DR), two had dry age-related macular degeneration (dAMD), one had idiopathic epiretinal membrane (iERM), and one was normal. Surprisingly, after DELP treatment, the BCVA improved by 0.2LogMAR in six eyes, 0.1LogMAR in three eyes, and remained unchanged in one eye. The vessel density (VD) in the fovea increased in six eyes, remained unchanged in three eyes, and decreased in one eye. The non-perfusion area (NPA) in the superficial capillary plexus (SCP) decreased in six eyes, remained unchanged in two eyes, and increased in two eyes. The NPA in the deep capillary plexus (DCP) decreased in eight eyes and remained unchanged in two eyes. A small amount of bleeding occurred in Patient 3's right eye, and no other adverse events were observed post-treatment.<br><br>CONCLUSIONS: In this case series, the DELP treatment showed a potentially significant therapeutic effect on the BCVA and retinal microcirculation in AIS patients with good safety and provided a rationale for further investigation. At the same time, this treatment may provide an effective option for the treatment of eye diseases such as DR, iERM, and AMD.}, }
@article {pmid41397462, year = {2026}, author = {Liesenhoff, C and Krause, D and Eckardt, F and Lorger, A and Meyrl, C and Deiters, V and Hafner, M and Schiefelbein, J and Klaas, J and Schworm, B and Priglinger, SG and Siedlecki, J}, title = {Efficacy of 2 mg vs. High-Dose 8 mg Aflibercept in Neovascular Age Related Macular Degeneration.}, journal = {Klinische Monatsblatter fur Augenheilkunde}, volume = {243}, number = {2}, pages = {103-109}, doi = {10.1055/a-2760-5850}, pmid = {41397462}, issn = {1439-3999}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Female ; Male ; Aged ; Treatment Outcome ; Dose-Response Relationship, Drug ; Visual Acuity/drug effects ; *Wet Macular Degeneration/drug therapy/diagnosis ; Aged, 80 and over ; Intravitreal Injections ; Angiogenesis Inhibitors/administration &amp; dosage ; }, abstract = {PURPOSE: To investigate the efficacy of switching treatment from 2 mg aflibercept to high-dose 8 mg aflibercept in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: The database was screened for eyes with nAMD switched from 2&#x2009;mg to 8&#x2009;mg aflibercept. Demographic data, multimodal imaging, treatment parameters and outcomes were recorded. Efficacy of 2&#x2009;mg vs. 8&#x2009;mg aflibercept was compared four injections prior to, and four injections after switching by analysing central subfield thickness (CST), subretinal fluid (SRF) and intraretinal fluid (IRF) as well as visual acuity (VA).<br><br>RESULTS: Sixteen consecutive eyes of 16 patients (mean age 78.5&#x2009;&#xb1;&#x2009;5.5 years) were identified. There were 13 women (81.3%) and 3 men (18.7%). Prior to switching, mean anti-vascular endothelial growth factor (VEGF) treatment duration for nAMD was 8.1&#x2009;&#xb1;&#x2009;2.1 years and pretreatment amounted to a mean of 27.8&#x2009;&#xb1;&#x2009;23.6 injections. Mean injection intervals were similar prior to and after switching (5.05 vs. 5.13 weeks; p&#x2009;=&#x2009;0.76). CST remained stable before and after switching (p&#x2009;=&#x2009;0.25). After switching, the percentage of eyes with a dry macula increased from 0% to 37.5% (p&#x2009;=&#x2009;0.02) and the percentage of eyes with SRF decreased from 93.8% to 56.3% (p&#x2009;=&#x2009;0.037). There was a trend, but no significant effect towards a reduction of IRF (18.8% to 6.3%, p&#x2009;=&#x2009;0.60). Visual acuity remained stable irrespective of treatment (p&#x2009;=&#x2009;0.78).<br><br>CONCLUSIONS: Concerning CST on OCT, no clear advantage of high-dose 8&#x2009;mg aflibercept over conventional 2&#x2009;mg aflibercept was seen in this study. However, with high-dose 8&#x2009;mg aflibercept the number of eyes with a dry macula increased, and the amount of eyes with SRF decreased significantly. In pretreated eyes, the analysis of macular fluid compartments (as compared to CST) might be more sensitive for comparing treatment effects between 2&#x2009;mg and 8&#x2009;mg aflibercept.}, }
@article {pmid41398283, year = {2025}, author = {Antonietti, M and Mercado, C and Smiddy, WE and Schwartz, SG}, title = {Central retinal vein occlusion following intravitreal injections: a case series highlighting multifactorial risk.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {12}, pmid = {41398283}, issn = {2056-9920}, support = {GR004596-1//Research to Prevent Blindness Unrestricted Grant/ ; }, abstract = {INTRODUCTION: Intravitreal injections are standard treatment for various manifestations of age-related macular degeneration (AMD) but are associated with rare complications, including central retinal vein occlusion (CRVO). This report describes three cases of CRVO following intravitreal injections in patients with AMD.<br><br>METHODS: Retrospective case series describing three patients with AMD who developed CRVO after intravitreal injections.<br><br>RESULTS: CRVO occurred after ranibizumab (Lucentis, South San Francisco, CA), brolucizumab (Beovu, Novartis, Basel, Switzerland), and pegcetacoplan (Syfovre, Apellis, Waltham, MA) injections. All patients had multiple systemic vasculopathic risk factors. No intraocular inflammation or vasculitis was observed on examination, and fluorescein angiography was not performed. Visual outcomes were poor despite anti-VEGF treatment. None of the three patients developed neovascular glaucoma under our observation. The timing relationship between injection and CRVO varied, and causality could not be established.<br><br>CONCLUSION: CRVO may occur after intravitreal injections across different drug classes, even with agents that have low inflammatory potential. These cases highlight the multifactorial nature of this event and the importance of considering systemic vasculopathy when evaluating post-injection complications.}, }
@article {pmid41398318, year = {2026}, author = {Keshet, Y and Ngo, WK and Salcedo-Ledesma, A and Walia, JJ and Spaide, RF}, title = {Quantitative assessment of hyperreflective dots in the outer nuclear layer over neovascular lesion components.}, journal = {Eye (London, England)}, volume = {40}, number = {3}, pages = {363-368}, pmid = {41398318}, issn = {1476-5454}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Aged ; Male ; Female ; *Wet Macular Degeneration/diagnosis/diagnostic imaging ; Aged, 80 and over ; Subretinal Fluid/diagnostic imaging ; *Choroidal Neovascularization/diagnosis ; Middle Aged ; Microglia/pathology ; }, abstract = {OBJECTIVES: To evaluate the outer nuclear layer for hyperreflective dots (HRD), a proposed imaging correlate of retinal microglia, in eyes with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: High-resolution optical coherence tomography (OCT) of eyes with nAMD was evaluated with the aid of a custom ImageJ plugin that automatically identified HRD and plotted them on the corresponding near infrared (IR) fundus image. Areas of subretinal fluid (SRF), double layer sign (DLS), and the area of neovascularisation as imaged by OCT angiography (A) were mapped to the near-IR image. The number of HRD overlying these regions was tabulated.<br><br>RESULTS: There were 38 eyes of 38 patients. SRF was present in 23 eyes, there was a median 8.5 HRD /mm[2] over this area. DLS was present in all eyes and with a median of 6.5 HRD/mm[2] over this area. Neovascularisation was detectable using OCTA with a median of 6.8 HRD/mm[2]. The density of HRD/mm[2] was not significantly different over areas of DLS with fluid compared to areas of DLS without SRF (P&#x2009;=&#x2009;0.22). The median HRD/mm[2] for uninvolved areas of the retina was 0.7, a difference that was significantly less than over areas of SRF, DLS, and OCTA detected neovascularisation (P&#x2009;<&#x2009;0.001 for all comparisons).<br><br>CONCLUSIONS: There is an aggregation of HRD in the outer retina over lesion components of nAMD. These HRD may be present in response to SRF, but their existence over regions of the neovascular lesion without SRF suggests that additional factors are involved in their recruitment.}, }
@article {pmid41398938, year = {2025}, author = {Kose, H and Ozkan, B and Kanli, A and Karabas, LV and Akpinar, G and Kasap, M and Sumer, F}, title = {Evaluation of protein profile in vitreous samples of patients with naive age-related macular degeneration using proteomic approaches.}, journal = {BMC geriatrics}, volume = {25}, number = {1}, pages = {1019}, pmid = {41398938}, issn = {1471-2318}, mesh = {Humans ; *Proteomics/methods ; Female ; Male ; Aged ; Prospective Studies ; *Macular Degeneration/metabolism/diagnosis ; *Vitreous Body/metabolism/chemistry ; Case-Control Studies ; *Eye Proteins/metabolism ; Aged, 80 and over ; Middle Aged ; Biomarkers/metabolism ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) represents one of the most common causes of permanent vision impairment in individuals over 50 years of age.<br><br>METHODS: This study aims to characterize AMD using proteomic analysis to enhance diagnosis and treatment strategies. In a prospective case-control clinical trial, vitreous fluids (VF) from thirteen AMD patients were collected during surgery and analyzed by 2DE-based MALDI TOF-TOF MS/MS. PANTHER and STRING analyses were performed to investigate the biological relationships between the identified proteins and to determine relevant cellular pathways.<br><br>RESULTS: A total of 11 proteins were differentially regulated between AMD patients and healthy controls. Among them, Apolipoprotein E was significantly up-regulated (&#x2191;3-fold), while ten proteins, including alpha-crystallin A chain (&#x2193;779-fold), beta-crystallin B2 (&#x2193;232-fold), and haptoglobin (&#x2193;15-fold), were markedly down-regulated. These quantitative differences underscore the critical role of lipid metabolism, oxidative stress response, and inflammation in AMD pathogenesis.<br><br>CONCLUSION: The identified proteins are related to biological regulation, retinal protection, and regulation of inflammation and angiogenesis processes. The up-regulation of Apolipoprotein E highlights its involvement in lipid metabolism and inflammatory modulation, while the sharp down-regulation of crystallin family proteins suggests compromised retinal protection against oxidative stress and apoptosis. These protein alterations provide new insights into AMD pathogenesis and may serve as potential biomarkers for early diagnosis and novel therapeutic targets in managing the disease.}, }
@article {pmid41399598, year = {2025}, author = {Flindris, K and Gorgoli, K and Koumpoulis, I}, title = {A Case Series of Bacillary Layer Detachment (BALAD) in Neovascular Age-Related Macular Degeneration (nAMD): A Novel Optical Coherence Tomography (OCT) Biomarker.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e96819}, pmid = {41399598}, issn = {2168-8184}, abstract = {Bacillary layer detachment (BALAD) is a newly recognized optical coherence tomography (OCT) finding, defined as a split at the photoreceptor inner segment (myoid zone) resulting in a dome-shaped intraretinal fluid cavity. BALAD has been reported in various chorioretinal diseases and may serve as a novel structural OCT biomarker of severe exudation. We present a case series of BALAD in neovascular age-related macular degeneration (nAMD) to characterize its multimodal imaging features and discuss its diagnostic and prognostic significance. Three patients with active nAMD exhibited BALAD on spectral-domain OCT. In each instance, OCT cross-sections showed a sharply demarcated hyporeflective intraretinal cavity beneath an intact external limiting membrane (ELM) and above the ellipsoid zone (EZ). OCT angiography (OCTA) revealed an underlying high-flow choroidal neovascular network corresponding to the BALAD in all cases. All three patients initially had significant visual impairment. Two patients were treated with serial intravitreal anti-vascular endothelial growth factor (VEGF) injections, resulting in rapid resolution of the BALAD cavity, reabsorption of subretinal and intraretinal fluid, and marked improvement in best-corrected visual acuity (e.g., from 20/400 to 20/40). The third patient, who declined treatment, developed persistent BALAD with progressive subfoveal fibrosis and no visual recovery. BALAD in nAMD indicates an aggressive disease phenotype with intense outer retinal fluid accumulation and photoreceptor layer schisis. Prompt anti-VEGF therapy was associated with anatomical recovery and vision improvement in the treated cases. Recognizing BALAD on OCT and OCTA is clinically important, as it differentiates intraretinal from subretinal pathology and underscores the need for early, aggressive treatment to mitigate irreversible retinal damage in nAMD.}, }
@article {pmid41399815, year = {2025}, author = {Leozappa, M and Mavilio, A and Durante, G and Piccinni, L and Miggiano, A}, title = {SING IMT telescopic intraocular lens implantation in a patient with inverse retinitis pigmentosa: A case report.}, journal = {American journal of ophthalmology case reports}, volume = {40}, number = {}, pages = {102479}, pmid = {41399815}, issn = {2451-9936}, abstract = {PURPOSE: To report the off-label use of the SING IMT telescopic intraocular lens (IOL) (Samsara Vision) in a patient with inverse retinitis pigmentosa (RP) and cataracts, evaluating its impact on visual acuity and functional outcomes.<br><br>OBSERVATIONS: A 77-year-old female with inverse RP, bilateral cataracts, hypertension, and hypercholesterolemia presented with hand motion visual acuity (&#x2265;2.3 LogMAR) bilaterally, assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at 2 meters. An external telescopic simulator improved visual acuity to 6 letters (1.58 LogMAR) in the left eye. Preoperative assessments, including optical coherence tomography, fundus autofluorescence, and electrophysiological testing, confirmed central macular degeneration and supported left-eye SING IMT implantation. Phacoemulsification with SING IMT implantation was performed, followed by a visual rehabilitation program. By 6 months, visual acuity reached 6 ETDRS letters (1.58 LogMAR) at 3 meters. Functional improvements included reading, writing, sewing, and television viewing, with enhanced autonomy and mood. Mild corneal edema resolved within 1 week, and no posterior capsular opacification or cystoid macular edema occurred during 8 months of follow-up.<br><br>CONCLUSION AND IMPORTANCE: This case reporting use of the SING IMT in inverse RP demonstrates its potential to improve vision and quality of life in patients with central vision loss from retinal dystrophies, surpassing typical cataract surgery outcomes. The 2.5x magnification and structured rehabilitation were key to functional gains. Larger studies are needed to validate efficacy and refine patient selection.}, }
@article {pmid41400582, year = {2025}, author = {Ma, H and Li, S and Le, Y and Stanford, D and Freeman, WM and Ding, XQ}, title = {Single Cell RNAseq Analysis of Thyroid Hormone Effects on Retinal Glial Cells.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2025.1221}, pmid = {41400582}, issn = {2152-5250}, abstract = {Thyroid hormone (TH) signaling regulates cellular metabolism and stress response in the retina. Increased TH levels in circulation are associated with a higher incidence of age-related macular degeneration. Furthermore, stimulation of TH signaling induces retinal degeneration in mice, which is accompanied by the activation of retinal glial cells. Here, we investigated the transcriptional changes induced by triiodothyronine (T3) in retinal glial cells using single-cell RNA sequencing (scRNAseq) and bioinformatic analyses. One-month-old C57BL/6 mice were given T3 (20 μg/ml in drinking water) for four weeks, after which their retinal cells were collected to assess viability and undergo scRNAseq. The resulting data were analyzed using the Seurat package, visualized by the Loupe Browser, and Ingenuity Pathway Analysis. Analyses of differentially expressed genes (DEGs) in Müller cells, astrocytes, and microglia revealed significant enrichment in pathways associated with stress, immune response, and degeneration. Müller cells exhibited upregulation of mitochondrial dysfunction, acute-phase response, and sirtuin signaling pathways. Astrocytes displayed downregulation of synaptogenesis, neurovascular coupling, cAMP response elements, and calcium signaling. Microglia showed upregulation of coordinated lysosomal expression and regulation signaling, systemic lupus erythematosus in T cells, and multiple sclerosis signaling, and downregulation of actin-binding Rho activating signaling, retinoic acid receptor activation signaling, and IL-17 signaling. The distinct and overlapping transcriptional responses suggest that each retinal glial cell type plays a specific and coordinated role in adapting to stress. This study offers new insights into TH-induced retinal stress and degeneration at the transcriptional and pathway-level responses of retinal glial cells.}, }
@article {pmid41402599, year = {2026}, author = {Zhou, WD and Dong, L and Yang, YH and Zhao, HQ and Zhang, RH and Li, YT and Yu, CY and Li, HY and Wu, HT and Shi, XH and Shao, L and Wei, WB}, title = {Retinal single-cell blood velocity in eyes with varied axial length using adaptive optics scanning laser ophthalmoscopy.}, journal = {Eye (London, England)}, volume = {40}, number = {2}, pages = {268-274}, pmid = {41402599}, issn = {1476-5454}, mesh = {Humans ; Adult ; Male ; *Ophthalmoscopy/methods ; Female ; Middle Aged ; *Axial Length, Eye/pathology ; Young Adult ; *Myopia/physiopathology ; Blood Flow Velocity/physiology ; *Retinal Vessels/physiology/physiopathology ; *Retinal Artery/physiology ; }, abstract = {BACKGROUND: To investigate the hemodynamic changes in the retinal vasculature of the macular region in eyes with axial myopia.<br><br>METHODS: Individuals with varying axial lengths were included in this study. Inclusion criteria was the absence of any ocular or systemic diseases. A commercial adaptive optics scanning laser ophthalmoscopy was used to capture images of retinal vessels within the 5&#xb0;-10&#xb0; areas above and below the foveal centre. This system provided noninvasive imaging of single blood cells and automatically calculated blood velocity while detecting the flow direction. Vessels were classified based on their diameter.<br><br>RESULTS: The study included 90 patients (180 eyes; 35 (38.9%) men) with a mean age of 34.3&#x2009;&#xb1;&#x2009;12.2 years (range: 19-62 years) and a mean axial length of 25.8&#x2009;&#xb1;&#x2009;1.9&#x2009;mm (range: 21.4-30.6&#x2009;mm). The mean blood velocity in retinal arteries and veins was 35.2&#x2009;&#xb1;&#x2009;11.4&#x2009;mm/s and 34.9&#x2009;&#xb1;&#x2009;13.2&#x2009;mm/s, respectively. Single-cell blood velocity was significantly increased with longer axial length in large retinal arteries (diamater&#x2265;100&#x3bc;m) (B&#x2009;=&#x2009;2.73; &#x3b2;&#x2009;=&#x2009;0.32; P&#x2009;=&#x2009;0.01); and medium retinal arteries (diameter<100&#x3bc;m) (B&#x2009;=&#x2009;1.83; &#x3b2;&#x2009;=&#x2009;0.27; P&#x2009;=&#x2009;0.003). Correspondingly, the blood velocity of medium retinal arteries in the myopic group was significantly higher than that in the non-myopic group (t&#x2009;=&#x2009;3.37; P&#x2009;=&#x2009;0.001). Single-cell blood velocity was significantly increased with longer axial length in medium retinal veins (diameter <110 &#x3bc;m) (B&#x2009;=&#x2009;2.0; &#x3b2;&#x2009;=&#x2009;0.3; P&#x2009;=&#x2009;0.016). Correspondingly, the blood velocity of medium retinal veins in the myopic group was significantly higher than that in the non-myopic group (t&#x2009;=&#x2009;2.25; P&#x2009;=&#x2009;0.03).<br><br>CONCLUSIONS: Single-cell retinal blood velocity was significantly increased with longer axial length. These findings suggest that the hemodynamic changes observed in axial myopia, including higher arterial and venous blood velocities, may provide a potential explanation for the lower prevalence of diabetic retinopathy, age-related macular degeneration, and branch retinal vein occlusion reported in previous epidemiological studies.}, }
@article {pmid41402601, year = {2026}, author = {Sadeghi, E and Chhablani, J}, title = {Response to: 'Comment on 'Correlation of retino-choroidal thickness and vascular metrics with drusen volume as a severity marker of age-related macular degeneration".}, journal = {Eye (London, England)}, volume = {40}, number = {2}, pages = {281}, pmid = {41402601}, issn = {1476-5454}, }
@article {pmid41404347, year = {2025}, author = {Attia, M and Pavlovic, T and Muliawan, A and Tuya, F and Mihalatos, M and Iwanicki, M and Kang-Mieler, J}, title = {Therapeutic potential of taurine in a pigmented rat model of age-related macular degeneration.}, journal = {Frontiers in ophthalmology}, volume = {5}, number = {}, pages = {1701761}, pmid = {41404347}, issn = {2674-0826}, abstract = {PURPOSE: To investigate the potential protective effects of taurine supplementation against retinal degeneration in an animal model of mild dry age-related macular degeneration (AMD).<br><br>METHODS: To test the effects of a taurine supplement in mild dry AMD, sodium iodate (NaIO3)-induced retinal degeneration model was used. Two administration methods, intraperitoneal (IP) and intravenous (IV), were used to deliver NaIO3 in pigmented Long Evans rats to generate mild and severe dry AMD, respectively. Structural abnormalities were evaluated in vivo using near-infrared (IR) reflectance fundus imaging and optical coherence tomography (OCT). Using the slow progressive mild AMD model, we investigated the neuroprotective effects of oral taurine supplementation (1.5% w/v in drinking water) against NaIO3-induced retinal degeneration over 20 weeks. In addition, a human Retinal Pigment Epithelium (RPE, hTERT-RPE1) cell culture model was used to directly assess taurine's ability to protect against NaIO3-related oxidative stress.<br><br>RESULTS: The high-dose IV model (80 mg/kg) exhibited extensive and severe retinal damage, with ONL thinning by 64.2% and total retinal thickness (TRT) by 47.6%, predominantly in the peripapillary region. In contrast, the lower-dose IP model (50 mg/kg) displayed milder, more gradual deterioration (outer nuclear layer (ONL) thinning by 19.4% and TRT by 11.5%). Oral taurine supplementation significantly preserved ONL and TRT in vivo and supported RPE-1 cell survival, proliferation, and motility, under NaIO3 conditions.<br><br>CONCLUSION: Taurine supplementation provided significant structural protection against NaIO3-induced damage both in vivo and in cell culture, demonstrating its potential as a therapeutic candidate for mitigating mild dry AMD progression.}, }
@article {pmid41404584, year = {2025}, author = {Che, S and Ma, Y and Cao, J}, title = {Association between serum carotenoid concentrations and risk of major age-related eye diseases among middle-aged and older adults.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1596799}, pmid = {41404584}, issn = {2296-858X}, abstract = {BACKGROUND: Age-related eye diseases are the main causes of progressive and irreversible vision loss in aging populations worldwide. Carotenoids, as a group of common natural antioxidants, can suppress free radicals produced by complex physiological reactions, thereby protecting the eyes from the effects of oxidative stress, cell apoptosis, and mitochondrial dysfunction. The present study aims to explore the association between serum carotenoid concentrations and risk of major age-related eye diseases among middle-aged and older adults in the United States.<br><br>METHODS: This study involved 1,478 participants aged &#x2265;50&#x202f;years from the 2005-2006&#x202f;cycles of the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of prevalence of cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) in relation to serum carotenoid concentrations.<br><br>RESULTS: Compared to participants in the first quartile, those in highest quartile of serum &#x3b1;-carotene (OR: 0.37; 95% CI: 0.21-0.64), &#x3b2;-carotene (OR: 0.57; 95% CI: 0.33-0.95), lutein/zeaxanthin (OR: 0.45; 95% CI: 0.27-0.76), and total carotenoid (OR: 0.58; 95% CI: 0.35-0.97) were negatively associated with risk of cataract; those in highest quartile of serum &#x3b2;-carotene (OR: 0.30; 95% CI: 0.11-0.77) and &#x3b2;-cryptoxanthin (OR: 0.28; 95% CI: 0.12-0.68) were negatively associated with risk of diabetic retinopathy; and those in highest quartile of lycopene (OR: 0.37; 95% CI: 0.18-0.78) was negatively associated with risk of AMD. In addition, subgroup analysis results indicated that participants in highest quartile of serum &#x3b1;-carotene (OR: 0.16; 95% CI: 0.08-0.32), &#x3b2;-carotene (OR: 0.40; 95% CI: 0.21-0.75), lycopene (OR: 0.46; 95% CI: 0.24-0.87), lutein/zeaxanthin (OR: 0.45; 95% CI: 0.25-0.84), and total carotenoid (OR: 0.41; 95% CI: 0.22-0.77) concentrations were negatively associated with risk of any ocular disease among female participants. By contrast, no associations were observed among male participants.<br><br>CONCLUSION: Our study demonstrated that higher serum concentrations of carotenoids were negatively associated with the risk of age-related eye diseases, particularly among middle-aged and older female participants.}, }
@article {pmid41405093, year = {2025}, author = {Suzuki, T and Terao, R and Nagahara, M and Hayashi, K and Azuma, K and Shinzawa, K and Moriwaki, K and Shiraya, T and Honjo, M and Ueta, T}, title = {iPLA2β Protects Retinal Pigment Epithelium From Ferroptosis in a Sodium Iodate-Induced Model of Dry AMD.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {55}, pmid = {41405093}, issn = {1552-5783}, mesh = {Animals ; *Ferroptosis/physiology/drug effects ; *Retinal Pigment Epithelium/pathology/metabolism/drug effects ; Iodates/toxicity ; Disease Models, Animal ; Mice ; Mice, Knockout ; Electroretinography ; *Group VI Phospholipases A2/physiology ; Mice, Inbred C57BL ; Oxidative Stress ; *Macular Degeneration/chemically induced/metabolism ; Blotting, Western ; Real-Time Polymerase Chain Reaction ; Lipid Peroxidation ; }, abstract = {PURPOSE: Ferroptosis, characterized by lipid peroxidation, has been implicated in retinal pigment epithelium (RPE) degeneration in dry age-related macular degeneration (AMD). This study aimed to investigate the role of calcium-independent phospholipase A2 group VI (iPLA2β) in protecting RPE cells from oxidative stress using a sodium iodate (NaIO3)-induced dry AMD model.<br><br>METHODS: The iPLA2&#x3b2; knockout (KO) and wild-type (WT) mice were subjected to NaIO3 administration. Retinal structure and function were evaluated by histology and electroretinography. The involvement of ferroptosis was assessed by quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Pharmacological intervention experiments used ferrostatin-1, &#x3b1;-tocopherol, and necrostatin-1s to evaluate protective effects. Western blotting was performed for RIP3 phosphorylation, and RIP3 KO mice were used to further assess necroptosis involvement.<br><br>RESULTS: The iPLA2&#x3b2; KO mice exhibited normal retinal morphology and function under baseline conditions. NaIO3 exposure caused pronounced RPE and photoreceptor degeneration, a characteristic downregulation of genes responsive to ferroptotic stress, elevated lipid peroxidation, and impaired visual function, which were markedly rescued by ferrostatin-1 and &#x3b1;-tocopherol, and partially by necrostatin-1s. NaIO3 did not induce RIP3 phosphorylation, and necrostatin-1s appeared to exert antioxidative effects. RIP3 KO mice developed severe RPE degeneration after NaIO3 exposure, significantly attenuated by necrostatin-1s. These findings indicate that lipid peroxidation-mediated ferroptosis, rather than necroptosis, is the primary mechanism of NaIO3-induced retinal degeneration, particularly at low doses of NaIO3.<br><br>CONCLUSIONS: The iPLA2&#x3b2; functions as a key suppressor of lipid peroxidation-mediated RPE degeneration in the NaIO3 model. Targeting ferroptosis-particularly via iPLA2&#x3b2;-may represent a potential therapeutic approach for protecting the RPE from oxidative stress-induced injury in dry AMD, although further validation in human tissues will be necessary.}, }
@article {pmid41405094, year = {2025}, author = {Enzendorfer, ML and Mai, J and Riedl, S and Bogunovic, H and Menten, MJ and Rueckert, D and Fritsche, LG and Prevost, AT and Sivaprasad, S and Pfau, M and Scholl, HPN and Lotery, AJ and Sacu, S and Schmidt-Erfurth, U}, title = {Functional Outcomes Across High-Risk OCT-Based Phenotypes in Intermediate Age-Related Macular Degeneration-PINNACLE Study Report 11.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {54}, pmid = {41405094}, issn = {1552-5783}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Angiogenesis Inhibitors/therapeutic use ; *Macular Degeneration/physiopathology/diagnosis ; Phenotype ; *Retina/physiopathology/pathology ; Retinal Drusen/physiopathology ; *Tomography, Optical Coherence/methods ; *Visual Acuity/physiology ; Visual Field Tests ; Visual Fields/physiology ; }, abstract = {PURPOSE: To evaluate the association between structural optical coherence tomography (OCT) biomarkers and functional outcomes in intermediate age-related macular degeneration (iAMD) and to investigate whether stratifying eyes by OCT-based biomarkers identifies phenotypes of iAMD with impaired visual function.<br><br>METHODS: The baseline cohort of the PINNACLE trial underwent OCT imaging, microperimetry, best-corrected visual acuity (BCVA), and low-luminance visual acuity (LLVA) testing. OCT volumes were assessed for the presence of different morphologic features. Drusen volume and outer nuclear layer (ONL) and ellipsoid zone (EZ) thickness were quantified. Linear mixed-effect models evaluated associations between each feature and functional outcomes, including a stratification into phenotypes based on significant OCT morphology with each eye assigned to a single group.<br><br>RESULTS: This analysis included 247 eyes of 190 patients (mean age, 74.2 &#xb1; 7.4 years). The presence of subretinal drusenoid deposits (SDDs) and markers of retinal atrophy were significant contributors to lower mean retinal sensitivity (P < 0.05). Also, higher drusen volume and lower ONL and EZ thickness were associated with lower sensitivity. Significant changes in BCVA, LLVA, and low-luminance deficits (LLDs) were associated with increasing drusen volume and the presence of hyperreflective foci (HRF). Significant functional differences were found between individual phenotypic groups, especially highlighting functional deficit in eyes with signs of early atrophy.<br><br>CONCLUSIONS: Integrating comprehensive analyses of structural OCT biomarkers with functional assessments revealed distinct phenotypic subtypes of iAMD that are associated with significant functional deficits. Particularly, early atrophy markers should be considered for patient selection and risk assessment in clinical trials and routine practice.}, }
@article {pmid41406245, year = {2026}, author = {Borrelli, E and Reibaldi, M}, title = {The importance of imaging biomarkers for predicting outcomes in neovascular AMD.}, journal = {European journal of ophthalmology}, volume = {36}, number = {2}, pages = {185-186}, doi = {10.1177/11206721251407415}, pmid = {41406245}, issn = {1724-6016}, }
@article {pmid41406248, year = {2026}, author = {Bartolomeo, N and Barbosa, M and Pannatier Schuetz, Y and Castro, DG and Nascimbeni, AC and Barry, MP and Ambresin, A}, title = {Pigment epithelial detachment as a biomarker for faricimab treatment outcomes in naïve neovascular age-related macular degeneration.}, journal = {European journal of ophthalmology}, volume = {36}, number = {2}, pages = {296-303}, doi = {10.1177/11206721251400508}, pmid = {41406248}, issn = {1724-6016}, mesh = {Humans ; Retrospective Studies ; *Retinal Detachment/diagnosis/drug therapy/etiology ; Male ; Female ; Tomography, Optical Coherence ; Visual Acuity/physiology ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Intravitreal Injections ; *Retinal Pigment Epithelium/pathology ; Angiogenesis Inhibitors/therapeutic use ; Fluorescein Angiography ; Biomarkers ; Aged, 80 and over ; Treatment Outcome ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Middle Aged ; Antibodies, Bispecific ; }, abstract = {ObjectiveTo assess baseline pigment epithelial detachment (PED) and other OCT biomarkers for predicting response to faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD).DesignThis was an observational, retrospective, single-arm, monocentric cohort study.Subjects and methodsFifty-seven eyes of 51 patients with naive nAMD-associated PED and treated with faricimab were included in the study. Best-corrected visual acuity (BCVA) and OCT were performed at baseline, monthly until Month 4, and at Months 6, 9, and 12. Fluid volume dynamics and other OCT biomarkers were quantified using an AI-based tool.ResultsAt Month 12, mean BCVA increased by 4 letters (P < 0.01), mean CRT decreased by 66.2 µm (P < 0.0001), and mean maximum PED height decreased by 70.4 µm (P < 0.001). AI-based PED dynamics showed rapid and sustained reductions from 488.2 nL at baseline to 166.6 nL at Month 12 (P < 0.0001), with more profound reductions in serous versus fibrous PED volume. All AI-quantified OCT biomarkers were significantly (P < 0.0001) changed from baseline after the loading phase. OCT biomarkers, PED, and fluid dynamics during the loading phase were correlated with functional and anatomic outcomes at Month 4 and Month 12.ConclusionsFaricimab had a rapid, profound and sustained drying effect on the retinas of eyes with nAMD and PED, with marked reductions in OCT biomarkers after loading and sustained to Month 12. These improvements coincided with significant improvements in BCVA. PED height, type, and volume at baseline correlated with short- and long-term treatment outcomes.}, }
@article {pmid41407269, year = {2026}, author = {Khanani, AM and Danzig, CJ and Heier, JS and Jaffe, GJ and Kaiser, PK and Lally, DR and Patel, SS and Vajzovic, L and Weng, CY and Patel, H and Clark, J and Desai, D and Luo, D and Henry, E and Holz, FG and , }, title = {Avacincaptad Pegol for Geographic Atrophy Secondary to Age-Related Macular Degeneration: Two-Year Efficacy and Safety Results from the GATHER2 Phase 3 Trial.}, journal = {Ophthalmology}, volume = {133}, number = {4}, pages = {451-465}, doi = {10.1016/j.ophtha.2025.12.011}, pmid = {41407269}, issn = {1549-4713}, mesh = {Humans ; Male ; Female ; *Geographic Atrophy/drug therapy/etiology/diagnosis ; Aged ; *Aptamers, Nucleotide/therapeutic use/adverse effects/administration &amp; dosage ; *Visual Acuity/physiology ; Treatment Outcome ; Double-Blind Method ; Aged, 80 and over ; Follow-Up Studies ; *Polyethylene Glycols/therapeutic use/administration &amp; dosage/adverse effects ; Tomography, Optical Coherence ; *Macular Degeneration/complications/drug therapy/diagnosis ; Intravitreal Injections ; Middle Aged ; Fluorescein Angiography ; Complement Inactivating Agents/therapeutic use/adverse effects ; }, abstract = {PURPOSE: Avacincaptad pegol (ACP) is a pegylated RNA aptamer that inhibits complement C5. The efficacy and safety of ACP 2 mg was investigated in GATHER2, with positive year 1 results published. Herein, 2-year results are reported.<br><br>DESIGN: Phase 3, randomized, sham-controlled study (ClinicalTrials.gov identifier, NCT04435366).<br><br>PARTICIPANTS: Patients with non-center point-involving geographic atrophy (GA).<br><br>METHODS: Eligible patients were randomized 1:1 to receive monthly ACP 2 mg (n = 225) or sham (n = 222) for 1 year. At month 12, patients who received ACP 2 mg were randomized again 1:1 to dosing every month (EM; n = 96) or every other month (EOM; n = 93) with ACP 2 mg. Patients who had received monthly sham continued with sham (n = 203).<br><br>MAIN OUTCOME MEASURES: The safety and efficacy of ACP versus sham administration over 2 years and the effect of ACP EM or EOM dosing in year 2.<br><br>RESULTS: Overall, 175 and 184 patients in the ACP and sham group completed the study at year 2, respectively. At 2 years, treatment with ACP demonstrated a continued reduction in GA growth (slope) with both ACP EM and EOM versus sham. From baseline to year 2, the mean rate of GA area growth was 4.46 mm[2] (standard error [SE], 0.25 mm[2]) with ACP EM and 5.18 mm[2] (SE, 0.17 mm[2]) with sham, a difference in growth of 0.724 mm[2] (95% confidence interval [CI], 0.133-1.315 mm[2]; P = 0.0165), representing a 14% difference. From baseline to year 2, the mean rate of GA area growth was 4.20 mm[2] (SE, 0.25 mm[2]) with ACP EOM, a difference in growth of 0.976 mm[2] (95% CI, 0.377-1.575 mm[2]; nominal P = 0.0015) versus sham, representing a 19% difference. The incidence of choroidal neovascularization (study eye) was 11.6% with ACP (all treated) versus 9.0% with sham over 2 years. No events of retinal vasculitis, ischemic optic neuropathy, or serious intraocular inflammation occurred over 2 years.<br><br>CONCLUSIONS: Dosing of ACP 2 mg, either EM or EOM, continued to reduce GA growth versus sham therapy over 2 years with no new safety signals compared with year 1.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41407273, year = {2026}, author = {Poudel, S and Cui, Y and Meng, T and Liang, W and Zhou, K and Cheng, R and Zhao, L and Yuan, T and Kaffash, E and Halquist, MS and Ma, JX and Xu, Q}, title = {Long-acting fenofibrate-loaded microparticles for treating retinal disorders.}, journal = {International journal of pharmaceutics}, volume = {689}, number = {}, pages = {126503}, pmid = {41407273}, issn = {1873-3476}, support = {R01 EY033477/EY/NEI NIH HHS/United States ; R01 EY034510/EY/NEI NIH HHS/United States ; R01 EY033330/EY/NEI NIH HHS/United States ; R01 EY034742/EY/NEI NIH HHS/United States ; R01 EY019309/EY/NEI NIH HHS/United States ; UG3 EY036558/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Fenofibrate/administration &amp; dosage/pharmacokinetics/pharmacology/chemistry ; Delayed-Action Preparations/administration &amp; dosage ; Male ; PPAR alpha/agonists ; Diabetes Mellitus, Experimental/drug therapy ; Rabbits ; *Diabetic Retinopathy/drug therapy ; Rats ; Mice ; Rats, Sprague-Dawley ; Intravitreal Injections ; Particle Size ; Hypolipidemic Agents/administration &amp; dosage ; Mice, Inbred C57BL ; Retina/drug effects/metabolism ; Mice, Knockout ; Receptors, LDL/genetics ; }, abstract = {Age-related macular degeneration (AMD) and Diabetic retinopathy (DR) are the most common forms of retinal disorders and are the leading causes of vision loss. Traditional treatments such as anti-VEGF therapies often require repeated intravitreal injections. Up to 40 % DR/AMD patients do not adequately respond to the anti-VEGF therapies. Therefore, non-VEGF therapies with alternative mechanisms are needed to address these unmet clinical needs. Fenofibrate (an FDA-approved low-cost oral drug) is a peroxisome proliferator-activated receptor-α (PPARα) agonist. We developed large-sized fenofibrate-loaded biodegradable microparticles capable of achieving high drug loading (up to 25 wt%) and sustained in vitro release exceeding six months (larger particles that load more drug and last longer). These long-acting Feno-MP exhibited desired particle size suitable for intravitreal injection (IVT) through fine gauge needles. The lead Feno-MP-F6 maintained sustained drug levels in the retina for at least 6 months following a single intravitreal injection without obvious toxic issues in rats and rabbits. This study investigated a 6-month-long therapeutic effects of a single dose of fenofibrate-loaded microparticles (Feno-MP) via a non-VEGF, PPARα-dependent mechanism in streptozotocin (STZ)-induced diabetic rats (a DR model), Vldlr[-/-] mice (a wet-AMD model), and Abca4[-/-]/Rdh8[-/-] mice (a dry-AMD model). Comprehensive analyses revealed broad therapeutic benefits across all the three disease models. In the STZ-induced DR model, one single IVT dose of Feno-MP restored both photopic and scotopic electroretinogram (ERG) responses, decreased leukostasis, and enhanced blood-retinal barrier function over a period of 6 months. In Vldlr[-/-] mice, a wet-AMD model, Feno-MP effectively reduced both subretinal and intraretinal neovascularization and decreased retinal vascular leakage for at least 6 months. In Abca4[-/-]/Rdh8[-/-] mice, single Feno-MP treatment preserved photoreceptors, increased cone photoreceptors survival and improved mitochondrial function up to 6 months. Our study showed that Feno-MP may become a promising therapy for DR, wet-AMD and even dry-AMD with only 1-2 IVT injections/year. This work represents the approach to repurpose the oral drug fenofibrate for long-lasting intraocular delivery through a sustained release system.}, }
@article {pmid41408005, year = {2026}, author = {Kayembe-Mulumba, B and Leffondré, K and Larsen, PP and Hucteau, &#xc9; and Korobelnik, JF and Delcourt, C and Delyfer, MN}, title = {Association of current Statin use with incident age-related macular degeneration: using time-varying propensity scores.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {3}, pages = {731-741}, pmid = {41408005}, issn = {1435-702X}, support = {Fondation Bordeaux Universit&#xe9;//Fondation Bordeaux Universit&#xe9;/ ; Mutuelles AXA//Mutuelles AXA/ ; Th&#xe9;a Pharma//Th&#xe9;a Pharma/ ; Macu-Life Project//Macu-Life Project/ ; }, mesh = {Humans ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Aged ; Female ; Male ; Incidence ; *Propensity Score ; Prospective Studies ; *Macular Degeneration/epidemiology/diagnosis ; Follow-Up Studies ; France/epidemiology ; Aged, 80 and over ; Time Factors ; Risk Factors ; Disease Progression ; *Population Surveillance ; }, abstract = {PURPOSE: Statins exhibit pleiotropic properties that may influence age-related macular degeneration (AMD) progression. However, since their prescription is predominant in older populations at high cardiovascular risk, a lack of robust approach to control for confounding by indication could partly explain controversial results in previous studies. We therefore analyzed the association of current statin use with incident AMD using time-varying propensity score-based inverse probability of treatment weighting (IPTW).<br><br>METHODS: Analysis of data from the ALIENOR study, a 14-year French prospective population-based cohort of 963 adults aged 73 years and older in Bordeaux, followed every 2-3 years (2006-2020), with repeated assessments of statin use through a face-to-face questionnaire. AMD status was assessed using retinal multimodal imaging every 2-3 years (2006-2020). Incident intermediate and advanced AMD were analyzed separately. Combining time-varying IPTW balancing and covariates adjustment, we fitted time-dependent Cox proportional hazards models to estimate adjusted hazard ratios (aHRs [95% confidence intervals]) for incident AMD associated with current statin use (defined as using statin within the last three years prior to the current visit).<br><br>RESULTS: Over a median follow-up of 7 years, cumulative incidence was 36% and 10% among the participants analyzed for intermediate (n&#x2009;=&#x2009;475) and advanced (n&#x2009;=&#x2009;692) AMD, respectively. After accounting for confounding by indication, current statin use was not associated with increased hazards of intermediate (aHR: 1.02 [0.72-1.45]) and advanced (aHR: 1.08 [0.61-1.91]) AMD. Analyses of statin subtypes (lipophilic and hydrophilic) and all lipid-lowering agents consistently yielded non-significant association with the hazards of AMD. Findings were consistent across sensitivity analyses.<br><br>CONCLUSION: These findings suggest that, after controlling for confounding by indication, statins may not substantially influence the risk of developing intermediate or advanced AMD in older adults, despite the biological plausibility.}, }
@article {pmid41408289, year = {2025}, author = {Kantor, AB and Rickert, M and Cheng, H and Flanagan, K and Salgotra, V and Suppahia, A and Ryu, JK and Widboom, PF and Warfield, JR and Akassoglou, K and Stavenhagen, JB}, title = {Development of a humanized anti-fibrin monoclonal antibody for the treatment of neuroinflammatory and retinal diseases.}, journal = {Journal of neuroinflammation}, volume = {23}, number = {1}, pages = {19}, pmid = {41408289}, issn = {1742-2094}, abstract = {UNLABELLED: Vascular dysfunction and subsequent innate immune activation are key players of neurodegenerative, retinal, and inflammatory diseases, including Alzheimer's disease (AD), multiple sclerosis (MS), diabetic retinopathy (DR), and age-related macular degeneration (AMD). At sites of vascular damage, conversion of the blood coagulation protein fibrinogen to fibrin exposes a cryptic inflammatory epitope, γ377–395, which can bind CD11b/CD18 and CD11c/CD18 complement receptors on microglia, macrophages, and dendritic cells. Genetic targeting of the fibrin γ377–395 epitope or its pharmacologic inhibition with the mouse monoclonal antibody 5B8 protects from inflammation and neurodegeneration in AD and MS mouse models. Here, we present the development of THN391, a first-in-class humanized antibody, to neutralize fibrin toxicity without adverse anticoagulant effects for the treatment of neurodegenerative, retinal, and inflammatory diseases. THN391 was affinity matured with 100-fold greater affinity than 5B8, engineered to lack Fc effector function, and have improved developability properties for clinical use. THN391 blocks the interaction of fibrin with CD11b/c and does not bind fibrinogen nor interfere with coagulation, consistent with the crystal structure of its binding interface to the γ377–395 epitope. THN391 and its Fc wild-type counterpart THN313 showed preclinical efficacy in experimental autoimmune encephalomyelitis (EAE) mouse models of MS and in a rodent model of retinal disease. Both THN391 and THN313 reduced demyelination, inflammatory foci, and clinical scores in EAE, demonstrating that anti-fibrin γ377-395 antibodies function as pure antagonists, blocking fibrin from activating CD11b/c complement receptors. THN391 was as effective as the standard of care vascular endothelial growth factor (VEGF) antagonists in reducing laser-induced neovascular lesions in a rat model of neovascular macular degeneration. Taken together, these results support the clinical development of THN391 for neurological diseases and ophthalmic indications.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-025-03650-w.}, }
@article {pmid41408394, year = {2026}, author = {Giraldo-Suarez, WY and Bonilla-Escobar, FJ and Lozano-Cruz, E}, title = {Comment on: 'Photobiomodulation-induced choriocapillaris perfusion enhancement and outer retinal remodelling in intermediate age-related macular degeneration: a promising therapeutic approach with short-term results'.}, journal = {Eye (London, England)}, volume = {40}, number = {3}, pages = {431}, pmid = {41408394}, issn = {1476-5454}, }
@article {pmid41411005, year = {2026}, author = {Lee, WK and Wong, TY and Chen, SJ and Sun, X and Cheung, CMG and Silva, R and Ricci, F and Zhang, X and Machewitz, T and Schulze, A and Schmidt-Ott, UM and Zhao, M and Hasanbasic, Z and Leal, S and Iida, T and , }, title = {Aflibercept 8 mg in Polypoidal Choroidal Vasculopathy: Post Hoc Analysis of the PULSAR Randomized Clinical Trial.}, journal = {JAMA ophthalmology}, volume = {144}, number = {2}, pages = {129-137}, pmid = {41411005}, issn = {2168-6173}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; *Choroid/blood supply ; *Choroidal Neovascularization/drug therapy/diagnosis/physiopathology ; Dose-Response Relationship, Drug ; Fluorescein Angiography ; Fundus Oculi ; Intravitreal Injections ; Polypoidal Choroidal Vasculopathy ; *Polyps/drug therapy/diagnosis/physiopathology ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; }, abstract = {IMPORTANCE: In the Study of the Effects of High-Dose Aflibercept Injected Into the Eye of Patients With an Age-Related Disorder That Causes Loss of Vision Due to Growth of Abnormal Blood Vessels at the Back of the Eye (PULSAR) phase 3 randomized clinical trial, treatment with aflibercept, 8 mg, demonstrated noninferior (4-letter margin) best-corrected visual acuity (BCVA) gains vs aflibercept, 2 mg, in participants with neovascular age-related macular degeneration (nAMD). This post hoc subgroup analysis evaluated clinical outcomes in participants with polypoidal choroidal vasculopathy (PCV).<br><br>OBJECTIVE: To compare the efficacy and safety of aflibercept, 8 mg vs 2 mg, monotherapy among participants with PCV in the PULSAR trial.<br><br>This was a post hoc subgroup analysis of the PULSAR randomized clinical trial. The setting included hospitals and clinics in 12 countries where indocyanine green angiography (ICGA) was performed to identify PCV. Included were a subgroup of adults with nAMD enrolled in the PULSAR trial with ICGA-confirmed PCV. Study data were analyzed from August 2020 to July 2022.<br><br>INTERVENTIONS: Participants were randomly assigned 1:1:1 to aflibercept, 8 mg, every 12 weeks or 16 weeks, or aflibercept, 2 mg, every 8 weeks, each after 3 initial monthly doses. From week 16, dosing intervals in the treatment arms receiving 8 mg every 12 weeks and every 16 weeks were shortened if predefined disease activity criteria were met at prespecified visits.<br><br>MAIN OUTCOMES AND MEASURES: Least-squares (LS) mean change in BCVA from baseline at week 48.<br><br>RESULTS: A total of 139 participants were included in this analysis. ICGA-confirmed PCV was present in 44 participants in the treatment group receiving aflibercept, 8 mg, every 12 weeks (mean [SD] age, 72.2 [8.1] years; 50% male), 41 participants receiving 8 mg every 16 weeks (mean [SD] age, 73.2 [8.7] years; 63% male), and 54 participants receiving 2 mg every 8 weeks (mean [SD] age, 72.6 [8.2] years; 69% male). Mean baseline BCVA letter score (approximate Snellen) was 56.3 (20/80), 60.1 (20/63), and 57.6 (20/80), respectively, with 41, 37, and 51 participants completing week 48 and receiving a mean (SD) of 6.1 (0.4), 5.1 (0.5), and 7.0 (0.2) injections, including 68 of 78 (87%) treated with aflibercept, 8 mg, who maintained dosing intervals of 12 weeks or longer. In the treatment arms receiving aflibercept, 8 mg, every 12 and 16 weeks and aflibercept, 2 mg, every 8 weeks, LS mean BCVA change from baseline at week 48 was +9.5, +8.4, and +9.1 letters, respectively (estimated difference, 0.40; 95% CI, -4.4 to 5.2 letters for 8 mg every 12 weeks vs 2 mg every 8 weeks; -0.7; 95% CI, -4.6 to 3.2 letters for 8 mg every 16 weeks vs 2 mg every 8 weeks), and polypoidal lesions were absent in 37%, 47%, and 38% of participants, respectively, who completed week 48.<br><br>CONCLUSIONS AND RELEVANCE: Results of this post hoc analysis of the PULSAR randomized clinical trial in participants with PCV demonstrated similar visual and anatomic outcomes with aflibercept, 8 mg vs 2 mg, as administered in this trial, supporting the use of aflibercept, 8 mg, as an alternative monotherapy for PCV.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04423718.}, }
@article {pmid41412300, year = {2026}, author = {Holt, CA and Niedert, C and Gedtal, M and Virgili, G and Hogg, RE and Qureshi, R}, title = {Prognostic factors for age-related macular degeneration progression: An overview of systematic reviews.}, journal = {Survey of ophthalmology}, volume = {71}, number = {3}, pages = {759-773}, doi = {10.1016/j.survophthal.2025.12.003}, pmid = {41412300}, issn = {1879-3304}, mesh = {Humans ; Disease Progression ; *Macular Degeneration/diagnosis ; Prognosis ; *Systematic Reviews as Topic ; Tomography, Optical Coherence/methods ; Risk Factors ; }, abstract = {Age-related macular degeneration (AMD) is a progressive and irreversible degenerative disease of the retina. Slowing progression to late AMD is the only way to prevent vision loss. Given that AMD treatments are noncurative, understanding the personal characteristics associated with progression is of critical importance for people with increased AMD risk. We conducted an overview of systematic reviews and meta-analyses (SRMAs) to assess the scope of the existing literature on prognostic factors (PFs) for AMD progression. We included all systematic reviews of PFs for the progression of AMD from early or intermediate to late. We used the Cochrane Eyes and Vision Database of Systematic Reviews (current to September, 2024). We identified 64 potentially relevant studies in the database and included 17 SRMAs, which most commonly studied functional or structural ocular (10/17), lifestyle (7/17), and intervention-related factors (7/17). Across all reviews, 218 PFs were reported. We extracted 79 and grouped these into 20 distinct types of PFs across 8 categories. The modifiable PFs with most evidence for slowing progression were increased dietary supplementation with antioxidants and multivitamins and reduced smoking. Most PFs were non modifiable. Although most PFs may not be targetable, by integrating high-risk optical coherence tomography findings, monitoring relevant comorbidities, and considering individual lesion characteristics, clinicians may better predict disease trajectories and support patients in slowing progression and preserving vision. Notably, no reviews studied social determinants as potential PFs for AMD progression, representing a critical gap in the evidence base. Future reviews should investigate social, systemic, and AI-identified biomarkers to provide a more comprehensive understanding of AMD progression.}, }
@article {pmid41412389, year = {2026}, author = {Hasbolat, H and Christensen, UC and Lund-Andersen, C}, title = {Vitreous Hemorrhage Due to Posterior Vitreous Detachment: Incidence of Retinal Detachment and Spontaneous Clearance during Observation.}, journal = {Ophthalmology}, volume = {133}, number = {4}, pages = {487-494}, doi = {10.1016/j.ophtha.2025.11.014}, pmid = {41412389}, issn = {1549-4713}, mesh = {Humans ; Male ; Female ; *Vitreous Hemorrhage/etiology/epidemiology/diagnosis ; *Retinal Detachment/epidemiology/etiology/diagnosis ; Retrospective Studies ; *Vitreous Detachment/complications/diagnosis ; Aged ; Incidence ; Middle Aged ; Remission, Spontaneous ; Vitrectomy ; Follow-Up Studies ; Aged, 80 and over ; Visual Acuity ; Risk Factors ; }, abstract = {PURPOSE: To investigate the natural course of vitreous hemorrhage (VH) due to posterior vitreous detachment (PVD).<br><br>DESIGN: Retrospective chart review.<br><br>PARTICIPANTS: Consecutive patients with VH due to presumed PVD between January 1, 2017, and December 31, 2021. Patients were followed conservatively.<br><br>METHODS: Patients with a first episode of VH at a large eye hospital were included retrospectively through review of medical charts. Patients with a history of proliferative diabetic retinopathy, retinal venous occlusion, or wet age-related macular degeneration were excluded.<br><br>MAIN OUTCOME MEASURES: Patients were followed for a minimum of 2 years until one of the following outcomes occurred: spontaneous VH clearing, rhegmatogenous retinal detachment (RRD), vitrectomy for persistent VH, or referral to a medical retinal service.<br><br>RESULTS: We included 366 patients (366 eyes); mean age was 65.2 years (standard deviation, 10.8), and 42.9% were women. Vitreous hemorrhage obscured the fundus in 295 eyes (80.6%). Vitreous hemorrhage cleared spontaneously in 227 eyes (62%), whereas RRD occurred in 61 eyes (17%). Rhegmatogenous retinal detachment plateaued at 20 days, indicating a time-dependent pattern. The risk of retinal detachment was significantly higher in men (hazard ratio [HR], 2.90 [1.64-5.12], P < 0.001) compared with women. Older patients exhibited a lower risk of RRD (HR, 0.27; 95% confidence interval [CI], 0.13-0.59, P < 0.001 in the 65- to 73-year age group and HR, 0.25; 95% CI, 0.10-0.63, P = 0.003 in the 73- to 94-year age group). Spontaneous clearing was associated with the density of VH. After 60 days, only 48% of the eyes cleared spontaneously. Thirty-six eyes did not clear, requiring vitrectomy after a median duration of 98 days (62.75-140.75).<br><br>CONCLUSIONS: This study demonstrates that VH presumed secondary to PVD showed great variability but generally took several months to clear, with 62% resolving spontaneously. However, 17% developed RRD, the majority during the first 3 weeks. Male gender and young age increased RRD risk. These findings highlight the importance of vigilant monitoring during the early phase and indicate that individual patient characteristics may guide management strategy. Further prospective studies are warranted to refine risk stratification and optimize management protocols in this patient population.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid41413355, year = {2026}, author = {Regillo, C and Kaiser, PK and Kertes, PJ and Gillies, M and Maio-Twofoot, T and Lawrence, D and Holz, FG}, title = {TALON phase IIIb study: 64 week results of brolucizumab versus aflibercept using treat-and-extend for neovascular age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {40}, number = {3}, pages = {369-375}, pmid = {41413355}, issn = {1476-5454}, mesh = {Humans ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage/adverse effects ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Male ; Female ; Aged ; Visual Acuity/physiology ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage/adverse effects ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; Aged, 80 and over ; Tomography, Optical Coherence ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage/adverse effects ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Double-Blind Method ; }, abstract = {OBJECTIVE: To compare the efficacy and safety of brolucizumab 6 mg and aflibercept 2 mg in patients with neovascular age-related macular degeneration (nAMD) using an identical 4-week adjustment Treat-and-Extend regimen.<br><br>METHODS: Patients received brolucizumab (n&#x2009;=&#x2009;366) or aflibercept (n&#x2009;=&#x2009;368) at Weeks 0, 4, 8 and 16, followed by 4-week interval adjustments depending on disease activity (DA) up to a maximum treatment interval of 16 weeks (q16w). After introduction of the urgent safety measure (USM), patients in either arm requiring a 4-week interval were discontinued from study treatment and moved to standard of care (SoC).<br><br>RESULTS: At Week 64, more brolucizumab patients had a last treatment interval of q16w with no DA vs aflibercept (28.4% vs 12.2%). In the brolucizumab arm, 22.4%, 26.0% and 23.2% of patients were on treatment intervals of 12, 8 and 4 weeks (on SoC after USM), respectively, compared with 23.9%, 22.0% and 41.8% in the aflibercept arm. The average change in best-corrected visual acuity (letters) from baseline at Weeks 60 and 64 was comparable (brolucizumab: +4.7; aflibercept: +4.9). Average change in central subfield thickness (&#xb5;m) at Weeks 60 and 64 was -182.9&#x2009;&#xb5;m in the brolucizumab arm vs -167.5&#x2009;&#xb5;m with aflibercept. Incidence of ocular adverse events (AEs), serious ocular AEs and AEs of special interest in the brolucizumab vs aflibercept arms were 31.1% vs 27.7%, 2.7% vs 0.8%, 6.0% vs 1.6%, respectively.<br><br>CONCLUSIONS: The Week 64 results in TALON reaffirmed those reported at Week 32, demonstrating extended treatment intervals and an overall favourable benefit/risk profile for brolucizumab in patients with nAMD.}, }
@article {pmid41415014, year = {2025}, author = {Selya, A}, title = {Associations between Electronic Cigarettes, Smokeless Tobacco, and Age-related Macular Degeneration in the 2017 United States National Health Interview Survey.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251405729}, pmid = {41415014}, issn = {2474-1272}, }
@article {pmid41417677, year = {2026}, author = {Berco, E and Kozlov, Y and Ostrovsky, M and Tuli, R and Kin Man Lee, T and Samocha, K and Shcolnik, E and Goldfeather Ben Zaken, S and Shoham-Hazon, N}, title = {Comparative Real-World Efficacy of Anti-Vascular Endothelial Growth Factor Agents in Neovascular Age-Related Macular Degeneration: A Multicenter Retrospective Study.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {249}, number = {1}, pages = {50-60}, pmid = {41417677}, issn = {1423-0267}, mesh = {Humans ; Retrospective Studies ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Ranibizumab/administration &amp; dosage ; Female ; *Visual Acuity ; Intravitreal Injections ; Male ; *Bevacizumab/administration &amp; dosage ; Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis ; Treatment Outcome ; Aged ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; Aged, 80 and over ; Fundus Oculi ; Dose-Response Relationship, Drug ; }, abstract = {UNLABELLED: <p>Introduction: This study directly compared the real-world effectiveness of bevacizumab, aflibercept 2 mg, and ranibizumab as first-line treatments for neovascular age-related macular degeneration (nvAMD).<br><br>METHODS: A multicenter retrospective cohort of treatment-na&#xef;ve nvAMD eyes managed with a treat-and-extend regimen in Israel and Canada. Primary outcomes were changes in visual acuity (VA) and central retinal thickness (CRT). Secondary outcomes included treatment burden (total injections and final maintained interval), non-response (persistent/worsening exudation or functional decline despite adequate treatment), non-extension (final interval of 4 weeks), and absence of active exudation.<br><br>RESULTS: A total of 322 eyes received bevacizumab (n = 174), aflibercept (n = 110), or ranibizumab (n = 38) over a mean follow-up of 16.75 &#xb1; 12.66 months. Mean VA improved from 0.77 &#xb1; 0.47-0.60 &#xb1; 0.45 logarithm of the minimum angle of resolution following an average of 10.5 &#xb1; 6.3 injections. Aflibercept produced greater CRT reduction (-51.94 &#x3bc;m; p < 0.001), fewer injections (-2.35; p = 0.001), longer final intervals (+2.14 weeks; p < 0.001), and lower odds of non-response (adjusted odds ratio [aOR] 0.016; p < 0.001) and non-extension (aOR 0.128, p < 0.001) versus bevacizumab. It showed the largest mean VA gain, just short of significance on multivariable analysis (p = 0.059). Ranibizumab showed greater CRT reduction (-44.53 &#x3bc;m; p = 0.012) and lower non-extension odds (aOR 0.079; p = 0.001) than bevacizumab but did not significantly reduce treatment burden or improve VA.<br><br>CONCLUSION: In this first real-world, head-to-head comparison, aflibercept and ranibizumab outperformed bevacizumab in key anatomic and treatment-efficiency outcomes, with aflibercept showing the most consistent advantages. These findings highlight clinically relevant differences among anti-vascular endothelial growth factor agents and underscore the importance of real-world data to guide nvAMD management. </p>.}, }
@article {pmid41418433, year = {2026}, author = {Song, SY and Lee, SH and Park, JW and Lim, HK and Seo, JW and Park, DH and Cho, SS}, title = {Protective effects of a 1:1 mixture of 7,17-dihydroxy-DHA and 10,17-dihydroxy-DHA (SF) against blue light-induced retinal damages in A2E-laden ARPE-19 Cells.}, journal = {Tissue &amp; cell}, volume = {99}, number = {}, pages = {103287}, doi = {10.1016/j.tice.2025.103287}, pmid = {41418433}, issn = {1532-3072}, mesh = {Humans ; *Light/adverse effects ; *Retinal Pigment Epithelium/drug effects/pathology/radiation effects/metabolism ; *Docosahexaenoic Acids/pharmacology ; Apoptosis/drug effects/radiation effects ; Cell Line ; Cell Survival/drug effects/radiation effects ; Lutein/pharmacology ; *Protective Agents/pharmacology ; Oxidative Stress/drug effects ; *Retina/pathology/drug effects/radiation effects ; Blue Light ; Retinoids ; }, abstract = {In this study, we investigated the anti-age-related macular degeneration (AMD) effects of SF, a 1:1 mixture of 7,17-dihydroxy-docosahexaenoic acid (DHA) and 10,7-dihydroxy-DHA, in human retinal pigmented epithelial (RPE) cells. Cytotoxicity in RPE cells was first confirmed, while non-toxicity was confirmed at concentrations below 2 μg/mL. Irradiation of RPE cells with bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E) and blue light resulted in a cell viability of less than 80 %, whereas SF treatment increased cell viability in a concentration-dependent manner. In addition, apoptosis induced by A2E and blue light was found to be regulated by lutein and SF. Lutein and SF treatments regulated the Bcl family, with SF showing stronger efficacy in regulating Bax and Bad expression than lutein. Furthermore, SF affected MAPKs, particularly by regulating the expression of JNK and p-38. SF may have similar effects on the expression of inflammatory proteins and pro-inflammatory cytokines at 5 μg/mL and 2 μg/mL concentrations of lutein and SF. Lastly, SF appeared to regulate the expression of Nrf2, OH-1, SOD1, and 4-HNE, which are biomarkers of oxidative and carbonyl stress. In conclusion, SF may exert its protective effects by regulating various signaling pathways in response to A2E and blue light stimulation at the cellular level.}, }
@article {pmid41420177, year = {2025}, author = {Wang, K and Tian, T and Chen, Z and He, X and Xiang, Y and Zuo, G and Cheng, S}, title = {Therapeutic potential of curcumin in ophthalmic diseases: mechanisms and clinical applications.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1408}, pmid = {41420177}, issn = {1479-5876}, mesh = {*Curcumin/therapeutic use/pharmacology ; Humans ; *Eye Diseases/drug therapy ; Animals ; Antioxidants/therapeutic use ; Clinical Trials as Topic ; }, abstract = {Ocular diseases impacting both the front and back segments of the eye are major contributors to worldwide vision loss. Curcumin, extracted from the rhizome of Curcuma longa, is a lipophilic polyphenol whose broad pharmacologic profile, including antioxidant, anti-inflammatory, antimutagenic, antimicrobial, and antineoplastic, renders it an attractive prospect for ocular therapeutics. However, much of the existing research primarily focuses on the general mechanisms of curcumin in the human body, with a lack of comprehensive reviews specifically addressing its mechanisms in ophthalmic diseases. Therefore, this review aims to explore curcumin's therapeutic potential in ophthalmic disorders and examine its mechanisms of action in terms of its anti-inflammatory, antioxidant, anti-angiogenic, neuroprotective roles, and antibacterial effects. The influence of curcumin on a range of ocular diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, cataracts, dry eye disease, pterygium, and uveitis, was also discussed. An analysis of preclinical and clinical studies conducted over the past 5 years suggested that curcumin holds promise as a therapeutic agent for various eye disorders. Furthermore, the review addressed the challenges faced in the clinical translation of curcumin in ophthalmology, such as issues related to dosage, formulation, and long-term safety. Despite curcumin's promising efficacy in preclinical models, several hurdles remain in its clinical application, highlighting the need for further research to facilitate its broader use in ophthalmic treatment.}, }
@article {pmid41420782, year = {2026}, author = {Lopez, J and de Carlo Forest, TE and Azargui, S and Gill, ZS and Lisker-Cervantes, A and Gnanaraj, R and Lynch, AM and Palestine, AG and Mandava, N and Mathias, MT and Manoharan, N and Grove, N and Bradley, C and Patnaik, JL}, title = {Visual functioning and geographic atrophy imaging characteristics in age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {4}, pages = {927-934}, pmid = {41420782}, issn = {1435-702X}, support = {Research to Prevent Blindness//Research to Prevent Blindness/ ; Frederic C. Hamilton Macular Degeneration Foundation//Frederic C. Hamilton Macular Degeneration Foundation/ ; Helene and Marshall Abrahams AMD Research Fund//Helene and Marshall Abrahams AMD Research Fund/ ; UM1 TR004399/TR/NCATS NIH HHS/United States ; UM1 TR004399/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Geographic Atrophy/diagnosis/physiopathology/etiology ; *Visual Acuity/physiology ; Male ; Cross-Sectional Studies ; Female ; Aged ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Macular Degeneration/physiopathology/diagnosis/complications ; *Fovea Centralis/pathology ; Aged, 80 and over ; Fundus Oculi ; Follow-Up Studies ; Surveys and Questionnaires ; Middle Aged ; *Registries ; }, abstract = {PURPOSE: To investigate the relationship between visual functioning as measured by the National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25) and geographic atrophy (GA) imaging characteristics including foveal involvement, multifocal lesions, and GA size.<br><br>METHODS: This cross-sectional cohort study included patients from the University of Colorado Age-related macular degeneration (AMD) registry, enrolled between July 2014 and May 2023, who had GA in at least one eye and completed the VFQ-25 at time of study enrollment. GA size was averaged between the two eyes for each patient. General linear modeling was used to assess the association between GA imaging characteristics with the outcome of Rasch-transformed VFQ-25 scores.<br><br>RESULTS: A total of 140 AMD patients with GA and VFQ-25 scores were included in the study. LogMAR visual acuity for the better-seeing eye of each patient was negatively associated with Rasch-transformed VFQ scores (-3.03, standard error (SE): 0.46, p&#x2009;<&#x2009;0.0001). Foveal involvement in both eyes was significantly associated with worse Rasch-transformed scores when compared to those without foveal involvement in either eye (-1.33, SE: 0.38, p&#x2009;=&#x2009;0.0006). Multifocal lesions in both eyes compared with unifocal lesions in both eyes had no significant difference in score (p&#x2009;=&#x2009;0.179). GA size was significantly associated with worse VFQ-25 scores (-0.09, SE: 0.02), p&#x2009;<&#x2009;0.0001), which did not remain significant after adjustment for LogMAR of both eyes (p&#x2009;=&#x2009;0.137).<br><br>CONCLUSIONS: We found bilateral foveal involvement and averaged GA size were significantly associated with worse Rasch-transformed VFQ-25 scores, but these associations did not remain significant after adjustment for visual acuity. Unilateral GA was significantly associated with better scores. This study highlights the impact GA imaging characteristics and bilateral involvement have on visual functioning.<br><br>KEY MESSAGES: WHAT IS KNOWN: Geographic atrophy (GA) in age-related macular degeneration negatively impacts visual functioning, and prior studies suggest that both lesion characteristics and visual acuity contribute to patient-reported outcomes.The gold-standard for Telangiectatic capillaries (TelCaps) detection is indocyanine green angiography, which is invasive and may not be readily available in all settings.<br><br>WHAT IS KNEW: Bilateral foveal involvement and larger GA size were significantly associated with worse visual functioning as measured by Rasch-transformed VFQ-25 scores.Infrared reflectance imaging complemented by optical coherence tomography B-scans are effective in the detection and measurement of TelCaps, which appeared to be dynamic lesions that remodel over time. Patients with unilateral GA reported better visual functioning, underscoring the importance of preserving vision in the better-seeing eye.Eyes with DME and TelCaps with at least one year of follow-up ended up with persistent edema and stable or worse vision after injection therapy.}, }
@article {pmid41421557, year = {2026}, author = {Lai, A and Issa, M and Pereira, A and Ghafri, MA and Dollin, M and Hurley, B and Chhablani, J and Yan, P}, title = {Age-related choroidal atrophy: A systematic review of multimodal imaging, clinical features, and differentiation from other forms of macular degeneration.}, journal = {Survey of ophthalmology}, volume = {71}, number = {3}, pages = {774-779}, doi = {10.1016/j.survophthal.2025.12.005}, pmid = {41421557}, issn = {1879-3304}, mesh = {Humans ; *Choroid/pathology/diagnostic imaging ; *Multimodal Imaging/methods ; *Macular Degeneration/diagnosis ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Geographic Atrophy/diagnosis ; Atrophy ; Diagnosis, Differential ; Retinal Pigment Epithelium/pathology ; Fundus Oculi ; }, abstract = {We conducted a systematic review on the clinical and imaging characteristics of age-related choroidal atrophy (ARCA) that distinguish ARCA from age-related macular degeneration (AMD) and geographic atrophy (GA). Studies were included if they reported on ARCA using clinical or multimodal imaging criteria and differentiated it from AMD and GA. Extracted data included subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), inner retinal layer thicknesses, and fundus findings. Risk of bias was assessed using the Joanna Briggs Institute checklists. Narrative synthesis and descriptive statistics were performed (PROSPERO (ID: CRD420251041101)). Seven studies (n = 329 patients) met inclusion criteria. ARCA was characterized by choroidal thinning (mean SFCT: 69.8-96.45 µm), preserved retinal pigment epithelium (RPE) on fundus autofluorescence, scleral visibility, and fundus features including peripapillary atrophy (83.3 %), tessellated fundus, and pseudodrusen. Compared to control, patients with ARCA had significantly thinner peripapillary nerve fiber layer (mean: 84.2 µm vs. 90.2 µm; p = 0.047) and reduced mean ganglion cell layer, macular internal plexiform layer and CVI. ARCA contrasts with AMD and GA by its distinct imaging features, less severe visual impairment, higher glaucoma prevalence (35.3 %), and more favorable response to anti-vascular endothelial growth factor agents when choroidal neovascularization is present. ARCA is a distinct clinical entity characterized by specific choroidal and retinal findings on multimodal imaging including lower CVI, thin SFCT, preserved RPE with scleral visibility, peripapillary atrophy, and inner retinal thinning. Further studies are warranted to standardize diagnostic criteria and understand long-term outcomes of ARCA.}, }
@article {pmid41422350, year = {2026}, author = {Zhang, C and Gilead, N and Jiang, Z and Fenner, BJ and Tan, AC and Chan, HH and Teo, KYC and Cheung, CMG}, title = {Cuticular drusen in Asian neovascular age-related macular degeneration: Clinical features and polypoidal choroidal vasculopathy association.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {3}, pages = {743-751}, pmid = {41422350}, issn = {1435-702X}, support = {OFLCG23 may-0032//National Medical Research Council Open Fund Large Collaborative Grant/ ; }, }
@article {pmid41422988, year = {2026}, author = {Ghosh, S and Parua, P and Jana, K and Ghosh, SK and Ghosh, A and Debnath, B and Halder, J and Sahoo, RK and Rai, VK and Dash, P and Das, C and Kar, B and Ghosh, G and Rath, G}, title = {Recent advances of novel nanoformulations combatting blue light hazards in the retina.}, journal = {Experimental eye research}, volume = {264}, number = {}, pages = {110806}, doi = {10.1016/j.exer.2025.110806}, pmid = {41422988}, issn = {1096-0007}, mesh = {Humans ; *Light/adverse effects ; *Retina/radiation effects ; *Retinal Diseases/etiology/drug therapy/prevention &amp; control ; *Drug Delivery Systems/methods ; *Nanoparticles ; Animals ; Oxidative Stress/drug effects ; *Antioxidants/administration &amp; dosage ; Blue Light ; }, abstract = {Exposure to blue light significantly threatens retinal health, affecting approximately 73 % of the global population. It impairs vision, lowers the quality of life, and adds to public health challenges. Its treatment is getting difficult due to chronicity, limited drug efficacy, side effects, and ocular barriers that hinder conventional drug delivery. Nanoformulations (NFs) have gained attention as adaptable drug delivery systems (DDSs), offering controlled release and customizable physicochemical characteristics. Their application in ocular therapy has shown promise for targeting both anterior and posterior segments of the eye. By accommodating a broad spectrum of therapeutic agents, these nanocarriers help address the limitations of traditional retinal drug delivery methods and offer potential in mitigating blue light-induced retinal damage. Several NFs have shown significant promise in addressing blue light hazards and the retina-related diseases through various mechanisms. Nano-based formulations offer promising strategies for protecting the retina and treating retinal diseases caused by blue light exposure. Antioxidant-loaded liposomes and hydrogels, such as those containing lutein and zeaxanthin, help reduce oxidative stress. In contrast, curcumin-loaded nanoparticles (Cur-NPs) mitigate inflammation in conditions like age-related macular degeneration (AMD) and diabetic retinopathy (DR). Polymeric NPs enable gene-specific silencing of pathogenic targets, and metallic NPs enhance photothermal therapy by selectively destroying abnormal retinal cells. These advanced delivery systems, including protective nanofilms, offer improved bioavailability, targeted delivery, and minimal side effects, making them effective tools in combating retinal damage. This review emphasizes the potential of NFs for advanced drug delivery against blue light-induced retinal hazards, highlighting pharmaceutical and pharmacological findings, recent insights, key challenges, and proposed solutions for a better future.}, }
@article {pmid41423015, year = {2026}, author = {Chen, X and Zhuang, X and He, G and Li, M and Zhang, X and Pu, J and Ji, Y and Zhang, Y and Hao, X and Wen, F}, title = {Increased choroidal stromal volume and altered choriocapillaris perfusion in neovascular AMD: An SS-OCTA association study.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {57}, number = {}, pages = {105327}, doi = {10.1016/j.pdpdt.2025.105327}, pmid = {41423015}, issn = {1873-1597}, mesh = {Humans ; Female ; Male ; Cross-Sectional Studies ; *Choroid/blood supply/diagnostic imaging/pathology ; Aged ; *Tomography, Optical Coherence/methods ; Middle Aged ; *Wet Macular Degeneration/diagnostic imaging/pathology ; Fluorescein Angiography/methods ; Aged, 80 and over ; *Choroidal Neovascularization/diagnostic imaging ; }, abstract = {PURPOSE: This study aimed to characterize quantitative choroidal metrics using swept-source optical coherence tomography angiography (SS-OCTA) across different stages associated with neovascular age-related macular degeneration (nAMD) and to identify structural and vascular associations.<br><br>METHODS: This cross-sectional study utilized SS-OCTA to quantify 6.0 &#xd7; 6.0 mm&#xb2; macular choriocapillaris flow density (CCFD), choroidal volume (CV), choroidal stromal volume (CSV), and choroidal vascular volume (CVV), choroidal stromal index (CSI), choroidal vascularity index (CVI) and CSV/CVV ratio. Comparisons were conducted between each pair of three groups: control eyes from healthy participants, fellow eyes and nAMD affected eyes from the same unilateral nAMD patients (fellow eyes representing a potential preclinical stage).<br><br>RESULTS: The study included 230 healthy control eyes from 116 age- and sex- matched participants, 110 unaffected fellow eyes and 104 nAMD affected eyes from 110 unilateral nAMD patients. Median CCFD was 45.33% (IQR: 4.82%) in controls, 46.50% (IQR: 2.35%) in fellow eyes and 44.41% (IQR: 6.68%) in nAMD eyes. Significant differences were found between controls and fellow eyes (Adjusted P = 0.003) and between fellow eyes and nAMD eyes (Adjusted P < 0.001). Median CSV was significantly higher in both unaffected fellow eyes (5.92 mm&#xb3;, IQR: 2.67 mm&#xb3;; Adjusted P = 0.006) and nAMD affected eyes (6.12 mm&#xb3;, IQR: 2.71 mm&#xb3;; Adjusted P = 0.012) compared to controls (5.49 mm&#xb3;, IQR: 2.00 mm&#xb3;). Other absolute volumes also showed significant intergroup differences: CV differed between control and fellow eyes (Adjusted P = 0.033), while CVV differed significantly only between affected and fellow eyes (Adjusted P = 0.015). In contrast, normalized compositional metrics (CSI, CVI and CSV/CVV ratio) showed no significant intergroup differences (all Adjusted P > 0.05). Multivariate regression analysis in nAMD affected eyes revealed an overall inverse correlation between CSV and CCFD, with this relationship reaching statistical significance the superior nasal, nasal, inferior temporal, inferior and inferior nasal quadrants (P < 0.05).<br><br>CONCLUSION: This cross-sectional study demonstrated an association between increased CSV and the presence of nAMD, including in high-risk fellow eyes. The inverse correlation between CSV and CCFD in nAMD eyes suggested a potential interplay between stromal expansion and microvascular compromise. These findings highlighted increased CSV as a candidate biomarker that warranted investigation in future longitudinal studies to determine its prognostic value for nAMD development.}, }
@article {pmid41424614, year = {2025}, author = {Song, X and Gao, G and Ye, K and Xu, P and Wang, Y and Zhang, S and Zheng, D and Ge, J and Zhong, X}, title = {Subretinal suspensions of hiPSC-derived retinal pigment epithelium cells form functional monolayers in NOD-SCID mice facilitating treatment of advanced retinal diseases.}, journal = {Regenerative therapy}, volume = {30}, number = {}, pages = {503-514}, pmid = {41424614}, issn = {2352-3204}, abstract = {INTRODUCTION: Transplantation of human induced pluripotent stem cells derived retinal pigment epithelium (hiPSC-RPE) is regarded as one of the most promising strategies for advanced retinal degenerative diseases leading to blindness, such as age-related macular degeneration. Despite its therapeutic potential, this approach is encumbered by critical challenges, notably the survival of donor RPE cells post-transplantation and the successful reconstruction of a functional RPE layer.<br><br>METHODS: With our previously reported strategy, abundant hiPSC-RPEs were generated from human induced pluripotent stem cells. These cells were characterized in vitro by morphology, marker expression and function. Further, hiPSC-RPE cell suspensions were injected into the eyes of NOD-SCID mice. Animals were monitored by optical coherence tomography screening and color fundus imaging to evaluate the survival of hiPSC-RPEs. Polarity, maturity, integration and phagocytosis of hiPSC-RPEs were analyzed histologically.<br><br>RESULTS: hiPSC-RPE cells exhibited a cobblestone morphology with abundant microvilli and tight junctions, expressed RPE specific molecular markers, and possessed ability to phagocytize photoreceptor outer segments (POS), thereby resembling the characteristics of the native human RPE cells. Following transplantation into NOD-SCID mice, the cells survived for the 8-week testing period and formed a highly organized monolayer in regions with an intact Bruch's membrane (BM) in the host retina. The reconstructed RPE layer expressed both human-specific and RPE-specific markers with POS phagocytic function. No severe adverse effects, such as malignant tumors or infections, were observed.<br><br>CONCLUSIONS: These findings demonstrate that hiPSC-RPE suspensions can survive and form RPE monolayers with morphological and functional features analogous to those of native human RPE cells in the host retina with a healthy BM. Our study may facilitate the development of cell-based therapies for treatment of advanced retinal degenerations.}, }
@article {pmid41425305, year = {2025}, author = {Jensen, EG and Jakobsen, TS and Schnabolk, G and Wilson, K and Rask-Pedersen, M and Jensen, N and Andersen, GR and Thiel, S and Aagaard, L and Rohrer, B and Askou, AL and Corydon, TJ}, title = {Nanobody-based gene therapy targeting complement component C3 reduces choroidal neovascularization in mice.}, journal = {Molecular therapy. Methods &amp; clinical development}, volume = {33}, number = {4}, pages = {101620}, pmid = {41425305}, issn = {2329-0501}, abstract = {Wet age-related macular degeneration (wAMD) is a leading cause of vision loss and is characterized by choroidal neovascularization (CNV). Current CNV management requires multiple treatments and lacks long-term efficiency, creating a need for better therapeutics. wAMD pathogenesis is associated with excessive activation of the complement system, contributing to retinal damage. Therefore, we generated a vector expressing the small alternative pathway-targeting nanobody, hC3Nb1, to treat wAMD. We demonstrate that hC3Nb1 is efficiently expressed and secreted by mammalian cells and shows full alternative pathway and partial classical pathway inhibition in vitro. A dual-promoter approach was used to generate a lentiviral-based vector for co-expression of hC3Nb1 and marker protein eGFP. Profound and safe hC3Nb1-expression, along with its secretion from the retinal pigment epithelium (RPE), was confirmed following subretinal injection of nanobody expressing-vector in mice. The therapeutic potential of vector-encoded hC3Nb1 was demonstrated in vitro by protecting RPE from complement-mediated stress, and in vivo by reducing laser-induced CNV sizes in a mouse model consistent with complement inhibition. For the first time, nanobodies expressed in the eye are used therapeutically, and our findings suggest that hC3Nb1-based gene therapy may be a safe and long-acting treatment for wAMD and other chorioretinal diseases with dysregulated complement activation.}, }
@article {pmid41425574, year = {2025}, author = {Li, P and Wang, Q and Yang, Y and Ding, Z}, title = {Autoimmune thyroid disease and human health: a systematic review of Mendelian randomization studies.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1689498}, pmid = {41425574}, issn = {1664-3224}, mesh = {Humans ; *Mendelian Randomization Analysis ; *Thyroiditis, Autoimmune/genetics/epidemiology ; Genetic Predisposition to Disease ; *Autoimmune Diseases/genetics ; }, abstract = {UNLABELLED: We systematically summarized current Mendelian randomization (MR) evidence on the causal relationships between autoimmune thyroid disease (AITD) and a wide range of human health outcomes. Original MR studies related to AITD published up to March 1, 2025, were retrieved from PubMed and Embase. For studies investigating the same exposure-outcome associations, meta-analyses were performed to synthesize the evidence after excluding overlapping samples where applicable. The methodological quality of the included studies was assessed using the STROBE-MR checklist. A total of 123 MR publications met the inclusion criteria. MR analyses indicated that AITD significantly increased the risk of coronary atherosclerosis, deep venous thrombosis, chronic obstructive pulmonary disease, major depression, diabetic neuropathy, carpal tunnel syndrome, neuromyelitis optica spectrum disorder, diabetic retinopathy, childhood absence epilepsy, rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, inflammatory bowel disease, crohn's disease, vitiligo, myasthenia gravis, alopecia areata, type 1 and type 2 diabetes, sarcoidosis, frozen shoulder, drug eruptions, cataract, early age-related macular degeneration, pernicious anemia, Helicobacter pylori infection, temporomandibular disorders, migraine, frailty, primary biliary cholangitis, knee osteoarthritis, gout, and osteoporosis, while decreasing the risk of lung cancer, polyneuropathies, allergic rhinitis, telomere length, and serum vitamin A levels. The included MR studies were of high methodological quality and provided robust evidence supporting the bidirectional relationships between AITD and various health outcomes. These findings emphasize the importance and necessity of preventing and managing AITD while offering new perspectives and directions for future research on its prevention and treatment.<br><br>https://www.crd.york.ac.uk/prospero/, identifier CRD42023469038.}, }
@article {pmid41425744, year = {2025}, author = {Johari Moghadam, MM and Montazeri, F and Feldman, S and Lee, SC and Yiu, G and Moshiri, A and Emami-Naeini, P and Moussa, K and Park, SS}, title = {Longitudinal Choriocapillaris and Retinal Vascular Flow Changes on OCTA with Progression to Advanced AMD.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {4651-4662}, pmid = {41425744}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate retinal and choriocapillaris (CC) vascular flow changes on optical coherence tomography angiography (OCTA) associated with progression of intermediate age-related macular degeneration (iAMD) to geographic atrophy (GA) or neovascular AMD (nAMD).<br><br>PATIENTS AND METHODS: This retrospective, longitudinal cohort study included 68 eyes from 50 patients with iAMD at baseline who underwent OCTA and clinical examination at baseline and at 24 months. Quantitative analysis of CC flow deficits (FDs) and superficial capillary plexus vessel density (VD) was performed at baseline and after 24 months by comparing eyes that progressed to GA or nAMD to eyes that remained stable.<br><br>RESULTS: Over 24 months, 7 eyes (10.3%) developed GA and 9 eyes (13.2%) developed nAMD, including 2 that progressed to both. Eyes that developed GA had significantly greater CC FD total area at baseline when compared with stable iAMD eyes (p=0.013) and developed significant decrease in parafoveal VD (p=0.026) and full macular VD (p=0.019) after GA onset. In contrast, eyes that developed nAMD showed no significant OCTA differences at baseline when compared to stable iAMD eyes but developed a new significant increase in CC FD total area (p=0.044) and FAZ perimeter (p=0.036) after nAMD onset (p=0.044).<br><br>CONCLUSION: In iAMD eyes progressing to GA, CC ischemia was detectable before GA onset, with subsequent retinal VD loss after GA development. In iAMD eyes progressing to nAMD, CC ischemia developed concurrent with neovascularization. OCTA-derived CC and retinal flow metrics may serve as non-invasive biomarkers to stratify iAMD eyes at risk for progression.}, }
@article {pmid41425747, year = {2025}, author = {Helland-Hansen, BA and Sverstad, A and Petrovski, G and Larsen, SE}, title = {Dynamic Pupillary Responses in Age-Related Macular Degeneration: A Controlled Clinical Study Using High-Frequency Video-Oculography.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {4689-4707}, pmid = {41425747}, issn = {1177-5467}, abstract = {PURPOSE: To investigate whether dynamic pupillary responses differ between patients with age-related macular degeneration (AMD) and healthy controls (HC), and to evaluate their potential as functional biomarkers using high-frequency, VR-based video-oculography.<br><br>METHODS: A controlled clinical study included 17 AMD patients and 17 age-matched HCs; four AMD participants were excluded for low recording quality. Dynamic pupillary responses were recorded with the BulbiCam video-oculography system (400 Hz), which presented independent monocular light stimuli through multiple permutations of bright (300 cd/m&#xb2;) and dark (5 cd/m&#xb2;) conditions. Measured variables included pupil diameter, latency, peak velocity, and pupil diameter-time integral (PDTI). Each eye was tested separately, and repeated sessions were analysed for reliability (intraclass correlation coefficient, ICC), repeatability (agreement index, AI), and stability (stability index, SI). Group differences were assessed using analysis of variance (ANOVA) and receiver operating characteristic (ROC) analysis.<br><br>RESULTS: AMD eyes showed larger steady-state pupil diameter and higher PDTI than controls (p < 0.05). First peak velocity was reduced in the worst eye only, while latencies were unchanged. PDTI and diameter demonstrated high reliability and stability across repetitions, and ROC analysis confirmed effective group discrimination.<br><br>CONCLUSION: High-frequency VR pupillometry detected reproducible functional alterations in AMD, consistent with impaired macular photoreceptor input but preserved reflex transmission. PDTI and diameter serve as diagnostic (population-level) and monitoring (patient-level) biomarkers, offering a non-invasive and objective method for AMD detection and follow-up in clinical and research settings.}, }
@article {pmid41426719, year = {2025}, author = {Agius, D and Mamo, J and Calleja, N and Smith, AF and Carbonaro, F}, title = {Estimating the costs and quality of life impact of vision loss in the population aged 50-80 years in Malta: evidence from The Malta Eye Study.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1706208}, pmid = {41426719}, issn = {2296-2565}, mesh = {Humans ; Aged ; *Quality of Life ; Aged, 80 and over ; Male ; Middle Aged ; Female ; Malta/epidemiology ; *Vision Disorders/economics/epidemiology ; *Cost of Illness ; *Health Care Costs/statistics &amp; numerical data ; Prevalence ; }, abstract = {BACKGROUND: Visual impairment and related ocular conditions impose substantial direct, indirect, and intangible costs, encompassing healthcare expenses, productivity losses, and reduced quality of life. Despite the global relevance of visual impairment, no comprehensive cost analysis has yet been conducted in an older adult Maltese population aged 50-80 years.<br><br>METHODS: Prevalence estimates from the population-based Malta Eye Study were used to calculate indirect costs via the gross national income per capita method with disability weight assumptions. Direct medical costs for key ocular conditions, including refractive error, cataract, age-related macular degeneration, diabetic retinopathy, and glaucoma, were estimated using prevalence, hospital, and private data performance indices and relevant cost data, enabling estimation of service coverage and unmet care needs. Intangible costs were derived from quality-of-life measures using the National Eye Institute Visual Function Questionnaire-39 to calculate disability weights and years lived with disability (YLD).<br><br>RESULTS: The productivity losses from blindness and moderate-severe visual impairment among individuals aged 50-80 were estimated at &#x20ac;16.0 million per annum (95% CI &#x20ac;6.0-&#x20ac;43.0 million). The estimated annual direct medical costs from the main ocular causes were estimated to sum up to &#x20ac;53.4 million (95% CI &#x20ac;44.6-&#x20ac;67.0 million), with unmet needs amounting to &#x20ac;20.8 million (95% CI &#x20ac;15.5-&#x20ac;28.5 million). Cataract (56.9%) and refractive error (24.5%) accounted for the highest shares of such costs. Vision-related quality of life correlated with the severity and laterality of visual impairment. Mild unilateral visual impairment carried the highest YLD rate 2264.4 YLDs per 100,000 while uncorrected refractive error carried the highest YLD rate among the visually impairing causes (2452.7 YLDs per 100,000).<br><br>DISCUSSION: Visual impairment imposes a considerable economic and quality-of-life burden on an older adult population in Malta, driven largely by cataracts, refractive error, and productivity losses. These results emphasize the need for preventive and treatment strategies and underscore the importance of future cost-benefit and cost-effectiveness analyses to help guide eye health policy in Malta.}, }
@article {pmid41427444, year = {2025}, author = {Yi, C and Luo, C and Zhao, J and Roubeix, C and Lechner, J and Penalva, R and Yang, N and Liu, J and Wang, Q and Chakravarthy, U and Sennlaub, F and Chen, M and Xu, H}, title = {Long-term low-dose aspirin promotes laser-induced choroidal neovascularization through suppressing TSP-1 expression.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1716229}, pmid = {41427444}, issn = {1662-5102}, abstract = {PURPOSE: To investigate the impact of low-dose, long-term aspirin use on neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Adult C57BL/6J or Thbs-1[-/-] mice were treated with daily aspirin (1.25 mg/kg) for 8 weeks before being subjected to laser-induced choroidal neovascularization (CNV). The animals were left for 7-10 days with continued aspirin use before the eyes were collected for further investigations. Bone marrow-derived macrophages (BMDMs) and primary retinal pigment epithelial (RPE) cells were treated with different concentrations of aspirin (1, 10, 100 &#x3bc;M) for two days before being subjected to LPS+IFN&#x3b3; for 16 h. The expression of cytokine genes was evaluated by qRT-PCR. The concentrations of thrombospondin-1 (TSP-1) were measured by ELISA.<br><br>RESULTS: Aspirin treatment did not affect circulating immune cell profiles in normal mice but significantly increased CD11b[+] cells in laser-induced CNV mice. The treatment significantly increased the severity of laser-induced CNV and reduced serum levels of TSP-1. In vitro aspirin treatment upregulated Tnfa and Ccl22, down-regulated Thbs-1 mRNA expression, and reduced TSP-1 production in LPS+IFN&#x3b3;-treated M1 BMDMs but not RPE cells. Thbs-1[-/-] mice developed severe laser-induced CNV, which was not affected by aspirin intervention. nAMD patients had significantly lower serum levels of TSP-1 than healthy controls, although no significant difference was found between nAMD patients with and without aspirin use.<br><br>CONCLUSION: Low-dose long-term aspirin use promoted the severity of laser-induced CNV by down-regulating TSP-1. Lower serum levels of TSP-1 may be a risk factor for nAMD. The long-term ocular safety of aspirin should be validated in prospective cohorts.}, }
@article {pmid41428610, year = {2025}, author = {Muzi, A and Gregori, G and Mangoni, L and Mogetta, V and Chhablani, J and Fruttini, D and Fiore, T and Rizzo, C and Mariotti, C and Lupidi, M}, title = {Functional and Structural Impact of Switching to Bevacizumab in neovascular-AMD Patients Treated with Aflibercept or Ranibizumab.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721251409237}, doi = {10.1177/11206721251409237}, pmid = {41428610}, issn = {1724-6016}, abstract = {PurposeTo evaluate the functional and structural outcomes in patients with neovascular age-related macular degeneration (nAMD) switched from ranibizumab or aflibercept to bevacizumab.MethodsThis retrospective study included 197 eyes of 192 patients (mean age 83 ± 6 years; 38% male). Patients previously treated with ranibizumab (n = 79) or aflibercept (n = 118) were transitioned to bevacizumab. Best-corrected visual acuity (BCVA) was recorded with ETDRS charts and converted to logMAR. Spectralis SD-OCT was used to evaluate intraretinal and subretinal fluid, presence of retinal pigment epithelium detachment (PED), PED height and central retinal thickness (CRT) at baseline and after 6 months.ResultsMean BCVA decreased from 0.4 ± 0.3 to 0.5 ± 0.4 logMAR (p = 0.048). The proportion of eyes with intraretinal or subretinal fluid rose from 27% to 69% (p = 0.017). Subgroup analysis indicated greater functional and structural worsening in younger patients and in those switched from aflibercept. Mean PED height showed a non-significant increase from 163 ± 94 to 166 ± 95 µm (p = 0.091), mean PED height showed a non-significant increase from 163 ± 94 to 166 ± 95 µm (p = 0.091). In contrast, mean CRT increased substantially from 294 ± 30 µm at baseline to 310 ± 26 at 6 months (p (p < 1 × 10[-7]).ConclusionsSwitching from ranibizumab or aflibercept to bevacizumab may lead to reduced visual function and an increase in structural-OCT markers of disease activity, including greater intraretinal/subretinal fluid, CRT and worsening PED features, particularly in younger individuals and in eyes previously treated with aflibercept.}, }
@article {pmid41429246, year = {2026}, author = {Murray, M and Schifano, F and Chiappini, S and Corkery, JM and Guirguis, A}, title = {Potential Eye Disorders in People With and Without Type 2 Diabetes Mellitus Exposed to GLP-1 Receptor Agonists: An Examination of the FAERS (FDA Adverse Event Reporting System) Database.}, journal = {American journal of ophthalmology}, volume = {283}, number = {}, pages = {279-290}, doi = {10.1016/j.ajo.2025.12.015}, pmid = {41429246}, issn = {1879-1891}, mesh = {Humans ; *Diabetes Mellitus, Type 2/drug therapy ; Retrospective Studies ; *Adverse Drug Reaction Reporting Systems/statistics &amp; numerical data ; *Glucagon-Like Peptide-1 Receptor Agonists ; United States/epidemiology ; United States Food and Drug Administration/statistics &amp; numerical data ; *Hypoglycemic Agents/adverse effects/therapeutic use ; Female ; Male ; Databases, Factual ; Middle Aged ; Aged ; *Eye Diseases/chemically induced/epidemiology ; Glucagon-Like Peptides/adverse effects ; }, abstract = {PURPOSE: As use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for Type 2 diabetes (T2DM) and weight management increases, emerging research identifies various adverse drug reactions. This study aimed to expand this research base, focusing on eye disorders in people with and without T2DM, a novel consideration.<br><br>DESIGN: A retrospective clinical cohort disproportionality analysis of reports made to the Food and Drug Administration Adverse Event Reporting System (FAERS).<br><br>METHODS: FAERS was queried regarding selected GLP-1RAs. Python 3.11 was adopted to develop a program, quantifying reported cases between January 2017 - September 2025 (January 2022-September 2025 for tirzepatide) meeting the criteria for cases with and without T2DM. Main outcome measures Reporting Odds Ratios (RORs) >4.000 and 95% confidence intervals were calculated, with metformin and orlistat as controls.<br><br>RESULTS: Compared to metformin, semaglutide showed increased reporting of optic ischemic neuropathy (ROR: 12.269 [0.915-1.967]), cataract (ROR: 31.879 [2.463-4.461]) and retinopathy (ROR: 5.185 [0.556-2.736]) in T2DM patients, and retinopathy (ROR: 9.424 [1.081-3.406]) and retinal hemorrhage (ROR: 10.253 [0.319-4.336]) in non-T2DM patients. Tirzepatide showed increased reporting of optic ischemic neuropathy (ROR: 4.619 [0.726-2.335]) and macular degeneration (ROR: 15.579 [0.554-4.938]) in T2DM patients and eye swelling (ROR: 6.475 [0.407-3.329]) in non-T2DM patients. Liraglutide showed increased reporting of cataract (ROR: 53.866 [2.945-5.028]), diabetic retinopathy (ROR: 18.162 [1.753-4.045]) and macular degeneration (ROR: 26.261 [1.076-5.460]) in T2DM patients and cataract (ROR: 9.628 [1.387-3.142]) and macular degeneration (ROR: 9.557 [0.110-4.405]) in non-T2DM patients.<br><br>CONCLUSIONS: These results provide a signal of increased reporting of various eye disorders with GLP-1RA use compared to metformin across T2DM and non-T2DM patient cases. Further research is required to support these findings and confirm a biological causation.}, }
@article {pmid41429947, year = {2025}, author = {Gelir, F and Akan, T and Carmichael, OT and Bhuiyan, MS and Conrad, SA and Vanchiere, JA and Kevil, CG and Bhuiyan, MAN}, title = {Topological Feature Extraction from Multi-color Channels for Pattern Recognition: An Application to Fundus Image Analysis.}, journal = {Journal of imaging informatics in medicine}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10278-025-01791-1}, pmid = {41429947}, issn = {2948-2933}, support = {R01HL145753//Foundation for the National Institutes of Health/ ; P20 GM121307/GM/NIGMS NIH HHS/United States ; R01HL145753-01S1//Foundation for the National Institutes of Health/ ; R01HL172970//Foundation for the National Institutes of Health/ ; R01HL149264//Foundation for the National Institutes of Health/ ; R01HL145753-03S1//Foundation for the National Institutes of Health/ ; P20GM121307//Foundation for the National Institutes of Health/ ; }, abstract = {The automated analysis of medical images is crucial for early disease detection. In recent years, deep learning has become popular for medical image analysis. In this study, we employed color-based topological features with deep learning for pattern recognition. The data topology provides information about the image's shape and global features such as connectivity and holes. We used different color channels to identify changes in topological footprints by altering the image's color. We extracted topological, local binary pattern (LBP), and Gabor features and used machine learning and deep learning models for disease classification. The model's performance was tested using three open-source fundus image databases: the Asia Pacific Tele-ophthalmology Society (APTOS 2019) data, the Optic Retinal Image Database for Glaucoma Analysis (ORIGA), and the Automatic Detection Challenge on Age-Related Macular Degeneration (ICHALLENGE-AMD). We have found that topological features from different color models provide important information for disease diagnosis.}, }
@article {pmid41430144, year = {2025}, author = {Hengerer, FH and Stanzel, B and Hoyos-Chacon, J and Suarez, M and Beckers, S and Busatto, P and Badalà, F}, title = {Safety and efficacy of an extended macular vision intraocular lens (IOL) for age-related macular degeneration (AMD) in real-world settings.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {47}, pmid = {41430144}, issn = {1471-2415}, mesh = {Humans ; Retrospective Studies ; *Visual Acuity/physiology ; Female ; Male ; Aged ; *Lenses, Intraocular ; Aged, 80 and over ; *Macular Degeneration/surgery/physiopathology/complications ; *Lens Implantation, Intraocular ; Prosthesis Design ; Middle Aged ; Postoperative Complications ; Treatment Outcome ; }, abstract = {PURPOSE: To assess the safety and efficacy of the EyeMax Mono (SharpView Ophthalmology) extended macular vision intraocular lens (IOL), in patients with age-related macular degeneration (AMD) undergoing cataract surgery.<br><br>METHODS: This retrospective multicentre study analyzed real-world data from 196 AMD eyes (146 patients) across 15 medical centres in Europe. All eyes received the single-piece, hydrophobic acrylic, EyeMax Mono IOL. AMD severity was classified by the centre. Outcomes included intraoperative and postoperative complications and changes in corrected distance and near visual acuity (CDVA and CNVA, respectively).<br><br>RESULTS: The postoperative spherical equivalent was +&#x2009;1.25&#x2009;&#xb1;&#x2009;1.32 D. Postoperative LogMAR CDVA improved significantly from a baseline of 0.57&#x2009;&#xb1;&#x2009;0.38 to 0.38&#x2009;&#xb1;&#x2009;0.34 (n&#x2009;=&#x2009;191, p&#x2009;<&#x2009;0.001), while CNVA improved from 0.49&#x2009;&#xb1;&#x2009;0.32 at baseline to 0.35&#x2009;&#xb1;&#x2009;0.27 postoperatively (n&#x2009;=&#x2009;141, p&#x2009;<&#x2009;0.001). 63% gained&#x2009;>&#x2009;1 line of CDVA and 27.5% gained&#x2009;&#x2265;&#x2009;3 lines. For CNVA, 41.5% gained&#x2009;>&#x2009;1 line, and 21.8% gained&#x2009;&#x2265;&#x2009;3 lines. The greatest gains occurred in intermediate AMD eyes: CDVA&#x2009;+&#x2009;0.21 logMAR, CNVA&#x2009;+&#x2009;0.12 logMAR. Only 2.1% of eyes lost&#x2009;>&#x2009;1 line of CDVA or CNVA.<br><br>CONCLUSIONS: The EyeMax Mono intraocular lens (IOL) safely enhances both distant (CDVA) and near (CNVA) visual acuity in patients with age-related macular degeneration, particularly in eyes with intermediate AMD. These findings are consistent with those in the published scientific literature.}, }
@article {pmid41430718, year = {2025}, author = {Martins, B and Boia, R and Correia, D and Ribeiro-Rodrigues, T and Ramalho, J and Ambrósio, AF and Girão, H and Fernandes, R}, title = {Retinal pigment epithelium-derived extracellular vesicles mediate outer blood retinal barrier disruption in response to AMD-related stress.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {542}, pmid = {41430718}, issn = {1478-811X}, support = {Doctoral research fellowship 2020.04811//Foundation for Science and Technology (FCT, Portugal)/ ; CIBB (Center for Innovative Biomedicine and Biotechnology) research unit (UIDB/04539/Base/2020 and UIDP/04539/Programatico/2020)//Foundation for Science and Technology (FCT, Portugal)/ ; }, mesh = {*Extracellular Vesicles/metabolism ; Animals ; *Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/pathology/metabolism ; Swine ; *Blood-Retinal Barrier/metabolism/pathology ; Mice ; Lipopolysaccharides/pharmacology ; Mice, Inbred BALB C ; Humans ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss among the elderly, primarily affecting the central vision. This progressive degenerative disease is characterized by the dysregulation and degeneration of the retinal pigment epithelium (RPE), a crucial cell layer beneath the photoreceptors that maintains outer retinal homeostasis. Emerging evidence suggests that during AMD, stressed RPE cells release extracellular vesicles (EVs) carrying bioactive cargo, which may compromise the outer blood-retinal barrier (oBRB) and accelerate disease progression. This study explores the role of EVs released by RPE cells under pro-inflammatory conditions in disrupting retinal integrity.<br><br>METHODS: Highly polarized primary cultures of porcine RPE (pRPE) and porcine eyecups with the RPE exposed were treated with tumor necrosis factor (TNF), lipopolysaccharide (LPS), or EVs derived from inflamed RPE cells. Additionally, Balb/c mice were intravitreally injected with RPE-derived EVs.<br><br>RESULTS: We show that EVs secreted by the apical membrane domain of porcine RPE cells exposed to LPS or TNF impair the RPE monolayer in polarized cultures, disrupt the oBRB in ex vivo porcine eyecups, and induce retinal structural damage detected in vivo in Balb/c mice. Intravitreal injection of LPS-derived EVs triggers photoreceptor and RPE layers thinning, increases reactivity in astrocytes and M&#xfc;ller cells, promotes pro-inflammatory microglial activation and recruitment, particularly into the outer retina, and elevates retinal apoptosis. Mechanistically, matrix metalloproteinases (MMPs) activity mediates EV-induced RPE monolayer disruption, whereas MMPs activity inhibition mitigates these effects.<br><br>CONCLUSION: Our findings reveal a novel EV-driven mechanism contributing to retinal degeneration progression, highlighting inflammation-derived apical EVs as key players in diseases involving oBRB dysfunction. Targeting EV-mediated signaling and MMPs activity may offer therapeutic strategies for preserving retinal structure and function in inflammatory retinal diseases such as age-related macular degeneration.}, }
@article {pmid41432505, year = {2025}, author = {Yusef, Y and Avetisov, KS and Khalatyan, AS and Shishparenok, AN and Blinova, VG and Gladilina, YA and Zhdanov, DD}, title = {[Monocyte telomere length as a novel biomarker of macular atrophy and response to anti-VEGF therapy in age-related macular degeneration].}, journal = {Vestnik oftalmologii}, volume = {141}, number = {6}, pages = {52-61}, doi = {10.17116/oftalma202514106152}, pmid = {41432505}, issn = {0042-465X}, mesh = {Humans ; Male ; Female ; Aged ; Tomography, Optical Coherence/methods ; *Monocytes/metabolism/pathology ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Macular Degeneration/diagnosis/drug therapy ; Visual Acuity ; *Telomere/genetics ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Biomarkers ; *Macula Lutea/pathology/diagnostic imaging ; Treatment Outcome ; *Geographic Atrophy/diagnosis/drug therapy ; }, abstract = {UNLABELLED: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly. Monocyte telomere length is proposed as a marker of cellular senescence in this condition.<br><br>PURPOSE: This study investigated the association between monocyte telomere length and retinal parameters in different forms of AMD, as well as in patients receiving antiangiogenic therapy.<br><br>MATERIAL AND METHODS: Monocyte telomere length was measured in 84 patients (mean age 79&#xb1;9 years) divided into four groups: non-exudative AMD with geographic atrophy (neAMD-GA), neovascular AMD (nAMD) with macular atrophy (nAMD-MA), nAMD without MA, and controls. Monocytes were isolated using immunomagnetic separation, and telomere length was determined by quantitative PCR (qPCR). Retinal parameters were assessed via optical coherence tomography (OCT) of the macular region.<br><br>RESULTS: Significant telomere shortening was observed in AMD compared to the controls (p<0.05). In the nAMD-MA group, telomere length correlated positively with best-corrected visual acuity (BCVA) after treatment (rs=0.661; p=0.0014) and the type of atrophy (p<0.0001); shorter telomeres were associated with greater BCVA decline after therapy (rs=-0.452; p=0.0419). In nAMD without MA, telomere length correlated with reduced height of neuroepithelial detachment (NED) under anti-VEGF treatment (rs=0.50; p=0.0252). No significant associations were found in the neAMD-GA and control groups.<br><br>CONCLUSION: These findings highlight monocyte telomere length as a potential biomarker for predicting macular atrophy progression and treatment outcomes in AMD. Further research is needed to confirm these associations and to explore sex/ethnic disparities in telomere length in this disease.}, }
@article {pmid41432509, year = {2025}, author = {Neroeva, NV and Fursova, AZ and Faizrakhmanov, RR and Plyukhova, AA and Bobykin, EV and Gordeeva, MV and Karlova, EV and Bosov, ED and Nikiforova, AA}, title = {[Use of faricimab in neovascular age-related macular degeneration and diabetic macular edema in Russia. Results of the FARWATER retrospective study].}, journal = {Vestnik oftalmologii}, volume = {141}, number = {6}, pages = {82-91}, doi = {10.17116/oftalma202514106182}, pmid = {41432509}, issn = {0042-465X}, mesh = {Humans ; Male ; Female ; Russia/epidemiology ; Retrospective Studies ; *Macular Edema/drug therapy/diagnosis/etiology/physiopathology ; Visual Acuity/drug effects ; *Diabetic Retinopathy/drug therapy/diagnosis/complications/physiopathology ; Aged ; Treatment Outcome ; Angiogenesis Inhibitors/administration &amp; dosage ; Intravitreal Injections ; Middle Aged ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis ; Antibodies, Bispecific ; }, abstract = {UNLABELLED: Despite the positive outcomes of anti-VEGF therapy, neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) remain major medical and social challenges, and optimization of their treatment is an urgent need.<br><br>PURPOSE: This study evaluated the effectiveness of Vabysmo (faricimab) in the treatment of patients with nAMD and DME in real-world clinical practice in Russia.<br><br>MATERIAL AND METHODS: A multicenter retrospective analysis was conducted based on the medical records of 328 patients (370 eyes) with nAMD and 87 patients (112 eyes) with DME (both treatment-na&#xef;ve and previously treated with anti-VEGF agents) who received faricimab from July 2023 to February 2025. The following primary effectiveness indicators were assessed: changes in visual acuity (VA) and central retinal thickness (CRT) after the first four faricimab injections. Secondary outcome indicators included changes in VA, CRT, and selected disease biomarkers at 6, 12, and 18 months of treatment, as well as injection intervals during the maintenance phase.<br><br>RESULTS: After the first four consecutive faricimab injections, VA improved by 8.1 ETDRS letters (p<0.05) in the nAMD group and by 12.8 ETDRS letters (p<0.05) in the DME group. CRT decreased by 103.3 &#x3bc;m (p<0.05) and 177.4 &#x3bc;m (p<0.05), respectively. These improvements remained stable during further follow-up (8.78&#xb1;4.51 months in the nAMD group and 10.48&#xb1;5.24 months in the DME group, up to a maximum of 19 months in both groups). The proportion of patients who achieved injection intervals of &#x2265;12 weeks was 27.9% in the nAMD group and 38.5% in the DME group.<br><br>CONCLUSION: Faricimab demonstrated high clinical effectiveness in real-world settings in patients with nAMD and DME, with the potential to reduce the treatment burden for patients and the healthcare system.}, }
@article {pmid41432510, year = {2025}, author = {Fursova, AZ and Strunina, YV}, title = {[Analysis the frequency of using Aflibercept (8 mg) in the treatment of neovascular age-related macular degeneration and diabetic macular edema compared with other anti-VEGF agents].}, journal = {Vestnik oftalmologii}, volume = {141}, number = {6}, pages = {92-100}, doi = {10.17116/oftalma202514106192}, pmid = {41432510}, issn = {0042-465X}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Macular Edema/drug therapy/diagnosis/etiology ; Intravitreal Injections/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; *Diabetic Retinopathy/drug therapy/diagnosis/complications ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Ranibizumab/administration &amp; dosage ; Visual Acuity ; *Macular Degeneration/drug therapy/diagnosis ; }, abstract = {PURPOSE: This study aimed to evaluate the frequency of use of the drug aflibercept in the form of a 114.3 mg/mL, 0.263 mL solution for injection (hereinafter aflibercept 8 mg), compared with alternative anti-VEGF agents in adult patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) over a long-term period (2 years).<br><br>MATERIAL AND METHODS: A review of the literature was conducted to assess the frequency of administration of anti-VEGF drugs included in the Vital and Essential Drugs (VED) list as of 01.10.2025. Based on the results of published studies, an indirect comparison was performed evaluating the frequency of administration of aflibercept (114.3 mg/mL, 0.263 mL) with ophthalmic drugs used in clinical practice (aflibercept 40 mg/mL, 0.278 mL; brolucizumab 120 mg/mL, 0.23 mL; ranibizumab 10 mg/mL, 0.23 mL) in patients with nAMD and DME over 2 years of therapy. The difference in the number of injections should be interpreted as follows: a negative value indicates fewer injections of aflibercept 8 mg compared with brolucizumab 6 mg and ranibizumab 0.5 mg, while a positive value corresponds to fewer injections when compared with aflibercept 2 mg (as accepted in the original publication).<br><br>UNLABELLED: If the difference in frequency of drug administration was statistically significant, additional assessments were performed: the potential number of avoided injections when using a less frequent dosing regimen, and the potential number of additional patients who could receive such treatment.<br><br>RESULTS: Aflibercept 8 mg administered in dosing intervals extended up to 24 weeks for patients with nAMD was associated with a statistically significant reduction in the number of injections compared with aflibercept 2 mg: 2.37 (95% CI: 1.88 to 2.86) and 2.6 (95% CI: 2.11 to 3.09); with brolucizumab 6 mg: -1.82 (95% CI: -2.8 to -0.8) and -1.7 (95% CI: -3.0 to -0.4); with ranibizumab 0.5 mg: -7.17 (95% CI: -8.5 to -5.9) and -3.15 (95% CI: -3.7 to -2.6) in the first and second year, respectively.<br><br>UNLABELLED: Aflibercept 8 mg administered in dosing intervals extended up to 24 weeks for patients with DME was associated with a statistically significant reduction in the number of injections compared with aflibercept 2 mg: 3.57 (95% CI: 3.1 to 4.0) and 2.7 (95% CI: 2.1 tot 3.3); with brolucizumab 6 mg: -1.97 (95% CI: -2.5 to -1.4) and -1.56 (95% CI: -2.2 to -1.0) in the first and second year, respectively. In a similar comparison between aflibercept 8 mg and ranibizumab 0.5 mg (extended-interval regimen) in DME patients, the difference in the number of injections was 5.7 injections in both the first and second year; however, the value was calculated without determining the confidence interval (CI), which is a limitation of this study.<br><br>CONCLUSIONS: The use of aflibercept 8 mg in the treatment of nAMD and DME demonstrates a reduction in the number of intravitreal injections, accompanied by a significant reduction in the socioeconomic burden.}, }
@article {pmid41432839, year = {2025}, author = {Galindo, AM and Ohayon, A and Hod, K and Levin, MF and Geffen, N and Shulman, S}, title = {Real-world evidence of long-term durability and efficacy of faricimab as an advanced treatment line for NVAMD and DME.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {47}, pmid = {41432839}, issn = {1573-2630}, mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; Male ; Female ; Aged ; *Visual Acuity ; Angiogenesis Inhibitors/administration &amp; dosage ; *Macular Edema/drug therapy/diagnosis ; Follow-Up Studies ; Treatment Outcome ; Tomography, Optical Coherence/methods ; *Diabetic Retinopathy/drug therapy/diagnosis/complications ; Aged, 80 and over ; Time Factors ; *Wet Macular Degeneration/drug therapy/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography ; Middle Aged ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To evaluate the efficacy and durability of intravitreal Faricimab (Vabysmo) in patients with neovascular age-related macular degeneration (NVAMD) and diabetic macular edema (DME).<br><br>METHODS: A retrospective study was conducted at a tertiary ophthalmology center. Eyes with NVAMD or DME which had received previous Anti-vascular endothelial growth factor (A-VEGF) treatment before switching to Faricimab were included. Best-corrected visual acuity (BCVA), central subfield thickness (CST), and injection intervals were recorded at baseline and follow-up visits of up to 2.5 years.<br><br>RESULTS: A total of 192 eyes (160 with NVAMD and 32 with DME) from 155 patients were included. The mean patient age was 79.5&#x2009;&#xb1;&#x2009;9.6 years, with an average follow-up duration of 468.1&#x2009;&#xb1;&#x2009;120.4 days from baseline. In the NVAMD cohort, BCVA improved from 0.43&#x2009;&#xb1;&#x2009;0.33 logMAR at baseline to 0.34&#x2009;&#xb1;&#x2009;0.30 at 1.5 years (p&#x2009;<&#x2009;0.05). CST decreased significantly from a mean of 308.3&#x2009;&#xb1;&#x2009;65.3 Micrometers to 242.4&#x2009;&#xb1;&#x2009;44.8 Micrometers at two years (p&#x2009;<&#x2009;0.001). The mean interval between injections increased from a mean of 33.9&#x2009;&#xb1;&#x2009;9.6 days at baseline to 77.6&#x2009;&#xb1;&#x2009;42.6 days at two years, reflecting a significant extension throughout the observation period (p&#x2009;<&#x2009;0.001). In eyes with DME, CST declined from 403.6&#x2009;&#xb1;&#x2009;121.9 Micrometers at baseline to 303.2&#x2009;&#xb1;&#x2009;105.2 Micrometers at one year (p&#x2009;<&#x2009;0.001), while BCVA remained stable. Injection intervals extended from 34.4&#x2009;&#xb1;&#x2009;10.3 to 60.9&#x2009;&#xb1;&#x2009;20.5 days at one year (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: In this study of previously treated eyes with NVAMD and DME, Faricimab demonstrated sustained anatomical and functional benefits alongside meaningful injection interval extension.}, }
@article {pmid41432997, year = {2025}, author = {Liang, L and Song, Z and Li, Y and Li, H}, title = {The global disease burden and associated risk factors of age-related macular degeneration: a comprehensive analysis.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {50}, pmid = {41432997}, issn = {1573-2630}, mesh = {Humans ; *Macular Degeneration/epidemiology ; Male ; Female ; Risk Factors ; Prevalence ; Aged ; Global Burden of Disease/trends ; Middle Aged ; Global Health ; Disability-Adjusted Life Years ; Aged, 80 and over ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness among middle-aged and older adults, bringing a heavy health burden. Understanding the patterns of AMD disease burden and the risk factors associated with early AMD development is crucial for formulating targeted public health policies.<br><br>METHODS: We estimated the prevalence of AMD and disability-adjusted life year (DALY) using data from the 2021 Global Burden of Disease (GBD). Our analysis examined trends in prevalence and DALY by age, sex, and sociodemographic index (SDI) at global, regional, and national levels from 1990 to 2021. We performed data analysis using two Mendelian randomization (MR) samples to explore the causal relationship between lipid metabolism, nutrients, and early AMD risk. The primary analysis was conducted using the inverse variance weighting method, along with a range of sensitivity analyses.<br><br>RESULTS: In 2021, AMD's DALY was 570,000, the age-standardized prevalence rate (ASPR) was 94.00/100,000 (95% UI, 78.32-114.42), and the age-standardized disability rate (ASDR) was 6.78/100,000 (95% UI, 4.70-9.32). The burden of AMD showed a downward trend during the study period. The disease burden is closely related to socioeconomic development and is unevenly distributed, with a heavier burden in low sociodemographic index (SDI) regions, especially in southern and central sub-Saharan Africa. Age-specific DALYs showed a gradual increasing trend, with female DALYs higher than male DALYs in all age groups. Decomposition analysis showed that population growth led to an increase in AMD DALYs. Projections from the Bayesian Age-Period Cohort (BAPC) model indicate that global AMD DALYs may continue to rise by 2045. Additionally, multivariate Mendelian randomization (MVMR) evaluation results showed that triglycerides (TG) (OR, 0.82; 95% CI, 0.73-0.92; p&#x2009;=&#x2009;0.001) and high-density lipoprotein (HDL) (OR, 1.15; 95% CI, 1.04-1.28; p&#x2009;=&#x2009;0.009) were significantly associated with early AMD. For every one standard deviation increase in TG levels, the risk of AMD decreases by an average of 18%. Higher TG levels are a protective factor for early AMD. However, the effect of HDL on AMD is the opposite of that of TG. For every one standard deviation increase in HDL levels, the risk of AMD increases by an average of 15%. Higher HDL levels are a risk factor for AMD.<br><br>CONCLUSIONS: AMD remains a major health problem worldwide, especially in low SDI regions. Population growth and aging have the most significant impact on AMD DALYs. HDL was identified as a risk factor, while TG was identified as a protective factor. These findings highlight the need for targeted interventions in low SDI regions, including dietary control, early screening, and addressing socioeconomic factors through balanced dietary plans.}, }
@article {pmid41433217, year = {2026}, author = {Li, Y and Mou, B and Song, X}, title = {Long-Term Trends in the Global Burden of Age-Related Macular Degeneration: Sex Differences, Aging Effects, and Future Projections in Middle-Aged and Older Adults.}, journal = {Ophthalmic research}, volume = {69}, number = {1}, pages = {8-23}, pmid = {41433217}, issn = {1423-0259}, mesh = {Humans ; Female ; Male ; Aged ; *Macular Degeneration/epidemiology ; Middle Aged ; Prevalence ; Global Health ; Aged, 80 and over ; Global Burden of Disease/trends ; Disability-Adjusted Life Years/trends ; Sex Factors ; *Aging ; Risk Factors ; Sex Distribution ; Age Distribution ; Quality-Adjusted Life Years ; }, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a major cause of irreversible vision loss in middle-aged and older populations worldwide. Understanding its long-term epidemiological trends is essential for anticipating future healthcare needs and guiding preventive strategies. This study characterizes the global, regional, and national burden of AMD in adults aged ≥45 years, with a focus on sex disparities, aging effects, and projected trends.<br><br>METHODS: Using data from the Global Burden of Disease Study 2021, we analyzed the prevalence and disability-adjusted life years (DALYs) of AMD across age, sex, region, country, and Socio-Demographic Index (SDI) groups. We applied an age-period-cohort model to disentangle the effects of aging, temporal changes, and birth cohort on AMD risk. Frontier analysis was conducted to identify best-practice benchmarks in disease burden reduction. The association between SDI and AMD burden was assessed to evaluate health inequities. An autoregressive integrated moving average (ARIMA) model was used to project age-standardized DALY rate (ASDR) and prevalence rate from 2022 to 2036.<br><br>RESULTS: Between 1990 and 2021, the absolute number of AMD cases and DALYs nearly doubled. In 2021, both prevalence and DALY rates increased exponentially with age, with females exhibiting consistently higher rates across all age groups. The age-period-cohort model indicated a declining trend in AMD risk over successive birth cohorts, suggesting potential improvements in early-life or cumulative risk factors. Notably, the highest age-standardized rates were observed in low-SDI regions, highlighting significant global inequities in disease burden. ARIMA projections suggest a modest but concerning increase in the global ASDR, rising to 6.80 (95% CI: 5.82-7.78) by 2036, with female ASDR reaching 7.46 (95% CI: 6.29-8.63).<br><br>CONCLUSION: The burden of AMD remains substantial and is projected to grow, particularly among aging populations and in low-resource settings. The persistent sex disparity, especially the elevated burden in elderly women, calls for targeted screening and intervention programs. These findings emphasize the need for equitable, age- and sex-sensitive public health strategies to mitigate the rising impact of AMD in the coming decades.}, }
@article {pmid41435998, year = {2026}, author = {Li, Y and Yuan, S and Zhang, C and Hu, P and Huang, X and Zhou, J and Liu, D and Zhou, X}, title = {Engineered nanoparticles for subconjunctival delivery to the retinal pigment epithelium: A multi-target therapy for dry AMD.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {390}, number = {}, pages = {114563}, doi = {10.1016/j.jconrel.2025.114563}, pmid = {41435998}, issn = {1873-4995}, mesh = {*Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Animals ; Chitosan/chemistry/administration &amp; dosage ; *Nanoparticles/administration &amp; dosage/chemistry ; Humans ; *Macular Degeneration/drug therapy/metabolism/pathology ; *Lactoferrin/administration &amp; dosage/chemistry ; *Resveratrol/administration &amp; dosage ; Conjunctiva/metabolism ; Male ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism ; Drug Delivery Systems ; Oxidative Stress/drug effects ; }, abstract = {Dry age-related macular degeneration (dAMD) is a leading cause of irreversible blindness, driven by oxidative stress-induced retinal pigment epithelial (RPE) cell degeneration. Existing therapies suffer from poor bioavailability and insufficient multi-pathway modulation. To address this, we developed P(R)/T-Lf nanoparticles, a subconjunctivally administered nanotherapy co-loaded with resveratrol (Res) and dual-functionalized with trimethyl chitosan (TMC) and lactoferrin (Lf). The P(R)/T-Lf NPs exhibited: (1) prolonged ocular retention via TMC-mediated mucoadhesion and enhanced RPE targeting through Lf receptor binding; (2) sustained Res release over 35 days, effectively scavenging reactive oxygen species and inhibiting ferroptosis by downregulating NOX2, ACSL4, and COX2 while restoring GPX4; (3) superior therapeutic outcomes in NaIO3-induced dAMD models, preserving retinal morphology and function. Comparative studies demonstrated that P(R)/T-Lf NPs outperformed non-targeted controls. This nanoplatform provides a translation-ready strategy to concurrently tackle oxidative stress, inflammation, and ferroptosis via sustained, targeted delivery, representing a transformative approach for dAMD therapy.}, }
@article {pmid41437494, year = {2026}, author = {Jianjun, Y}, title = {Bilateral hypertensive retinopathy (grade 4): Case report and review of the literature on intravitreal injection anti-VEGF therapy.}, journal = {Clinical and experimental hypertension (New York, N.Y. : 1993)}, volume = {48}, number = {1}, pages = {2604831}, doi = {10.1080/10641963.2025.2604831}, pmid = {41437494}, issn = {1525-6006}, mesh = {Humans ; Intravitreal Injections ; *Hypertensive Retinopathy/drug therapy/complications ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Female ; Middle Aged ; Macular Edema/drug therapy/etiology ; Aged ; Visual Acuity ; Ranibizumab ; Choroidal Neovascularization/etiology/drug therapy ; Treatment Outcome ; Bevacizumab ; }, abstract = {OBJECTIVE: To introduce bilateral hypertensive retinopathy (HR) (grade 4) complicated with macular edema (ME) patients with binocular intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) treatment.<br><br>METHODS: Three cases of hypertensive retinopathy were observed. The fundus examination was consistent with HR (grade 4). The patients received anti-VEGF intraocular injection.<br><br>RESULTS: The patient's ME and optic nerve edema were significantly reduced, visual acuity was significantly improved, and a case of secondary choroidal neovascularization (CNV) in the fundus of HR (grade 4) was also noted.<br><br>CONCLUSIONS: The use of intravitreal anti-VEGF agents in stage IV hypertensive retinopathy appears satisfactory but not perfect. In severe cases with vitreous hemorrhage, early injection avoids vitrectomy.}, }
@article {pmid41438708, year = {2025}, author = {Liu, X and Wang, Y and Huang, J and Chen, L and Cai, T and Wang, Q and Li, S and Yu, G and Chen, Y and Luo, D and Ding, X}, title = {Sustained suppression of choroidal neovascularization by intraocularly stable tetrahedral network encapsulated miR-22-3p.}, journal = {Materials today. Bio}, volume = {35}, number = {}, pages = {102578}, pmid = {41438708}, issn = {2590-0064}, abstract = {Choroidal neovascularization (CNV), characterized by abnormal vessel growth and vascular leakage, is the hallmark of wet age-related macular degeneration (wAMD) and a leading cause of irreversible vision loss. Although anti-vascular endothelial growth factor (VEGF) therapies remain the current standard, their frequent administration and limited long-term efficacy highlight the need for novel treatments. Here, we developed a miR-22-3p-loaded tetrahedral framework nucleic acids (tFNAs-miR22) nanostructure and evaluated its efficacy in CNV suppression. The nanocomplex was structurally validated, exhibiting high assembly fidelity and superior intraocular stability compared to serum conditions. In a laser-induced CNV mouse model, a single intravitreal injection of tFNAs-miR22 significantly reduced lesion size and leakage by day 10, with efficacy comparable to aflibercept. In a rat model of stable and long-lasting CNV, tFNAs-miR22 demonstrated durable inhibition of vascular leakage by Day 21, showing greater persistence compared to aflibercept. This effect was dose-dependent, with the high-dose group outperforming aflibercept in suppressing leakage. Transcriptomic profiling of hypoxia-challenged HUVECs further revealed that tFNAs-miR22 modulates angiogenic pathways, including suppression of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) axis. These findings demonstrate the potent and long-lasting therapeutic effects of tFNAs-miR22, supporting its promise as a next-generation, gene-regulatory nanotherapy for sustained inhibition of CNV.}, }
@article {pmid41439215, year = {2026}, author = {Ueda-Arakawa, N and Sato, Y and Miyake, M and Takahashi, A and Mori, Y and Miyara, Y and Hara, C and Kitajima, Y and Maruko, R and Kawai, M and Ohnaka, M and Koizumi, H and Maruyama-Inoue, M and Yanagi, Y and Iida, T and Kondo, M and Sakamoto, T and Tsujikawa, A}, title = {Impact of Reticular Pseudodrusen on Clinical and Ocular Characteristics and Progression Rate of Geographic Atrophy in Japanese Patients.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100984}, pmid = {41439215}, issn = {2666-9145}, abstract = {PURPOSE: To elucidate the impact of reticular pseudodrusen (RPD) on the clinical and ocular characteristics and progression rate of geographic atrophy (GA) in Japanese patients.<br><br>DESIGN: A multicenter, retrospective, observational cohort study.<br><br>PARTICIPANTS: A total of 173 eyes from 173 Japanese patients (135 with conventional GA and 35 with pachychoroid GA) were included; 79 eyes with conventional GA were included in the follow-up group.<br><br>METHODS: Reticular pseudodrusen status, GA type (conventional/pachychoroid), GA location (central/noncentral), GA pattern (unifocal/multifocal), subfoveal choroidal thickness (SFCT), and fellow-eye status were assessed using multimodal imaging. The GA progression rate was calculated in both mm[2]/year and mm/year (square root transformation [SQRT]) after semiautomatic measurement of the GA area on fundus autofluorescence images.<br><br>MAIN OUTCOME MEASURES: Clinical and ocular characteristics and progression rate of GA according to RPD status.<br><br>RESULTS: Reticular pseudodrusen were observed in 42.4% (73 eyes) of the 173 study eyes, 54.1% of the eyes with conventional GA, and none of the eyes with pachychoroid GA. Among patients with conventional GA, those with RPD were significantly more female (56.2 vs. 30.6%, P = 0.003), had better visual acuity (0.31 vs. 0.50 in logarithm of the minimum angle of resolution, P = 0.03), a smaller SFCT (141.7 vs. 185.0 &#x3bc;m, P = 0.02), higher prevalence of noncentral (56.2 vs. 32.3%, P = 0.005) and multifocal GA (68.5 vs. 29.0%, P < 0.001), and bilateral late age-related macular degeneration (AMD) (93.1 vs. 65.0%, P < 0.0001) than those without RPD. The GA progression rate was significantly higher in eyes with RPD than in eyes without RPD (0.34 vs. 0.18 mm/year [SQRT], P < 0.001).<br><br>CONCLUSIONS: Reticular pseudodrusen are frequently observed in Japanese patients with conventional GA. Clinical and ocular characteristics differ according to the RPD status, similarly in White patients. Geographic atrophy in the presence of RPD progresses rapidly, at a rate comparable to that in White patients, and most patients with RPD exhibit bilateral late AMD. Given that RPD in eyes with GA constitutes a strong risk factor for both fast GA progression and bilateral late AMD, GA with RPD should be treated at an early stage prior to foveal involvement, even though GA in Asians has been reported to progress slowly.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41439218, year = {2026}, author = {Vo, A and Shen, LL and Pak, I and Taha, AT and Diaz, AZ and Stewart, JM}, title = {Association between Baseline Subfoveal Choroidal Thickness and Anatomical and Functional Outcomes in Geographic Atrophy.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100986}, pmid = {41439218}, issn = {2666-9145}, abstract = {OBJECTIVE: To investigate the relationship between baseline subfoveal choroidal thickness (SFChT) and both visual outcomes and geographic atrophy (GA) growth rate, and to assess whether SFChT mediates the treatment effect of oral metformin on GA progression.<br><br>DESIGN: Secondary analysis of a randomized controlled trial.<br><br>PARTICIPANTS: Seventy eyes (34 metformin; 36 observation) from 44 participants (21 metformin; 23 observation) with GA and &#x2265;6 months of follow-up in the METformin for the MINimization of Geographic Atrophy Progression study.<br><br>METHODS: Subfoveal choroidal thickness was measured from baseline OCT. We calculated GA area growth rate by subtracting the GA area at the first visit from the GA area at the last visit and dividing the result by the time interval. Geographic atrophy perimeter-adjusted growth rate was calculated by dividing GA area growth rate by the mean GA perimeter between the first and last visit.<br><br>MAIN OUTCOME MEASURES: Longitudinal changes in GA area and visual acuity.<br><br>RESULTS: Baseline SFChT was not significantly associated with baseline GA area (P = 0.51), baseline best-corrected visual acuity (BCVA) (P = 0.49), baseline low-luminance visual acuity (LLVA) (P = 0.85), or rim area focal hyperautofluorescence signals (P = 0.29). Baseline SFChT was not significantly associated with GA perimeter-adjusted growth rate (P = 0.74), the decline rate of BCVA (P = 0.14), and the decline rate of LLVA (P = 0.71). However, sensitivity analyses in GA subgroups found that baseline SFChT was associated with decreased rate of BCVA decline in patients with foveal-involving GA (Spearman &#x3c1; = 0.03, P = 0.03). Baseline SFChT did not significantly influence the effect of oral metformin on GA perimeter-adjusted growth rate (P = 0.78).<br><br>CONCLUSIONS: Greater baseline SFChT was significantly associated with slower BCVA decline in eyes with foveal-involving GA, suggesting a possible localized role of choroidal thickness in preserving central vision. However, SFChT was not associated with GA growth rate, LLVA decline, or baseline anatomical and functional measures. It also did not mediate the effect of oral metformin. While SFChT lacks prognostic value for GA progression overall, it may hold limited relevance for central vision outcomes in foveal-involving GA.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41441525, year = {2025}, author = {Cohen, R and Kerman, T and Trivizki, O}, title = {Bilateral Sterile Intraocular Inflammation Following Intravitreal Aflibercept 8 mg Injections: A Case Report.}, journal = {Reports (MDPI)}, volume = {8}, number = {4}, pages = {}, pmid = {41441525}, issn = {2571-841X}, abstract = {Background and Clinical Significance: To report a case of bilateral sterile intraocular inflammation following intravitreal aflibercept 8 mg (Eylea HD) injections. Case Presentation: An 89-year-old woman with bilateral neovascular age-related macular degeneration (nAMD) developed blurred vision and mild ocular pain in both eyes four days after receiving aflibercept 8 mg injections in both of her eyes. Examination revealed a marked anterior chamber reaction with Descemet's folds, 2+ vitreous cells, and 3+ vitreous haze bilaterally. Intraocular pressures were normal, and B-scan ultrasonography confirmed attached retinas with bilateral vitreous opacities. The clinical presentation initially raised concern for infectious endophthalmitis; however, the bilateral presentation, quiet conjunctivae, and prior history of sterile inflammation after aflibercept 2 mg supported a diagnosis of sterile intraocular inflammation. The patient was hospitalized and treated with intensive topical corticosteroids, antibiotics, and cycloplegics, resulting in rapid improvement and complete resolution of symptoms within four days with recovery of baseline vision. Conclusions: Intravitreal aflibercept 8 mg can be associated with bilateral sterile intraocular inflammation, even in patients who previously tolerated standard-dose aflibercept. Awareness of this potential adverse event is essential to avoid unnecessary interventions and to guide appropriate management.}, }
@article {pmid41443408, year = {2025}, author = {Joo, JH and Zhao, AH and Chalasani, M and Allan, KC and Rachitskaya, AV}, title = {Impact of Glucagon-Like Peptide-1 Receptor Agonists on Age-Related Macular Degeneration at a Tertiary Ophthalmology Center.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2025.12.014}, pmid = {41443408}, issn = {2468-6530}, abstract = {OBJECTIVE: There is ongoing debate in the literature on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on age-related macular degeneration (AMD). This study examines the effect of GLP-1RA on the risk of AMD development compared with other glucose-lowering medications at a single ophthalmology center.<br><br>DESIGN: Retrospective cohort study.<br><br>SUBJECTS: A total of 30 515 GLP-1RA users, 48 906 sodium-glucose transport protein 2 inhibitor (SGLT-2i) users, 286 066 metformin users, and 164 361 insulin users aged &#x2265;50 years had a 1-year minimum drug duration between 2016 and 2025. After propensity score matching (PSM), each cohort included 7561 patients. Patients with diabetic macular edema, severe or proliferative diabetic retinopathy, and with history of prior retinal surgeries were excluded.<br><br>METHODS: The relative risk (RR) of developing nonexudative AMD was measured at yearly drug duration intervals up to 3 years using logistic regression models controlling for age, sex, race, smoking status, and hemoglobin A1C percentage. Manual review was performed on a random sampling of AMD cases to optimize accuracy. Cox proportional hazards (CPHs) validation analyses in PSM cohorts were performed, matching additionally for body mass index, history of hypertension, chronic kidney disease, and diabetes duration.<br><br>MAIN OUTCOME MEASURES: The primary outcome was the RR of nonexudative AMD up to 3 years on GLP-1RAs compared with alternative antihyperglycemic agents.<br><br>RESULTS: Glucagon-like peptide-1 receptor agonist was associated with decreased risk of nonexudative AMD compared with metformin and insulin at all 3 years and compared with SGLT-2i only after 3 years of use (3 years: metformin relative risk [RR] = 0.25; 95% confidence interval [CI], 0.14-0.41; insulin RR = 0.28; 95% CI, 0.15-0.46; SGLT-2i RR = 0.42; 95% CI, 0.22-0.74). In PSM cohorts, CPH analyses showed a reduced risk only compared with insulin (hazards ratio = 0.45; 95% CI, 0.27-0.76).<br><br>CONCLUSIONS: Glucagon-like peptide-1 receptor agonist use was associated with a lower risk of nonexudative AMD compared with metformin, insulin, and SGLT-2i in logistic regression models. The risk reduction persisted for insulin in CPH analyses in smaller PSM cohorts.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41443587, year = {2026}, author = {Kwan, WC and Brunton, EK and Goris, T and Begeng, JM and Kameneva, T and Stoddart, PR and Ibbotson, MR and Richardson, RT and Tong, W}, title = {Hybrid optogenetic and electrical stimulation of retinal ganglion cells for artificial vision.}, journal = {Brain stimulation}, volume = {19}, number = {1}, pages = {103012}, doi = {10.1016/j.brs.2025.103012}, pmid = {41443587}, issn = {1876-4754}, mesh = {Animals ; *Retinal Ganglion Cells/physiology ; *Optogenetics/methods ; Mice, Transgenic ; Rats ; *Electric Stimulation/methods ; *Visual Prosthesis ; Mice ; Action Potentials/physiology ; }, abstract = {INTRODUCTION: Millions of adults worldwide experience severe visual impairment due to photoreceptor loss from retinal diseases such as retinitis pigmentosa and macular degeneration. Retinal prostheses that provide artificial vision by stimulating the surviving retinal ganglion cells (RGCs) have emerged as a promising therapy. However, all clinically approved retinal prostheses that use electrical stimulation face the issue of electrical spread. As such, the quality of restored vision provided by existing devices has been limited. Optogenetic approaches provide greater spatial precision, however, they have poor temporal properties compared to electrical stimulation.<br><br>MATERIALS AND METHODS: We developed an opto-electrical hybrid approach and surveyed this stimulation strategy in the retina of two animal models: normal-sighted transgenic mice that express ChR2-H134R in a sub-population of RGCs and the degenerated retina of Royal College of Surgeons rats with residual RGCs transduced with ChrimsonR. We conducted whole-cell patch clamp recordings and measured calcium transients with the biosensor GCaMP7s to determine single-cell and population responses to hybrid stimulation, respectively.<br><br>RESULTS: Hybrid stimulation reduced both electrical and optogenetic activation thresholds. Optical thresholds could be halved with electrical supplementation and synergistically, the opto-electrical coupling reduced the electrical intensity requirements to elicit action potentials by &#x223c;50&#xa0;% (p&#xa0;<&#xa0;0.0001). Additionally, hybrid stimulation evoked significantly higher firing frequencies, by an order of up to 2&#xd7;, when compared to electrical or optical-only methods (p&#xa0;<&#xa0;0.0001). These properties of hybrid stimulation were replicated in the diseased retina, where the reduced activation thresholds contributed to significantly reduced spread of activation compared to electrical stimulation alone (p&#xa0;<&#xa0;0.05), a challenge that persists in devices that utilize extracellular electrical stimulation. Hybrid stimulation improved the spatial resolution of RGC activation when applied at retina-electrode spacing reflective of current epiretinal and suprachoroidal devices.<br><br>CONCLUSION: Combining the optogenetic and electrical modes of activation enabled significant reductions of each component in the stimulus, leading to more localised stimulation when compared to electrical-only stimulation, while also reducing the optical intensity required for optogenetic activation.&#xa0;Together with improvements in response reliability, hybrid stimulation may not only improve the resolution and refresh rate of future visual prostheses but may also provide greater control in neuromodulation for any bionic device that interfaces with neural tissue.}, }
@article {pmid41443801, year = {2025}, author = {Ouchi, C and Hosokawa, MM and Kimura, S and Shiode, Y and Matoba, R and Morita, T and Morizane, Y}, title = {Real-World Outcomes of Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration in Patients Aged 85 or Older.}, journal = {Acta medica Okayama}, volume = {79}, number = {6}, pages = {405-412}, doi = {10.18926/AMO/69842}, pmid = {41443801}, issn = {0386-300X}, mesh = {Humans ; Aged, 80 and over ; Male ; Female ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; *Macular Degeneration/drug therapy ; Visual Acuity ; Ranibizumab/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Choroidal Neovascularization/drug therapy ; Retrospective Studies ; }, abstract = {We investigated the treatment outcomes of patients aged ≥85 years with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (anti-VEGF) therapy using either treat-and-extend (TAE) or pro re nata (PRN) regimens for 1 year in real-world clinical practice. Eighty-five eyes from 85 patients were included. Among them, types 1, 2, and 3 macular neovascularization and polypoidal choroidal vasculopathy were present in 27.1%, 17.6%, 18.8%, and 36.5%, respectively. TAE and PRN regimens were used in 43.5% and 56.5% of patients, respectively. At baseline, the PRN group was older and had worse best-corrected visual acuity (BCVA), greater central retinal thickness, and more intraretinal fluid than the TAE group. In the TAE group, the mean number of injections was 7.6, BCVA improved significantly, and all retinal fluid rates decreased. In the PRN group, the mean number of injections was 3.9, BCVA remained unchanged, and the rates of macular fibrosis and atrophy increased. No serious adverse events were observed in either group. Anti-VEGF therapy was safe for patients aged ≥ 85 years with nAMD, and the TAE regimen effectively improved BCVA in this population. BCVA remained unchanged in the PRN-treated patients, with baseline disease severity and/or undertreatment potentially influencing the outcomes.}, }
@article {pmid41444944, year = {2025}, author = {Khathami, AA and Baklola, M and Alalyani, MA and Aljuaid, AT and Alsaeed, R and Ghramah, AA and Aljuaid, OT and AlGarni, RH and Alshahrani, RS and Aldreweash, RS and Alshehri, RS and Albishi, SA and Almutairi, GM and Al-Bawah, N and Ghaith, KAA}, title = {Multimodal artificial intelligence in retinal vascular and neovascular macular diseases: a systematic review of diagnostic and prognostic applications.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {46}, doi = {10.1186/s12886-025-04561-3}, pmid = {41444944}, issn = {1471-2415}, mesh = {Humans ; *Artificial Intelligence ; Prognosis ; *Multimodal Imaging ; *Retinal Vein Occlusion/diagnosis ; *Wet Macular Degeneration/diagnosis ; Tomography, Optical Coherence ; *Diabetic Retinopathy/diagnosis ; }, abstract = {BACKGROUND: Retinal vascular diseases, including diabetic retinopathy (DR) and retinal vein occlusion (RVO), and neovascular macular diseases such as neovascular age-related macular degeneration (nAMD) are leading causes of vision loss worldwide. With the rapid growth of artificial intelligence (AI), multimodal approaches that integrate diverse imaging modalities and clinical data have emerged as powerful tools for improving diagnosis, prognosis, and risk stratification.<br><br>METHODS: This systematic review, conducted according to PRISMA 2020 guidelines, synthesized evidence on the diagnostic and prognostic applications of multimodal AI in retinal vascular diseases. Six databases (PubMed, Embase, Scopus, Web of Science, IEEE Xplore, and Cochrane Library) were searched for English-language studies published between 1 January 2019 and 1 November 2025. Eligible studies applied AI or machine learning models integrating two or more data modalities for diagnosis, prognosis, or prediction in DR, RVO, or AMD. Data extraction, quality appraisal, and narrative synthesis were performed.<br><br>RESULTS: From 11,659 identified records, 12 studies met the eligibility criteria. Multimodal AI systems consistently outperformed unimodal models and, in several cases, exceeded expert ophthalmologist performance. Diagnostic accuracy for AMD and polypoidal choroidal vasculopathy (PCV) ranged from 87% to 96%, with fusion-based approaches achieving area under the curve (AUC) values up to 0.989. Prognostic models predicting treatment response or recurrence in nAMD and RVO achieved AUCs between 0.972 and 0.980, surpassing both clinician and single-modality baselines. Hybrid and foundation models integrating imaging, clinical, and textual data demonstrated promising results but variable robustness. Most studies were retrospective, single-center, and exhibited moderate-to-high risk of bias, emphasizing the need for larger, prospective, multicenter validation to establish clinical applicability and generalizability.<br><br>CONCLUSION: Multimodal AI demonstrates superior diagnostic and prognostic performance compared to unimodal models and, in some cases, outperforms expert clinicians in managing retinal vascular diseases. Integrating complementary data sources, such as OCT, fundus imaging, and clinical information, enhances model accuracy and generalizability.}, }
@article {pmid41446234, year = {2025}, author = {Lewis, TR and Castillo, CM and Phan, S and Shores, CR and Hayase, KK and Kim, KY and Ellisman, MH and Alekseev, O and Burns, ME and Arshavsky, VY}, title = {RPE pseudopods maintain photoreceptor outer segment renewal despite subretinal space expansion in Adam9 knockout mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41446234}, issn = {2692-8205}, support = {P30 EY005722/EY/NEI NIH HHS/United States ; S10 OD034447/OD/NIH HHS/United States ; K08 EY033857/EY/NEI NIH HHS/United States ; R01 EY030451/EY/NEI NIH HHS/United States ; U24 NS120055/NS/NINDS NIH HHS/United States ; R01 EY024320/EY/NEI NIH HHS/United States ; R00 EY033763/EY/NEI NIH HHS/United States ; K99 EY033763/EY/NEI NIH HHS/United States ; }, abstract = {Vision begins in the outer segment compartment of photoreceptor cells, which is constantly renewed through the addition of membrane material at its base and ingestion of mature membranes at its tip by the retinal pigment epithelium (RPE). The close apposition of outer segments to the RPE is believed to be critical for maintaining this renewal process. Yet, in several retinal diseases, expansion of the subretinal space separating photoreceptors from the RPE does not immediately impact photoreceptor functionality. Here, we analyzed outer segment function and renewal in the Adam9 knockout mouse characterized by a major expansion of the subretinal space. Surprisingly, photoreceptor-RPE separation affected neither the sensitivity of photoreceptor light-responses nor the normal rate of outer segment renewal in this mouse prior to the onset of photoreceptor degeneration. The latter is achieved through the formation of elongated RPE "pseudopods" extending across the enlarged subretinal space to ingest outer segment tips. This work suggests that pseudopod formation may underlie the persistence of photoreceptor function in human diseases accompanied by photoreceptor-RPE separation, such as vitelliform macular dystrophy or age-related macular degeneration associated with subretinal drusenoid deposits.}, }
@article {pmid41448386, year = {2026}, author = {Wang, X and Delle, C and Nedergaard, M and Wostyn, P}, title = {Glymphatic transport and ocular diseases.}, journal = {Progress in retinal and eye research}, volume = {110}, number = {}, pages = {101433}, doi = {10.1016/j.preteyeres.2025.101433}, pmid = {41448386}, issn = {1873-1635}, mesh = {Humans ; *Glymphatic System/metabolism/physiology ; Animals ; *Eye Diseases/physiopathology/metabolism ; }, abstract = {The high metabolic demand of retinal neurons requires tightly regulated mechanisms to maintain homeostasis and ensure the efficient clearance of metabolic waste and excess water. Recent studies have identified a glymphatic-like system in the rodent eye, and growing evidence supports the existence of a similar pathway in the human eye, facilitating fluid exchange and waste removal. The ocular glymphatic system supports bidirectional flow along the optic nerve - anterograde from the retina and retrograde from the brain. In this review, we integrate findings from preclinical models and clinically grounded hypotheses to identify key contributors to glymphatic dysfunction in ocular diseases. These include impaired laminar barrier integrity, pathological perivascular space expansion, aquaporin-4 abnormalities, immature vasculature, and pathological immune activation. Glymphatic impairment has been implicated in murine models of glaucoma, diabetic retinopathy, and ocular manifestations of Alzheimer's disease. Additionally, disrupted glymphatic flow is suspected in papilledema, spaceflight associated neuro-ocular syndrome, and Terson syndrome. We further explore novel associations between glymphatic dysfunction and other blinding disorders such as myopic optic neuropathy, age-related macular degeneration, neuromyelitis optica spectrum disorders, and retinal vasculitis. In delineating these mechanistic links, this review provides a conceptual framework to guide future research in glymphatic contributions to ocular diseases.}, }
@article {pmid41448679, year = {2025}, author = {Oldham, E and Hall, RH and Jones, G and Modi, J and Ward, S and Magee, T and Fitzgerald, K and Magana, K and Hughes, G and Ford, AI and Vassar, M}, title = {Assessing uptake of the macular degeneration core outcome set in clinical trials: a cross-sectional study.}, journal = {BMJ open}, volume = {15}, number = {12}, pages = {e104705}, pmid = {41448679}, issn = {2044-6055}, mesh = {Humans ; *Clinical Trials as Topic/standards ; Cross-Sectional Studies ; *Macular Degeneration/therapy ; *Outcome Assessment, Health Care/standards ; }, abstract = {PURPOSE: Establishing comparability between measured outcomes in clinical trials poses a significant obstacle for systematic reviewers. Core outcome sets (COSs) were developed to address this issue. The macular degeneration (MD) COS is designed to standardise outcome measurement across clinical trials for MD. This study investigates the uptake of the MD COS in standardising outcome measurement across clinical trials.<br><br>DESIGN: Cross-sectional analysis METHODS: We conducted a search on ClinicalTrials.gov to locate MD clinical trials that were registered 5 years prior to COS publication through the search date of 26 June 2023 and obtained a pool of 2152 registered studies. After applying various inclusion and exclusion criteria, we analysed 159 trials. We then analysed the COS uptake using an interrupted time series analysis (ITSA) and performed performed analyses of variance (ANOVAs) and Pearson correlations to evaluate associations between trial characteristics and outcome measurement.<br><br>RESULTS: ITSA showed no significant change in uptake following the MD COS (2016): mean percentage of completion of the COS increased by 0.24% per month before publication (p=0.27) and by 0.07% per month after publication (p=0.62), indicating no meaningful post-publication slope change in COS use. For context, visual acuity was most commonly measured, while several patient-reported and disutility domains were infrequently captured.<br><br>CONCLUSION: No discernible patterns in COS usage for MD trials were observed. We recommend further collaboration between regulators and COS developers to help with COS uptake. Additionally, we suggest that further studies analyse adherence to COSs in respect to regulatory recommendations.}, }
@article {pmid41449919, year = {2026}, author = {Tang, J and Chen, J and Li, Z and Zhang, G and Zhu, L and Li, H and Su, W and Qin, S}, title = {Genetic Correlation and Mendelian Randomization Analyses Reveal Causal Links Between Metabolic-Associated Diseases or Risk Factors and Major Eye Diseases.}, journal = {Current eye research}, volume = {51}, number = {3}, pages = {320-331}, doi = {10.1080/02713683.2025.2585338}, pmid = {41449919}, issn = {1460-2202}, mesh = {Humans ; *Mendelian Randomization Analysis/methods ; Genome-Wide Association Study ; Risk Factors ; *Eye Diseases/genetics ; *Polymorphism, Single Nucleotide ; Male ; Genetic Predisposition to Disease ; Female ; Cataract/genetics ; *Metabolic Diseases/genetics ; Macular Degeneration/genetics ; }, abstract = {PURPOSE: This study aims to elucidate the causal relationships and shared genetic architecture between metabolic-associated diseases and risk factors-including hypertension, type 1 diabetes (T1D), type 2 diabetes (T2D), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and body mass index (BMI)-and primary vision-threatening eye disorders, involving glaucoma, cataracts, refractive disorders, and age-related macular degeneration (AMD).<br><br>METHODS: We analyzed genome-wide association study (GWAS) summary statistics from > 500&#xa0;000 individuals of European ancestry in the FinnGen, UK Biobank, and MRC-IEU databases to ensure adequate sample size. Linkage disequilibrium score regression (LDSC) was applied to estimate genetic correlations, while two-sample Mendelian randomization (MR) was performed to assess causal effects. Furthermore, a bidirectional Mendelian Randomization was further conducted to examine the directionality of associations between hypertension and cataracts.<br><br>RESULTS: This study was the first to reveal genetic correlations and causal effects of hypertension on cataracts, particularly senile cataracts. MR analysis provided evidence that hypertension is causally associated with an increased risk of cataracts, particularly senile cataract, whereas the reverse association was not supported. Additionally, LDL cholesterol was suggested as a protective factor for AMD, while HDL cholesterol was associated with an increased risk. The LDSC analysis also indicated a suggestive genetic correlation between T2D and both cataracts and glaucoma, but not for T1D.<br><br>CONCLUSION: This study provides comprehensive evidence of genetic correlations and potential causal relationships between metabolic-associated conditions and major eye diseases contributing to vision loss.}, }
@article {pmid41450867, year = {2026}, author = {Mukherjee, S and Nagarkar, A and Prasad, M and Agron, E and Weber, C and Chew, EY and De Silva, T}, title = {A Datasheet for Age-Related Eye Disease Study 2 on the Database of Genotypes and Phenotypes.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100953}, pmid = {41450867}, issn = {2666-9145}, abstract = {OBJECTIVE: To provide a comprehensive summary of the controlled-access Age-Related Eye Disease Study 2 (AREDS2) data elements, encompassing phenotypic, imaging, dietary, genetic, and ancillary data.<br><br>DESIGN: Dataset description of a multicenter, phase III, randomized clinical trial evaluating lutein + zeaxanthin, &#x3c9;-3, or both long-chain polyunsaturated fatty acid supplementation in intermediate age-related macular degeneration (AMD). Secondary randomization was offered to all AREDS2 participants to evaluate varying levels of zinc and the potential for elimination of &#x3b2;-carotene, which increases the risk of lung cancer in smokers.<br><br>PARTICIPANTS: A total of 4203 participants aged 50-85 years with bilateral intermediate AMD (bilateral large drusen &#x2265;125 &#x3bc;m) or intermediate AMD in one eye and advanced AMD in the other eye were enrolled at 82 clinical centers between 2006 and 2008.<br><br>METHODS: Participants attended annual clinic visits, including eye examinations, visual acuity, slit lamp, intraocular pressure, and imaging that included stereoscopic 30&#xb0; color fundus (fields 1-3) and fundus reflex images in all participants, while fundus autofluorescence images and spectral-domain OCT images were acquired in selected clinics. Telephone contacts at 3 and 6 months and annually thereafter collected adverse events and reinforced visit compliance.<br><br>MAIN OUTCOME MEASURES: Progression to advanced AMD (central geographic atrophy or neovascular AMD), incidence of cataract surgery, and loss of &#x2265;15 letters (&#x2265;3 lines) of visual acuity from baseline.<br><br>RESULTS: Controlled-access data are archived under the database of Genotypes and Phenotypes (dbGaP) website with the accession number phs002015.v2.p1. The data elements include main-study phenotype tables plus multiple ancillary-study tables with cardiovascular, cognitive, nutritional biochemistry, and genetic data. Additional data include dietary assessments, image gradings, visual acuity testing, and cataract surgery documentation. Blood or saliva from >2000 participants was collected; exome-chip data from >1800 and whole-genome sequencing from 1363 participants, including 488 who also participated in the original AREDS, are available under the International AMD Genomics Consortium and dbGaP.<br><br>CONCLUSIONS: The AREDS2 dataset's rigorous interventional design, standardized longitudinal ophthalmic imaging gradings, comprehensive dietary and genetic information, and ancillary cardiovascular and cognitive assessments constitute an invaluable resource for elucidating AMD progression, informing nutritional strategies, and artificial intelligence-driven diagnostics.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41451083, year = {2025}, author = {Chen, X and Li, H and Jiao, Z and Liu, Y and Wu, Y and Qiu, X and Zou, Y and Liu, G}, title = {Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and age-related macular degeneration: insights from two observational studies.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1724938}, pmid = {41451083}, issn = {2296-858X}, abstract = {OBJECTIVES: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is an innovative measure for assessing cardiovascular disease risk, primarily associated with lipid profiles. Lipid metabolism disorders have been reported to be associated with age-related macular degeneration (AMD), yet the relationship between NHHR and AMD has not been previously explored. This study primarily aims to investigate the potential association between NHHR and the prevalence of AMD.<br><br>METHODS: A comprehensive cross-sectional stratified survey using the National Health and Nutrition Examination Survey (NHANES) dataset of the US was conducted, including 4,017 participants aged 40&#x202f;years and older, from 2005 to 2008. The NHHR was calculated as [Total Cholesterol (TC)&#x202f;-&#x202f;High-Density Lipoprotein Cholesterol (HDL-C)]/HDL-C. Data on AMD were derived from retinal photography. Logistic regression, stratified analysis, RCS curve, ROC/AUC, and subgroup interaction analysis were used to explore the relationship between NHHR and AMD. Meanwhile, patients who visited the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine (PHFT, China) between November 2021 and September 2025 were recruited retrospectively. All participants who met the study inclusion criteria were screened from the hospital-wide integrated informatics platform for clinical research. Finally, the clinical data of 96 eligible participants of PHFT were included in this study for conducting external validation analysis.<br><br>RESULTS: The cross-sectional study from NHANES included 4,017 participants, of whom 3,678 (91.56%) had no AMD and 339 (8.44%) exhibited AMD. The external validation study from PHFT consisted of 48 patients with AMD and 48 non-AMD participants. Both studies indicated that compared with the non-AMD group, the AMD group had a significantly lower NHHR (p&#x202f;<&#x202f;0.01). In the fully adjusted Model, when NHHR was stratified into tertiles, the results showed that for each one-unit increase in NHHR, the risk of AMD in individuals in the highest tertile was reduced by 33.1 and 76.8%, respectively. The results of the RCS curve and threshold effect analyses from the two studies confirmed a negative correlation trend between the two variables (p&#x202f;<&#x202f;0.05). The subgroup and interaction analysis, based on data from the NHANES, shows consistent associations between NHHR and AMD across various subgroups.<br><br>CONCLUSION: Our preliminary research indicates that NHHR might be a reliable independent indicator of the risk of developing AMD. In the future, large-scale sample studies and more prospective research are still needed to confirm our findings.}, }
@article {pmid41452565, year = {2026}, author = {Koizumi, H and Honda, S and Yasukawa, T and Kishino, G and Sekiryu, T and Schulze, A and Yamashita, T and Schmidt-Ott, U and Zhao, M and Zhang, X and Berliner, AJ and Chu, KW and Reed, K and Cheng, Y and Bhore, R and Vitti, R and Fujita, I and Leal, S and Iida, T and , }, title = {Intravitreal aflibercept 8 mg in patients from Japan with neovascular age-related macular degeneration: 48-week subgroup analysis of the PULSAR trial.}, journal = {Japanese journal of ophthalmology}, volume = {70}, number = {1}, pages = {139-149}, pmid = {41452565}, issn = {1613-2246}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Intravitreal Injections ; *Visual Acuity ; Double-Blind Method ; Male ; Female ; Japan/epidemiology ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/epidemiology ; Tomography, Optical Coherence ; Treatment Outcome ; Dose-Response Relationship, Drug ; Fluorescein Angiography ; Follow-Up Studies ; Time Factors ; Aged, 80 and over ; Angiogenesis Inhibitors/administration &amp; dosage ; Middle Aged ; Fundus Oculi ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Macula Lutea/pathology ; }, abstract = {PURPOSE: To evaluate the 1-year efficacy and safety of aflibercept 8 mg compared with aflibercept 2 mg in a pre-specified analysis of patients from Japan with neovascular age-related macular degeneration (nAMD) included in PULSAR.<br><br>STUDY DESIGN: PULSAR (NCT04423718) was a global, phase 3, randomized, double-masked, non-inferiority study of adults with nAMD. Patients were randomized 1:1:1 to receive aflibercept 8 mg every 12 weeks (8q12), or every 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following three initial monthly doses in all groups.<br><br>METHODS: This subgroup analysis of Japan and non-Japan cohorts from PULSAR evaluated changes from baseline in best-corrected visual acuity (BCVA), central subfield retinal thickness, durability and safety outcomes.<br><br>RESULTS: In the Japan subgroup, least squares (LS) mean (95% CI) changes from baseline in BCVA at week 48 were +6.5 (+0.7, +12.3), +7.9 (+5.1, +10.6), and +4.7 (-0.5, +9.9) letters for patients in the 8q12 (n = 31), 8q16 (n = 33), and 2q8 (n = 33) groups, respectively. The majority of patients in the 8q12 (82.1%) and 8q16 (93.8%) groups maintained their randomized dosing intervals through Week 48. Ocular treatment-emergent adverse events were reported in 35.5%, 30.3%, and 39.4% of patients in the Japan subgroup in 8q12, 8q16, and 2q8 groups, respectively. Similar efficacy and safety results were observed in the non-Japan subgroup.<br><br>CONCLUSION: Aflibercept 8 mg has similar efficacy and safety to aflibercept 2 mg when administered at extended dosing intervals in both the Japan and non-Japan subgroups, consistent with the overall PULSAR results.}, }
@article {pmid41453515, year = {2025}, author = {Myers, WK and Heath, G and Rohrer, B}, title = {Rate of Age-Related Macular Degeneration in Patients Prescribed Glucagon-Like Peptide-1 Receptor Agonists or Other Weight Loss Therapies.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, pmid = {41453515}, issn = {2468-6530}, support = {I01 BX003050/BX/BLRD VA/United States ; T32 GM132055/GM/NIGMS NIH HHS/United States ; I01 RX000444/RX/RRD VA/United States ; R01 EY030072/EY/NEI NIH HHS/United States ; IK6 BX004858/BX/BLRD VA/United States ; }, abstract = {PURPOSE: To compare the hazard of age-related macular degeneration (AMD) among nondiabetic, weight loss-eligible adults prescribed glucagon-like peptide-1 receptor agonists (GLP-1 RAs; semaglutide or liraglutide) versus other weight loss (OWL) pharmacotherapies (phentermine, orlistat, setmelanotide, phentermine-topiramate, or bupropion-naltrexone).<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Adults aged &#x2265;50 years without diabetes who met the criteria for weight loss pharmacotherapy and were prescribed GLP-1 RAs or OWL medications were included. Before matching, 60&#x2009;336 patients were included in the GLP-1 RA group and 21 609 in the OWL cohort; after matching, 20&#x2009;959 patients remained in each cohort.<br><br>METHODS: Cohorts were constructed using de-identified data from the TriNetX Research Network (June 2021-October 2025). Nondiabetic status was defined as the absence of a diabetes mellitus diagnosis, hemoglobin A1c &#x2265;6.5%, or metformin or insulin use. Patients met criteria for weight loss pharmacotherapy with documentation of an obesity diagnosis, body mass index (BMI) &#x2265;30 kg/m[2], or BMI &#x2265;27 kg/m[2] with dyslipidemia or hypertension, recorded within 1 year before initiation. Inclusion required &#x2265;2 prescriptions for a single study medication &#x2265;6 months apart. Patients with recorded medication cross-exposure or outcome diagnoses before index were excluded. Cohorts were matched for demographics, established AMD risk factors, covariates influencing treatment allocation, access to ophthalmic care, and proxies for social determinants of health using 1:1 propensity score matching. Outcomes were assessed using Cox proportional hazards models.<br><br>MAIN OUTCOME MEASURES: Hazard ratios (HRs) of nonexudative AMD, exudative AMD, and any AMD (exudative, nonexudative, or unspecified). Changes in BMI and hemoglobin A1c were analyzed to contextualize findings.<br><br>RESULTS: Compared with OWL pharmacotherapies, GLP-1 RAs were associated with a lower hazard of nonexudative AMD (HR, 0.47; 95% confidence interval [CI], 0.28-0.78) and any AMD (HR, 0.61; 95% CI, 0.43-0.85), with no difference for exudative AMD (HR, 0.63; 95% CI, 0.30-1.32). Body mass index and hemoglobin A1c were similar over follow-up.<br><br>CONCLUSIONS: Among nondiabetic adults aged &#x2265;50 years eligible for weight loss pharmacotherapy, prescriptions for GLP-1 RAs were associated with a lower incidence of nonexudative and any (nonexudative, exudative, or unspecified) AMD diagnoses compared with OWL medications. The difference in new exudative AMD diagnoses was not statistically significant.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41453674, year = {2026}, author = {Palakkan, AA and Kumar, GS}, title = {Retinal organoids in age-related macular degeneration: Promise, pitfalls, and progress.}, journal = {Experimental eye research}, volume = {264}, number = {}, pages = {110831}, doi = {10.1016/j.exer.2025.110831}, pmid = {41453674}, issn = {1096-0007}, mesh = {Humans ; *Organoids/pathology ; *Macular Degeneration/pathology ; *Retina/pathology ; Animals ; }, abstract = {Recent advancements in organoid technology have revolutionized our understanding of organ development and disease modelling. However, despite significant progress, retinal organoids continue to face several limitations, including imperfect architecture, incomplete maturation, limited functional integration, and lack of vascularization. These challenges hinder their potential as accurate models of human retinal biology and disease. In this review, we examine the currently available models of age-related macular degeneration, evaluate the potential of retinal organoids, and discuss their respective advantages and limitations. We also explore strategies to overcome the existing challenges in retinal organoid systems, drawing parallels from progress made in other organoid fields, where similar limitations have been addressed. Implementing these strategies may enhance the structural and functional fidelity of retinal organoids, thereby improving their utility in modelling retinal disorders and advancing regenerative medicine.}, }
@article {pmid41454061, year = {2026}, author = {Guo, S and Liu, R and Liu, Y and Liu, F}, title = {Comment on "Correlation of retino-choroidal thickness and vascular metrics with drusen volume as a severity marker of age-related macular degeneration".}, journal = {Eye (London, England)}, volume = {40}, number = {2}, pages = {280}, pmid = {41454061}, issn = {1476-5454}, }
@article {pmid41455312, year = {2026}, author = {Zhang, M and Bi, H and Guo, D}, title = {Advances in study of endoplasmic reticulum stress in ophthalmic diseases: an overview.}, journal = {Biochemical and biophysical research communications}, volume = {797}, number = {}, pages = {153182}, doi = {10.1016/j.bbrc.2025.153182}, pmid = {41455312}, issn = {1090-2104}, mesh = {*Endoplasmic Reticulum Stress ; Humans ; *Eye Diseases/pathology/metabolism ; Animals ; Endoplasmic Reticulum/metabolism/pathology ; Diabetic Retinopathy/pathology/metabolism ; }, abstract = {The endoplasmic reticulum (ER) is a vital intracellular organelle in protein synthesis, folding, and modification. When cells experience excessive protein synthesis, glucose metabolism disorders, or calcium imbalance, the ER can become damaged or overburdened, triggering ER stress. Dysregulated ER stress can lead to various pathophysiological processes, including apoptosis, inflammation, protein aggregation, and lipid metabolism abnormalities. These processes are closely associated with the onset and progression of numerous diseases. Notably, many ophthalmic conditions, such as age-related macular degeneration, glaucoma, and diabetic retinopathy, are intricately linked to ER stress. This review provides a concise overview of the role of ER stress in the development and progression of ophthalmic diseases. It also explores the potential of targeting ER stress as a therapeutic approach for these conditions. By modulating ER stress and its associated pathways, new therapeutic strategies may be developed to improve patient outcomes. Future research should aim to elucidate the specific molecular mechanisms linking ER stress to ophthalmic diseases and to validate the efficacy and safety of interventions targeting ER stress, offering new perspectives and methods for the prevention and treatment of ophthalmic diseases.}, }
@article {pmid41455821, year = {2025}, author = {Haghighi, T and Gholami, S and Sokol, JT and Biswas, A and Lim, JI and Leng, T and Thompson, AC and Tabkhi, H and Alam, MN}, title = {Compact vision language models enable efficient and interpretable optical coherence tomography through layer-specific multimodal learning.}, journal = {Communications medicine}, volume = {6}, number = {1}, pages = {32}, pmid = {41455821}, issn = {2730-664X}, support = {R15EY035804//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; AI4Health seed garnt//UNC | University of North Carolina at Charlotte (UNC Charlotte)/ ; R21 EY035271/EY/NEI NIH HHS/United States ; R21EY035271//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R15 EY035804/EY/NEI NIH HHS/United States ; }, abstract = {BACKGROUND: Translating the intricate anatomical signatures of retinal disease from optical coherence tomography (OCT) B-scans into clear, accurate clinical narratives demands algorithms that seamlessly fuse visual features with domain expertise.<br><br>METHODS: We curated a multimodal dataset of 40,000 OCT B-scans from public repositories and private clinical cohorts, each paired with expert-validated summaries spanning six conditions: diabetic macular edema, diabetic retinopathy, geographic atrophy, drusen, choroidal neovascularization, and healthy retina. We introduce LO-VLM, a compact (247M parameter) vision-language model (VLM) that infuses anatomical guidance into both encoder and decoder for free-form summary generation and multiclass disease classification. Benchmarking against state-of-the-art RetinaVLM, LLaVA-Med, and a ViT vision only model demonstrates superior performance.<br><br>RESULTS: In a blinded evaluation by three board certified retina specialists, LO-VLM narratives achieves a mean = 8.5 (standard deviation = 1.15) out of 10, compared to a mean = 5.5 (standard 32 deviation = 1.13) for RetinaVLM (p < 0.0001). In quantitative evaluations, LO-VLM achieves an SBERT similarity of 80.3% and a BERTScore F1 of 71.5%, representing improvements of 8.2% and 28.8% over specialized VLM baselines. For disease classification, LO-VLM reaches 96% accuracy (F1 = 96%), outperforming ViT by 13% and exceeding medical VLM benchmarks by over 62% (p < 0.05).<br><br>CONCLUSIONS: By reconciling interpretability with computational efficiency, LO-VLM establishes a paradigm for efficient AI models in OCT interpretation.}, }
@article {pmid41457155, year = {2025}, author = {Yang, S and Mu, D and Li, X}, title = {Luteolin alleviates angiogenesis in HUVECs by inhibiting VEGFA expression: integrating network pharmacology and experimental validation.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {3706}, pmid = {41457155}, issn = {2045-2322}, mesh = {Humans ; *Luteolin/pharmacology ; *Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; *Vascular Endothelial Growth Factor A/metabolism/genetics ; Network Pharmacology ; Cell Movement/drug effects ; Signal Transduction/drug effects ; *Neovascularization, Pathologic/drug therapy/metabolism ; Macular Degeneration/drug therapy/metabolism/pathology ; Protein Interaction Maps/drug effects ; *Neovascularization, Physiologic/drug effects ; Cell Proliferation/drug effects ; Angiogenesis ; }, abstract = {To analyze the potential therapeutic value and mechanism of luteolin in age-related macular degeneration (AMD) using network pharmacology and cellular experiments. SHD-compound targets were retrieved from the TCMSP database, while AMD-related targets were extracted from OMIM and DisGeNET databases. Overlapping targets were identified via Venny 2.1. A PPI network was constructed using the STRING database, followed by functional enrichment analysis of overlapping targets via Metascape. Pharmacological networks were mapped using Cytoscape. For cellular experiments, the optimal concentration of luteolin was determined by CCK-8 assay. Human umbilical vein endothelial cells (HUVECs) were divided into: Control group (Without any intervention), Model group (VEGF165-induced model), and Treatment group (VEGF165-induced + luteolin). Angiogenesis was evaluated via scratch, transwell migration, invasion, and tube formation assays. VEGFA protein expression was assessed by Western blot. We identified 157 SHD-compound targets and 87 AMD-related targets, yielding 6 overlapping targets (ESR1, PON1, SOD1, APOB, VEGFA, IL6). PPI networks and enrichment analysis revealed that luteolin in SHD may inhibit AMD neovascularization via VEGFA signaling pathways. The concentration of luteolin (25 µmol/L) used in the experiments was selected based on the dose-response results. In vitro assays showed the Treatment group exhibited: significantly reduced horizontal migration (scratch assay, p < 0.05), decreased vertical migration (transwell assay, p < 0.05), suppressed invasion (p < 0.05), and inhibited tube formation (p < 0.05). Western blot confirmed reduced VEGFA expression in the treatment group (p < 0.05). Luteolin alleviates angiogenesis in HUVECs by inhibiting VEGFA expression, highlighting its potential as a therapeutic candidate for neovascular AMD.}, }
@article {pmid41457739, year = {2025}, author = {Kanthar, T and Vatcharavongvan, P and Prasert, V}, title = {Retrospective Analysis of Intervention Effectiveness in Preventing Glaucoma Blindness in a Tertiary Care Setting.}, journal = {Journal of evaluation in clinical practice}, volume = {31}, number = {8}, pages = {e70341}, doi = {10.1111/jep.70341}, pmid = {41457739}, issn = {1365-2753}, mesh = {Humans ; Male ; Retrospective Studies ; *Blindness/prevention &amp; control/etiology/epidemiology ; Female ; Thailand/epidemiology ; Middle Aged ; Cross-Sectional Studies ; Aged ; *Glaucoma/complications/therapy ; Tertiary Care Centers ; Risk Factors ; Trabeculectomy ; }, abstract = {RATIONALE: The global prevalence rate of glaucoma blindness is extremely high and is a leading cause of irreversible blindness. Despite many advancements in treatment, evaluating glaucoma blindness remains challenging due to the long time required for its development and the combined use of treatment modalities.<br><br>AIMS AND OBJECTIVES: To evaluate the effectiveness of various treatment modalities in preventing glaucoma-related blindness using a 5-year retrospective study from a tertiary care hospital in Thailand.<br><br>METHODS: A retrospective, cross-sectional study was conducted on 1031 glaucoma patients diagnosed between October 2017 and September 2022. Patients with advanced pterygium, corneal opacity, or macular degeneration were excluded. Data on demographics, clinical characteristics, and treatment modalities (medications, phacoemulsification with intraocular lens implantation [PE with IOL], laser iridotomy [LI], and trabeculectomy) were analyzed. Blindness was defined according to WHO criteria. Multivariate logistic regression assessed associations between blindness and risk factors.<br><br>RESULTS: Of the 1031 patients, 21.0% experienced blindness. Secondary glaucoma (SG) had the highest blindness rate (33.5%) compared to primary open-angle glaucoma (POAG, 19.0%) and primary angle-closure glaucoma (PACG, 19.9%). Multimodal interventions significantly reduced blindness in POAG (adjusted OR: 0.57; 95% CI: 0.38-0.87; p&#x2009;=&#x2009;0.027), but no significant benefit was observed in PACG or SG. PE with IOL showed the lowest blindness rate (14.9%), while trabeculectomy had the highest (47.2%). Treatment initiation within 5 years of diagnosis did not significantly affect blindness rates.<br><br>CONCLUSION: Multimodal interventions effectively reduce blindness in POAG but not in PACG or SG. Future studies should explore the impact of adherence, IOP fluctuation, and secondary glaucoma etiology on outcomes to optimize treatment strategies.}, }
@article {pmid41458157, year = {2025}, author = {Duan, MM and Qi, H and Tu, X}, title = {Knowledge-enhanced AI drives diagnosis of multiple retinal diseases in fundus fluorescein angiography.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1703606}, pmid = {41458157}, issn = {2296-634X}, abstract = {PURPOSE: This study aimed to develop and validate a deep learning model for the accurate multi-class classification of six retinal diseases using fundus fluorescein angiography (FFA) images.<br><br>METHODS: We applied a knowledge-enhanced pre-training strategy (KeepFIT) using a ResNet-50 image encoder on two large FFA corpora: a curated atlas and a clinical report dataset. The resulting visual encoder was fine-tuned to classify six conditions, including diabetic retinopathy and macular degeneration. The model's performance and generalizability were assessed on two independent test sets, one of which was sourced from an external institution.<br><br>RESULTS: Our proposed deep learning model, leveraging a knowledge-enhanced pre-training strategy, demonstrated robust performance in classifying six distinct retinal diseases using fundus fluorescein angiography images. The model achieved a strong and consistent micro-average area under the curve (AUC) of 0.92 across two independent test sets. Notably, it showed excellent classification performance for critical conditions such as venous occlusion (VO) and neovascular age-related macular degeneration (nAMD), with AUC values reaching 0.95 and 0.96, respectively.<br><br>CONCLUSION: The knowledge-enhanced pre-training strategy significantly improves the diagnostic accuracy and generalizability of deep learning models for FFA analysis. This approach provides a scalable and effective framework for automated retinal disease screening, holding significant potential for clinical decision support, especially in resource-limited settings.}, }
@article {pmid41458191, year = {2026}, author = {Li, N and Dang, Y}, title = {Atypical Retinitis Pigmentosa With Macular Sparing in a Patient With Compound Heterozygous ABCA4 Variants: A Case Report and Diagnostic Challenge.}, journal = {Clinical case reports}, volume = {14}, number = {1}, pages = {e71545}, pmid = {41458191}, issn = {2050-0904}, abstract = {Inherited retinal dystrophies are a complex group of disorders causing progressive vision loss. The ABCA4 gene is associated with a wide spectrum of retinopathies, most commonly Stargardt disease, which is characterized by central macular degeneration. Retinitis Pigmentosa (RP) is a less common but recognized ABCA4-associated phenotype, typically involving severe, pan-retinal degeneration. A 25-year-old male presented with a 5-year history of nyctalopia and progressive peripheral visual field loss. Best-corrected visual acuity was 1/20 in the right eye and 20/20 in the left eye. Fundus examination revealed pale optic discs, attenuated retinal arteries, and peripheral bone spicule-like pigment deposits, with notable sparing of the macula. Genetic analysis identified compound heterozygous variants in the ABCA4 gene: a known pathogenic variant, c.4793C>A (p.Ala1598Asp), inherited from his father, and a novel variant, c.1769A>G (p.Asp590Gly), inherited from his mother. The novel variant was re-evaluated according to ACMG/AMP guidelines and classified as likely pathogenic based on its absence in population databases, co-segregation with disease, and high in silico prediction scores. This case presents a diagnostic challenge, with a clinical phenotype of macular sparing RP and strong genetic evidence implicating ABCA4. These findings expand the potential phenotypic spectrum of ABCA4-retinopathy and underscore the critical role of genetic testing in diagnosing patients with atypical presentations of inherited retinal disease. Further investigation is needed to fully elucidate the pathogenic mechanism of the novel variant and its contribution to this unusual clinical picture.}, }
@article {pmid41458648, year = {2025}, author = {Kayabaşı, M and Karataş, E and Ayhan, Z and Kartı, &#xd6; and Saatci, AO}, title = {Evolution of the Onion Ring Sign in Radiation Retinopathy.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e97758}, pmid = {41458648}, issn = {2168-8184}, abstract = {A 53-year-old male with a history of radiation therapy for thyroid ophthalmopathy was followed up for chronic bilateral vision loss and macular edema refractory to multiple intravitreal treatments for over 19 years. His clinical course included multiple intravitreal injections including triamcinolone acetonide, bevacizumab, pegaptanib, ranibizumab, aflibercept 2 and 8 mg, and dexamethasone implant. At the 17th year of follow-up, spectral-domain optical coherence tomography (OCT) revealed intensely hyperreflective, horizontally layered deposits within intraretinal cystic spaces without posterior shadowing, consistent with the onion ring sign. Fundoscopic examination showed highly refractile, golden-yellow lipid exudates corresponding to these OCT findings. Unlike previously reported cases of age-related macular degeneration and diabetic retinopathy, where these deposits were located primarily beneath or above the retinal pigment epithelium, the deposits in this patient were located within the inner retinal layers. The present case demonstrates that the onion ring sign may develop in long-standing radiation retinopathy, likely reflecting the cumulative effects of chronic vascular injury and persistent macular edema. The recognition of this OCT feature may aid in understanding the natural history, chronicity, and metabolic burden of retinal vascular disorders.}, }
@article {pmid41458867, year = {2025}, author = {Matsuo, T and Matsuo, N}, title = {Long-Term Outcome of Xenon-Arc Photocoagulation for Retinopathy of Prematurity in the 1970s in Japan: Eleven Patients With 32- to 49-Year Follow-Up.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e97797}, pmid = {41458867}, issn = {2168-8184}, abstract = {OBJECTIVES: Photocoagulation or cryocautery, or their combinations, are the standard of care for retinopathy of prematurity at the recommended timing, which is based on the International Classification of Retinopathy of Prematurity. In Japan, the effectiveness of xenon-arc photocoagulation and cryocautery in retinopathy of prematurity was reported on an empirical basis first in 1968, and became the standard of care in retinopathy of prematurity in the 1970s, 10 years earlier compared with the other countries. In this study, we reported the up to 49 years visual outcome of 11 patients with retinopathy of prematurity who underwent xenon-arc photocoagulation and cryocautery in the 1970s.<br><br>METHODS: A retrospective review was made on the medical records of 11 consecutive patients who underwent xenon-arc photocoagulation for retinopathy of prematurity in the years 1974 to 1980, and were followed up until the period from 2009 to 2025. The birthweight ranged from 865 g to 2300 g at a median of 1350 g, and the gestational age at birth ranged from 27 weeks to 36 weeks at a median of 30 weeks. The corrected gestational age at the time of photocoagulation ranged from 32 weeks to 53 weeks, with a median of 37 weeks. Oxygen was given to all 11 patients, except for one who was born in the earliest year 1974. The retinopathy of prematurity was at stage 3 in both eyes of seven patients, with plus disease signs in four patients, at stage 2 with and without plus disease in two patients, at stage 2 and stage 3 in each eye of one patient, and at stage 1 with plus disease in both eyes of one patient. The entire 360-degree photocoagulation was given in seven patients, while partial photocoagulation was applied in four patients. Additional cryocautery was applied in six patients.<br><br>RESULTS: The age at the last visit ranged from 32 to 49 years with a median of 46 years. At the last visit, seven patients showed the best-corrected visual acuity in decimals of 0.8 or better in both eyes. One dizygotic twin showed no light perception in the phthisic right eye and 0.1 in the left eye with macular degeneration and nystagmus after he underwent cataract surgery at the age of 34 years. The other twin had the best-corrected visual acuity of 0.5 in the right eye and 0.02 in the left eye due to macular degeneration after he underwent cataract surgeries in both eyes at the age of 36 years. Two patients developed rhegmatogenous retinal detachment in one eye at the age of 44 and 41 years, respectively, and underwent vitrectomy with silicone oil tamponade, resulting in visual acuity of 0.1 and 0.3, respectively. Two patients experienced vitreous hemorrhage in one eye, which was absorbed spontaneously at the ages of 37 years and 42 years, respectively. One patient underwent partial scleral buckling for localized rhegmatogenous retinal detachment. No patient used intraocular pressure-lowering eyedrops.<br><br>CONCLUSION: Most patients with xenon-arc photocoagulation for retinopathy of prematurity in the 1970s maintained standard levels of visual acuity up to 49 years in the follow-up. Cataract, retinal detachment, and vitreous hemorrhage were noted as late complications and were coped with on an individual basis. The conclusion would have a meaning, even though not novel, that the patients with retinopathy of prematurity would have benefited from the xenon-arc photocoagulation and cryocautery.}, }
@article {pmid41460325, year = {2026}, author = {Sadda, SR and Wykoff, CC and Chowers, I and Korobelnik, JF and Narayana, R and Pappuru, RR and Holz, FG and Guymer, R and Cheung, CMG and Boyer, DS and Ip, M and Niessen, HG and Holenkamp, N and Durbin, M and Magazzeni, S and Cairns, AM and Ciller, C and Jovic, N and Blair, J and De Zanet, S and Lee, AY}, title = {Initiation of a global consortium to study the progression of age-related macular degeneration: RIMR AMD consortium report # 1.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {4}, pages = {935-943}, pmid = {41460325}, issn = {1435-702X}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Disease Progression ; *Macular Degeneration/diagnosis ; *Macula Lutea/pathology/diagnostic imaging ; }, abstract = {PURPOSE: To describe the design and organizational structure of a global collaborative consortium aimed at aggregating longitudinal multimodal imaging data to better understand the progression of age-related macular degeneration (AMD) and facilitate therapeutic development.<br><br>METHODS: The Ryan Initiative for Macular Research (RIMR) AMD Consortium was established as a nonprofit organization, bringing together academic institutions, biopharmaceutical companies, and imaging technology providers. The consortium collects, de-identifies, and harmonizes longitudinal optical coherence tomography (OCT) data, as well as associated clinical metadata, from multiple international clinical centers using a cloud-based infrastructure. Imaging data is converted and stored in DICOM format, and associated clinical data is mapped to the OMOP Common Data Model. All analyses are conducted within a secure cloud environment, supporting both built-in and member-contributed artificial intelligence (AI) tools.<br><br>RESULTS: As of the time of reporting, the Consortium has ingested over 100,000 OCT volumes from more than 5,000 subjects across 7 global cohorts spanning 4 continents and 3 major OCT platforms. Based on information provided by the data providers, the dataset encompasses a wide range of AMD stages, from normal aging to late-stage neovascular or atrophic AMD, with longitudinal follow-up extending beyond 15 years for some subjects. A data harmonization pipeline has been established to convert all ingested OCT data to the DICOM standard and is thus ready for automated analysis to gain disease-related insights.<br><br>CONCLUSIONS: The RIMR AMD Consortium represents a novel model for global collaboration in AMD research, enabling the pooling and analysis of heterogeneous imaging data while addressing privacy, regulatory, and interoperability challenges. This framework may serve as a model for similar initiatives in other ocular diseases.}, }
@article {pmid41460363, year = {2025}, author = {Wang, C and Li, H and Wang, T and Li, X and Liu, J and Deng, A and Jiao, X}, title = {The gut-eye axis in blinding eye diseases: microbiota-driven immune dysregulation and immunomodulatory therapies.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {57}, pmid = {41460363}, issn = {1573-2630}, support = {2024BSQD05//the Doctoral Startup Fund of the Affiliated Hospital of Shandong Second Medical University/ ; ZR2025QC815//the Shandong Provincial Natural Science Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; Animals ; Probiotics/therapeutic use ; Dysbiosis ; *Immunomodulation ; *Eye Diseases/therapy/microbiology/immunology ; }, abstract = {PURPOSE: To synthesize recent (2020-2025) advances on how gut, oral, and ocular-surface microbiota contribute to major blinding eye diseases, dry eye disease (DED), non-infectious uveitis, glaucoma, optic neuropathy, age-related macular degeneration (AMD), and diabetic retinopathy (DR), and to evaluate the therapeutic potential of microbiome-based interventions.<br><br>METHODS: PubMed and Web of Science were searched (January 2020-October 2025) using the terms "gut microbiota", "ocular diseases", and "immunomodulatory therapies". Eligible studies included original human and animal research demonstrating microbial dysbiosis or testing microbiome-directed therapies. Data were synthesized thematically across microbial composition, immune-metabolic mechanisms, and intervention outcomes.<br><br>RESULTS: Across all six diseases, dysbiosis was consistently characterized by depletion of anti-inflammatory taxa such as Akkermansia, Ruminococcaceae, and other short-chain fatty acid (SCFA) producers, with enrichment of pro-inflammatory bacteria including Proteobacteria, Staphylococcus, and Porphyromonas gingivalis. These changes were associated with increased intestinal permeability, systemic lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO), Th17 (T helper 17)/Treg (regulatory T cell) imbalance, and loss of SCFA-mediated neuroprotection. Probiotics containing Lactobacillus or Bifidobacterium improved tear stability and reduced inflammation in preclinical and pilot clinical studies, while high-fiber diets ameliorated lesions in age-related macular degeneration (AMD) and diabetic retinopathy (DR). Fecal microbiota transplantation confirmed microbial causality but revealed donor-dependent effects, and engineered Lactobacillus expressing angiotensin-converting enzyme 2 (ACE2) or Ang-(1-7) preserved retinal integrity in diabetic models.<br><br>CONCLUSIONS: Microbial dysbiosis acts as a common driver of immune-metabolic dysfunction in blinding eye diseases. Microbiome-targeted strategies show promising efficacy in experimental systems, but large, longitudinal human trials are needed for clinical translation.}, }
@article {pmid41462510, year = {2025}, author = {Inoda, S and Takahashi, H and Hashimoto, Y and Yoshida, H and Takahashi, H and Takayama, T and Tsuchiya, S and Matsumoto, D and Kawashima, H and Kaburaki, T and Yanagi, Y}, title = {One year outcomes of intravitreal faricimab for treatment Naïve neovascular AMD and associations with baseline aqueous humor cytokines.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {44717}, pmid = {41462510}, issn = {2045-2322}, abstract = {UNLABELLED: This study investigated the one-year real-world clinical outcomes of intravitreal faricimab (IVF) in treatment-naïve neovascular age-related macular degeneration (nAMD) and its association with aqueous humor cytokine profiles. Thirty-four eyes of 32 nAMD patients, who received initial IVF at Jichi Medical University were included. These eyes showed significant improvements in central retinal subfield thickness (CST), central choroidal thickness (CCT), and best-corrected visual acuity (BCVA) one year post-IVF (all P < 0.01). Among 24 measurable cytokines, only VEGF-A was significantly higher in eyes with a dry macula at week 16 (P = 0.0030). Three cytokines were significantly higher in eyes with longer injection interval. Higher levels of galectin-1 and VCAM-1, and lower levels of P-selectin, were correlated with greater CST reduction (P = 0.020, 0.0061, and 0.012, respectively). Conversely, five cytokines including Ang-1 were correlated with greater BCVA improvement (all P < 0.05). In conclusion, an anatomical perspective faricimab demonstrated anatomical efficacy for VEGF-driven nAMD in the loading phase, while multiple cytokines associated with vascular instability or fibrosis appear to contribute to its durability. Notably, Ang-1 may be linked to visual improvement, suggesting that the neurotrophic effects of Ang-1 could be enhanced by Ang-2 inhibition.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-28911-9.}, }
@article {pmid41462634, year = {2025}, author = {Lin, HD and Tsai, RK and Wen, YT and Liu, PK}, title = {HDGF Protects Retinal Pigment Epithelium from Glyoxal-Induced Ferroptosis via SIRT1/PGC-1α/Nrf2 Pathway.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, pmid = {41462634}, issn = {2076-3921}, support = {MOST 109-2314-B-037-039//National Science and Technology Council, Taiwan/ ; MOST 110-2314-B-037-115//National Science and Technology Council, Taiwan/ ; KMUH109-9R50//Kaohsiung Medical University Hospital, Taiwan/ ; KMUH110-0R50//Kaohsiung Medical University Hospital, Taiwan/ ; }, abstract = {Age-related macular degeneration (AMD) is driven in part by the accumulation of reactive metabolites like glyoxal (GO), which induces retinal pigment epithelium (RPE) degeneration. Here, we demonstrate that GO triggers ferroptosis in human ARPE-19 cells, as characterized by iron-dependent lipid peroxidation, glutathione depletion, and reactive oxygen species (ROS) accumulation. This ferroptotic cell death is coupled with profound mitochondrial dysfunction, featuring network fragmentation and the downregulation of the key regulators MFN2, PGC-1α, and SIRT1. We identify hepatoma-derived growth factor (HDGF) as a potent protector against GO-induced damage. HDGF operates through a dual mechanism: it activates the p38 MAPK/AKT and SIRT1/PGC-1α axes to restore mitochondrial biogenesis and homeostasis, while concurrently enhancing the glutathione/GPX4 antioxidant system to suppress ferroptosis. This cytoprotective action is mediated via the PGC-1α/Nrf2 pathway, which integrates the enhancement of antioxidant defenses with the preservation of mitochondrial integrity. Our findings establish HDGF as a novel therapeutic agent for AMD, uniquely capable of concurrently targeting the interconnected pathways of ferroptosis and mitochondrial dysfunction, thereby addressing a critical unmet need in retinal disease treatment.}, }
@article {pmid41462675, year = {2025}, author = {Tundo, GR and Zingale, GA and Pandino, I and Peroni, E and Sbardella, D and Bocedi, A}, title = {The Interplay Between the Ubiquitin-Proteasome System and Oxidative Stress: A Future Perspective in Eye Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, pmid = {41462675}, issn = {2076-3921}, abstract = {Redox unbalance, a molecular trait common to neurodegenerative conditions and para-physiological processes like aging, is a critical factor in disease development and in exacerbating progression. The mechanism by which redox imbalance perturbs cellular homeostasis is strongly linked to the activity and function of the ubiquitin-proteasome system (UPS). The UPS, along with autophagy, is the primary intracellular proteolytic system, regulating targeted proteolysis and removing damaged proteins. Consequently, the UPS serves also as the first line of defense for cellular recovery following exposure to redox stressors. Paradoxically, the composition and function of the UPS can also be negatively targeted by redox unbalance through a vicious cycle. The alterations in redox balance and UPS biological mechanisms are involved in the etiopathogenesis of chronic eye disorders. These disorders encompass a diverse repertoire of pathologies affecting the retinal layers (e.g., age-related macular degeneration, diabetic retinopathy) and the optic nerve (e.g., glaucoma). Nowadays, the comprehension of the interplay between proteostasis and oxidative redox status remains pivotal for identifying new therapeutic approaches. Encouragingly, a number of anti-oxidant compounds have been reported to modulate proteasome activity against redox insults in vitro and in vivo. Furthermore, these compounds provide cytoprotective roles in both in vitro and animal models of eye diseases. Therefore, this review highlights recent research on the interplay of the UPS with oxidative stress in physio-pathological conditions, focusing on the onset and progression of ocular diseases, thereby providing new insights into UPS-oxidative stress interaction.}, }
@article {pmid41462709, year = {2025}, author = {Szewczyk-Roszczenko, OK and Pietruszyńska, M and Iwańska, IA and Roszczenko, P and Bielawski, K and Gornowicz, A and Bielawska, A}, title = {Plant-Based Care and Therapy in Ophthalmology.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, pmid = {41462709}, issn = {2076-3921}, abstract = {Oxidative stress, inflammation, and environmental factors contribute significantly to the development of ocular disorders, including dry eye disease, conjunctivitis, and age-related degenerative changes. In recent years, growing attention has been directed toward natural compounds and plant-derived extracts with potential protective and therapeutic effects on eye health. This work provides an overview of selected bioactive substances, such as carotenoids (β-carotene), flavonoids, vitamins C and E, and phytochemicals derived from plants. These agents exhibit antioxidative, anti-inflammatory, antimicrobial, and regenerative properties that may support ocular surface integrity, reduce oxidative damage, and improve visual performance. The integration of such natural remedies into ocular health strategies may offer complementary benefits to conventional therapies.}, }
@article {pmid41462921, year = {2025}, author = {Machida, A and Kurihara, J and Hirata, Y and Machida, E and Murakami, R and Oka, A and Yoneda, A and Tsuiki, E and Oishi, A}, title = {Flexible Loading Phase Treat-and-Extend Regimen with Faricimab for Neovascular Age-Related Macular Degeneration: A Real-World Study.}, journal = {Biomedicines}, volume = {13}, number = {12}, pages = {}, pmid = {41462921}, issn = {2227-9059}, support = {Nos. 22K09793 and 25K20183//Japan Society for the Promotion of Science/ ; }, abstract = {Background/Objectives: We aimed to evaluate the efficacy of a flexible loading-phase treat-and-extend regimen using faricimab, in which the number of loading-phase intravitreal injections was tailored to individual disease activity. Methods: This observational cohort study included 50 treatment-naïve eyes with neovascular age-related macular degeneration, treated with faricimab in Japan; approximately half of the eyes had polypoidal choroidal vasculopathy (PCV). Disease activity after one injection was assessed at the second visit (4 weeks later) to determine the treatment interval for subsequent injections. The primary outcome measure was the injection interval and visual/anatomical outcomes at 1 year after treatment initiation. Results: Of the 50 eyes, 43 completed a 1-year follow-up, including 27 eyes with PCV. The mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.35 ± 0.32 to 0.19 ± 0.3 over 1 year. Overall, 60.5% achieved 16-week intervals, and 74.4% reached intervals of ≥12 weeks. A shorter loading phase (two or three injections) was associated with fewer total injections and higher rates of fluid resolution, without compromising visual outcomes. The presence of PCV and ellipsoid zone disruption were identified as risk factors for failure to extend treatment intervals beyond 16 weeks. Conclusions: A flexible loading-phase treat-and-extend regimen using faricimab yields outcomes comparable to those of the TENAYA protocol, with fewer injections, despite the high proportion of eyes with PCV. This simple approach is straightforward in design and may reduce treatment burden while maintaining efficacy.}, }
@article {pmid41463016, year = {2025}, author = {Giorgianni, F and Beranova-Giorgianni, S}, title = {Proteasome and Ribosome Ubiquitination in Retinal Pigment Epithelial (RPE) Cells in Response to Oxidized Low-Density Lipoprotein (OxLDL).}, journal = {Biomedicines}, volume = {13}, number = {12}, pages = {}, pmid = {41463016}, issn = {2227-9059}, support = {N/A//Retina Research Foundation/ ; }, abstract = {Background/Objectives: Oxidative stress plays a significant role in the development and progression of age-related macular degeneration (AMD). Retinal pigment epithelium (RPE) cells are specialized multifunctional cells indispensable for the maintenance of vision. The dysfunction and death of RPE cells in the macula characterize the onset and development of AMD. Of the various toxic agents that impact the health of the RPE, particular focus has been given to various forms of lipoproteins and their cytotoxic derivatives normally present in the retina. Oxidized low-density lipoprotein (OxLDL), derived from LDL in a pro-oxidative environment, is found adjacent to RPE cells as part of drusen, extracellular deposits that are a hallmark feature of AMD. OxLDL is a potent inflammatory agent and it has been implicated in cardiovascular and neurodegenerative conditions. The cellular molecular mechanisms triggered by OxLDL are only partially understood. The focus of this study was to characterize changes in the proteome of RPE cells after exposure to OxLDL, with a focus on the characterization and quantification of ubiquitinated proteins. Methods: Identification and quantification were performed with a high-resolution LC-MS/MS-based proteomics workflow after immune-enrichment for ubiquitinated peptides. Results: In total, out of the more than 1000 RPE ubiquitinated peptides quantified, OxLDL treatment caused a significant increase in ubiquitinated peptides compared to LDL and untreated cells. Principal component analysis (PCA) of the differentially ubiquitinated proteins (265) reduced the data complexity in two main groups of variables (proteins). Conclusions: Gene ontology enrichment analysis of the grouped proteins with the highest loading contribution to principal component 1 (PC1) and principal component 2 (PC2) revealed significant ubiquitination changes upon OxLDL treatment in proteins of the ubiquitin-proteasome system (UPS) responsible for proteasome-mediated catabolic processes and in protein members of the cellular translation machinery.}, }
@article {pmid41463332, year = {2025}, author = {Yu, X and Fan, H and Zhang, H and Li, X}, title = {Mechanisms and Functions of Chromophore Regeneration in the Classical Visual Cycle: Implications for Retinal Disease Pathogenesis and Therapy.}, journal = {Biomolecules}, volume = {15}, number = {12}, pages = {}, pmid = {41463332}, issn = {2218-273X}, support = {82371044, 82171042, 82171085//National Natural Science Foundation of China/ ; TJWJ2023XK009//Tianjin Health Commission Key Discipline Special Project/ ; }, mesh = {Humans ; Animals ; *Retinal Diseases/therapy/metabolism/pathology ; *Retinaldehyde/metabolism ; cis-trans-Isomerases/metabolism/genetics ; Genetic Therapy ; Retinal Pigment Epithelium/metabolism ; Regeneration ; Retinoid Isomerohydrolase ; }, abstract = {11-cis-retinal, the indispensable chromophore of photoreceptor opsins, is fundamental for light detection and the initiation of visual signal transduction. Its synthesis and regeneration through the visual cycle are critical not only for phototransduction but also for maintaining retinal homeostasis. Disruption of key enzymes, such as retinal pigment epithelium (RPE)65 and retinol dehydrogenases, results in toxic retinoid accumulation, oxidative stress, and progressive photoreceptor degeneration. These pathological mechanisms contribute to inherited and acquired retinal diseases, including Stargardt disease type 1, age-related macular degeneration, Leber congenital amaurosis, retinitis pigmentosa, and fundus albipunctatus. Recent therapeutic advances, ranging from gene replacement therapy with RPE65 (voretigene neparvovec, Luxturna[®]) to small-molecule modulators and antioxidant strategies, underscore the translational potential of targeting chromophore metabolism. This review outlines molecular processes underlying chromophore synthesis and regeneration, elucidates how disruptions in these processes contribute to inherited and acquired retinal pathologies, and evaluates existing and emerging therapeutic strategies that target chromophore metabolism. We highlight ongoing challenges and critical knowledge gaps to guide future investigations on basic science, translational research, and clinical practice. This review provides a comprehensive overview of the molecular mechanisms, current therapeutic approaches, and outstanding challenges, with a focus on future intervention directions.}, }
@article {pmid41464830, year = {2025}, author = {Bellucci, C and Virgili, M and Romano, A and Tedesco, SA and Mora, P}, title = {Laser Speckle Flowgraphy (LSFG) in Age-Related Macular Degeneration and Diabetic Retinopathy: A Systematic Review of Recent Literature.}, journal = {Journal of clinical medicine}, volume = {14}, number = {24}, pages = {}, pmid = {41464830}, issn = {2077-0383}, abstract = {Background: Laser Speckle Flowgraphy (LSFG) is a non-invasive imaging technology that quantitatively evaluates retinal and choroidal blood flow by analyzing speckle patterns generated by laser light scattering. This systematic review summarizes the application of LSFG in two major degenerative retinal diseases: age-related macular degeneration (AMD) and diabetic retinopathy (DR). Methods: A comprehensive literature search (2010-2025) was conducted in PubMed, Cochrane Library and EMBASE according to PRISMA guidelines. Twenty-three studies including a total of 974 eyes (191 AMD, 783 DR) were analyzed. Results: In AMD, LSFG detected baseline reductions in choroidal and retinal perfusion in non-exudative disease, often extending beyond atrophic regions. Anti-VEGF injections produced acute reductions in MBR, particularly with brolucizumab, with partial recovery over time; drug-specific differences suggest a potential impact on geographic atrophy progression. In DR, LSFG revealed early microvascular dysfunction even in asymptomatic eyes. Retinal and choroidal MBR and blowout score correlated with HbA1c, DR severity, and inflammatory mediators. Intravitreal anti-VEGF therapy consistently reduced retinal and choroidal MBR and RFV, while conventional panretinal photocoagulation decreased choroidal flow and vascular caliber more robustly than patterned laser, reflecting oxygenation-driven VEGF modulation. Low baseline MBR predicted higher central macular thickness and reduced therapeutic response in diabetic macular edema. Conclusions: LSFG provides reproducible, rapid, and non-invasive quantitative insights into ocular hemodynamics across degenerative retinal diseases. Its integration into multimodal imaging may facilitate early diagnosis, support personalized management, and assist in the prognostic assessment of retinal and choroidal vascular disorders.}, }
@article {pmid41465162, year = {2025}, author = {Lee, Y and Kim, S and Seo, JH}, title = {Causal Association Between Psoriasis and Age-Related Macular Degeneration: A Two-Sample Mendelian Randomization Study.}, journal = {Genes}, volume = {16}, number = {12}, pages = {}, pmid = {41465162}, issn = {2073-4425}, support = {VHSMC25017//research grant from the Veterans Health Service Medical Centre/ ; }, mesh = {Humans ; *Macular Degeneration/genetics/epidemiology ; *Psoriasis/genetics/complications ; Mendelian Randomization Analysis/methods ; Polymorphism, Single Nucleotide/genetics ; Genome-Wide Association Study ; *Genetic Predisposition to Disease ; }, abstract = {BACKGROUND/OBJECTIVES: Psoriasis and age-related macular degeneration (AMD) may share immune-related pathophysiologic characteristics. However, few studies have investigated the relationship between psoriasis and AMD. We assessed the possible causal link between psoriasis and AMD in European populations.<br><br>METHODS: Single-nucleotide polymorphisms associated with psoriasis exposure were employed as instrumental variables (IVs) based on genome-wide significance (p < 5.0 &#xd7; 10-8) in the FinnGen genome-wide association study (GWAS). The GWAS data for AMD were obtained from 11 studies performed by the International AMD Genomics Consortium. We performed a two-sample Mendelian randomisation (MR) study to estimate causal effects using the inverse-variance weighted, weighted median, and MR-Egger methods, as well as the MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) test.<br><br>RESULTS: We observed significant causal associations of psoriasis with AMD. Using the weighted median method, the odds ratio (OR) was 1.09 (95% CI = [1.03-1.16] and p = 0.005), and using the MR-PRESSO test, the OR was 1.04 (95% CI = [1.00-1.09] and p = 0.043).<br><br>CONCLUSIONS: A potential causal association between psoriasis and AMD underscores the need to investigate inflammation as a risk factor for AMD.}, }
@article {pmid41466299, year = {2025}, author = {Hanson, RLW and Airody, A and Saad, A and Gale, RP}, title = {Early Detection Of neovascular age-Related mAcular Degeneration in the cOmmunity assessing persistence, adherence and acceptability: study protocol for the DORADO randomized controlled trial.}, journal = {Trials}, volume = {27}, number = {1}, pages = {78}, pmid = {41466299}, issn = {1745-6215}, support = {RE23_016_331617//Roche Products/ ; }, mesh = {Humans ; Early Diagnosis ; Quality of Life ; Tomography, Optical Coherence ; Randomized Controlled Trials as Topic ; Visual Acuity ; Time Factors ; United Kingdom ; *Patient Compliance ; *Patient Acceptance of Health Care ; *Wet Macular Degeneration/diagnosis ; Predictive Value of Tests ; *Community Health Services ; }, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in the Western world, with an estimated 40,000 newly diagnosed cases in the UK every year. Early detection and treatment of nAMD are important to achieve good visual acuity and quality-of-life (QoL) outcomes. Whilst early treatment of the second eye, following detection using optical coherence tomography (OCT) imaging, has shown maintenance of visual acuity and health-related QoL and reduced health and social care costs, there is a paucity of information about the benefits of early detection of nAMD in the first eye. In particular, although it is reasonable to consider a form of targeted screening of those most likely to develop nAMD, it is unclear if those invited would adhere to such a programme.<br><br>METHODS: In this randomized controlled trial, 130 participants will be recruited from community-based eye healthcare practices within the UK whilst attending their routine appointment. Participants will be randomized to either a standard care arm to attend a further follow-up appointment at 12&#xa0;months, or an intervention arm, attending every 3&#xa0;months for assessment. The end of study is at 12&#xa0;months. All participants will complete the NEI-VFQ-25, MacDQoL, PHQ9 and EQ-5D-3L questionnaires at baseline and 12&#xa0;months. In addition, all participants and recruiting investigators will complete the Theoretical Framework of Acceptability questionnaire at 12&#xa0;months.<br><br>DISCUSSION: The DORADO study aims to assess the persistence and adherence to and acceptability of a community-based programme for the early detection of nAMD.<br><br>TRIAL REGISTRATION: ISRCTN10005321. Registered on 08 November 2024.}, }
@article {pmid41466814, year = {2025}, author = {Awan, B and Elsaigh, M and Hesham Gamal, M and Elbahnasawy, SE and Badee, M}, title = {Integrating Human Expertise With Artificial Intelligence (AI) Models for Optical Coherence Tomography (OCT) Retinal Fluid and Pathology Quantification: A Systematic Review.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e100223}, pmid = {41466814}, issn = {2168-8184}, abstract = {Artificial intelligence (AI) and intensive learning show promise in ophthalmology, using optical coherence tomography (OCT) to diagnose conditions such as diabetic retinopathy. However, precise segmentation of retinal fluid remains challenging, especially in atypical cases and low-quality scans. In hospital settings, manual segmentation is time-consuming; however, integrating human expertise with AI could improve efficiency and accuracy in quantifying retinal pathologies. This review assesses the efficacy of human-AI collaborative workflows for enhancing the accuracy, efficiency, and clinical utility of retinal pathology quantification in OCT. We conducted a systematic review of the literature from 2021 to 2025 across three databases: PubMed, Web of Science, and Scopus. This review included nine studies that quantified retinal pathology using human-AI collaborative workflows in OCT. Two independent reviewers screened the records, extracted relevant data, including study design, AI architecture, and performance metrics, and assessed the quality of the studies using the Quality Assessment of Diagnostic Accuracy Studies - 2nd version (QUADAS-2) and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tools. This systematic review of nine AI-OCT studies (2021-2025) found that hybrid AI-clinician workflows achieved expert-level reliability for 11 of 13 retinal biomarkers across cohorts of 16-1,097 individuals. AI architectures, including U-Net variants, polypoidal choroidal vasculopathy (PCV)-Net, and custom convolutional neural networks (CNNs), performed well for well-defined features such as retinal layers (Dice 0.94), intraretinal/subretinal fluid (Dice 0.61-0.67), and atrophic areas (F1 0.78-0.89), but struggled with complex biomarkers like sub-retinal pigment epithelium (sub-RPE) lesions (Dice 0.11). Clinician agreement on fluid volumes was strong (Pearson r > 0.85), though volumetric errors increased in atrophic regions. These workflows reduced processing time by over 50% compared with manual grading while improving monitoring precision for neovascular age-related macular degeneration (AMD) and retinitis pigmentosa complications in both single-center and international trial settings. Combining AI quantification with clinician expertise enhances both the accuracy and efficiency of retinal pathology assessments. This integration supports personalized treatment planning and facilitates large-scale research. Hybrid approaches address AI's limitations, highlighting their practicality for clinical use in ophthalmology. We suggest incorporating hybrid AI-human workflows in clinical practice to improve the efficiency and accuracy of OCT analysis. Future developments in AI should focus on standardized training for complex biomarkers, such as sub-RPE lesions.}, }
@article {pmid41466880, year = {2025}, author = {Zhang, J and Xia, T and Zhang, D and Yang, X}, title = {Exploring the Link Between Sleep Duration and Visual Impairment and Major Eye Diseases: National Health and Nutrition Examination Survey 2005-2008.}, journal = {BioMed research international}, volume = {2025}, number = {}, pages = {1229050}, pmid = {41466880}, issn = {2314-6141}, mesh = {Humans ; Male ; Female ; Middle Aged ; Aged ; *Vision Disorders/epidemiology/physiopathology ; *Eye Diseases/epidemiology/physiopathology ; Nutrition Surveys ; *Sleep/physiology ; Adult ; Cross-Sectional Studies ; Prevalence ; Glaucoma/epidemiology/physiopathology ; United States/epidemiology ; Visual Acuity ; Sleep Duration ; }, abstract = {OBJECTIVE: This study is aimed at investigating the association between sleep duration and visual impairment, as well as its relationship with major eye diseases, using data from a large-scale population-based survey.<br><br>METHODS: This cross-sectional study investigated the prevalence of visual impairment and major eye conditions among 5231 individuals aged 40 and older, utilizing data from the NHANES 2005-2008 survey. Sleep duration was categorized as short (<&#x2009;7&#x2009;h), normal (7-9&#x2009;h), and long (>&#x2009;9&#x2009;h). Visual impairment was defined as corrected visual acuity <&#x2009;20/40, and major eye diseases included cataract surgery, diabetic retinopathy, age-related macular degeneration, glaucoma, any retinopathy, any ocular disease, and any objectively determined ocular disease. Univariate and multivariate logistic regression were used to assess associations between sleep duration, visual impairment, and major eye diseases. Stratified analyses were further conducted based on diabetes and hypertension status.<br><br>RESULTS: The long sleep group demonstrated a significantly higher prevalence of vision impairment, cataract surgery, glaucoma, as well as any ocular disease and any objectively determined ocular disease compared to the normal and short sleep groups (all p < 0.05). After adjusting for confounders, long sleep duration was significantly associated with visual impairment (OR: 2.44, 95% CI: 1.09-5.49, p = 0.035), glaucoma (OR: 3.38, 95% CI: 1.06-10.8, p = 0.042), and any objectively determined ocular disease (OR: 2.24, 95% CI: 1.08-4.65, p = 0.035). No significant associations were found between short sleep duration and visual impairment or major eye diseases after controlling for confounders. In the nondiabetic population, long sleep was significantly related to glaucoma, any objectively determined ocular disease, and visual impairment. Among hypertensive patients, long sleep was associated with glaucoma.<br><br>CONCLUSION: Long sleep duration is independently associated with visual impairment, glaucoma, and any objectively determined ocular disease. Longitudinal studies are needed to validate current results and explore causal mechanisms.}, }
@article {pmid41467621, year = {2025}, author = {Martins Teixeira, L and Barbosa, MG and Menezes de Faria, F and Ramos, AA and Suemoto, CK and de Moraes Rebello Pinho, PJ and Lima Costa, MF and Ferri, CP}, title = {Association between visual impairment and dementia in older Brazilian adults: findings from the ELSI-Brazil study.}, journal = {Aging &amp; mental health}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/13607863.2025.2606363}, pmid = {41467621}, issn = {1364-6915}, abstract = {OBJECTIVE: To investigate the association between visual impairment (VI)-including self-reported near and distance vision and common ophthalmologic conditions-and dementia in a nationally representative sample of older Brazilian adults.<br><br>METHODS: This study is a secondary analysis using baseline data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), which surveyed 5,249 individuals aged 60&#x2009;years and older. Dementia was identified using an algorithm based on cognitive and functional performance. Visual status was assessed through self-report, distinguishing near and distance VI, along with self-reported diagnoses of ophthalmologic conditions. Logistic regression models adjusted for sociodemographic, clinical, and lifestyle variables were used.<br><br>RESULTS: Dementia was identified in 364 participants (6.9%). Distance VI was associated with dementia (adjusted OR: 1.68; 95% CI: 1.56-2.44), and there was a significant linear trend between worse self-reported distance vision and greater odds of dementia (p&#x2009;=&#x2009;0.003). Neither near VI nor any specific ophthalmologic conditions (cataract with/without surgery, glaucoma, macular degeneration, or diabetic retinopathy) were associated with dementia in the adjusted models.<br><br>CONCLUSION: In this nationally representative sample, self-reported distance VI was associated with dementia. This finding may indicate both a modifiable risk factor and an early marker of cognitive decline, warranting longitudinal research.}, }
@article {pmid41467813, year = {2026}, author = {Zhu, J and Yu, X and Wen, C and Zhang, Y and Kuang, X and Sun, N and Tang, S and Xiao, B and Xiao, S and Wang, X and Wu, K and Zhang, Q and Shen, H}, title = {Thalidomide Synergistically Regulates Cell Cycle and Endoplasmic Reticulum Stress to Alleviate RPE Oxidative Damage Through the E2F2-FBXO5 Pathway.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {1}, pages = {e71387}, doi = {10.1096/fj.202502444R}, pmid = {41467813}, issn = {1530-6860}, support = {2024A1515013099//GDSTC | Natural Science Foundation of Guangdong Province ()/ ; 2024A03J0264//Scientific and Technological Planning Project of Guangzhou City ()/ ; 2025QZLH06//State Key Laboratory of Ophthalmology (SKLO)/ ; }, mesh = {*Endoplasmic Reticulum Stress/drug effects ; Animals ; *Oxidative Stress/drug effects ; *Thalidomide/pharmacology ; Mice ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Humans ; Signal Transduction/drug effects ; *E2F2 Transcription Factor/metabolism ; *Cell Cycle/drug effects ; Mice, Inbred C57BL ; Macular Degeneration/metabolism/drug therapy/pathology ; Male ; }, abstract = {Thalidomide, a glutamate derivative with teratogenicity, possesses anti-inflammatory, immunomodulatory, and anti-angiogenic properties that enable its use in treating refractory diseases unresponsive to conventional therapies. Dry age-related macular degeneration (AMD), characterized by retinal pigment epithelium (RPE) degeneration and lacking effective therapies, represents a significant unmet medical need. Our findings demonstrated that thalidomide significantly restores mitochondrial function, alleviates G2/M phase cell cycle arrest, and suppresses sustained endoplasmic reticulum (ER) stress in oxidatively injured RPE cells. Mechanistically, these effects are coordinated through E2F2 activation, which subsequently regulates FBXO5 expression. Moreover, thalidomide was able to ameliorate oxidative stress-induced retinal structural disorders and RPE degeneration, and improve visual function in mice. In summary, this study elucidates that thalidomide synergistically regulates cell cycle progression and endoplasmic reticulum homeostasis through the E2F2-FBXO5 signaling pathway, providing a new drug candidate and therapeutic target for the prevention and treatment of dry AMD.}, }
@article {pmid41468573, year = {2026}, author = {Spaide, RF}, title = {Pilot Study of Choroidal Synphlebia.}, journal = {Retina (Philadelphia, Pa.)}, volume = {46}, number = {3}, pages = {410-416}, pmid = {41468573}, issn = {1539-2864}, mesh = {Humans ; Male ; Middle Aged ; Retrospective Studies ; Female ; *Tomography, Optical Coherence/methods ; Pilot Projects ; *Choroid/blood supply ; Aged ; Fluorescein Angiography/methods ; *Central Serous Chorioretinopathy/diagnosis ; Fundus Oculi ; Visual Acuity ; Multimodal Imaging ; Adult ; Aged, 80 and over ; }, abstract = {PURPOSE: To describe the multimodal imaging characteristics and clinical associations of choroidal synphlebia, a newly recognized configuration of the choroidal venous system.<br><br>METHODS: This retrospective study analyzed patients imaged with the DREAM swept-source OCT system (Intalight, San Jose, CA), capable of deep choroidal penetration. Choroidal synphlebia was defined as a confluent vascular structure &#x2265;750 &#xb5; m in smallest lateral or vertical dimension. The multimodal imaging characteristics were evaluated.<br><br>RESULTS: Nineteen eyes of 16 patients (mean age 63.2 years; eight male) were identified. Associated diagnoses included central serous chorioretinopathy in 16 eyes, neovascular age-related macular degeneration in 2, and myopia in 1. Three patients had bilateral involvement. Two morphologic patterns were observed: (1) broad confluence of large choroidal veins forming a lobulated venous lake and (2) a caput medusa-type arrangement with smaller tributaries converging radially into a dilated central channel. The lesions often occurred near presumed choroidal watershed zones. Macular neovascularization was present in seven eyes. In several central serous chorioretinopathy cases, subretinal fluid was resistant to photodynamic therapy but responsive to faricimab.<br><br>CONCLUSION: Choroidal synphlebia represents a distinct choroidal venous phenotype characterized by fusion or coalescence of major veins with a lack of visible vessels in the overlying Sattler's layer and inner choroid. Alterations in the capacitance, resistance, and pressure distribution in the venous drainage system appear to be affected by synphlebia lesions. Recognition of synphlebia may provide insight into choroidal hemodynamics and may help explain atypical or treatment-resistant central serous chorioretinopathy and neovascular presentations.}, }
@article {pmid41469343, year = {2025}, author = {Fedirko, PA and Babenko, TF and Pilmane, M and Medvedovska, NV and Junga, A and Yaroshenko, ZS and Dorichevska, RY and Garkava, NA}, title = {CURRENT ACHIEVEMENTS AND TOPICAL ISSUES IN RADIATION OPHTHALMOLOGY: POST-CHORNOBYL EXPERIENCE.}, journal = {Problemy radiatsiinoi medytsyny ta radiobiolohii}, volume = {}, number = {30}, pages = {126-142}, doi = {10.33145/2304-8336-2025-30-126-142}, pmid = {41469343}, issn = {2313-4607}, mesh = {*Chernobyl Nuclear Accident ; Humans ; *Cataract/etiology/pathology/epidemiology ; *Radiation Exposure/adverse effects ; *Radiation Injuries/epidemiology/pathology/etiology ; Ukraine/epidemiology ; Radiation, Ionizing ; Occupational Exposure/adverse effects ; *Ophthalmology/trends ; *Eye/radiation effects/pathology ; }, abstract = {The Chornobyl disaster - a largescale nuclear accident that caused significant radiation exposure to large populations of people. The work of ophthalmologists who studied its consequences radically changed scientists' understanding of the effects of ionizing radiation on the organ of vision. Before the Chornobyl accident, it was widely believed that the organ of vision was relatively resistant to the effects of ionizing radiation. It was thought that the most likely effect of radiation exposure was radiation cataracts, which were considered a deterministic effect.The objective of this study is analyze epidemiological, clinical, and experimental data on the ophthalmologicaleffects of radiation obtained after the Chоrnobyl disaster. Materials and methods. The criteria for inclusion in the analytical review were peer reviewed publications in the scientometric databases PubMed/MEDLINE, Scopus, Web of Science, and manually selected works devoted to the study of the ophthalmological consequences of the Chornobyl disaster, other radiation incidents, and the consequences of occupational radiation exposure, published in the period after the Chornobyl disaster.Results. Studies conducted after the Chornobyl disaster have significantly changed the understanding of theeffects of ionizing radiation on the vision organ. It has been shown that the eye is extremely sensitive to radiation exposure and is one of the most vulnerable structures of the body. Analyzing the results of longterm post-Chornobyl studies, we can distinguish four groups of ophthalmological diseases that occur in people affected by the Chornobyl disaster: the first group is specific radiation damage to the eye, the appearance of which is possible only as a result of ionizing radiation exposure; the second group is diseases that under normal conditions occur mainly in elderly people and the development of which is accelerated as a result of radiation exposure; the third group is functional changes that were detected in radiationexposed people; and the fourth group includes effects that occurred in people irradiated in utero.}, }
@article {pmid41469516, year = {2025}, author = {Li, D and Ou, Q and Gao, F and Wang, X and Zhu, L and Zhou, Y and Xu, JY and Jin, C and Wang, J and Zhang, J and Li, J and Bi, Y and Lu, L and Xu, GT and Tian, H}, title = {CRX is an intrinsic suppressor of epithelial‒mesenchymal transition in retinal pigment epithelial cells: a promising therapeutic avenue for subretinal fibrosis.}, journal = {Cell death &amp; disease}, volume = {17}, number = {1}, pages = {156}, pmid = {41469516}, issn = {2041-4889}, support = {24ZR1470100//Natural Science Foundation of Shanghai (Natural Science Foundation of Shanghai Municipality)/ ; }, mesh = {*Epithelial-Mesenchymal Transition/genetics ; Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; Animals ; Fibrosis ; *Trans-Activators/metabolism/genetics ; *Homeodomain Proteins/metabolism/genetics ; Mice ; Signal Transduction ; Macular Degeneration/pathology/metabolism/genetics ; Transforming Growth Factor beta1/metabolism/pharmacology ; Choroidal Neovascularization/pathology/metabolism/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Epithelial Cells/metabolism ; beta Catenin/metabolism ; YAP-Signaling Proteins ; }, abstract = {The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is one of the significant pathogenic mechanisms for the formation of subretinal fibrosis in age-related macular degeneration (AMD). Multiple signaling pathways that promote EMT have been well described, yet the endogenous signaling pathways that inhibit EMT within RPE cells remain largely elusive. In this study, we confirmed the expression of CRX in human RPE cells and human embryonic stem cell-derived RPE (ESC-RPE) cells. By employing sub-culture to disrupt intercellular connections and thereby inhibit the Hippo signaling pathway, combined with TGF-β1 treatment in vitro to mimic the microenvironment for the formation of subretinal fibrosis, it was revealed that Hippo/YAP1 and TGF-β1 synergistically promoted the nuclear translocation of β-catenin, and the latter bound to TCF7 to inhibit the expression of CRX. Overexpression of CRX was capable of suppressing the occurrence of EMT in ESC-RPE cells. CRX exerted its inhibitory effect on EMT partly by upregulating the expression of PPP2R2B. In the laser-induced choroidal neovascularization mouse model, the nuclear translocation of CRX took place in RPE cells, and overexpression of CRX played an inhibitory role in the formation of subretinal fibrosis. This study has identified CRX as an endogenous signaling molecule that inhibits EMT in RPE cells and has provided a new research target and treatment strategy for the treatment of wet AMD and the inhibition of subretinal fibrosis formation.}, }
@article {pmid41470194, year = {2025}, author = {Busquets, MA and Garfinkel, RA and Sambhara, D and Mohan, N and Nahen, K and Benyamini, G and Loewenstein, A}, title = {Home Monitoring for the Management of Age-Related Macular Degeneration: A Review of the Development and Implementation of Digital Health Solutions over a 25-Year Scientific Journey.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {12}, pages = {}, pmid = {41470194}, issn = {1648-9144}, mesh = {Humans ; *Macular Degeneration/therapy/diagnosis ; Telemedicine/trends ; Monitoring, Physiologic/methods ; Digital Health ; }, abstract = {The management of age-related macular degeneration (AMD) presents a significant challenge attributable to high disease heterogeneity. Patient realization of symptoms is poor and it is urgent to treat before permanent anatomic damage results in vision loss. This is true for the initial conversion from non-exudative intermediate AMD (iAMD) to exudative AMD (nAMD), and for the recurrence of nAMD undergoing treatment. Starting from the essential requirements that any practical solution needs to fulfill, we will reflect on how persistent navigation towards innovative solutions during a 25-year journey yielded significant advances towards improvements in personalized care. An early insight was that the acute nature of AMD progression requires frequent monitoring and therefore diagnostic testing should be performed at the patient's home. Four key requirements were identified: (1) A tele-connected home device with acceptable diagnostic performance and a supportive patient user interface, both hardware and software. (2) Automated analytics capabilities that can process large volumes of data. (3) Efficient remote patient engagement and support through a digital healthcare provider. (4) A low-cost medical system that enables digital healthcare delivery through appropriate compensation for both the monitoring provider and the prescribing physician services. We reviewed the published literature accompanying first the development of Preferential Hyperacuity Perimetry (PHP) for monitoring iAMD, followed by Spectral Domain Optical Coherence Tomography (SD-OCT) for monitoring nAMD. Emphasis was given to the review of the validation of the core technologies, the regulatory process, and real-world studies, and how they led to the release of commercial services that are covered by Medicare in the USA. We concluded that while during the first quarter of the 21st century, the two main pillars of management of AMD were anti-VEGF intravitreal injections and in-office OCT, the addition of home-monitoring-based digital health services can become the third pillar.}, }
@article {pmid41470237, year = {2025}, author = {Anitua, E and Muruzabal, F and Recalde, S and de la Fuente, M and Reparaz, I and Azkargorta, M and Elortza, F and Alkhraisat, MH}, title = {Proteomic Insights into the Retinal Response to PRGF in a Mouse Model of Age-Related Macular Degeneration.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {12}, pages = {}, pmid = {41470237}, issn = {1648-9144}, support = {ZL-2021/00557//Basque Government/ ; }, mesh = {Animals ; Mice ; Disease Models, Animal ; *Proteomics/methods ; Mice, Inbred C57BL ; *Macular Degeneration/physiopathology/drug therapy ; *Retina/drug effects/physiopathology ; *Intercellular Signaling Peptides and Proteins/therapeutic use/pharmacology ; Signal Transduction/drug effects ; Iodates ; Oxidative Stress/drug effects ; Geographic Atrophy ; }, abstract = {Background and Objectives: The aim of this study is to employ quantitative proteomics to elucidate the molecular mechanism and signaling pathways modulated by plasma rich in growth factors (PRGF) in a murine model of geographic atrophy (GA)-like retinal degeneration. Materials and Methods: C57BL/6J mice were used as a model GA-like retinal degeneration by a single systemic NaIO3 administration. Animals were divided into three groups: Control (PBS), Disease (NaIO3 + PBS), and PRGF-treated (NaIO3 + PRGF). After 7 days, retinas and retinal pigment epithelium were collected for proteomic analysis. Proteins were extracted, digested using the FASP method, and analyzed by Data-Independent Acquisition (DIA-PASEF) mass spectrometry; data were processed with DIA-NN and statistically analyzed with Perseus. Functional pathway analysis was performed using Ingenuity Pathway Analysis. Results: A total of 6511 proteins were identified. The Disease model showed the expected deregulation of pathways related to oxidative stress, inflammation, and fibrosis. Comparison between the PRGF and Control groups showed that PRGF significantly reduced oxidative and cellular stress proteins/pathways. In the same way, when PRGF and Disease groups were compared, PRGF treatment showed a significant reduction in pathways associated with inflammation, oxidative stress, and cellular stress. PRGF also activated several homeostatic pathways not only related to neuroprotective pathways but also with the lipid deposition (drusen) reduction. All these results suggest that PRGF treatment exerts a protective effect against NaIO3-induced retinal damage. Conclusions: These findings suggest that PRGF effectively mitigates the degenerative effects of NaIO3 by activating specific protective and compensatory signaling pathways in the retina. PRGF is indicated as a promising new therapeutic option for ameliorating age-related macular degeneration progression.}, }
@article {pmid41471372, year = {2025}, author = {Park, S and Won, J and Heo, JB and Kang, J and Oh, YW and Park, G and Lee, G and Lee, JH and Song, GY and Kang, W and Oh, S}, title = {The Therapeutic Effect of a Biodegradable Long-Acting Intravitreal Implant Containing CGK012 on Neovascular Age-Related Macular Degeneration by Promoting β-Catenin Degradation.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {12}, pages = {}, pmid = {41471372}, issn = {1424-8247}, support = {RS-2023-00259081//Ministry of Science and ICT, Ministry of Trade, IndKorea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfareustry, and Energy, and Ministry of Health and Welfare/ ; }, abstract = {Background/Objectives: Neovascular age-related macular degeneration (nAMD) poses a serious threat to the eyesight of older adults, representing a leading cause of irreversible vision loss. Anti-vascular endothelial growth factor (anti-VEGF) treatments are effective but require repeated intraocular injections and show poor responses in some patients. CGK012 is a novel derivative of decursin that inhibits the Wnt/β-catenin pathway. This study aimed to elucidate the mode of action of CGK012 and examine its therapeutic effects. Methods: We performed in vitro cellular studies in a retinal pigment epithelial (RPE) cell line (ARPE-19) and human umbilical vein endothelial cells (HUVECs). We examined the in vivo efficacy of CGK012-loaded implants in laser-induced choroidal neovascularization (CNV) rabbit models. We also determined the implants' in vitro dissolution, intraocular release, and disposition characteristics. Results: CGK012 decreased angiogenic/proinflammatory factor expression and suppressed the epithelial-mesenchymal transition (EMT) in RPE cells by promoting intracellular β-catenin degradation. Additionally, it repressed the expression of cyclin D1 and c-myc, downstream target genes of β-catenin, and inhibited HUVEC capillary tube formation. CGK012-loaded poly (lactic-co-glycolic acid) (PLGA) intravitreal implants significantly reduced vascular leakage in a laser-induced CNV rabbit model. Notably, CGK012 released from the implant was highly permeable to retina/choroid tissue and downregulated β-catenin, angiogenic/inflammatory factors, and vimentin in the rabbit model. The CGK012 concentration reached a plateau at 28-42 days in the vitreous humor and decayed with a half-life of 14 days without systemic exposure. Conclusions: Our findings demonstrate that CGK012 implants prevent choroidal neovascularization through the Wnt/β-catenin pathway suppression and produce high concentrations of CGK012 in the posterior eye segment with prolonged release. Thus, these implants provide more therapeutic choices for nAMD treatment.}, }
@article {pmid41472698, year = {2025}, author = {Keim, D and Dehne, M and Miller, P and Jérôme, V and Bahnemann, J and Freitag, R}, title = {High-Efficiency l‑PEI-Based Transfection of ARPE-19 Cells Using a Multiparametric Approach and Automated Polyplex Formation with a 3D-Printed Microfluidic System.}, journal = {Chem &amp; bio engineering}, volume = {2}, number = {12}, pages = {695-710}, pmid = {41472698}, issn = {2836-967X}, abstract = {Nonviral gene delivery offers promise for treating age-related macular degeneration (AMD), a major cause of blindness. Genetic modification of retinal pigment epithelium (RPE) cells is a potential therapeutic strategy for AMD. This study presents a multiparametric approach to enhance nonviral transfection of human ARPE-19 cells using linear poly-(ethylenimine) (l-PEI, 25 kDa) as a delivery agent for plasmid DNA (pDNA). The transfection protocol was optimized by adjusting the N/P ratio through nucleic acid concentration, varying polymer density, reducing transfection volume, and minimizing contact time between cells and polyplexes. Under optimized conditions, transfection efficiency (TE) reached 88% with ∼85% viability. A semi-automated method for polyplex formation was developed using a 3D-printed microfluidic system, thereby enabling standardized production. This optimized protocol was successfully adapted to the microfluidic system without compromising TE or viability. This semi-automated approach represents a step toward the scalable and reproducible application of l-PEI-based transfection technologies for future therapeutic use.}, }
@article {pmid41475545, year = {2025}, author = {Sun, D and Tseng, VL and Yu, F and Coleman, AL}, title = {Cardiovascular Risk and Eye Health: A Cohort Study of the Pooled Cohort Equations and Ocular Disease Incidence.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2025.12.021}, pmid = {41475545}, issn = {1549-4713}, abstract = {PURPOSE: We assessed whether the Pooled Cohort Equations (PCE) cardiovascular risk score, used in primary care, is associated with the future age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), retinal vein occlusion (RVO), and hypertensive retinopathy (HTR).<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: We used electronic health record data from the All of Us (AoU) Research Program. Participants aged 40 to 79 years had to have complete variables for PCE calculation within a 6-month period between 2009 and 2015. We excluded participants with preexisting atherosclerotic cardiovascular disease or any of the 5 ocular diseases before the baseline PCE period. A total of 35 909 adults were included in this study.<br><br>METHODS: Individual-level PCE score was computed and categorized into 4 PCE risk categories: low (<5%), borderline (5%-7.4%), intermediate (7.5%-19.9%), and high (&#x2265;20%). Time-to-event analyses included Kaplan-Meier curves and univariate and multivariable Cox proportional hazards regression models. The primary multivariable models adjusted for race, body mass index, chronic kidney disease, and education (not included in PCE to avoid overadjustment). Concordance index (C-index) was reported to assess model performance. Sensitivity analyses tested varied follow-up durations (5, 6, and 7 years) and, in a prespecified component-adjustment sensitivity set, sequentially added PCE components (age, smoking, diabetes).<br><br>MAIN OUTCOME MEASURES: Diagnoses of AMD, glaucoma, DR, RVO, or HTR.<br><br>RESULTS: Higher PCE risk categories were significantly associated with increased risk of ocular diseases. In the primary models, compared with the low-risk group, the high-risk group had the highest hazard ratios for AMD (6.22), DR (5.93), glaucoma (2.33), RVO (3.38), and HTR (4.47) (all P < 0.001). Adjusted C-indices were highest for AMD (0.72), DR (0.751), and HTR (0.768), and moderate for glaucoma (0.625) and RVO (0.654). Findings were consistent in different follow-up periods. In component-adjustment sensitivity models, PCE-AMD association was largely explained by age, whereas associations for DR and HTR remained robust.<br><br>CONCLUSIONS: In the AoU population, the single composite metric PCE meaningfully stratifies future risk for multiple ocular diseases, using information already available in primary care. This suggests PCE could be incorporated into primary care settings to identify individuals who would benefit from earlier ophthalmologic evaluation and prevention strategies.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.}, }
@article {pmid41475683, year = {2025}, author = {Bianchi, MJ and Sunness, JS and Applegate, CA}, title = {Reading Speed Patterns in Eyes with Geographic Atrophy and Good Visual Acuity.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2025.12.020}, pmid = {41475683}, issn = {2468-6530}, }
@article {pmid41476611, year = {2025}, author = {Raghavan, D and Jeakle, O and Berry, Y and Victor, M and Thummel, R}, title = {Microglia response and function in a chronic model of photoreceptor damage.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1699271}, pmid = {41476611}, issn = {2296-634X}, abstract = {BACKGROUND: Retinal neurodegenerative diseases, including diabetic retinopathy and age-related macular degeneration, are characterized by the slow, chronic degeneration of photoreceptors. We previously used a chronic low light (CLL) exposure to model slow photoreceptor degeneration in adult zebrafish. Here, we investigate transcriptional, morphological, and functional responses of microglia in the CLL model.<br><br>METHODS: Microglia-specific gene expression analysis was mined from our previously reported 3' RNA-seq data performed at 8 time points during 28 days of CLL exposure. Morphological changes were performed on retinas collected at various time points using immunohistochemistry. Microglial inhibition was accomplished pharmacologically with dexamethasone and genetically using the irf8-/- mutant fish. Finally, we returned the CLL-treated fish to normal light/dark conditions to test whether photoreceptors could recover in the context of chronic stress.<br><br>RESULTS: CLL induced dynamic, time-dependent upregulation of microglia-specific genes consistent with pro-inflammatory and pro-resolving function. Dexamethasone treatment reduced microglial numbers and exacerbated rod and cone outer segment damage, whereas irf8-/- mutants exhibited partial protection against photoreceptor damage. Notably, despite prolonged stress and damage during the CLL exposure, photoreceptor outer segments returned to near-baseline morphology after 28 days of normal light/dark recovery conditions.<br><br>DISCUSSION: Overall, these findings suggest that microglial function in chronic retinal injury is context-dependent as pharmacological and genetic methods of inhibition produced contrasting outcomes depending upon microglial polarization.}, }
@article {pmid41479851, year = {2025}, author = {Zhang, E and Bylund, R and Zhang, A and Massop, D}, title = {Alpha-Gal Syndrome Allergy to Intravitreal Administration of Anti-Vascular Endothelial Growth Factor Agents.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251400700}, pmid = {41479851}, issn = {2474-1272}, abstract = {Purpose: To describe a case of allergic reaction to intravitreal (IVT) injection of antivascular endothelial growth factor (anti-VEGF) medications in patients with alpha-gal syndrome. Methods: A single case was evaluated. Results: A 57-year-old woman with a known diagnosis of alpha-gal syndrome was evaluated. Clinical presentation, prior treatment history, and response to different anti-VEGF agents were reviewed. The patient presented with worsening vision in her right eye due to a subfoveal choroidal neovascular membrane secondary to neovascular age-related macular degeneration in the right eye. She had experienced a systemic allergic reaction following an IVT injection of bevacizumab, but subsequently tolerated ranibizumab without any adverse effects, resulting in improvement in her vision. Conclusions: Bevacizumab, aflibercept, and faricimab are recombinant immunoglobulins produced by DNA technology in Chinese hamster ovary cells, which may contain galactose-α-1,3-galactose (alpha-gal), a potential allergen for patients with alpha-gal syndrome. Patients with alpha-gal syndrome may develop allergic reactions to certain IVT anti-VEGF agents derived from mammalian expression systems. Ranibizumab, produced using an Escherichia coli expression and lacking alpha-gal, seems to be a safe and effective option for patients with alpha-gal syndrome requiring IVT anti-VEGF therapy.}, }
@article {pmid41479867, year = {2025}, author = {Priyanka, P and Khullar, S and Singh, M and Morya, AK and Sharma, B and Periasamy, B and Moharana, B and Morya, R}, title = {Role of gut microbiomes in different ocular pathologies: A systematic review.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {16}, number = {4}, pages = {113488}, pmid = {41479867}, issn = {2150-5330}, abstract = {BACKGROUND: The gut microbiome is integral to human health, with emerging research underscoring its potential impact on ocular health through the gut-eye axis. Various ocular disorders, such as dry eye syndrome, retinal vascular diseases, macular degeneration, and glaucoma, may be influenced by gut dysbiosis, which could significantly contribute to their development and progression.<br><br>AIM: To evaluate the influence of the gut microbiome on the pathogenesis and progression of various ocular diseases.<br><br>METHODS: An extensive search of the scientific literature was undertaken by adhering to Preferred Reporting Items for Systematic Reviews &amp; Meta-Analyses standards, using PubMed (MEDLINE), Scopus, EMBASE, and the Cochrane Library as sources to locate studies addressing the relationship between the gut microbiome and human health. To capture all relevant publications, search terms were systematically applied across these major databases, without limiting the search by language or publication date. Inclusion criteria covered randomized controlled trials, non-randomized controlled trial, prospective studies, cross-sectional studies, and case-control studies. Out of the 3077 articles, 36 full texts were included in the review.<br><br>RESULTS: Ocular health appears to be shaped by the gut microbial community through mechanisms such as immune regulation, preservation of the blood-retinal barrier, and the generation of protective metabolites. Disturbances in this microbial balance can provoke measurable alterations in host immunity, providing a plausible immunopathogenic pathway that connects intestinal dysbiosis with eye disease. Both laboratory models and early human data suggest that targeted interventions, including prebiotics, probiotics, synbiotics, and faecal microbiota transfer, hold therapeutic potential.<br><br>CONCLUSION: The gut-eye relationship reflects a multifaceted interaction in which the intestinal microbiome contributes to ocular health through complex biological pathways. Integrating microbiome assessments into diagnostic methods can revolutionize disease management through early detection and targeted interventions. Further, randomised controlled clinical trials are necessary for ocular diseases to prove causal relationships.}, }
@article {pmid41480395, year = {2025}, author = {Zeppieri, M and Visalli, F and Musa, M and Avitabile, A and Giglio, R and Tognetto, D and Gagliano, C and D'Esposito, F and Cappellani, F}, title = {Novel developments in retinal regeneration: Advances and future outlooks in stem cell therapy.}, journal = {World journal of stem cells}, volume = {17}, number = {12}, pages = {111374}, pmid = {41480395}, issn = {1948-0210}, abstract = {Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, and Stargardt disease, are primary contributors to irreversible vision loss globally. Due to the scarcity of effective curative treatments, stem cell therapy has emerged as a revolutionary advancement in ophthalmology. In the last ten years, significant advancements have been achieved in the derivation of retinal pigment epithelium and photoreceptor precursors from human embryonic stem cells and induced pluripotent stem cells, with initial clinical trials indicating safety and potential efficacy. Innovative delivery platforms, such as biodegradable scaffolds, microcarrier suspensions, and minimally invasive subretinal devices, are tackling prior challenges related to cell survival and integration. Simultaneously, gene-edited and patient-specific induced pluripotent stem cells are positioned to surmount immunological and ethical constraints. Future combinatorial strategies that incorporate stem cells with gene therapy, CRISPR-mediated editing, and bioengineered retinal organoids offer potential for personalized and regenerative methodologies. Nonetheless, enduring functional integration, immune tolerance, and oncogenic safety continue to pose significant challenges. To effectively transition from laboratory research to clinical application, collaborative frameworks among academic institutions, biotechnology companies, and regulatory agencies will be crucial for unlocking the complete therapeutic potential of stem cell-based treatments for retinal diseases. Stem cell therapy has transitioned from a distant promise to an advancing reality set to transform retinal care.}, }
@article {pmid41480686, year = {2026}, author = {Oltra, M and Martínez-Santos, M and Ybarra, M and Pires, M and Ceresoni, C and Gomis-Coloma, C and Medina-Trillo, C and Sancho, J and Barcia, J}, title = {miR‑205: A dual regulator of angiogenesis in health and disease (Review).}, journal = {International journal of molecular medicine}, volume = {57}, number = {2}, pages = {}, pmid = {41480686}, issn = {1791-244X}, mesh = {*MicroRNAs/genetics/metabolism ; Humans ; *Neovascularization, Pathologic/genetics/metabolism ; Animals ; Extracellular Vesicles/metabolism/genetics ; *Neovascularization, Physiologic/genetics ; Cell Proliferation ; Angiogenesis ; }, abstract = {The present study evaluated the role of microRNA (miR)‑205 as a dual regulator of angiogenesis, exhibiting both pro‑angiogenic and anti‑angiogenic effects depending on the biological context. miRs are small non‑coding sequences that regulate gene expression at the post‑transcriptional level and can be transported in extracellular vesicles (EVs), allowing them to modulate biological processes remotely. miR‑205 is involved in multiple cellular processes, such as proliferation, migration, apoptosis and angiogenesis. In angiogenesis its function is contradictory: On one hand, it can inhibit blood vessel formation by suppressing pro‑angiogenic factors such as VEGF and ANG‑2, as demonstrated in diseases such as psoriasis, thyroid cancer and diabetic retinopathy. However, in other contexts, miR‑205 promotes angiogenesis by inhibiting anti‑angiogenic genes such as PTEN and HITT, facilitating the activation of the PI3K/AKT pathway and cell proliferation in ovarian cancer and thrombosis. Additionally, the present study highlighted the role of EVs in transferring miR‑205 between cells, thereby influencing angiogenesis and disease progression. Studies in myocardial infarction and cancer models have demonstrated that EVs enriched in miR‑205 can affect blood vessel formation and tumor progression. Similarly, in ocular diseases such as macular degeneration and diabetic retinopathy, miR‑205 encapsulated in EVs has shown therapeutic potential by regulating VEGF levels. In conclusion, miR‑205 emerges as a promising therapeutic target for angiogenic diseases. Its application in EV‑based therapy could represent an innovative strategy for treating vascular disorders. However, further studies are needed to fully understand its mechanisms of action and optimize its clinical application.}, }
@article {pmid41481850, year = {2025}, author = {Yuan, M and Alsoudi, A and Alshaikhsalama, A and Rahimy, E}, title = {Systemic medications and their impact on age-related macular degeneration development and progression: a review of current evidence.}, journal = {Current opinion in ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICU.0000000000001198}, pmid = {41481850}, issn = {1531-7021}, abstract = {PURPOSE OF REVIEW: This review examines commonly prescribed systemic medications and their possible associations with age-related macular degeneration (AMD) development and progression. With the limitations and risks of current intravitreal therapies, there is growing interest in oral pharmacotherapy for AMD management. The following review synthesizes observational studies, meta-analyses, and ongoing clinical trials to evaluate the potential effects of commonly used systemic medications on AMD.<br><br>RECENT FINDINGS: Metformin demonstrates conflicting evidence, with several meta-analyses and large cohort study showing reduced AMD odds, while a recent randomized phase II trial found no effect on geographic atrophy progression. For statins, emerging evidence suggests that treatment duration exceeding 2&#x200a;years and medium-intensity to high-intensity dosing may confer protection against AMD development. Aspirin demonstrates discordant results between different study designs: two large randomized controlled trials showed no benefit for AMD, while a 10-year observational study suggested protective effects.Fenofibrates show promise in preclinical models but require additional clinical investigation. Danicopan also shows modest effects in complement-related disorders and is currently undergoing a phase 2 trial to evaluate efficacy in patients with geographic atrophy. Finally, dopamine agonists appear to improve visual acuity and reduce subretinal fluid and central retinal thickness in newly diagnosed exudative AMD, as shown in an open-label pilot study, but require further investigation.<br><br>SUMMARY: Multiple systemic medications have highlighted mixed or stage-dependent benefits on AMD development and progression. Some agents such as metformin and aspirin have shown conflicting findings, having been evaluated in randomized trials and large observational studies. Other medications including GLP-1 agonists, dopamine agonists, statins, fenofibrates, and danicopan show early promise in more limited studies, but require further clinical validation.}, }
@article {pmid41482136, year = {2025}, author = {Bala, S and Allan, KC and Decker, NL and Abbass, NJ and Joo, JH and Zhao, A and Talcott, KE and Rachitskaya, AV}, title = {Glucagon-like peptide-1 receptor agonists: What ophthalmologists need to know.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2025.12.007}, pmid = {41482136}, issn = {1879-3304}, abstract = {Initially designed for the treatment of type-2 diabetes, glucagon-like peptide-1 receptor agonists (GLP-1RA) are multifaceted agents with promising neuroprotective and anti-inflammatory properties. The majority of the research exploring the relationship between GLP-1RA use and ophthalmic disease comes from large database studies or secondary-analysis of randomized controlled trials investigating GLP-1RAs in cardiovascular disease and obesity. Current evidence regarding the impact of GLP-1 receptor agonists on ophthalmic diseases remains inconsistent, with studies reporting both protective and detrimental effects. For example, there are conflicting findings of an effect on diabetic retinopathy and non-arteritic anterior ischemic optic neuropathy, as well as age-related macular degeneration, with GLP-1RA use. In contrast, GLP-1RAs have more consistently demonstrated a protective effect against idiopathic intracranial hypertension, glaucoma and dry-eye disease. Importantly, the majority of the clinical ophthalmic studies are from large electronic health record databases. Overall, limitations in the design of these studies, such as the lack of manual chart review and potential miscoding of diagnosis or treatments, prohibit a more granular analysis of comprehensive ocular endpoints. As a heterogenous medication class with differing structures, potencies, and mechanisms of action, we outline the ophthalmic effects of all Food and Drug Administration-approved GLP-1RAs. We discuss the proposed mechanisms of ocular effects and GLP-1RA use, examine the current literature investigating the impact of GLP-1RAs on ophthalmic disease, discuss the effects of specific GLP-1RAs, and outline the perioperative considerations of this medication class.}, }
@article {pmid41482231, year = {2026}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {Can Omega-3 Fatty Acids Serve as a Preventive Strategy for Age-Related Macular Degeneration? A Systematic Review and Meta-Analysis.}, journal = {The Journal of nutrition}, volume = {156}, number = {2}, pages = {101289}, pmid = {41482231}, issn = {1541-6100}, mesh = {Humans ; *Macular Degeneration/prevention &amp; control ; *Fatty Acids, Omega-3/administration &amp; dosage/therapeutic use ; Dietary Supplements ; Aged ; Docosahexaenoic Acids ; Eicosapentaenoic Acid ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults. While anti-vascular endothelial growth factor (anti-VEGF) therapies are available for neovascular AMD (nAMD), effective preventive strategies remain limited. Long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have biological plausibility for retinal protection through structural roles in photoreceptor membranes and anti-inflammatory lipid mediator pathways.<br><br>OBJECTIVES: This study aimed to synthesize contemporary evidence regarding omega-3 fatty acids in AMD prevention, with emphasis on subtype-specific associations, differences by omega-3 species, and contrasts between dietary intake and supplementation evidence.<br><br>METHODS: This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidance and registered the protocol in PROSPERO (CRD420251122413). PubMed, ScienceDirect, and the Cochrane Library were searched from inception to August 2, 2025. Eligible studies included observational studies of dietary &#x3c9;-3 PUFA exposure in adults aged 50 years or older with AMD outcomes. Random-effects models models were used to pool adjusted effect estimates comparing the highest versus lowest &#x3c9;-3 exposure categories. Prespecified subgroup analyses were performed by AMD subtype (early AMD, advanced AMD, nAMD, and geographic atrophy [GA]) and &#x3c9;-3 species (EPA, DHA, and alpha-linolenic acid [ALA]). Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Publication bias was evaluated using funnel plots and Egger's regression test.<br><br>RESULTS: Eighteen studies were included. Higher &#x3c9;-3 intake was associated with reduced odds of AMD overall (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.70-0.96; p = 0.01), with moderate heterogeneity (I&#xb2; = 61%). Subtype analyses demonstrated stronger associations for nAMD (OR 0.57, 95% CI 0.40-0.81) and GA (OR 0.65, 95% CI 0.45-0.94), and a smaller association for early AMD (OR 0.83, 95% CI 0.72-0.97), whereas advanced AMD was not significantly different between high and low intake groups (OR 0.81, 95% CI 0.49-1.33; p = 0.41). In &#x3c9;-3 species analyses, higher EPA intake was associated with lower AMD odds (OR 0.61, 95% CI 0.38-0.97; p = 0.04), while DHA showed a borderline association (OR 0.73, 95% CI 0.53-1.01; p = 0.05); ALA was not associated with benefit (OR 1.00, 95% CI 0.84-1.20; p = 0.96). Time-to-event pooling showed no significant long-term risk reduction (hazard ratio [HR] 0.98, 95% CI 0.84-1.15; p = 0.83). Funnel plot asymmetry was observed, and Egger's test suggested small-study effects (p = 0.04).<br><br>CONCLUSIONS: Higher dietary intake of marine-derived &#x3c9;-3 PUFAs is associated with reduced odds of AMD. However, long-term risk reduction was not demonstrated in time-to-event analyses, and small-study effects were suggested. These findings support the possibility that dietary patterns emphasizing &#x3c9;-3-rich seafood may contribute to AMD risk reduction, whereas the effectiveness of isolated &#x3c9;-3 PUFA supplementation for AMD prevention remains uncertain and warrants confirmation in future prospective studies and larger randomized controlled trials with long-term follow-up.}, }
@article {pmid41483391, year = {2026}, author = {Peng, Y and Zhang, Y and Kam, KW and Ho, M and Sezto, S and Au, S and Yim, CC and Zhang, X and Ng, MPH and Ip, P and Young, A and Pang, CP and Tham, CC and Chen, LJ and Yam, JC}, title = {Dynamic frailty trajectories and risk of age-related macular degeneration: a prospective cohort study in UK Biobank.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {41483391}, issn = {2509-2723}, support = {14102422//General Research Fund/ ; C7149-20G//Collaborative Research Fund/ ; 11220206//Health and Medical Research Fund/ ; 10210246//Health and Medical Research Fund/ ; 09202466//Health and Medical Research Fund/ ; 82425017//National Natural Science Foundation of China/ ; 82171089//National Natural Science Foundation of China/ ; WW/SC/rc/SIEF2324/0366/24vw//Strategic Impact Enhancement Fund/ ; TL/JF/rc/SIEF2223/0759/23vw//Strategic Impact Enhancement Fund/ ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the aging population. Although frailty has been recognized as a potential risk factor, previous studies relying on static assessments cannot capture its dynamic nature. This study aims to prospectively evaluate the association between dynamic frailty trajectories and incident AMD. The baseline cohort included 462,573 UK Biobank participants who were free of AMD and had frailty phenotype (FP) data at enrollment. Among them, 53,059 with at least one follow-up FP assessment comprised the trajectory cohort. Participants were categorized as nonfrail, prefrail, or frail based on their FP scores. Annualized frailty progression (ΔFP/year) was estimated via linear regression. Cox models assessed hazard ratios (HRs) and 95% confidence intervals (CIs) for AMD. During a median follow-up of 11.8 years in the baseline cohort, 13,428 incident AMD cases (2.9%) were documented. Prefrail (HR:1.14; 95% CI:1.10-1.18) and frail (HR:1.36; 95% CI: 1.26-1.47) individuals had significantly higher AMD risks compared to nonfrail participants. In the frailty trajectory analysis with a median follow-up duration of 3.3 years, 852 incident AMD cases (1.6%) were recorded. Each 1-point FP increase conferred 28% higher AMD risk (HR: 1.28; 95% CI: 1.18-1.38), while each 0.1-point/year ΔFP increase independently elevated risk by 15% (HR: 1.15; 95% CI: 1.10-1.21). Compared to stable nonfrail, prefrailty aggravation showed highest AMD risk (HR: 2.26; 95% CI: 1.51-3.37), followed by frailty alleviation (HR: 1.73; 95% CI: 0.98-3.04) and frailty maintenance (HR: 1.72; 95% CI: 0.86-3.41). Progressive frailty trajectories, independent of baseline status, is associated with increased incident AMD risk. Early interventions targeting frailty progression may mitigate AMD risk in aging populations.}, }
@article {pmid41484209, year = {2026}, author = {Donato, L and Zerti, D and Babiloni-Chust, I and Passacantando, M and Flati, V and Feligioni, M and Carl, M and Rinaldi, C and Poggi, L and D'Angelo, R and Maccarone, R}, title = {Comprehensive transcriptomic analysis reveals canonical and novel pathways modulated by nanoceria in mammalian retinal degeneration.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {3689}, pmid = {41484209}, issn = {2045-2322}, support = {2022PWMW5A//Ministry of University and Research (MUR, Italy) through the PRIN (Progetti di Rilevante Interesse Nazionale) 2022 grant/ ; }, mesh = {Animals ; *Cerium/pharmacology/administration &amp; dosage/chemistry ; Rats ; *Retinal Degeneration/genetics/metabolism/drug therapy/pathology ; Gene Expression Profiling ; Signal Transduction/drug effects ; *Transcriptome/drug effects ; Disease Models, Animal ; Retina/metabolism/drug effects/pathology ; Oxidative Stress/drug effects ; Nanoparticles ; Male ; Light/adverse effects ; }, abstract = {Retinal neurodegenerative diseases such as Age-related Macular Degeneration (AMD) and Retinitis Pigmentosa cause irreversible vision loss due to the limited regenerative capacity of the mammalian retina. Cerium oxide nanoparticles (nanoceria) are emerging therapeutics against oxidative stress and inflammation, major drivers of photoreceptor degeneration, and have demonstrated morphological and functional neuroprotection in preclinical models. However, the genome-wide transcriptional mechanisms underlying these effects remain incompletely characterized. We performed retinal transcriptomic analysis in a rat AMD model induced by intense light and treated intravitreally with nanoceria. Six groups were analyzed: control, light damage, vehicle, nanoceria, vehicle + light damage, and nanoceria + light damage. Light damage activated inflammatory and apoptotic programs, with upregulation of cytokines (Tnf, Il6, Il1b, Ccl2) and downregulation of photoreceptor genes (Rho, Pde6a/b, Gnat1). Nanoceria treatment counteracted these effects, suppressing pro-inflammatory mediators, restoring antioxidative genes (Nfe2l2, Gclc, Sod2), and enhancing neuroprotective factors (Bdnf, Cntf, Ngf). Pathway analyses revealed inhibition of TNF/NF-κB/IL-17 signaling and activation of PI3K-Akt, JAK-STAT, and neurotrophin pathways. Unexpectedly, nanoceria also modulated amino acid and insulin metabolism (Ass1, Cps1, Insr, Irs1, Slc2a4) and reactivated transcription factors (Ascl1, Sox2, Notch1) typically silent in adult retina. Our findings highlight nanoceria as a multifunctional therapeutic that mitigates retinal degeneration by coordinating oxidative, inflammatory, and regenerative responses. Together with prior morphological and functional validations, these results support the translational potential of nanoceria for treating retinal neurodegenerative diseases.}, }
@article {pmid41484254, year = {2026}, author = {Askarinejad, A and Lip, GYH and Lip, PL}, title = {An association between atrial fibrillation and age-related macular degeneration: looking beyond mere coincidence.}, journal = {Eye (London, England)}, volume = {40}, number = {3}, pages = {285-287}, pmid = {41484254}, issn = {1476-5454}, }
@article {pmid41486361, year = {2026}, author = {Kim, JH and Park, SM and Choi, SI and Kim, DI and Sohn, J and Lee, WK}, title = {Short-term outcomes and choroidal morphological changes following aflibercept therapy in pachychoroid neovasculopathy.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {1798}, pmid = {41486361}, issn = {2045-2322}, mesh = {Humans ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Female ; Male ; *Choroid/drug effects/pathology/blood supply ; Middle Aged ; *Choroidal Neovascularization/drug therapy/pathology ; Aged ; Treatment Outcome ; Visual Acuity/drug effects ; Tomography, Optical Coherence ; Prospective Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Adult ; Retina/drug effects/pathology ; }, abstract = {To evaluate the short-term outcomes and choroidal morphological changes after three monthly aflibercept injections for pachychoroid neovasculopathy (PNV). Twenty-nine treatment-naïve patients with PNV were enrolled in this prospective phase IV clinical trial. All patients received three monthly injections of aflibercept. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured at baseline and at week 12 (4 weeks after the third injection). Additionally, changes in the subfoveal choroidal thickness (SCT), largest choroidal vessel diameter, and area of the choriocapillaris-Sattler's and Haller's layers between baseline and week 12 were assessed. The BCVA improved from 67.5 ± 10.8 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 74.3 ± 10.7 letters at week 12. CRT decreased from 348.5 ± 77.4 μm at baseline to 254.3 ± 72.9 μm at week 12. Complete resolution of the retinal fluid was observed in 86.2% of cases at week 12. At baseline and 12 weeks, the SCT measured 388.3 ± 77.4 μm and 344.9 ± 91.9 μm, respectively, while the diameter of the largest choroidal vessel measured 280.3 ± 62.0 μm and 247.8 ± 57.6 μm, respectively. The areas of the choriocapillaris-Sattler's layer and Haller's layer at the corresponding time points were 0.56 ± 0.14 mm[2] and 0.57 ± 0.14 mm[2], and 1.56 ± 0.42 mm[2] and 1.40 ± 0.45 mm[2], respectively. Aflibercept loading injections for PNV resulted in both short-term visual and anatomical improvements. Notably, the reduction in the area of Haller's layer and choroidal vessel diameter after treatment suggests that aflibercept exerts an impact on this region of the choroid.}, }
@article {pmid41488355, year = {2025}, author = {Zhang, Q and Zhang, H and Shi, X and Li, J and Wang, C and Zhou, H and Shan, C}, title = {Noninvasive transcranial brain stimulation for eye diseases and visual dysfunctions: A systematic review of RCTs.}, journal = {iScience}, volume = {28}, number = {12}, pages = {114111}, pmid = {41488355}, issn = {2589-0042}, abstract = {Noninvasive transcranial brain stimulation (NTBS) has emerged as a potential therapeutic approach for eye diseases and visual dysfunctions. This systematic review evaluates the evidence from 23 randomized controlled trials examining the application of NTBS, including transcranial electrical stimulation and transcranial magnetic stimulation, in conditions such as amblyopia, myopia, visual field defects, glaucoma, diabetic retinopathy, macular degeneration, and blepharospasm. Studies assessed outcomes such as visual acuity, contrast sensitivity, and visual perception, with variable effects observed across trials. Most studies reported no serious adverse events, indicating that NTBS is safe and feasible. However, conclusive evidence regarding its efficacy remains elusive due to varied interventions, inconsistent outcome measures, and methodological limitations. Future research with higher methodological rigor is needed to optimize stimulation parameters and explore integration with adjunctive therapies.}, }
@article {pmid41490049, year = {2025}, author = {Dor, O and Cohen, M and Shahar-Gonen, M and Loewenstein, A and Peto, T and Wright, D and Shor, R and Havilio, M and Benyamini, G and Wen, Q and Shomron, N and Zur, D}, title = {Anti-VEGF Therapy Switching in Neovascular Age-Related Macular Degeneration: Insights from Automated Volumetric Retinal Fluid Analysis.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004756}, pmid = {41490049}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate the efficacy of switching from bevacizumab to ranibizumab or aflibercept in neovascular age-related macular degeneration (nAMD) using automated volumetric retinal fluid analysis.<br><br>METHODS: This retrospective study included 186 eyes with nAMD showing inadequate response after &#x2265;3 bevacizumab injections. Patients were switched to a second-line anti-VEGF agent and categorized as early (3-5 injections) or late (&#x2265;6 injections) switchers. Optical coherence tomography (OCT) scans were analyzed using the Notal-OCT Analyzer (NOA&#x2122;), an AI-based algorithm for retinal fluid quantification. Parameters included total retinal fluid (TRF), intraretinal fluid (IRF) volume, subretinal fluid (SRF) volume, pigment epithelial detachment (PED) volume, central subfield thickness (CST), and visual acuity (VA), assessed at baseline, post-bevacizumab, and following three injections of the new agent.<br><br>RESULTS: Early switchers showed an increase in TRF from 105nL to 158nL after bevacizumab, then a reduction to 20nL post-switch (p<0.001); PED volume decreased post-switch (p=0.010). Late switchers showed fluid reductions both after bevacizumab and post-switch (TRF: p<0.001; PED: p=0.007). CST significantly improved only in early switchers (p=0.004), while VA changes were not statistically significant.<br><br>CONCLUSIONS: Automated fluid analysis reliably quantifies treatment response in nAMD. Early switchers showed worsening after bevacizumab, while late switchers had partial responses. These findings highlight the potential of automated analysis to support more individualized, data-driven treatment strategies. Prospective studies are required to confirm impact on patient outcomes.}, }
@article {pmid41490202, year = {2025}, author = {Peschaut, T and Seidel, G and Sommer, M and Kruger, M and Nadvornik, C and Werkl, PJ}, title = {Recurrent sterile endophthalmitis following intravitreal Faricimab: A case report.}, journal = {Retinal cases &amp; brief reports}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICB.0000000000001854}, pmid = {41490202}, issn = {1937-1578}, abstract = {PURPOSE: Despite its low risk profile and high efficacy described in several studies, there appears to be an increasing number of reports describing sterile inflammatory reactions following intravitreal administration of Faricimab. Purpose of this case report is to highlight the occurrence of recurrent sterile endophthalmitis following repeated intravitreal Faricimab administration, emphasizing the need for awareness and careful monitoring of this adverse reaction.<br><br>METHODS AND RESULTS: We present the case of an 83-year-old caucasian woman, who was treated with intravitreal Faricimab for neovascular age-related macular degeneration (nAMD) in her left eye (OS). Shortly after the first administration, she experienced progressive, painless visual deterioration, along with a pronounced inflammatory reaction in the anterior and posterior segments, including granulomatous keratic precipitates. Based on these findings, the diagnosis of endophthalmitis was made. Following hospital admission, immediate treatment led to resolution of the condition and recovery of visual acuity.On the first day after the second administration of Faricimab, the patient again experienced painless visual deterioration accompanied by a severe inflammatory reaction OS. Immediate treatment once more resulted in resolution of the condition and recovery of visual acuity. In both instances, no microbial growth was detected in fungal cultures or aerobic and anaerobic cultures from aqueous humor and vitreous samples.<br><br>CONCLUSION: We present a case of recurrent endophthalmitis in the same patient following two intravitreal administrations of Faricimab. Considering the clinical presentation and course, as well as the microbiological findings, a sterile inflammatory reaction is likely in both instances.}, }
@article {pmid41490387, year = {2025}, author = {Franco, JJ and Wubben, TJ}, title = {Emerging solutions for neovascular age-related macular degeneration.}, journal = {Current opinion in ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICU.0000000000001199}, pmid = {41490387}, issn = {1531-7021}, abstract = {PURPOSE OF REVIEW: To summarize emerging therapeutic strategies for neovascular (wet) age-related macular degeneration (nAMD), with emphasis on recent translational and clinical developments.<br><br>RECENT FINDINGS: The nAMD treatment landscape is rapidly evolving. Gene therapies (e.g. ABBV-RGX-314, ADVM-022, and 4D-150) have demonstrated sustained intraocular anti-VEGF expression with reduced injection burden in phase 2 and 3 programs, validating the 'biofactory' concept. Tyrosine kinase inhibitors delivered via intravitreal or suprachoroidal implants (e.g. EYP-1901, OTX-TKI, and CLS-AX) show potential for twice-yearly or less frequent dosing. Moreover, emerging therapeutic approaches increasingly target non-VEGF pathogenic pathways, reflecting a shift toward mechanistically diverse vascular stabilization and neuroprotection strategies. These include multitargeted biologics that couple anti-angiogenic and anti-inflammatory effects (e.g. KSI-501, IBI-302, and AG-73305), as well as agents modulating FGF2 signaling, Wnt activation, complement regulation, and cellular metabolism.<br><br>SUMMARY: Therapeutic innovation in nAMD is transitioning from incremental refinements in intravitreal anti-VEGF delivery to strategies aimed at extending durability or targeting alternative contributory pathways. Long-term safety, efficacy, and durability will determine which of these candidates redefine standard care.}, }
@article {pmid41490968, year = {2026}, author = {Mastropasqua, R and Quarta, A and Passamonti, M and Lorenzi, C and Ruggeri, ML and Gironi, M and Persavalli, C and Belloni Baroni, L and De Santis Ciacci, C and Aloia, R and Della Penna, N and Toto, L and Carpineto, P and Mastropasqua, L}, title = {Macular pigment optical density following lutein scleral iontophoresis in intermediate age-related macular degeneration: A six-month pilot study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328403}, pmid = {41490968}, issn = {1468-2079}, abstract = {PURPOSE: To evaluate the effects of scleral iontophoresis lutein delivery on macular pigment optical density (MPOD), retinal anatomy and function in patients with intermediate age-related macular degeneration (iAMD).<br><br>METHODS: This prospective pilot study included 15 phakic eyes from patients with iAMD. All participants underwent a single session of trans-scleral iontophoresis with a liposomal lutein formulation. MPOD, central macular thickness (CMT), choroidal vascularity index (CVI) and retinal sensitivity (RS) were assessed at baseline (T0), and at 1&#x2009;month (T1), 3&#x2009;months (T2) and 6&#x2009;months (T3).<br><br>RESULTS: MPOD showed a significant overall change across time points (&#x3c7;&#xb2;=11.01, p=0.012), with significant differences between T1 and T3 (p=0.006) and T2 and T3 (p=0.018). CMT significantly decreased at T3 compared with earlier visits (p&#x2264;0.002). RS declined at early time points (T1 and T2 vs T0; p=0.027&#x2009;and p=0.002, respectively), while CVI exhibited modest reductions by T2 and T3 (p=0.021&#x2009;and p=0.017). A significant inverse correlation was found between &#x394;MPOD and &#x394;RS at T2-T0 (&#x3c1;=-0.520, p=0.035). Best-corrected visual acuity remained stable across all visits.<br><br>CONCLUSIONS: The inverse correlation between MPOD change and RS decline at 3&#x2009;months raises the possibility that early augmentation of MP may provide a protective functional effect. These data support the short-term feasibility of scleral iontophoresis for targeted lutein delivery.}, }
@article {pmid41491306, year = {2026}, author = {Kikushima, W and Sakurada, Y and Fukuda, Y and Yoneyama, S and Kotoda, Y and Tsuru, DV and Kashiwagi, K}, title = {Brolucizumab versus aflibercept in treating exudative age-related macular degeneration: a 12-month pro re nata regimen.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {4739}, pmid = {41491306}, issn = {2045-2322}, abstract = {We compared 12-month treatment outcomes of intravitreal injections of brolucizumab (IVBr) with aflibercept (IVA) for treatment-naïve exudative age-related macular degeneration (AMD). Patients were given three monthly IVBr or IVA injections and were followed up monthly for 12 months. Additional injections were given if exudation or hemorrhage recurred. The study included 339 eyes in 339 patients divided into the IVBr or IVA groups. In both groups, central retinal thickness (CRT) and subfoveal choroidal thickness significantly decreased, and best-corrected visual acuity (BCVA) significantly improved at the 12-month visit. BCVA improvement was similar in both groups (P = 0.27). Age, baseline BCVA, and thickness of the central retina and subfoveal choroid were associated with the 12-month BCVA. The proportion of patients who did not require additional injections was 33% in the IVBr and 30% in the IVA group (P = 0.58). The number of additional injections showed a trend favoring IVBr over IVA but the difference was insignificant (P = 0.055). Age, risk alleles of ARMS2 A69S, and baseline CRT were associated with shorter retreatment-free period. In conclusion, IVBr achieved similar visual and anatomic treatment outcomes to IVA with a trend toward requiring fewer additional injections during 12-month follow-up of as-needed regimen for exudative AMD.}, }
@article {pmid41491515, year = {2026}, author = {Wang, JX and Wei, WB}, title = {[Research status of subretinal fibrosis in age-related macular degeneration].}, journal = {[Zhonghua yan ke za zhi] Chinese journal of ophthalmology}, volume = {62}, number = {1}, pages = {66-72}, doi = {10.3760/cma.j.cn112142-20250804-00330}, pmid = {41491515}, issn = {0412-4081}, support = {82220108017, 82141128//National Natural Science Foundation of China/ ; 2024-1-2052//The Capital Health Research and Development of Special/ ; Z201100005520045//Science &amp; Technology Project of Beijing Municipal Science &amp; Technology Commission/ ; SZSM202311018//Sanming Project of Medicine in Shenzhen/ ; }, mesh = {*Macular Degeneration/pathology ; Humans ; Animals ; Fibrosis ; *Retina/pathology ; Disease Models, Animal ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss in individuals aged 65 years and older. In the advanced stage of the disease, subretinal fibrotic scars develop, leading to irreversible vision impairment. The formation of subretinal scars is driven by interactions among various cellular and molecular components, involving multiple pathological processes including immune responses and inflammatory reactions; however, the exact underlying mechanism remains elusive. This review summarizes the current animal models and experimental studies employed to investigate its mechanism and explore novel therapeutic targets.}, }
@article {pmid41492569, year = {2026}, author = {Faghihi, S and Eshkoly-Lior, T and Feo, A and Sarraf, D}, title = {Atypical presentation of macular serpiginous choroiditis masquerading as age related macular degeneration.}, journal = {American journal of ophthalmology case reports}, volume = {41}, number = {}, pages = {102491}, pmid = {41492569}, issn = {2451-9936}, abstract = {PURPOSE: To describe a case of macular serpiginous choroiditis (SC) masquerading as age related macular degeneration.<br><br>METHOD: Multimodal imaging (MMI), including ultra-widefield fundus autofluorescence and fluorescein and indocyanine green angiography werer performed. Cross-sectional and en face optical coherence tomography (OCT) and OCT angiography (OCTA) facilitated the correct diagnosis of this masquerade condition.<br><br>RESULTS: A 57-year-old woman, with a history of long-standing vision loss in the left eye (OS), presented with acute vision loss in the right eye (OD). Color fundus photography showed a focal macular lesion central OD and an irregular atrophic macular scar central OS. OCT OD displayed large drusenoid lesions in the macula OD and a macular scar OS. OCTA showed evidence of inner choroidal ischemia central OD corresponding to the drusenoid lesions without shadow artifact OD. A diagnosis of macular serpiginous choroiditis was rendered OD and the patient was started on immunomodulatory therapy (IMT) including oral steroids and increasing dosages of mycophenolate therapy. After three months of follow-up, the visual acuity remarkably improved, the drusenoid lesions completely resolved on OCT, and choroidal ischemia completely regressed on OCTA OD.<br><br>CONCLUSION: Placoid disorders can masquerade as AMD. We present an unusual case of macular serpiginous choroiditis with new onset drusenoid lesions driven by inner choroidal ischemia on OCTA and with resolution following IMT. OCTA can be an invaluable tool to correctly diagnose placoid conditions which is essential to guide therapeutic considerations.}, }
@article {pmid41493078, year = {2026}, author = {Zobor, D and Munk, MR}, title = {Distinguishing Inherited Retinal Disease From Age-Related Macular Degeneration: Clinical Red Flags, Diagnostic Strategy, and the Expanding Role of Genetic Testing.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {54}, number = {1}, pages = {3-5}, doi = {10.1111/ceo.70055}, pmid = {41493078}, issn = {1442-9071}, }
@article {pmid41493658, year = {2026}, author = {Tan, X and Kang, J and Zhao, H and Fang, F and Xia, Y and Luo, C and Zou, Y and Li, Y}, title = {GPR40 Attenuates Age-Related Macular Degeneration by Suppressing Retinal Microglial NLRP3 Inflammasome Activation Via ERK Signaling.}, journal = {Inflammation}, volume = {49}, number = {1}, pages = {29}, pmid = {41493658}, issn = {1573-2576}, support = {82360213//the National Natural Science Foundation of China/ ; 202305AC160073//the Yunnan Provincial Young and Middle - Aged Academic and Technical Leaders Reserve Talents Project/ ; 202401AY070001-172/174//the Yunnan Provincial Department of Science and Technology - Kunming Medical University Joint Fund for Applied Basic Research/ ; ZKF2024048/ ZKF2024047//The National Key Clinical Specialty Project in Ophthalmology/ ; 2024Y927//Yunnan Provincial Department of Education Scientific Research Fund Project/ ; }, mesh = {Animals ; *Receptors, G-Protein-Coupled/metabolism ; *Microglia/metabolism/drug effects/pathology ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/antagonists &amp; inhibitors ; *Macular Degeneration/metabolism/prevention &amp; control/chemically induced/pathology ; Mice ; *Inflammasomes/metabolism ; *MAP Kinase Signaling System/physiology/drug effects ; *Retina/metabolism/pathology ; Mice, Inbred C57BL ; }, abstract = {Retinal neuroinflammation is a key pathological feature of age-related macular degeneration (AMD), primarily driven by aberrant microglial cell activation. The expression and role of G-protein-coupled receptor 40 (GPR40), in AMD remain unclear. To investigate this pathology, we established a sodium iodate-induced mouse model of non-exudative AMD and performed in vitro experiments using LPS-stimulated microglial cells. The results showed that activation of the GPR40 receptor significantly promoted the polarization of microglial cells from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, effectively inhibiting neuroinflammation. Mechanistic studies revealed that GPR40 negatively regulates the ERK signaling pathway, inhibiting NLRP3 inflammasome activation and the release of pro-inflammatory cytokines such as IL-1β and TNF-α. In both in vivo and in vitro experiments, GPR40 activation protected photoreceptors by suppressing neuroinflammation caused by excessive microglial activation. In conclusion, this study reveals, for the first time, the critical role of GPR40 in regulating retinal neuroinflammation and its molecular mechanism. It highlights the potential therapeutic value of targeting the GPR40-ERK signaling axis to control the neuroinflammatory cascade and delay the progression of AMD and other retinal degenerative diseases.}, }
@article {pmid41494750, year = {2026}, author = {Balser, S and Capsius, B and Hole, R and Papp, A and Preissinger, N and Rozenknop, A and Tiko, T}, title = {Randomised, double-masked trial to compare the efficacy, safety and immunogenicity of the biosimilar aflibercept FYB203 with reference aflibercept in patients with neovascular age-related macular degeneration.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {1}, pages = {}, pmid = {41494750}, issn = {2397-3269}, mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Double-Blind Method ; Male ; Female ; *Recombinant Fusion Proteins/administration &amp; dosage ; Aged ; *Biosimilar Pharmaceuticals/administration &amp; dosage/therapeutic use/adverse effects ; Intravitreal Injections ; *Visual Acuity ; Middle Aged ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence ; Follow-Up Studies ; }, abstract = {OBJECTIVE: Biosimilars are helping to reduce the cost burden of treatment and widen patient access to therapies. This multicentre trial compared the efficacy, safety and immunogenicity of the biosimilar aflibercept FYB203 with reference aflibercept in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS AND ANALYSIS: Patients aged &#x2265;50 years with newly diagnosed nAMD and a best-corrected visual acuity (BCVA) between 20/40 and 20/200 Snellen equivalent were randomised (1:1) to double-masked treatment with 2&#x2009;mg FYB203 or EU-approved reference aflibercept by intravitreal injection every 4 weeks for three doses (baseline, weeks 4 and 8) then every 8 weeks up to week 48. The primary efficacy endpoint was the change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 8 in the study eye. Therapeutic equivalence of FYB203 and reference aflibercept was demonstrated if, depending on the regulatory requirement with respect to the significance level, the two-sided 90.4% and 95.2%&#x2009;CIs were within the predefined equivalence interval of (-3.5 to 3.5) ETDRS letters.<br><br>RESULTS: A total of 433 patients received treatment with FYB203 (n=215) or reference aflibercept (n=218). Mean improvement in BCVA from baseline to week 8 was 6.6 ETDRS letters with FYB203 and 5.6 ETDRS letters with reference aflibercept, with an estimated mean treatment difference of 1.0 and the two-sided 90.4%&#x2009;CI (-0.3 to 2.2) and 95.2%&#x2009;CI (-0.6 to 2.5) fully contained within the pre-defined equivalence margins, confirming therapeutic equivalence between FYB203 and reference aflibercept. Safety and immunogenicity profiles were similar between groups.<br><br>CONCLUSION: Although conducted during the COVID-19 pandemic in a potentially vulnerable elderly population and affected by geopolitical disruption in Ukraine, mitigation measures minimised the overall impact of these events. FYB203 demonstrated therapeutic equivalence to reference aflibercept in patients with nAMD, supporting similar clinical performance across all approved indications.<br><br>TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT04522167; EudraCT: 2019-003923-39.}, }
@article {pmid41495013, year = {2026}, author = {Li, H and Weiss, CE and Pandiyan, VP and Nanni, D and Liu, T and Kung, PW and Tan, B and Barathi, VA and Schmetterer, L and Sabesan, R and Ling, T}, title = {Optoretinography reveals rapid rod photoreceptor movement upon rhodopsin activation.}, journal = {Light, science &amp; applications}, volume = {15}, number = {1}, pages = {58}, pmid = {41495013}, issn = {2047-7538}, support = {I010/2024 [2082/44/2024]//Singapore Eye Research Institute (SERI)/ ; RS19/20; RG28/21//Ministry of Education - Singapore (MOE)/ ; NMRC/CG/C010A/2017; MOH-001748-00//MOH | National Medical Research Council (NMRC)/ ; Startup Grant//Nanyang Technological University (NTU)/ ; unrestricted grant//Research to Prevent Blindness (RPB)/ ; P30 EY001730/EY/NEI NIH HHS/United States ; L40 AI172024/AI/NIAID NIH HHS/United States ; NRF-CRP24-2020-0001//National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore)/ ; L30 AI172024/AI/NIAID NIH HHS/United States ; NMRC/CG/M010/2017/Pre-Clinical; NMRC/CG21APR1010-SAMURAI/Pre-Clinical Core Platform/2021_SERI//MOH | National Medical Research Council (NMRC)/ ; U01EY032055; EY029710//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; NRF-NRFF14-2022-0005//National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore)/ ; R01 EY029710/EY/NEI NIH HHS/United States ; U01 EY032055/EY/NEI NIH HHS/United States ; }, abstract = {Rod photoreceptors are essential for vision under dim light conditions and are highly vulnerable in retinal degenerative diseases. Here, we demonstrate that both human and rodent rods undergo a minute and rapid contraction of their outer segments upon photoisomerization, the first step of phototransduction. The contraction is explained as an electromechanical manifestation of the rod early receptor potential generated in the disk membranes, which is challenging to access in electrophysiology. The in vivo optical imaging of light-evoked electrical activity in rodent rods was facilitated by an ultrahigh-resolution point-scan optical coherence tomography (OCT) system, combined with an unsupervised learning approach to separate the light-evoked response of the rod outer segment tips from the retinal pigment epithelium-Bruch's membrane complex. In humans, an adaptive optics line-scan OCT facilitated high-speed recordings in rods. The non-invasive in vivo optical imaging of rhodopsin activation extends the diagnostic capability of optoretinography, and may facilitate personalized, objective assessment of rod dysfunction and visual cycle impairment in inherited and age-related macular degeneration.}, }
@article {pmid41497268, year = {2026}, author = {Gong, X and Feng, J and Han, Y and Tang, G and Yin, Y and Li, J and Liu, Y and Zhang, J and Song, J and Bi, H}, title = {Research progress on glycolytic reprogramming in ophthalmic diseases.}, journal = {PeerJ}, volume = {14}, number = {}, pages = {e20478}, pmid = {41497268}, issn = {2167-8359}, mesh = {Humans ; *Glycolysis ; *Eye Diseases/metabolism ; Animals ; *Retina/metabolism ; Uveal Neoplasms/metabolism ; Energy Metabolism ; Uveal Melanoma ; Melanoma/metabolism ; Glaucoma/metabolism ; Cellular Reprogramming ; }, abstract = {The retina is one of the most energy-demanding tissues in the human body. Retinal energy metabolism is primarily dominated by aerobic glycolysis, with more than 80% of the glucose consumed being converted to lactic acid. As a highly energy-consuming tissue, the metabolic characteristics of the retina, especially aerobic glycolysis, are essential for maintaining retinal cell function during normal physiological processes. However, in disease states, this metabolic balance is disrupted, leading to a range of pathological changes. There is currently growing evidence that metabolic reprogramming is a pathological cause of diseases such as retinal degeneration, uveal melanoma, and glaucoma. This article reviews the mechanisms involved in metabolic reprogramming in ocular diseases and describes relevant therapeutic targets. Despite the many advances, the regulatory mechanisms of metabolic reprogramming in ophthalmic diseases still need to be thoroughly investigated, and new therapeutic strategies are expected to be developed based on this in the future.}, }
@article {pmid41497650, year = {2025}, author = {Pandala, N and De Melo Haefeli, L and Khan, A and Steffan, H and Miller, J and Stone, EM and Han, IC and Lavik, EB and Mullins, RF and Tucker, BA}, title = {Acriflavine delivery via Polyurethane nanocapsules to treat neovascular age-related macular degeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.22.695712}, pmid = {41497650}, issn = {2692-8205}, abstract = {Choroidal neovascularization is a complication associated with retinal diseases such as age-related macular degeneration (AMD), a leading cause of vision loss in the developed world. Choroidal neovascular membrane (CNVM) refers to the abnormal growth of blood vessels in the retina which results in exudation and/or hemorrhage, leading to photoreceptor damage and vision loss. Currently first-line treatment for CNVM include intravitreal injections of vascular endothelial growth factor (VEGF)-binding antibodies that prevent the growth of these leaky blood vessels. Unfortunately, anti-VEGF drugs often require frequent injections, and prolonged VEGF inhibition has been associated with retinal atrophy and decreased long term effectiveness in some patients. This study presents the use of Acriflavine, a small molecule HIF1α inhibitor loaded polyurethane nanocapsules to treat CNVM in a rat model. Fourteen days following laser injury and intravitreal drug administration, CMVM size was significantly reduced in acriflavine nanocapsule and free acriflavine treated animals as compared to drug free controls. Moreover, acriflavine nanocapsules reduce CNVM incidence compared to drug free controls by approximately 25%. Among the different delivery routes tested, intravitreal delivery of acriflavine nanocapsules was found to be superior to subretinal and suprachoroidal delivery for reducing CNVM area without causing significant damage to the neural retina. This paper presents the synthesis, characterization and the effectiveness of the polyurethane based acriflavine delivery system in treating choroidal neovascularization.}, }
@article {pmid41497719, year = {2025}, author = {Zhang, M and Wang, Y and Feng, L and Zhang, P and Li, Y and Chen, H}, title = {Massive Hemorrhage in PCV Is Associated With Lower-Than-Normal VEGF Level and Dramatically Elevated Inflammatory Cytokine Levels in Aqueous Mingxuan.}, journal = {Journal of ophthalmology}, volume = {2025}, number = {}, pages = {9272271}, pmid = {41497719}, issn = {2090-004X}, abstract = {PURPOSE: To compare the aqueous cytokine profile in polypoidal choroidal vasculopathy (PCV) with or without massive hemorrhage and typical neovascular age-related macular degeneration (nAMD).<br><br>METHODS: The present comparative study included 81 treatment-na&#xef;ve eyes from 75 patients (PCV with massive hemorrhage 20 eyes, PCV without massive hemorrhage 19 eyes, typical nAMD 19 eyes, and cataract control 23 eyes). 10 cytokines (VEGF, IL-6, IL-8, MCP-1, ICAM-1, VCAM-1, IP-10, G-CSF, and IFN-&#x3b3;, IL-10) in the aqueous humor were measured by cytometric bead array.<br><br>RESULTS: VEGF levels in PCV with massive hemorrhage (median 5.20&#x2009;pg/mL) were significantly lower than that in PCV without massive hemorrhage (median 34.76&#x2009;pg/mL, p = 0.003) and typical nAMD (median 43.88&#x2009;pg/mL, p < 0.001). They were even lower than that in normal cataract controls (median 22.02&#x2009;pg/mL, p = 0.037). Multiple inflammatory cytokines were dramatically elevated in PCV with massive hemorrhage. IL-6, IL-8, MCP-1, ICAM-1, and IP-10 levels were significantly higher in PCV with massive hemorrhage than that in the other three groups. VCAM-1 levels were significantly higher in PCV with massive hemorrhage than that in typical nAMD and in control. G-CSF and IFN-&#x3b3; levels were significantly higher in PCV without massive hemorrhage than that in control. IL-10 levels were significantly higher in PCV with massive hemorrhage than that in typical nAMD.<br><br>CONCLUSIONS: This pilot study showed that PCV with massive hemorrhage had a lower-than-normal VEGF level in aqueous humor and inflammation may be actively involved in the pathogenesis of massive hemorrhage in PCV.}, }
@article {pmid41499325, year = {2026}, author = {Karam, M and Baeshen, M and Alfuzaie, R and Mohammad, M and Alshatti, A and Samet, A and Paez-Escamilla, M and Sun, V}, title = {Efficacy of Faricimab in Neovascular Age-Related Macular Degeneration: A Single-Arm Systematic Review and Meta-Analysis.}, journal = {Ophthalmic research}, volume = {69}, number = {1}, pages = {43-55}, pmid = {41499325}, issn = {1423-0259}, mesh = {Humans ; *Visual Acuity ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Tomography, Optical Coherence ; Treatment Outcome ; Macula Lutea/pathology ; Antibodies, Bispecific ; }, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss and requires long-term anti-vascular endothelial growth factor therapy. This study aimed to evaluate the efficacy and safety of faricimab in patients with nAMD.<br><br>METHODS: This systematic review and meta-analysis were performed according to the PRISMA guidelines to identify studies assessing faricimab in nAMD. Primary outcomes included visual acuity, central macular thickness (CMT), and dry macula rate. Secondary outcomes included macular status, central choroidal thickness (CCT), and complications. A random-effects model was used to calculate pooled mean with 95% confidence intervals.<br><br>RESULTS: Out of the 365 studies identified, 21 studies were included, comprising a total sample size of 1,864 eyes of 1,791 patients. Post-operatively, there was a statistically significant improvement in corrected distance visual acuity (standardized mean difference [SMD]: -0.122, 95% p = 0.039) and CMT (SMD: -3.672, p = 0.010). Similarly, there was a significant improvement in the rate of dry macula at the final follow-up visit (event rate: 0.529; p < 0.05). For the secondary outcomes, there was a statistically significant improvement in CCT (SMD: -0.199, p = 0.026) and in the rate of macular exudates (0.452, p < 0.05), specifically intraretinal fluid (0.140, p < 0.05) and subretinal fluid (0.271, p < 0.05). Complications secondary to faricimab injections included hemorrhagic pigment epithelial detachment with a rate of 0.120 (p < 0.05) and retinal pigment epithelium tear with a rate of 0.025 (p < 0.05).<br><br>CONCLUSIONS: The use of faricimab injection in patients with nAMD is safe and effective, resulting in significant improvements in a myriad of visual measures and OCT parameters.}, }
@article {pmid41499990, year = {2026}, author = {Chen, C and Wang, C and Li, H and Wang, T and Jiao, X}, title = {Sweet poison for the eyes: High-Fructose diets as drivers of metabolic disruption and ocular diseases - Insights and therapeutic horizons.}, journal = {Experimental eye research}, volume = {264}, number = {}, pages = {110852}, doi = {10.1016/j.exer.2026.110852}, pmid = {41499990}, issn = {1096-0007}, mesh = {Humans ; *Fructose/adverse effects ; *Eye Diseases/metabolism/etiology ; Metabolic Syndrome/metabolism ; Animals ; *Diet/adverse effects ; }, abstract = {Excess consumption of added sugars, commonly delivered through sucrose and high-fructose corn syrup, has increased in parallel with obesity, metabolic syndrome, and type 2 diabetes. These systemic metabolic disturbances are consistently associated with a range of ocular conditions. However, whether high-fructose intake exerts independent and fructose-specific effects on ocular tissues remains uncertain, because most human evidence is indirect, often mediated through metabolic syndrome phenotypes, and frequently confounded by mixed dietary exposures and total energy intake. This review synthesizes mechanistic pathways that are plausibly enriched by fructose biology, including hepatic fructose metabolism with ATP depletion and uric acid generation, oxidative and inflammatory signaling, altered lipid handling, and gut barrier and microbiome perturbations. We evaluate how these systemic changes may intersect with ocular surface homeostasis, retinal neurovascular integrity, intraocular pressure regulation, and choroidal and macular vulnerability. Across dry eye disease, diabetic retinopathy, glaucoma-related outcomes, age-related macular degeneration and choroidal neovascular responses, and cataract, we distinguish fructose-specific exposure studies from metabolic syndrome only and mixed diet reports, and we emphasize limitations related to exposure definition, replication, and translation to humans. Overall, current evidence supports the view that excess fructose may amplify ocular susceptibility in metabolically stressed states, but direct causal links in humans remain preliminary. We conclude by outlining methodological priorities and testable study designs needed to clarify fructose-specific contributions to ocular disease risk. Some experimental findings, particularly those related to ocular-surface responses, originate from single research groups and require independent replication, underscoring that current evidence remains preliminary and hypothesis-generating.}, }
@article {pmid41500346, year = {2026}, author = {Dal Cortivo, G and Longo, C and Müller, B and Avesani, A and Pacchiana, R and Weller, M and Marino, V and Lytvynchuk, L and Stieger, K and Dell'Orco, D}, title = {Protein delivery to the eye: assessing therapeutic potential across inner and outer retina.}, journal = {International journal of pharmaceutics}, volume = {690}, number = {}, pages = {126568}, doi = {10.1016/j.ijpharm.2026.126568}, pmid = {41500346}, issn = {1873-3476}, mesh = {Animals ; Swine ; *Retina/metabolism ; *Guanylate Cyclase-Activating Proteins/administration &amp; dosage/metabolism ; Mice ; Liposomes ; Mice, Inbred C57BL ; Drug Delivery Systems ; Humans ; Protein Transport ; }, abstract = {Protein-based therapeutics represent a promising approach for treating diseases of the retina, yet effective delivery systems and translational models remain limited. We developed a robust ex vivo framework utilizing murine and porcine retinal explants to investigate protein delivery mechanisms for both peripheral and central retinal regions. Using guanylate cyclase-activating protein-1 (GCAP1) as a retina-specific model protein and mCardinal2 as a non-retina-specific control, we demonstrated spontaneous protein internalization and accumulation in photoreceptors and ganglion cells following single-dose administration. In murine explants, myristoylated GCAP1 exhibited sustained retention and appropriate subcellular targeting in rod photoreceptors over 96 h without inducing tissue damage. Porcine explants, which better recapitulate human macular architecture, revealed differential protein trafficking dependent on post-translational modifications. Retinal tissue showed preferential uptake and retention of retina-specific proteins over foreign proteins, suggesting sophisticated protein-specific recognition mechanisms. Liposomal encapsulation enhanced initial uptake of non-retina-specific proteins but did not improve long-term retention. This experimental platform provides a valuable tool for screening protein therapeutics, optimizing delivery formulations, and investigating protein-selective cellular uptake mechanisms, with direct implications for developing treatments for inherited retinal degenerations, age-related macular degeneration, and optic nerve pathologies.}, }
@article {pmid41500399, year = {2026}, author = {Wang, Y and Liu, X and Zeng, S and Yang, W and Cao, F and Hou, S}, title = {The role and mechanism of post-translational modifications (PTMs) in immune-related eye diseases.}, journal = {Experimental eye research}, volume = {264}, number = {}, pages = {110851}, doi = {10.1016/j.exer.2026.110851}, pmid = {41500399}, issn = {1096-0007}, mesh = {Humans ; *Protein Processing, Post-Translational/physiology ; *Eye Diseases/immunology/metabolism ; Animals ; *Eye Proteins/metabolism ; }, abstract = {Post-translational modifications (PTMs) encompass the spectrum of chemical covalent alterations that proteins undergo after being synthesized from mRNA. These modifications typically involve the covalent bonding of chemical groups or small protein molecules to the amino acid backbones or side chains. Currently, over 650 types of PTMs have been identified, including significant ones such as phosphorylation, ubiquitination, SUMOylation, methylation, acetylation, glycosylation, among other novel varieties like lactylation. However, a systematic review of PTMs associated with immune-mediated ocular diseases remains conspicuously absent in current literature. To fully understand the role of PTM in immune eye diseases, this review systematically introduces the regulatory mechanisms and functions of several important PTMs. Furthermore, this review also encapsulates the mechanisms of PTMs in several pivotal immune-related ocular conditions, specifically uveitis, age-related macular degeneration (AMD), dry eye disease (DED), and diabetic retinopathy (DR). By integrating current evidence, this work not only clarifies the pathogenic contributions of specific PTMs but also identifies their potential as therapeutic targets. Finally, we discuss future research directions and the challenges of translating PTM-based interventions into clinical practice for ocular immune disorders.}, }
@article {pmid41501669, year = {2026}, author = {Luo, Y and Xia, Y and Gong, X and Hao, M and Wei, Q and Liao, L}, title = {GLP-1 receptor agonists in eye disease: a comprehensive review of current research and future potential.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {12}, pmid = {41501669}, issn = {1471-2415}, abstract = {OBJECTIVE: To synthesize the current preclinical and clinical evidence on the utility and potential mechanisms of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as a therapeutic strategy for major ophthalmic diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration.<br><br>METHODS: A comprehensive literature search was conducted to synthesize the current preclinical and clinical evidence. Electronic databases including PubMed, Embase, and Web of Science were searched from inception until August 2025 using keywords such as &#x201c;GLP-1 receptor agonist,&#x201d; &#x201c;diabetic retinopathy,&#x201d; &#x201c;glaucoma,&#x201d; &#x201c;age-related macular degeneration,&#x201d; &#x201c;ocular disease,&#x201d; and &#x201c;neuroprotection.&#x201d; The search focused on identifying preclinical studies, large-scale retrospective cohort studies, and post-hoc analyses of major clinical trials that evaluated the utility and potential mechanisms of GLP-1RAs in ophthalmic diseases. Studies were screened for relevance based on title and abstract, and full texts were retrieved for detailed assessment.<br><br>RESULTS: Despite heterogeneity in study designs and populations, a largely consistent association was found between GLP-1RA use and a reduced incidence of glaucoma. For diabetic retinopathy, the evidence was nuanced, indicating potential long-term neurovascular protection but also a risk of transient early worsening. For age-related macular degeneration, findings were dichotomous, suggesting a protective effect against non-exudative forms but a potential increased risk for neovascular disease.<br><br>CONCLUSION: GLP-1RAs show significant promise as a potential disease-modifying therapy for neurodegenerative and inflammatory eye diseases, acting through both systemic metabolic improvements and direct ocular mechanisms, representing a paradigm shift beyond their metabolic indications.}, }
@article {pmid41501830, year = {2026}, author = {Fang, J and Huang, Y and Li, B and Du, Y}, title = {Role and regulation of kinases in age-related macular degeneration.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {227}, pmid = {41501830}, issn = {1479-5876}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of chronic blindness in the elderly and causes retinal pigment epithelium (RPE) and photoreceptor cells to degenerate and die. However, the specific pathogenic mechanism of AMD has yet to be explored. The development of new AMD therapeutics is urgently required.<br><br>MAIN BODY: Studies have shown that kinases are increasingly important in AMD pathogenesis and treatment. Inhibition of apoptosis in retinal cells, such as RPE cells, maintenance of normal cellular metabolism, and preservation of normal autophagy are among the pathways involved in treating AMD. This is associated with kinase-related pathways, such as the PI3K/Akt, MAPK/ERK, JAK/STAT, mTOR, Ang-Tie, and AMPK signaling pathways.<br><br>CONCLUSIONS: In this review, we highlight recent advances in kinase-related pathways in treating AMD, to provide new directions for the prevention and treatment of AMD.}, }
@article {pmid41502314, year = {2026}, author = {Lee, S and Choi, J and Yu, SY and Kim, K}, title = {Quantitative optical coherence tomography angiography biomarkers Following a Switch to Brolucizumab in Neovascular age-related macular degeneration.}, journal = {Korean journal of ophthalmology : KJO}, volume = {}, number = {}, pages = {}, doi = {10.3341/kjo.2025.0144}, pmid = {41502314}, issn = {2092-9382}, abstract = {PURPOSE: To evaluate functional and anatomical outcomes, including vessel morphology parameters on swept-source optical coherence tomography angiography (SS-OCTA), in eyes with neovascular age-related macular degeneration (nAMD) switched to brolucizumab.<br><br>METHODS: This retrospective study included 37 eyes with nAMD that were switched from other anti-vascular endothelial growth factor (VEGF) agents to intravitreal brolucizumab. Best-corrected visual acuity (BCVA), injection intervals, central subfield thickness (CST), pigment epithelial detachment (PED) and presence of retinal fluid were compared between baseline and 12 months post-switch. SS-OCTA images were analyzed to quantify macular neovascularization (MNV) area, vessel density, fractal dimension (FD), and lacunarity.<br><br>RESULTS: Switching to brolucizumab significantly extended injection intervals and reduced CST, PED height and retinal fluid, while maintaining BCVA at 12 months. Quantitative OCTA analysis showed reductions in MNV area and FD following the switch. When compared with the preceding 12 months of other anti-VEGF therapy, FD still showed a significant reduction after brolucizumab treatment (p = 0.019). Intraocular inflammation occurred in 1 eye and resolved with topical corticosteroids.<br><br>CONCLUSIONS: Intravitreal brolucizumab demonstrated favorable anatomical improvements and maintained visual outcomes over 12 months. Quantitative OCTA biomarkers, particularly FD, may serve as imaging indicators of disease activity and treatment response in eyes with nAMD undergoing a therapy switch.}, }
@article {pmid41503694, year = {2026}, author = {Hua, Z and Zhu, Q and Yang, J and Tang, M and Yin, J and Zhan, D}, title = {Mendelian Randomization Study of Age-Related Macular Degeneration and Inflammatory Bowel Disease.}, journal = {Current eye research}, volume = {51}, number = {4}, pages = {461-469}, doi = {10.1080/02713683.2025.2602902}, pmid = {41503694}, issn = {1460-2202}, mesh = {Humans ; *Mendelian Randomization Analysis/methods ; *Macular Degeneration/genetics/epidemiology ; *Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; *Inflammatory Bowel Diseases/genetics/complications/epidemiology ; Risk Factors ; C-Reactive Protein/metabolism ; Male ; }, abstract = {PURPOSE: To investigate the causal relationship between age-related macular degeneration (AMD) and inflammatory bowel disease (IBD) by Mendelian randomization (MR) analysis.<br><br>METHODS: The single nucleotide polymorphism data of IBD and AMD were obtained from the Integrative Epidemiology Unit (IEU) Open genome-wide association study database. MR analysis contained MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode. Sensitivity analysis was executed to ensure the reliability of results, containing heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis. Multivariable Mendelian randomization analysis was carried out to investigate potential confounding factors such as C-reactive protein, smoking, vitamin D deficiency. Genes corresponding to the instrumental variables (IVs) and functional enrichment analysis were executed.<br><br>RESULTS: MR analysis showed a positive correlation between IBD and AMD (P&#x2009;<&#x2009;0.05, OR > 1). Sensitivity analyses also did not reveal heterogeneity and horizontal pleiotropy. C-reactive protein, smoking, and vitamin D deficiency had no significant effect on AMD (P&#x2009;>&#x2009;0.05). Genes corresponding to IVs were mainly associated with monocyte differentiation, cytokine receptor activity, etc., and act on signaling pathways such as Th17 cell differentiation, and there was a complex network of molecular-cell regulation.<br><br>CONCLUSION: Our study explored and demonstrated the causal relationship between IBD and AMD through MR analysis, which provided an important reference and direction for future research and treatment related to AMD.}, }
@article {pmid41504873, year = {2026}, author = {Stettler, I and Romano, F and Nigalye, A and Lains, I and Choi, H and Ding, X and Bennett, CF and Overbey, KM and Ploumi, I and Garg, I and Katz, R and Kasetty, M and Vingopoulos, F and Vavvas, DG and Miller, JW and Husain, D and Miller, JB}, title = {Assessing the role of macular pigment optical volume in non-neovascular age-related macular degeneration: associations with rod-mediated dark adaptation and disease progression.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {4}, pages = {963-973}, pmid = {41504873}, issn = {1435-702X}, mesh = {Humans ; Disease Progression ; Female ; Male ; Cross-Sectional Studies ; Aged ; *Tomography, Optical Coherence/methods ; *Dark Adaptation/physiology ; *Fluorescein Angiography/methods ; *Macular Pigment/metabolism ; Follow-Up Studies ; *Macular Degeneration/diagnosis/physiopathology/metabolism ; *Macula Lutea/pathology/diagnostic imaging/metabolism ; Middle Aged ; Fundus Oculi ; *Visual Acuity ; Aged, 80 and over ; *Retinal Rod Photoreceptor Cells/physiology ; }, abstract = {PURPOSE: To characterize macular pigment optical volume (MPOV) across non-neovascular age-related macular degeneration (AMD) stages and in healthy controls, and to explore its associations with dark adaptation (DA) time and long-term AMD progression.<br><br>DESIGN: Cross-sectional and longitudinal observation study including patients with non-neovascular AMD (early, intermediate, advanced) per Beckman classification and age-similar controls with no retinal disease. All eyes had good-quality dual-wavelength autofluorescence imaging (Spectralis Investigational MPOD Module).<br><br>METHODS: DA was assessed using the AdaptDx[&#xae;] extended protocol (LumiThera, Poulsbo, WA). MPOV was calculated for three concentric circles centered on the fovea at radii of 1&#xb0;, 2&#xb0;, and 6&#xb0;. AMD progression was determined through consultation of follow-up clinical and imaging data. Mixed-effects linear regression models evaluated baseline differences between AMD and control eyes, and across non-neovascular AMD stages. Progression risk was assessed using mixed-effectsCox proportional hazards models adjusted for age, AREDS2 use, lens opacities, and fellow eye status.<br><br>RESULTS: Our analysis included 110 AMD eyes (58 patients; median age 72, 56.9% female) and 51 control eyes (26 patients; median age 64, 53.9% female). AMD eyes had significantly higher MPOV than controls when calculated at all eccentricities (1, 2, and 6&#xb0;, all p<0.01). In controls, higher MPOV at all eccentricities was associated with shorter DA time (p<0.05) - a relationship not observed in AMD eyes. Of 108 AMD eyes with follow-up (median, 53.1 months), 24 eyes (22.9%) progressed to a more advanced stage. Higher MPOV values at all eccentricities were independently associated with increased progression risk (all p<0.05) CONCLUSIONS: AMD eyes show greater MPOV values than controls, especially in intermediate stages. While MPOV correlated with better DA performance in healthy eyes, this relationship was absent in AMD, suggesting a more complex interaction in diseased retina.}, }
@article {pmid41508137, year = {2026}, author = {Rubio, AP and Dunn, J and Borthwick, J and Saunders, S and Tochel, C and Anderson, H and Coull, L and Javidi, M and Cloete, H and McTrusty, A and Penny, J and MacGillivray, T and Tatham, AJ and Jackson, T and Porteous, C and Strang, N and Dhillon, B and Bernabeu, MO}, title = {Beyond the dataset: integrating public voices in data science.}, journal = {Research involvement and engagement}, volume = {12}, number = {1}, pages = {2}, pmid = {41508137}, issn = {2056-7529}, support = {TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; }, abstract = {The digitalisation of health data has helped drive initiatives like the Scottish Collaborative Optometry-Ophthalmology Network eResearch (SCONe), which links retinal images from community optometry practices with other routinely collected health data to enhance disease detection. As data-driven approaches expand throughout the healthcare system, patient and public involvement and engagement (PPIE) is increasingly recognised as essential for improving the quality, relevance, and acceptability of health research. However, despite growing endorsement, challenges remain, including inconsistent terminology, varying levels of involvement, limited implementation guidance, and a lack of evidence on its impact. These challenges are even more pronounced in data science, particularly within large-scale research, where PPIE is often underreported, leaving the field without a clear framework for meaningful implementation. This article offers a reflective account of the challenges and barriers encountered by SCONe in developing a PPIE strategy. By documenting this process, it provides insights into the complexities of implementing PPIE in large research consortia and offers practical guidance for future initiatives seeking to enhance the impact and relevance of public partnerships in large scale data science research.}, }
@article {pmid41509408, year = {2025}, author = {Chacin Ruiz, EA and Swindle-Reilly, KE and Ford Versypt, AN}, title = {Modeling and Design of Multi-layered Cylindrical Microcapsules for Intravitreal Controlled Release.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.29.696951}, pmid = {41509408}, issn = {2692-8205}, abstract = {Chronic diseases often require repeated oral or local administration, which can compromise patient compliance. In wet age-related macular degeneration (AMD), current therapies rely on intravitreal injections of anti-vascular endothelial growth factor agents every four to six weeks to maintain therapeutic drug levels. Controlled-release drug delivery systems offer a promising alternative by reducing injection frequency and extending drug release. In this study, we developed a continuum diffusion model to describe drug transport through porous polymeric microcapsules, implemented using the finite element method in COMSOL Multiphysics. The case study focused on cylindrical microcapsules fabricated with either a single polycaprolactone (PCL) layer or a bi-layered chitosan-PCL structure, tested at two capsule sizes and three salt leaching concentrations. Bovine serum albumin and bevacizumab were used as model drugs. Parameter estimation was performed using published release data, with a progressive fitting strategy that carried forward parameters from simpler systems into more complex designs. The model reproduced experimental release profiles across formulations and identified key transport parameters governing release dynamics, including porosity, tortuosity, and mass transfer rates. Design exploration revealed that polymer thickness was the dominant factor controlling release, while addition of the chitosan layer moderated the initial burst and extended therapeutic delivery. This framework demonstrates how computational modeling can reduce experimental burden, guide design optimization, and support the development of long-acting intravitreal drug delivery systems to treat wet AMD by linking drug release kinetics to design variables.}, }
@article {pmid41509480, year = {2025}, author = {Alizadeh, AM and Lin, B and Seiler, M and Lyon, DC}, title = {Restoration of Higher-Order Cortical Processing in Rat V2 by Retinal Sheet Transplants in Degenerated Rats.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41509480}, issn = {2692-8205}, support = {P30 EY034070/EY/NEI NIH HHS/United States ; R01 EY032948/EY/NEI NIH HHS/United States ; R01 EY031834/EY/NEI NIH HHS/United States ; P50 GM076516/GM/NIGMS NIH HHS/United States ; P30 CA062203/CA/NCI NIH HHS/United States ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of central vision loss, and effective treatment options are limited once photoreceptors and the retinal pigment epithelium (RPE) are lost. In advanced stages, vision restoration requires strategies that replace or bypass degenerated retinal circuitry. Retinal sheet transplantation using fetal neural retinal tissue has emerged as a promising intervention, demonstrating long-term survival, integration with the host retina, and partial restoration of light-driven responses. We previously showed that such transplants can restore fundamental visual response properties in the primary visual cortex (V1) of rapidly degenerating rats. However, it remains unclear whether restored retinal input can support higher-order cortical computations that depend on the integration of classical and extra-classical receptive field mechanisms. In this study, we extend this investigation by evaluating whether fetal retinal sheet transplants can restore extra-classical surround modulation in neurons of higher visual areas (V2). Fetal retinal sheets (E18-E19) derived from donor rats were transplanted into one eye of Rho-S334ter line-3 rats at ages P41-P78, when rod degeneration is nearly complete and cones are largely nonfunctional. Animals were assessed 2.2-9.3 months post-surgery using in vivo extracellular single-unit recordings from V2, optokinetic testing, OCT imaging, and histology. Control groups included normal-vision rats, age-matched degenerated rats (AMC), and sham-operated line-3 rats. Transplants survived long term, developed laminated and rosetted photoreceptor structures, and integrated with the host retina. Optokinetic testing revealed significant improvement in spatial acuity in transplanted eyes compared with degenerated controls beginning at three months post-surgery. Transplanted rats exhibited a markedly higher proportion of visually responsive V2 neurons than degenerated animals (21.0% vs. 8.2%). They also showed significantly shorter response latencies and larger visually evoked response amplitudes, indicating improved transmission of retinal signals to the cortex. To quantify surround suppression, neurons were tested with sinusoidal gratings confined to the classical receptive field and gratings extended to full-field size. Transplanted rats displayed robust surround suppression properties similar to normal controls, including significantly reduced firing rates and narrower tuning under full-field conditions. A Support Vector Machine (SVM) classifier trained on net responses to CRF and FF stimulus sizes reliably distinguished control and transplanted neurons from degenerated ones but could not separate control from transplant, further indicating similar response properties in these two groups. These findings provide the first demonstration that retinal sheet transplants restore not only basic visual responses but also higher-order cortical mechanisms involving extra-classical surround suppression. This recovery of surround suppression in V2 suggests that transplanted retinal tissue can re-establish functionally meaningful circuits capable of supporting complex visual processing. The results underscore the therapeutic potential of retinal sheet transplantation for advanced retinal degenerative disease and provide the first evidence of surround suppression in the rat V2.}, }
@article {pmid41510605, year = {2026}, author = {Ma, C and Su, J and Liu, J and Zhao, T and Li, X and Cai, S and Ji, X and Wu, J and Wang, L and Xu, D}, title = {Discovery of (3R,4R)-15: An Advanced Factor B Inhibitor Entering Phase 3 for Complement-Mediated Diseases.}, journal = {Journal of medicinal chemistry}, volume = {69}, number = {2}, pages = {867-894}, doi = {10.1021/acs.jmedchem.5c03532}, pmid = {41510605}, issn = {1520-4804}, mesh = {Humans ; Animals ; Mice ; *Complement Factor B/antagonists &amp; inhibitors ; Structure-Activity Relationship ; Atypical Hemolytic Uremic Syndrome/drug therapy ; *Drug Discovery ; Hemoglobinuria, Paroxysmal/drug therapy ; *Complement Inactivating Agents/pharmacology/pharmacokinetics/chemistry/therapeutic use ; Complement Pathway, Alternative/drug effects ; }, abstract = {The alternative pathway (AP) of the complement system plays a critical role in the pathogenesis of various human diseases, including age-related macular degeneration (AMD), paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and several glomerular diseases. Although the approved drug Iptacopan is available, it requires twice-daily oral dosing, resulting in suboptimal patient compliance. Using a scaffold-hopping strategy, we identified the clinical candidate (3R,4R)-15, which exhibits potent inhibitory activity against factor B (FB) and the AP, with IC50 values of 10.2 nM and 59.3 nM, respectively. Furthermore, this compound exhibits significantly improved pharmacokinetic properties, including an oral bioavailability of 69.2% in mice. Preliminary clinical studies indicate that (3R,4R)-15 has promising efficacy in patients with PNH. Its once-daily dosing regimen also offers the potential to markedly improve patient compliance. (3R,4R)-15 is currently in Phase 3 trials evaluating its efficacy for the treatment of PNH.}, }
@article {pmid41510735, year = {2026}, author = {Fnu, G and Bhatt, P and Gupta, SV and Sharma, P and Sutariya, V}, title = {Formulation Development and In vitro Characterization of Nanoparticles of Pazopanib for Wet Macular Degeneration.}, journal = {Current drug delivery}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115672018385478251124140833}, pmid = {41510735}, issn = {1875-5704}, abstract = {INTRODUCTION: One of the primary causes of severe vision loss globally is age-related macular degeneration (AMD), and the mainstay of therapies for neovascular diseases is intravenous administration of anti-VEGF (vascular endothelial growth factor) drugs. The goal of this research is to create an effective delivery of anti-VEGF drugs to overcome the challenges associated with current therapy and adverse effects arising from repetitive intravitreal injections.<br><br>METHODS: Pazopanib (PZ) nanoparticles (NPs) have been generated to deliver the anti-VEGF drug to the posterior segment of the eye over an extended period via intravitreal injection. They were subsequently investigated for physicochemical and in vitro studies.<br><br>RESULTS: The PZ NPs were found to be nano-sized with a particle size of 132.1 &#xb1; 1.4 nm and a PDI of 0.125 &#xb1; 0.023. The results showed that the zeta potential was -20.12 &#xb1; 2.7 mV and the entrapment efficiency was 33.9 &#xb1; 2.5%. Up to seven days of controlled drug release was observed in an in vitro drug release study. The PZ NPs were further assessed for cell cytotoxicity, cellular uptake, and anti- VEGF assays in in vitro cell culture investigations employing human retinal pigment epithelium cells (ARPE-19). In vitro cell culture tests revealed that, in comparison to the drug solution, the PZ NPs formulation was well taken up by the cells and less cytotoxic, as well as exhibited greater antiangiogenic efficacy by inhibiting VEGF expression for an extended period of time.<br><br>DISCUSSION: The NPs demonstrated sustained drug release, driven by their controlled degradation kinetics. Increased potential intensity enhanced electrostatic repulsion, thereby improving NP stability. The low entrapment efficiency of PZ in the NPs was likely due to drug diffusion during emulsification and poor compatibility with the hydrophilic polymer matrix. For in vitro studies, ARPE-19 cells were selected due to their retinal pigment epithelial (RPE)-like properties, making them suitable for AMD drug testing. Efficacy (ELISA) assessments revealed that NP formulations had a stronger inhibitory effect than free drug solutions.<br><br>CONCLUSION: The proposed PZ NPs were successfully developed, characterized, and demonstrated potential application in the treatment of AMD.}, }
@article {pmid41510773, year = {2026}, author = {Bazan, NG}, title = {Elovanoids: linking nutrition to neuroprotection.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {29}, number = {2}, pages = {111-122}, doi = {10.1097/MCO.0000000000001198}, pmid = {41510773}, issn = {1473-6519}, mesh = {Humans ; *Neuroprotection ; *Docosahexaenoic Acids/metabolism/pharmacology ; *Neuroprotective Agents/pharmacology ; Animals ; Antioxidants/metabolism ; Macular Degeneration/prevention &amp; control ; Diet ; Aging ; }, abstract = {PURPOSE OF REVIEW: Elovanoids are homeostatic lipid mediators derived from the very long-chain n-3 polyunsaturated fatty acids, which are in turn derived from docosahexaenoic acid (DHA). The aim of this review is to summarize the latest research on these lipid mediators.<br><br>RECENT FINDINGS: Elovanoids beneficially modulate thioredoxin reductase 1, a key component in the activation of the cellular glutathione antioxidant system. Elovanoids prevent oligomeric amyloid-beta-induced senescence and inflammaging in retinal pigment epithelium and other cells. Rod cells' ability to use DHA to produce elovanoid precursors is decreased in age-related macular degeneration, a disease that causes photoreceptor loss and blindness.<br><br>SUMMARY: Elovanoids are molecular guardians of nervous system integrity that introduce a new aspect of neuroprotective signaling by serving as an initial line of defense when neural cell homeostasis is jeopardized. Appropriate diet contributes to healthy aging by providing the precursor (DHA) that favors elovanoid-mediated neuroprotection in conditions including stroke, traumatic brain injury, macular degeneration, Alzheimer's, and Parkinson's.}, }
@article {pmid41511370, year = {2026}, author = {Park, S and Song, YS and Feng, X and Sorenson, CM and Sheibani, N}, title = {Caffeine Mitigates Adenosine-Mediated Angiogenic Properties of Choroidal Endothelial Cells Through Antagonism of A1 Adenosine Receptor and PI3K-AKT Axis.}, journal = {Cells}, volume = {15}, number = {1}, pages = {}, pmid = {41511370}, issn = {2073-4409}, support = {P30 EY016665/EY/NEI NIH HHS/United States ; EY034646/EY/NEI NIH HHS/United States ; Research Award//Arthur and Nancy Nesbit AMD fund/ ; P30 CA014520/CA/NCI NIH HHS/United States ; AMD Research Award//Carl Marshall Reeves &amp; Mildred Almen Reeves Foundation/ ; EY030076/EY/NEI NIH HHS/United States ; AMD Research Award//Pat and Jay Smith AMD Innovation Fund/ ; R21 EY034646/EY/NEI NIH HHS/United States ; Endoument Fund//Retina Research Foundation/ ; Unrestricted award to the Department of Ophthalmology and Visual Science//Research to Prevent Blindness/ ; AMD Research Award//The Edward N. &amp; Della L. Thome Memorial Foundation/ ; R01 EY030076/EY/NEI NIH HHS/United States ; }, mesh = {*Endothelial Cells/drug effects/metabolism/pathology ; *Caffeine/pharmacology ; Animals ; *Choroid/pathology/blood supply ; Humans ; *Phosphatidylinositol 3-Kinases/metabolism ; *Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/drug effects ; *Choroidal Neovascularization/drug therapy/pathology/metabolism ; *Adenosine/metabolism/pharmacology ; *Receptor, Adenosine A1/metabolism ; Mice ; }, abstract = {Aging reduces the tissue regenerative capacity, promotes chronic inflammation, and contributes to neurodegenerative diseases, including age-related macular degeneration (AMD). AMD is a leading cause of vision loss in older adults and manifests as dry (atrophic) or wet (neovascular) disease. Although dry AMD is more prevalent, neovascular AMD (nAMD) causes the most severe vision impairment and remains a major public health burden. Oxidative stress-mediated inflammation and dysfunction of retinal pigment epithelium (RPE) cells and choriocapillaris drive early AMD. Neovascular AMD is marked by pathologic choroidal neovascularization (CNV), driven largely by dysregulated VEGF signaling. Anti-VEGF therapies are the current standard of care for nAMD but require frequent intravitreal injections, carry procedure-related risks, and are ineffective in a substantial subset of patients, underscoring the need for new therapeutic approaches. Caffeine, a widely consumed and well-tolerated adenosine receptor antagonist, has emerging relevance in vascular regulation and inflammatory signaling. Extracellular ATP and its metabolites, including adenosine, accumulate under stress and act through purinergic receptors to influence angioinflammatory processes. We recently showed that systemic caffeine administration suppressed CNV in vivo, an effect partly reproduced by the adenosine receptor A2A antagonist Istradefylline. Here, we investigated the cell-autonomous effects of caffeine on mouse choroidal endothelial cells, focusing on its role as an adenosine receptor antagonist and its potential to inhibit pathological neovascularization.}, }
@article {pmid41512710, year = {2026}, author = {Shanidze, NM and Agathos, CP and Ellmers, TJ and Young, WR}, title = {Links between central visual field loss and movement processing during walking.}, journal = {Gait &amp; posture}, volume = {125}, number = {}, pages = {110095}, pmid = {41512710}, issn = {1879-2219}, support = {90REGE0018/ACL/ACL HHS/United States ; K99 EY026994/EY/NEI NIH HHS/United States ; R00 EY026994/EY/NEI NIH HHS/United States ; T32 EY025201/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; *Walking/physiology ; *Postural Balance/physiology ; Middle Aged ; Case-Control Studies ; *Visual Fields/physiology ; Aged ; Attention/physiology ; Gait/physiology ; *Vision Disorders/physiopathology ; Contrast Sensitivity/physiology ; Adult ; }, abstract = {BACKGROUND: Central visual field loss (CFL) is the most common irreversible visual impairment in aging and is associated with higher fall risk and concerns about falling. This study explored the links between CFL severity, functional balance, and walking-related attentional processing implicated in reduced gait performance.<br><br>METHODS: In Study 1, 29 individuals with CFL and 29 age-matched controls completed the Timed Up and Go (TUG) test. In Study 2, 10 CFL participants and 10 controls performed the TUG while acceleration data were collected from head and trunk IMUs. For both studies, we assessed visual impairment severity (contrast sensitivity) and participants' attentional processing during walking (Gait-Specific Attentional Profile, G-SAP).<br><br>RESULTS: Both groups showed positive correlations between TUG duration and G-SAP subscales. G-SAP scores were lower in CFL participants with worse contrast sensitivity indicating reduced cognitive processing during walking. Worse contrast sensitivity was also associated with greater head and trunk acceleration and acceleration variability during walking, suggesting reduced gait stability. Higher rumination and conscious movement processing scores also correlated with improved segmental control in CFL.<br><br>SIGNIFICANCE: Increased cognitive processing of gait is associated with impaired functional balance. This association appears to be reversed in CFL, with severe visual deficit diverting cognitive resources from movement control. This altered strategy may prioritise the acquisition and processing of visuospatial information in CFL. The observed postural instability with increasing CFL severity and a lack of excessive cognitive involvement in movement control suggest heightened gait-specific attention could be leveraged for balance and gait training in CFL.}, }
@article {pmid41512983, year = {2026}, author = {Lishinsky-Fischer, N and Gharra, S and Nitzan, I and Chowers, I and Levy, J}, title = {Reduced Risk of Non-Neovascular AMD in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Propensity-Matched Cohort Study.}, journal = {American journal of ophthalmology}, volume = {284}, number = {}, pages = {153-160}, doi = {10.1016/j.ajo.2025.12.035}, pmid = {41512983}, issn = {1879-1891}, mesh = {Humans ; Female ; Male ; *Immune Checkpoint Inhibitors/therapeutic use ; Retrospective Studies ; Aged ; Middle Aged ; Incidence ; *Propensity Score ; Follow-Up Studies ; Risk Factors ; Aged, 80 and over ; *Neoplasms/drug therapy ; Melanoma/drug therapy ; *Macular Degeneration/epidemiology/prevention &amp; control/diagnosis ; }, abstract = {PURPOSE: To evaluate whether immune checkpoint inhibitors (ICIs), which modulate T-cell activity in cancer therapy, influence the risk of developing age-related macular degeneration (AMD).<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Adults aged &#x2265;60 years with a history of cancer, identified from the TriNetX Global Collaborative Network. Only patients who remained alive throughout the follow-up period were included.<br><br>METHODS: Two cohorts were constructed: patients who received ICIs and those who did not. Sub-analyses were conducted for patients with melanoma and for those with metastatic disease. Propensity score matching (1:1) was performed using demographic and clinical covariates. Kaplan-Meier estimates and Cox proportional hazards models assessed the association between ICI exposure and AMD incidence over 5 years.<br><br>MAIN OUTCOME MEASURES: Incidence of non-neovascular and neovascular AMD after ICI therapy.<br><br>RESULTS: After matching, 36,037 patients were included in each cohort. ICI-treated patients had a significantly lower risk of developing non-neovascular AMD (hazard ratio [HR], 0.77; 95% CI, [0.63, 0.93]; log-rank P = .0084) over a 5-year follow-up. No significant association was observed between ICI exposure and neovascular AMD. The protective association persisted in melanoma and metastatic subgroups.<br><br>CONCLUSIONS: In this large, multicenter cohort, ICI therapy was associated with a reduced risk of non-neovascular AMD in older adults with cancer. These findings suggest a potential protective role of T-cell modulation in AMD pathogenesis and highlight the need for further research into the retinal effects of ICIs.}, }
@article {pmid41513432, year = {2026}, author = {Zhou, J and He, Y and Wang, J and Wu, H and Huang, X and Cao, J and Tham, YC and Zhang, C and Cheng, CY and Ye, J}, title = {Exposure-wide approaches identifying modifiable factors for age-related macular degeneration.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328446}, pmid = {41513432}, issn = {1468-2079}, abstract = {PURPOSE: The present study aimed to systematically investigate modifiable factors for age-related macular degeneration (AMD) using novel exposure-wide strategies in a large cohort, and then assess the preventability of AMD.<br><br>METHODS: Using data from the UK Biobank (UKB), a total of 331 modifiable factors from seven categories were included. Exposures were first screened using Cox proportional hazards models with each examined individually, and associated exposures were then tested in a mutually adjusted model for final validation. We calculated joint effect scores by combining validated exposures based on the category and tested the joint associations with AMD. We eventually estimated population attributable fraction to assess the overall preventability of AMD.<br><br>RESULTS: A total of 478&#x2009;867 UKB participants were included. After a median of 13.63 years of follow-up, 10&#x2009;903 (2.28%) were diagnosed with incident AMD. Among all 331 modifiable factors, 177 passed the exposure-wide association scan, with 34 exposures remaining statistically significant after mutual adjustment, distributed in 5 categories. Joint effects of these categories were significantly associated with AMD even among populations with higher AMD Polygenic Risk Score. Overall, we estimated that 30.4%-45.1% of AMD cases could be prevented by intervening in these factors.<br><br>CONCLUSIONS: Modifiable factors across multiple categories are associated with AMD, and active interventions targeting these factors can reduce AMD incidence by 30.4%-45.1%. This study also underscores the need for a systematic approach in uncovering modifiable factors and providing population-level knowledge basis for disease prevention.}, }
@article {pmid41513729, year = {2026}, author = {Song, JR and Park, UC and Lee, CS and Cho, JJ and Kim, JY and Baek, SC and Jeong, A and Sharma, A and Kim, JH and Sagong, M and Woo, SJ and , }, title = {Real-world outcomes of ranibizumab biosimilars in various retinal diseases: a Korean multi-center experience-ROSE Korea Study.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {4220}, pmid = {41513729}, issn = {2045-2322}, support = {RS-2024-00512384//Ministry of Health and Welfare/ ; }, mesh = {Humans ; *Ranibizumab/therapeutic use/administration &amp; dosage/adverse effects ; Male ; Female ; Republic of Korea ; *Biosimilar Pharmaceuticals/therapeutic use/administration &amp; dosage/adverse effects ; Aged ; Retrospective Studies ; Middle Aged ; Intravitreal Injections ; Treatment Outcome ; *Retinal Diseases/drug therapy ; Visual Acuity/drug effects ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged, 80 and over ; Macular Degeneration/drug therapy ; Macular Edema/drug therapy ; }, abstract = {This study aims to investigate efficacy and safety of ranibizumab biosimilars (Amelivu[®] and LucenBS[®]) across retinal diseases in Korean clinical practice. This retrospective, multicenter study enrolled 1153 eyes from 1075 patients across five centers in South Korea between May 2022 and October 2024. Patients received intravitreal ranibizumab biosimilars for neovascular age-related macular degeneration, retinal vein occlusion with macular edema, diabetic macular edema, and other retinal diseases. Treatment-naïve eyes comprised 408 cases (35.4%), while 745 eyes (64.6%) had prior anti-VEGF treatment. Amelivu was administered to 1007 eyes with 3.1 ± 1.9 injections over 10.2 ± 6.1 months; LucenBS to 146 eyes with 3.1 ± 2.0 injections over 12.0 ± 4.9 months. Amelivu demonstrated significant BCVA(logMAR) improvements from baseline (0.63 ± 0.62) to 12 months (0.55 ± 0.61, P < 0.01). LucenBS maintained logMAR VA from 0.64 ± 0.63 to 0.63 ± 0.68 at 12 months (P = 0.40). Both biosimilars achieved significant CMT reductions through 12 months: Amelivu from 398.0 ± 169.4 μm to 323.0 ± 128.8 μm (P < 0.01); LucenBS from 368.7 ± 172.0 μm to 306.0 ± 144.1 μm (P < 0.01). Treatment-naïve eyes showed superior CMT reduction (111.8 μm) compared to previously treated eyes (53.5 μm). Only one injection-related adverse event occurred: asymptomatic anterior chamber cells in the Amelivu group, resolving with topical treatment. Ranibizumab biosimilars demonstrated visual stabilization and significant anatomical improvements across retinal diseases with excellent safety profiles.}, }
@article {pmid41513975, year = {2026}, author = {Cozzi, M and Airaldi, M and Barbieri, L and Sadda, SR and Staurenghi, G and Corvi, F}, title = {The impact of macular neovascularization development on geographic atrophy progression.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {4}, pages = {983-990}, pmid = {41513975}, issn = {1435-702X}, }
@article {pmid41514281, year = {2026}, author = {Almansa-García, AC and Armento, A and Cao, B and Petremann-Dumé, AS and Salmaso, S and Caliceti, P and Henes, C and Bolz, S and Kilger, E and Süsskind, D and Ueffing, M and Arango-Gonzalez, B}, title = {Safety and neuroprotective efficacy of the VCP inhibitor ML240 in large-animal and human retinal explants: a preclinical ex vivo study.}, journal = {BMC medicine}, volume = {24}, number = {1}, pages = {54}, pmid = {41514281}, issn = {1741-7015}, support = {AR1432/2-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; Humans ; *Retina/drug effects/pathology ; Swine ; *Valosin Containing Protein/antagonists &amp; inhibitors ; *Neuroprotective Agents/pharmacology/adverse effects ; Macaca ; }, abstract = {BACKGROUND: Retinal degenerative diseases represent a complex global health problem due to their significant impact on patients' daily lives and their highly heterogeneous pathogenesis, which challenges therapeutic development. Despite this complexity, many diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), share common features, including disrupted proteostasis, oxidative stress, and inflammatory responses, eventually leading to photoreceptor (PR) degeneration and vision loss. The inhibition of valosin-containing protein (VCP) has emerged as a promising mutation-independent therapeutic strategy for RP. However, clinical translation requires rigorous validation in models that closely reflect human retinal physiology.<br><br>METHODS: Organotypic retinal explants from porcine, macaque, and human donors were placed in an in vitro culture setup and treated with ML240, a selective VCP inhibitor, delivered either as a free compound or encapsulated in mPEG5kDa-cholane. Photoreceptor survival was assessed via TUNEL assay, outer nuclear layer (ONL) row quantification, and immunostaining. Retinal inflammation was evaluated by microglial staining. A dose-response study was performed to determine safety margins across species, and additional retinal markers were used to assess the preservation of non-photoreceptor retinal cell populations.<br><br>RESULTS: Porcine retinal explants exhibited progressive photoreceptor degeneration under ex vivo conditions. Treatment with ML240, particularly when formulated with mPEG5kDa-cholane, significantly reduced photoreceptor cell death and microglial activation. Macaque and human explants exhibited minimal to no signs of degeneration. Treatment did not affect morphological or histological features of the explant, demonstrating the safety of ML240 in the primate retina.<br><br>CONCLUSIONS: VCP inhibition via ML240 demonstrates an uncompromised safety profile in porcine, macaque, and human retinal explants. In addition, the neuroprotective activity of ML240 was evident in porcine tissue. Formulation with mPEG5kDa-cholane enhances the overall performance of the compound, supporting its use for future clinical application as a mutation-independent therapeutic approach for retinal degenerative diseases.}, }
@article {pmid41515537, year = {2025}, author = {Desmettre, T and Ledesma-Gil, G and Paques, M}, title = {Diagnostic Performance of Ring Aperture Retro Mode Imaging for Detecting Pigment Migration in Age-Related Macular Degeneration.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {1}, pages = {}, pmid = {41515537}, issn = {2075-4418}, abstract = {Background/Objectives: Pigment migration is a key biomarker of progression in age-related macular degeneration (AMD). This study assessed the diagnostic performance of ring aperture Retro mode (RAR) imaging for detecting pigment migration and compared its performance with established multimodal imaging techniques. Methods: This retrospective study included 80 eyes from 61 consecutive patients with AMD who underwent multimodal imaging with color fundus images (CFIs), fundus autofluorescence (FAF), RAR imaging (Mirante, NIDEK), and en face optical coherence tomography (OCT) with B-scans (Cirrus HD-OCT 5000, Zeiss). Two independent retina specialists graded the AMD stage and the presence of pigment migration across modalities. Sensitivity and positive predictive value (PPV) of RAR were calculated using en face OCT as the reference standard. Results: RAR demonstrated high diagnostic performance, with a sensitivity of 94.7% and a PPV of 93.4% relative to en face OCT. RAR frequently identified pigment migration that was not visible on CFI or FAF, particularly in early AMD and in eyes with media opacity. Distinct morphologic patterns-including hyperreflective foci, thickened retinal pigment epithelium, refractile drusen, and cuticular drusen-were consistently identifiable on RAR. In four eyes with geographic atrophy, RAR detected perifoveal pigment redistribution at least six months before foveal involvement was confirmed by OCT and FAF. Conclusions: RAR imaging is a rapid, sensitive, and clinically practical technique for detecting pigment migration in AMD. By complementing en face OCT and enhancing visualization in cases where standard imaging is limited, RAR may strengthen early disease surveillance, support prognostic assessment, and improve multimodal diagnostic workflows in routine practice.}, }
@article {pmid41516080, year = {2025}, author = {Bhandari, SK and Lee, S and Kim, HJ}, title = {Integrative Landscape of Dry AMD Pathogenesis, Models, and Emerging Therapeutic Strategies.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41516080}, issn = {1422-0067}, support = {20230632//the Bisa Research Grant of Keimyung University/ ; }, mesh = {Humans ; Animals ; *Geographic Atrophy/pathology/metabolism/drug therapy/etiology/therapy ; Disease Models, Animal ; *Macular Degeneration/pathology/metabolism/etiology/drug therapy ; Oxidative Stress ; Mitochondria/metabolism ; }, abstract = {Dry age-related macular degeneration (AMD) is the leading cause of central vision loss among the elderly, yet no curative treatment exists. While exudative AMD can be managed with anti-vascular endothelial growth factor (VEGF) therapy, dry AMD-accounting for more than 85% of cases-progresses insidiously from drusen accumulation to geographic atrophy (GA). Although the recent U.S. Food and Drug Administration (FDA) approvals of pegcetacoplan and avacincaptad pegol represent major milestones, their therapeutic effects remain modest. This review provides an integrated overview of the molecular and cellular mechanisms underlying dry AMD, highlighting key pathogenic pathways involving oxidative stress, lipid dysregulation, complement activation, mitochondrial impairment, and RPE-specific bisretinoid lipofuscin accumulation. We further summarize mechanistic mouse models that replicate these pathological processes and discuss how each model contributes to understanding the disease. Finally, we review current and emerging therapeutic strategies-including complement inhibitors, visual cycle modulators, and mitochondrial-protective approaches-and outline future directions for translational research. Collectively, this review synthesizes mechanistic insights, disease models, and therapeutic innovation to support the development of targeted and stage-specific interventions for dry AMD.}, }
@article {pmid41517415, year = {2025}, author = {Rodriguez-Vidal, C and Galletero Pandelo, L and Martínez-Alday, N and Bande, M and Blanco Teijeiro, MJ}, title = {Ultrasound-Enhanced Assessment of Vitreous Status in Exudative AMD: Associations with Neovascular Phenotypes, Treatment Burden, and Functional Outcomes.}, journal = {Journal of clinical medicine}, volume = {15}, number = {1}, pages = {}, pmid = {41517415}, issn = {2077-0383}, abstract = {Background/Objectives: The influence of the vitreoretinal interface on neovascular age-related macular degeneration (nAMD) remains poorly characterized. Most previous studies relied solely on macular optical coherence tomography (OCT), which provides limited information about global posterior vitreous detachment (PVD). This study evaluated (1) whether ultrasonography-defined PVD status differs between nAMD eyes and healthy controls, and (2) whether baseline PVD influences macular neovascularization (MNV) phenotype and functional outcomes following anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: In this prospective longitudinal study, treatment-naïve nAMD eyes and population-based healthy controls underwent dynamic B-scan ultrasonography and spectral-domain OCT. PVD was categorized as absent, partial, or complete. nAMD eyes received intravitreal aflibercept according to a treat-and-extend protocol and were followed for 12 months. Structural parameters-including subretinal fluid (SRF), intraretinal fluid (IRF), and central foveal thickness-along with best-corrected visual acuity (BCVA) were recorded. A multivariable linear regression model was performed to assess whether PVD independently predicted BCVA gain after adjusting for age, baseline BCVA, MNV subtype, SRF, atrophy, and number of injections. Results: Absence of PVD was significantly more frequent in nAMD eyes than in controls (p < 0.001), whereas complete PVD prevalence was comparable. In nAMD, absence of PVD was associated with a higher prevalence of MNV type 2 (p = 0.032), while partial/complete PVD correlated with type 1 lesions. After 12 months, eyes without PVD achieved the greatest visual improvement (mean BCVA gain +0.34 ± 0.26), outperforming eyes with complete PVD (p = 0.026). A multivariable model confirmed that absence of PVD was an independent predictor of greater BCVA gain (β = -0.27; 95% CI -0.42 to -0.12; p = 0.0008). Eyes with complete PVD required more injections (p = 0.046). SRF and foveal-thickness reductions occurred across groups, whereas IRF changes were similar. Conclusions: Ultrasonography-defined PVD status differs markedly between nAMD and healthy eyes and independently influences neovascular phenotype and functional response to anti-VEGF therapy. These findings underscore the physiological importance of the vitreoretinal interface and support the use of ocular ultrasonography as an adjunct tool for assessing global vitreous status in selected nAMD settings.}, }
@article {pmid41517652, year = {2022}, author = {Ledesma-Gil, G and Otero-Marquez, O and Alauddin, S and Tong, Y and Tai, K and Lloyd, H and Koci, M and Scolaro, M and Pillai, C and Ye, C and Govindaiah, A and Bhuiyan, A and Dhamoon, MS and Deobhakta, A and Lema, G and Narula, J and Rosen, RB and Yannuzzi, LA and Freund, KB and Smith, RT}, title = {Subretinal drusenoid deposits are strongly associated with coexistent high-risk vascular diseases.}, journal = {BMJ open ophthalmology}, volume = {7}, number = {1}, pages = {}, pmid = {41517652}, issn = {2397-3269}, abstract = {BACKGROUND/AIMS: Demonstrate that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to coexistent high-risk vascular diseases (HRVDs).<br><br>METHODS: Cross-sectional study. Two hundred AMD subjects (aged 51-100 years; 121 women, 79 men) were recruited. Spectral domain optical coherence tomography, autofluorescence and near-infrared reflectance imaging, and lipid profiles were obtained. Subjects were assigned by health history questionnaires into those with or without HRVDs, defined as: cardiac valve defect (eg, aortic stenosis), myocardial defect (eg, myocardial infarction) and stroke/transient ischaemic attack. Masked readers assigned subjects into two groups: SDD (with or without drusen) and drusen (only). Univariate testing was performed by &#x3c7;[2] test. We built multivariate regression models to test relationships of coexistent HRVD to SDD status, lipid levels and other covariates.<br><br>RESULTS: The prevalence of HRVD was 41.2% (40/97) and 6.8% (7/103) in the SDD and non-SDD groups, respectively (correlation of SDD with HRVD, p=9&#xd7;10[-9], OR 9.62, 95% CI 4.04 to 22.91). Multivariate regressions: only SDDs and high-density lipoprotein (HDL) in the first two HDL quartiles remained significant for HRVD (p=9.8&#xd7;10[-5], 0.021, respectively). Multivariate regression model: SDDs and an HDL in Q1 or Q2 identified the presence of HRVD with the accuracy of 78.5%, 95% CI 72.2% to 84.0%.<br><br>CONCLUSIONS: High-risk cardiovascular and neurovascular diseases were accurately identified in an AMD cohort from SDDs and HDL levels. The SDDs may be related to inadequate ocular perfusion resulting from the systemic vasculopathies. Further research with this paradigm is warranted and might reduce mortality and morbidity from vascular disease.}, }
@article {pmid41518379, year = {2026}, author = {Mhmud, H and Vermeulen, JP and Adanc, B and Klevering, JBJ and Groenink-Lindenhovius, C and Tigchelaar, OAM and Ponsioen, TL and Klaver, CCW and Witmer, AN}, title = {Real-world treatment outcomes of aflibercept versus bevacizumab for neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41518379}, issn = {1435-702X}, }
@article {pmid41518383, year = {2026}, author = {Tanaka, F and Mino, T and Moriguchi, Y and Nagahama, H and Sakai, H and Tamura, M and Akiba, M and Enaida, H}, title = {Exploratory investigation of OCTA-VISTA for longitudinal monitoring of neovascular age-related macular degeneration treatment.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41518383}, issn = {1435-702X}, support = {22K09792//KAKENHI/ ; }, }
@article {pmid41519100, year = {2026}, author = {Naux, G and Bellot, L and Le Pabic, E and Mouriaux, F and Maucourant, Y}, title = {[Efficacy and safety of switching from Eylea® and Lucentis® to Ranivisio® in exudative age-related macular degeneration and its impact on treatment costs].}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {2}, pages = {104757}, doi = {10.1016/j.jfo.2025.104757}, pmid = {41519100}, issn = {1773-0597}, mesh = {Humans ; *Ranibizumab/economics/adverse effects/administration &amp; dosage/therapeutic use ; Aged ; Male ; Female ; Intravitreal Injections/economics ; Aged, 80 and over ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/economics/administration &amp; dosage/adverse effects/therapeutic use ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/economics ; *Drug Substitution/economics/adverse effects ; Angiogenesis Inhibitors/economics/administration &amp; dosage/adverse effects/therapeutic use ; *Macular Degeneration/drug therapy/economics ; Middle Aged ; Health Care Costs/statistics &amp; numerical data ; Retrospective Studies ; }, abstract = {INTRODUCTION: The goal of this study was to investigate the efficacy and safety of therapeutic switch of intravitreal injections (IVT) from ranibizumab 10mg/mL (Lucentis®) and aflibercept 40mg/mL (Eylea®) to FYB201 (Ranivisio®) in exudative age-related macular degeneration (AMD). This study includes an analysis of the direct medical cost of managing exudative AMD. The data studied included the mean injection interval in the year preceding the switch and the 9 months following, the longest dry interval over this period, the change in central retinal thickness, tolerance data, the sum of visit costs, treatment costs and an estimate of transportation costs.<br><br>MATERIALS AND METHODS: Fifty-nine eyes of 46 patients treated for exudative AMD were included. Twenty-one eyes were treated with Lucentis&#xae; and 38 eyes with Eylea&#xae; before being switched to Ranivisio&#xae; between February 2023 and May 2024. The primary endpoint was the change in mean inter-injection interval in the pre-switch year versus the mean inter-injection interval in the 3 to 9 months post-switch.<br><br>RESULTS: Patients received a mean of 7.5 IVT of anti-VEGF per eye in the pre-switch year, with a mean inter-injection interval of 6.2 weeks in Treat-and-Extend (TaE) schedule. The switch resulted in an extension of the mean inter-injection interval to 7.1 weeks (P=0.0004) and an extension of the longest dry interval (7.5 versus 6.39, P=0.0057) in the following 3 to 9 months. A reduction in central retinal thickness was observed at 3 months (247&#x3bc;m versus 261&#x3bc;m, P=0.0067), and no adverse effects were noted. In the year prior to switch, total medical costs per patient amounted to &#x20ac;9,397, with &#x20ac;6,542.00 (70%) in medication costs, &#x20ac;2,035.50 (21%) in ophthalmologic follow-up costs and &#x20ac;819.60 (9%) in transportation costs. After the switch, with a mean Ranivisio&#xae; inter-injection interval of 7.1 weeks, the annual treatment cost per eye was estimated at &#x20ac;2,388.00 for 7.33 annual IVTs.<br><br>DISCUSSION: This study is consistent with data in the literature demonstrating the benefits of therapeutic switches in extending inter-injection intervals and improving retinal dryness, probably due to this method being a work-around for tachyphylaxis.<br><br>CONCLUSION: Switching from Eylea&#xae; and Lucentis&#xae; to Ranivisio&#xae; is effective in exudative AMD, with a good safety profile, and could help to reduce treatment costs.}, }
@article {pmid41519378, year = {2026}, author = {Jeong, H and Eppel, PS and Kaelber, DC and Singh, RP and Talcott, KE}, title = {Malabsorption Syndromes and Risk of Age-Related Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.01.002}, pmid = {41519378}, issn = {2468-6530}, abstract = {PURPOSE: Despite mechanistic links connecting malnutrition and gut microbiome with retinal health, clinical research exploring the relationship between malabsorption syndromes and age-related macular degeneration (AMD) remains limited. This study compared the risks of AMD diagnosis in patients with and without various malabsorption syndrome diagnoses.<br><br>DESIGN: Retrospective cohort study of aggregated, deidentified patient data from multiple health care organizations across the United States using the TriNetX US Collaborative Research Network in November 2025.<br><br>PARTICIPANTS: Adults with a cataract-related International Classification of Diseases (ICD) encounter diagnosis codes and no baseline AMD ICD encounter diagnosis codes were divided into groups based on the presence of ICD encounter diagnosis codes for celiac disease, ulcerative colitis (UC), Crohn's disease (CrD), chronic pancreatitis (CP), and short bowel syndrome (SBS). Within the CP cohort, patients with pancreatic enzyme replacement therapy (PERT) prescription orders were subanalyzed. For each cohort, a corresponding control cohort of patients without the respective ICD encounter diagnosis codes was created.<br><br>METHODS: The study and control cohorts were propensity-matched 1:1 on demographic factors, comorbidities, and disease-related conditions and prescription orders. The matched cohorts were compared on the risk of having AMD ICD encounter diagnoses.<br><br>MAIN OUTCOME MEASURES: Risk ratios (RRs) and 95% confidence intervals (CIs) of having an AMD ICD encounter diagnosis code with an accompanying retinal OCT Common Procedural Terminology code. Significance was defined as CI &#x2264;0.9 or &#x2265;1.1.<br><br>RESULTS: Compared with controls without inflammatory bowel diseases, the CrD cohort (n = 9537, RR = 1.42, CI = 1.15-1.74), but not the UC cohort (n = 15,039, RR = 1.28, CI = 1.09-1.51), had a higher risk of having early/intermediate AMD. Chronic pancreatitis was associated with an increased risk of AMD (n = 12,856, RR = 1.82, CI = 1.53-2.16), even in the PERT subset (n = 3812, RR = 1.83, CI = 1.35-2.48). Short bowel syndrome (n = 3747) was associated with an increased risk of advanced/exudative AMD (RR = 1.98, CI = 1.31-2.98), but not early/intermediate AMD (RR = 1.28, CI = 0.96-1.71). Celiac disease was not associated with increased AMD risk (n = 9315, RR = 1.09, CI = 0.88-1.35).<br><br>CONCLUSIONS: Chronic noninfectious causes of malabsorption syndromes-CrD, CP, and SBS-may represent underrecognized risk factors of AMD. This explorative study adds clinical evidence for a potential role of the gut-retina axis in the pathogenesis of AMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41519383, year = {2026}, author = {Chang, A and Sun, X and Iida, T and Lai, TYY and Wong, TY and Cheung, CMG and Lee, WK and Zhang, X and Schulze, A and Schmidt-Ott, UM and Zhao, M and Hasanbasic, Z and Leal, S and Chen, SJ and , }, title = {Intravitreal aflibercept 8 mg versus 2 mg in Asian patients with neovascular age-related macular degeneration: 48-week analysis of the Phase 3 PULSAR trial.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {15}, number = {1}, pages = {100278}, doi = {10.1016/j.apjo.2026.100278}, pmid = {41519383}, issn = {2162-0989}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Intravitreal Injections ; Male ; Female ; Aged ; *Visual Acuity ; Middle Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Angiogenesis Inhibitors/administration &amp; dosage ; Treatment Outcome ; Tomography, Optical Coherence ; Dose-Response Relationship, Drug ; Aged, 80 and over ; Follow-Up Studies ; Double-Blind Method ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Asian People ; Time Factors ; Fluorescein Angiography ; }, abstract = {PURPOSE: To evaluate 1-year efficacy and safety of aflibercept 8 mg in Asian patients with neovascular age-related macular degeneration (nAMD) in the PULSAR (NCT04423718) trial.<br><br>DESIGN: Subgroup analysis of the Phase 3 PULSAR trial.<br><br>METHODS: Patients aged &#x2265;&#x202f;50 years with nAMD were randomized to receive intravitreal aflibercept 8&#x202f;mg every 12 (8q12) or 16 (8q16) weeks, or aflibercept 2&#x202f;mg every 8 weeks (2q8), following 3 initial monthly injections. Outcomes included change from baseline in best-corrected visual acuity (BCVA) and central subfield retinal thickness (CRT), durability, and safety at week (W) 48.<br><br>FINDINGS: Overall, 234 Asian patients participated and received study treatment (8q12 [n&#x202f;=&#x202f;74], 8q16 [n&#x202f;=&#x202f;77], and 2q8 [n&#x202f;=&#x202f;83]). At W48, the least squares (LS) mean (95&#x202f;% CI) BCVA change from baseline was +&#x202f;9.9 (6.9, 12.9), +&#x202f;9.2 (7.1, 11.2), and +&#x202f;7.6 (4.7, 10.5) letters in the 8q12, 8q16, and 2q8 groups, respectively. The LS mean (95&#x202f;% CI) change in CRT from baseline to W48 for the 8q12, 8q16, and 2q8 groups was -141 (-152, -129), -156 (-167, -146), and -142 (-155, -129) &#xb5;m, respectively. Most patients receiving 8q12 (85&#x202f;%) or 8q16 (87&#x202f;%), maintained their randomized dosing interval, through W48. The safety profile of aflibercept 8&#x202f;mg was comparable to aflibercept 2&#x202f;mg.<br><br>CONCLUSIONS: Aflibercept 8&#x202f;mg was effective and well tolerated in Asian patients with nAMD, with demonstrated improvements in functional and anatomic outcomes comparable to aflibercept 2&#x202f;mg at W48. Aflibercept 8&#x202f;mg outcomes were achieved with fewer injections than with aflibercept 2&#x202f;mg, consistent with overall PULSAR results.}, }
@article {pmid41519611, year = {2026}, author = {Cornejo-Uixeda, S and Borrás-Blasco, J and Valcuende-Rosique, A and Gil, LP and Monteagudo-Martinez, N and Merino, V}, title = {Dosing interval optimization and persistence with faricimab in age-related macular degeneration: An observational study in real-world clinical practice.}, journal = {Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.farma.2025.12.002}, pmid = {41519611}, issn = {2171-8695}, abstract = {OBJECTIVE: To evaluate treatment persistence and dosing interval extension with faricimab in neovascular age-related macular degeneration (nAMD) in real-world practice.<br><br>METHODS: Retrospective observational study conducted in a tertiary hospital (March 2024-March 2025). Patients receiving faricimab (treatment-na&#xef;ve or pre-treated with anti-VEGF therapy), with &#x2265;1 post-loading dose, were included. Dosing intervals were analyzed at baseline, 6 and 12&#x202f;months, Adherence was assessed with the medication possession ratio (MPR), with >80% considered adherent. Persistence was defined as the time from treatment initiation to discontinuation or end of follow-up. Persistence was estimated using Kaplan-Meier survival analysis.<br><br>RESULTS: We included 129 patients (148 eyes), mean age 74.5&#x202f;&#xb1;&#x202f;8.85&#x202f;years; 55% were female. A total of 39 patients (30.2%) were treatment-na&#xef;ve and 90 (69.8%) were pretreated. At 12&#x202f;months, 48.8% of na&#xef;ve and 55.5% of pretreated patients achieved 8-12&#x202f;weeks intervals. Mean persistence was 12.2&#x202f;months (SD 0.2; 95% CI: 11.8-12.6). The median was not reached by the end of the study. Persistence rate was 93% at 6 and 12&#x202f;months. Only one patient discontinued due to inefficacy. No serious adverse events or endophthalmitis occurred.<br><br>CONCLUSIONS: Faricimab showed excellent persistence and extended dosing intervals in real-world practice. This is the first study specifically evaluating faricimab real-world persistence in nAMD.}, }
@article {pmid41519739, year = {2026}, author = {Thomsen, AK and Steffensen, MA and Gotfredsen, K and Vorum, H and Honoré, B and Nissen, MH and Sørensen, TL}, title = {CD8+ T cell aging is associated with macular neovascularization area change in neovascular age-related macular degeneration: a prospective cohort study.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {66}, pmid = {41519739}, issn = {1471-2415}, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is characterized by formation of macular neovascularization (MNV). The aging immune system plays an important role in nAMD pathogenesis. Loss of the costimulatory markers CD27 and CD28 on T cells and increased T cell differentiation is associated with immunosenescence and proinflammatory T cell activation. In this study we investigate the association between MNV area change following anti-VEGF treatment and the aging T cell profile in nAMD patients.<br><br>METHODS: This prospective cohort study included treatment-na&#xef;ve nAMD patients. Participants were examined with optical coherence tomography angiography at time of diagnosis and following loading dose to assess the MNV area change. A blood sample was analyzed for circulating aging T cell profile with flow cytometry for the costimulatory markers CD27, CD28, and CD56, as well as T cell differentiation (na&#xef;ve, central memory, and effector memory) of CD4+&#x2009;and CD8+&#x2009;T cells.<br><br>RESULTS: 54 eyes of 54 patients were included. A significant association was found between a reduction of MNV area and a reduction of the CD8+CD27- T cell proportion (&#x3b2;, 0.71; 95% CI, 0.17 to 1.26; P&#x2009;=&#x2009;0.035), as well as CD8+CD28- T cell proportion (&#x3b2;, 0.72; 95% CI, 0.20 to 1.23; P&#x2009;=&#x2009;0.035). A non-significant negative trend was observed between MNV area change and CD8&#x2009;+&#x2009;na&#xef;ve T cells (P&#x2009;=&#x2009;0.099).<br><br>CONCLUSION: Our results suggest that a less advanced aging T cell profile characterized by lower levels of CD8+CD27- and CD8+CD28- T cells is associated with a greater reduction of MNV area following anti-VEGF treatment in treatment-na&#xef;ve nAMD patients.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12886-025-04570-2.}, }
@article {pmid41520064, year = {2026}, author = {Hanson, RLW and Airody, A and Sivaprasad, S and McKibbin, M and Morland, AB and Peto, T and Chakravarthy, U and Gale, RP and , }, title = {Early detection of neovascular age-related macular degeneration in the second eye reduces intravitreal treatment burden: FASBAT report 2.}, journal = {Eye (London, England)}, volume = {40}, number = {4}, pages = {493-497}, pmid = {41520064}, issn = {1476-5454}, support = {OAP030A2401T//Novartis | Novartis Pharmaceuticals UK Limited (Novartis UK)/ ; }, mesh = {Humans ; Intravitreal Injections ; Visual Acuity/physiology ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Tomography, Optical Coherence ; Aged ; Male ; Female ; *Wet Macular Degeneration/diagnosis/drug therapy/physiopathology ; Ranibizumab/administration &amp; dosage ; Early Diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Bevacizumab ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; }, abstract = {BACKGROUND/OBJECTIVES: To investigate if early detection of neovascular age-related macular degeneration (nAMD) in the second eye is associated with a reduced number of intravitreal treatments compared with the first eye using data from the EDNA/FASBAT trial.<br><br>SUBJECTS/METHODS: Post-hoc analysis of 117 participants receiving standard clinical care during the FASBAT study. Assessments were at enrolment and at an average of 18.9 (SD&#x2009;=&#x2009;10.2) and 30.5 (SD&#x2009;=&#x2009;9.7) months in the first eye. Assessment of the second eye was made at the onset of nAMD (as participants were monitored for conversion) and at 12- and 24-months. The annualised injection rate for first eyes and the actual rate for second eyes are reported alongside visual acuity (VA) and optical coherence tomography (OCT) characteristics.<br><br>RESULTS: In second eyes the annualised number of treatments was lower both in year 1 (second eyes mean&#x2009;=&#x2009;6.4, SD&#x2009;=&#x2009;3.4 vs mean&#x2009;=&#x2009;7.2, SD&#x2009;=&#x2009;1.9 in first eyes) and in year 2 (second eyes mean&#x2009;=&#x2009;5.8, SD&#x2009;=&#x2009;2.9; versus mean&#x2009;=&#x2009;6.2, SD&#x2009;=&#x2009;2.7 in first eyes). Second eyes had better VA at the point of conversion to nAMD (mean&#x2009;=&#x2009;74.1, SD&#x2009;=&#x2009;9.9) compared with the first eyes at baseline (mean&#x2009;=&#x2009;55.6, SD&#x2009;=&#x2009;15.3) which was maintained until 24 months (second eye: mean&#x2009;=&#x2009;73.6, SD&#x2009;=&#x2009;9.9; first eye: mean&#x2009;=&#x2009;53.2, SD&#x2009;=&#x2009;19.3). Highly reflective material was detected less frequently in second eyes compared to first eyes at clinical visits.<br><br>CONCLUSIONS: Compared to first eyes, early detection of nAMD in the second eye is beneficial in terms of better maintenance of visual acuity, reduced intravitreal treatment burden, and improved anatomical findings after 2 years of treatment.}, }
@article {pmid41520727, year = {2026}, author = {Zhu, S and Zhang, J and Jiang, X and Peng, C and Liu, H and Qian, F}, title = {Biologics-device combinations: Enabling prolonged therapies in the posterior segment ocular disease.}, journal = {Advanced drug delivery reviews}, volume = {230}, number = {}, pages = {115773}, doi = {10.1016/j.addr.2026.115773}, pmid = {41520727}, issn = {1872-8294}, mesh = {Humans ; *Biological Products/administration &amp; dosage/therapeutic use ; *Eye Diseases/drug therapy ; Animals ; Intravitreal Injections ; }, abstract = {Posterior segment ocular diseases (e.g., age-related macular degeneration and diabetic retinopathy, etc.) often necessitate frequent intravitreal (IVT) injections of biologics, due to the rapid drug clearance and formidable ocular barriers. While molecular engineering strategies and high-concentration protein formulations could extend the administration intervals to a certain extent, they are confronted with critical challenges, protein aggregation, high viscosity, and limited duration. This has spurred the development of innovative biologics-device combination products, which represent a paradigm shift towards prolonged therapy. This comprehensive review examines the latest advancements of these combination platforms, including refillable implants (e.g., SUSVIMO®), encapsulated cell technology (e.g., ENCELTO™), and recombinant adeno-associated virus (rAAV) vectors (e.g., LUXTURNA®). The progress in biologics - device combination technologies has significantly reduced the frequency of ocular injections. However, substantial hurdles, such as instability caused by material-biologics interactions, potential risks during the sterilization and manufacturing processes, safety risks, and the evolving regulatory landscape, still need to be addressed. Achieving a balance between the stability of biologics and advanced device design, enhancing long-term safety, and developing responsive smart systems with real-time monitoring and feedback capabilities remain crucial for the advancement of next-generation ophthalmic therapies.}, }
@article {pmid41524001, year = {2026}, author = {Lischke, R and Krause, SM and Rauchegger, T and Haas, G and Koubek, M and Nowosielski, Y and Rehak, M}, title = {Intraocular inflammation after intravitreal injection of faricimab-a case series including one case of bilateral choroidal involvement.}, journal = {International journal of ophthalmology}, volume = {19}, number = {1}, pages = {185-192}, pmid = {41524001}, issn = {2222-3959}, abstract = {AIM: To report and analyze cases of sterile intraocular inflammation (IOI) following intravitreal faricimab injections in patients treated for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).<br><br>METHODS: This double-center case series included nine eyes of six patients who developed uveitis after faricimab therapy. Comprehensive clinical evaluation was performed, including slit-lamp examination, intraocular pressure (IOP) measurement, fluorescein and indocyanine green angiography (ICGA), and laboratory tests. Inflammatory responses were treated with topical or systemic corticosteroids, and patients were monitored for visual acuity and inflammatory activity.<br><br>RESULTS: The incidence of IOI was 0.8% per patient (Innsbruck) and 0.23% (Czechia), with inflammation typically occurring between the third and sixth injection (mean interval: 10d post-injection). Inflammatory presentations ranged from anterior uveitis to posterior segment involvement. One notable case demonstrated novel choroidal hypofluorescent lesions on angiography, suggesting deeper ocular involvement. The mean patient age was 76y; five of six affected patients were female. All cases responded to local and systemic corticosteroids, with full recovery of initial visual acuity.<br><br>CONCLUSION: Sterile IOI after faricimab appears to be a rare but relevant adverse event. Although the incidence falls within expected ranges for anti-vascular endothelial growth factor (anti-VEGF) agents, the observed choroidal involvement represents a potentially new safety signal. Prompt diagnosis and corticosteroid therapy are effective in all cases. Our findings support the need for vigilant post-marketing surveillance and further studies to better understand the underlying mechanisms and risk factors of faricimab-associated inflammation.}, }
@article {pmid41524032, year = {2026}, author = {Chu, J and Haddadin, RI and Gill, M}, title = {Successful Cataract Surgery in a Patient with a Port Delivery System Implant for Diabetic Macular Edema.}, journal = {Case reports in ophthalmology}, volume = {17}, number = {1}, pages = {26-31}, pmid = {41524032}, issn = {1663-2699}, abstract = {INTRODUCTION: The Port Delivery Platform (PDS) with ranibizumab is a novel, surgically implanted device designed for continuous intraocular anti-VEGF delivery, approved for neovascular age-related macular degeneration and other retinal vascular diseases, including diabetic macular edema (DME) and diabetic retinopathy. While it can reduce treatment burden, the PDS implant introduces unique surgical considerations, particularly during subsequent ocular procedures.<br><br>CASE PRESENTATION: We report a case of successful cataract extraction and intraocular lens implantation in a 72-year-old female with a PDS implant for DME, enrolled in the Pagoda trial. Cataract surgery was performed via clear corneal incisions while carefully avoiding manipulation of the conjunctiva or implant. The procedure was uneventful, and the implant remained stable intraoperatively and postoperatively. The patient experienced improved visual acuity and underwent an uncomplicated implant refill after 15 days with confirmation of adequate implant coverage at the 6-month follow-up.<br><br>CONCLUSION: This case highlights key surgical considerations to preserve implant integrity and conjunctival health during cataract surgery in eyes with PDS implants. To our knowledge, this is the first report of cataract surgery in a PDS-implanted eye outside a clinical trial, emphasizing that standard phacoemulsification techniques can be safely adapted with proper precautions in this context.}, }
@article {pmid41524223, year = {2026}, author = {Kong, L and Han, X and Qi, S and Li, D and Zhang, J and Zhang, L and Zhang, S and Jiang, Q and Yan, B and Zhao, C}, title = {MSC-Derived Exosomal lnc-AGT-3: A Novel Anti-Angiogenic Target in Age-Related Macular Degeneration Through p53 Signaling Pathway.}, journal = {Aging cell}, volume = {25}, number = {2}, pages = {e70377}, pmid = {41524223}, issn = {1474-9726}, support = {82530031//National Natural Science Foundation of China/ ; 82020108006//National Natural Science Foundation of China/ ; 82501299//National Natural Science Foundation of China/ ; //Open Research Funds of the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University./ ; }, mesh = {Humans ; *Exosomes/metabolism ; *RNA, Long Noncoding/metabolism/genetics ; *Tumor Suppressor Protein p53/metabolism ; *Mesenchymal Stem Cells/metabolism ; Signal Transduction ; *Macular Degeneration/genetics/metabolism/pathology ; Animals ; Mice ; *Angiogenesis Inhibitors/pharmacology ; Choroidal Neovascularization/genetics/pathology ; Male ; Female ; }, abstract = {Neovascular age-related macular degeneration (nAMD) is a major cause of irreversible vision impairment in elderly populations, characterized by pathological angiogenesis beneath the macula. Although anti-VEGF therapies have demonstrated clinical effectiveness, significant challenges including drug resistance and the need for frequent intravitreal injections persist. As natural nanovesicles, exosomes derived from mesenchymal stem cell (MSC) can mediate intercellular communication, making them an attractive alternative for modulating cellular processes. This study explored the anti-angiogenic effects of MSC-derived exosomes in nAMD, with particular emphasis on the role of a specific exosomal lncRNA lnc-AGT-3. Our results showed that lnc-AGT-3 expression was reduced in both nAMD patients and choroidal neovascularization (CNV) models, and its overexpression effectively inhibited pathological angiogenesis in vitro and in vivo. Mechanistically, lnc-AGT-3 enhanced the p53 signaling pathway by blocking the ubiquitination and degradation of p53 and ultimately inhibited neovascularization, a process potentially linked to its direct interaction with heterogeneous nuclear ribonucleoprotein K (hnRNP K). Our findings position MSC-derived exosomes enriched with lnc-AGT-3 as an innovative therapeutic paradigm for nAMD, acting through p53 pathway modulation to potentially overcome current treatment limitations.}, }
@article {pmid41524233, year = {2026}, author = {Li, Y and Zhang, Y and Wong, G and Kam, KW and Ho, M and Au, S and Zhang, XJ and Ng, MP and Ip, P and Young, AL and Pang, CP and Tham, CC and Chen, LJ and Yam, JC}, title = {Associations between the Mediterranean lifestyle and incident age-related eye diseases: a longitudinal analysis from the UK Biobank.}, journal = {Journal of global health}, volume = {16}, number = {}, pages = {04015}, pmid = {41524233}, issn = {2047-2986}, mesh = {Humans ; Female ; Male ; Aged ; United Kingdom/epidemiology ; Middle Aged ; Longitudinal Studies ; *Macular Degeneration/epidemiology ; *Glaucoma/epidemiology ; *Cataract/epidemiology ; Incidence ; *Diet, Mediterranean/statistics &amp; numerical data ; Prospective Studies ; Biological Specimen Banks ; Risk Factors ; Life Style ; UK Biobank ; }, abstract = {BACKGROUND: The Mediterranean lifestyle (MEDLIFE) is generally considered to have a positive effect on several health outcomes. However, little is known about its impact on age-related eye diseases. We aimed to assess the effect of MEDLIFE on the risk of three such diseases: cataract, glaucoma, and age-related macular degeneration (AMD).<br><br>METHODS: We included 113&#x2009;829 participants from the UK Biobank who were free of age-related eye diseases at baseline and followed them up prospectively for disease occurrence. Adherence to MEDLIFE was assessed using 25 items, categorised under three blocks: 'Mediterranean food consumption' (block 1), 'Mediterranean dietary habits' (block 2), and 'physical activity, rest, social habits' (block 3). We used a Cox proportional hazard model to examine the associations of the MEDLIFE index and each of its blocks with incident age-related eye diseases.<br><br>RESULTS: During a median follow-up of 10.5 years, 9954 cases of cataract, 1956 cases of glaucoma, and 1736 cases of AMD were identified. We noted an inverse association between the MEDLIFE index and new-onset cataract (P-value for trend&#x2009;=&#x2009;0.005). A one-point increment in the MEDLIFE score was associated with a 1.5% (95% confidence interval (CI)&#x2009;=&#x2009;0.7-2.3) reduction in the risk of cataract, and with a 2.4% (95% CI&#x2009;=&#x2009;0.5-4.3) reduction in AMD incidence. Analysis of MEDLIFE blocks indicated that block 2 (hazard ratio (HR)&#x2009;=&#x2009;0.97; 95% CI&#x2009;=&#x2009;0.95-0.99) and block 3 (HR&#x2009;=&#x2009;0.97; 95% CI&#x2009;=&#x2009;0.95-0.99) were associated with lower risk of cataract. Block 2 was further related to reduced risk of AMD (HR&#x2009;=&#x2009;0.95; 95% CI&#x2009;=&#x2009;0.91-0.99). Although we found no association between the MEDLIFE index and incident glaucoma, block 3 was associated with lower glaucoma risk (HR&#x2009;=&#x2009;0.94; 95% CI&#x2009;=&#x2009;0.90-0.98).<br><br>CONCLUSIONS: Higher adherence to MEDLIFE was associated with decreased incidence of cataract and AMD, while the 'physical activity, rest, and social interactions' block was related to a lower risk of glaucoma. Our findings suggest that MEDLIFE may serve as a potential behavioural intervention for preventing age-related eye diseases.}, }
@article {pmid41524752, year = {2026}, author = {Kilani, A and Vogt, D and Moysidi, V and Assaf, A and Wolf, A and Vounotrypidis, E}, title = {VEGF-inhibitor switch trial in poor-responsive neovascular age-related macular degeneration: assessing brolucizumab vs. faricimab: VISTA study.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41524752}, issn = {1435-702X}, abstract = {PURPOSE: To compare short-term (12 weeks) and long-term (48 weeks) anatomical and functional outcomes after switching to brolucizumab (BRZ) or faricimab (FAR) under a treat-and-extend (TAE) regimen without an initial loading phase in eyes with poor-responsive neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This retrospective, single-center study included eyes with poor-responsive nAMD previously treated with anti-VEGF agents that were switched to BRZ or FAR between 2022 and 2025. Functional outcomes (best-corrected visual acuity [BCVA]) and anatomical parameters (central subfield thickness [CST], fibrovascular pigment epithelial detachment [fvPED] height, intraretinal/subretinal fluid [IRF/SRF], subretinal hyperreflective material [SHRM]) were assessed at baseline, week 12, and week 48. Injection frequency, interval extension, and safety were recorded.<br><br>RESULTS: Sixty-six eyes (41 BRZ, 25 FAR) were included. At 12 weeks, BCVA remained stable (BRZ 0.49 logMAR, FAR 0.40; p&#x2009;=&#x2009;0.10). CST decreased significantly in both groups, greater with BRZ (243&#xa0;&#x3bc;m vs. 280&#xa0;&#x3bc;m; p&#x2009;=&#x2009;0.04). Mean injections (2.95 vs. 3.2; p&#x2009;=&#x2009;0.12) and intervals (5.9 vs. 5.6 weeks; p&#x2009;=&#x2009;0.90) were comparable; no intraocular inflammation (IOI) occurred. At 48 weeks, BCVA was numerically better with FAR (0.20 vs. 0.49 logMAR; p = 0.08). CST reduction was sustained andcomparable (259 &#xb5;m vs. 260 &#xb5;m; p = 0.50). FAR achieved greater fvPED reduction (110 &#xb5;m vs. 160 &#xb5;m; p = 0.022). BRZ required fewer injections (6.3 vs. 7.2; p = 0.009) with similar intervals (9.4 vs. 9.9 weeks; p = 0.80). Mild IOI occurred in two BRZ eyes (4.9%) and none with FAR.<br><br>CONCLUSIONS: In poor-responsive nAMD, switching to BRZ or FAR under a TAE regimen without upload achieved stable vision, sustained CST reduction, and comparable treatment burden over one year. FAR showed greater fvPED regression and a slight functional trend, while BRZ achieved faster fluid resolution with fewer injections.}, }
@article {pmid41524889, year = {2026}, author = {Chen, S and Wang, G and Guan, X and Wang, C and Xiao, Y and Li, X and Hong, S and Zhou, Y and You, Y and Fu, Y and Wang, Y and Zhang, Y and Zhao, H and Zhang, Y and Cheng, Y and Guo, H and Xie, H}, title = {Air pollutants, genetic susceptibility, and the risk of age-related macular degeneration: a large prospective cohort study.}, journal = {European journal of epidemiology}, volume = {41}, number = {2}, pages = {185-196}, pmid = {41524889}, issn = {1573-7284}, support = {82373667//National Natural Science Foundation of China/ ; 82171025//National Natural Science Foundation of China/ ; 2018YFC2000203//National Key Research and Development Program of China/ ; }, mesh = {Humans ; *Macular Degeneration/epidemiology/genetics ; Female ; Male ; *Air Pollutants/analysis/adverse effects ; *Genetic Predisposition to Disease ; Prospective Studies ; *Air Pollution/adverse effects/analysis/statistics &amp; numerical data ; Particulate Matter/analysis/adverse effects ; Aged ; Middle Aged ; *Environmental Exposure/adverse effects ; Risk Factors ; United Kingdom/epidemiology ; Nitrogen Oxides/analysis/adverse effects ; Proportional Hazards Models ; Nitrogen Dioxide/analysis/adverse effects ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide. However, evidence regarding the relationship between air pollution and AMD is limited, and the modifying effect of genetic susceptibility on this association remains unknown. A total of 445,237 participants without AMD at baseline were included from the UK Biobank. The concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), particulate matter (PM2.5, PM10, PM2.5-10) were collected by using land-use regression models. Air pollution score (APS) was constructed through summing each pollutant weighted by the regression coefficients with AMD from single-pollutant model. Cox proportional hazard models were used to evaluate hazard rations (HRs) and 95% confidence intervals (95%CIs) of associations between air pollutants and polygenic risk score (PRS) with incident AMD. During a median follow-up of 13.83 years, we observed 9,635 incident AMD events. The HR (95%CI) of incident AMD for each standard deviation increase in NO2, NOx, PM2.5, PM10, and APS were 1.04(1.02, 1.06), 1.03(1.01, 1.05). 1.04(1.02, 1.07), 1.02(1.00, 1.04), and 1.04(1.02, 1.06), respectively. Significant additive interaction effects of NO2, NOx, PM2.5-10, APS and PRS with incident risk of AMD were observed, with the relative excess risk due to the interaction (RERI), attributable proportion (AP), and their 95% CIs of 0.10(0.01, 0.18) and 0.05(0.01, 0.11) for NO2, 0.11(0.01, 0.19) and 0.05(0.02, 0.10) for NOx, 0.15(0.06, 0.23) and 0.08(0.03, 0.13) for PM2.5-10, and 0.12(0.03, 0.20) and 0.06(0.01, 0.11) for APS, respectively. Compared with participants exposed to low level of above air pollutants and low PRS, those exposed to high air pollution and high PRS had almost double incident risk of AMD [HR(95%CI) ranged from 1.83(1.68, 1.99) to 2.03(1.86, 2.21)]. Long-term exposure to air pollutants NO2, NOx, PM2.5, and PM10 showed positive associations with increased risk of AMD, which could be further enhanced by genetic susceptibility.}, }
@article {pmid41525679, year = {2026}, author = {Bindi, J and Choi, R}, title = {Novel Surgical Approach to Submacular Hemorrhage in the Setting of Extensive Pan-retinal Photocoagulation.}, journal = {Retinal cases &amp; brief reports}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICB.0000000000001865}, pmid = {41525679}, issn = {1937-1578}, abstract = {PURPOSE: To describe a novel surgical approach for managing submacular hemorrhage (SMH) in the setting of extensive panretinal photocoagulation (PRP) where conventional displacement techniques are limited by chorioretinal adhesions.<br><br>METHODS: We report the case of a 73-year-old monocular woman with neovascular age-related macular degeneration (AMD) and dense PRP scars who presented with an acute, fovea-involving SMH. A modified pars plana vitrectomy (PPV) was performed using submacular tissue plasminogen activator (tPA), perfluorocarbon liquid (PFCL) tamponade to direct blood toward three small retinotomies, active aspiration, and silicone oil placement.<br><br>RESULTS: This strategy achieved substantial clot evacuation and anatomic resolution. The patient's final visual acuity improved to 20/200.<br><br>CONCLUSION: Multiple small retinotomies with PFCL-assisted drainage may serve as a viable alternative surgical technique for SMH in eyes with extensive PRP scarring, where retinal adhesions preclude conventional displacement methods.}, }
@article {pmid41526441, year = {2026}, author = {Agarwal, D and Bhargava, A and Alsharif, MH and Saeed, S and Alsharif, NHM}, title = {Automatic diagnosis of age-related macular degeneration using machine learning and image processing techniques.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {5037}, pmid = {41526441}, issn = {2045-2322}, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults. Detecting AMD early can prevent the irreversible damage caused in later stages. Most existing methods detect drusens as a preliminary step for AMD detection, which is quite challenging as the drusens are present alongside other exudates in the retina. This paper presents a system for early diagnosis of dry AMD that does not rely on detecting drusens and integrates handcrafted features with machine learning and image processing techniques. The system performs several image processing tasks, including pre-processing a color fundus photograph of the retina, macula detection, Region-of-Interest (RoI) selection around the macula, and feature extraction from the RoI. Several texture and color features of the macula region are extracted and analyzed using t-test and ReliefF feature selection algorithms. Supervised classification techniques such as Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Naïve Bayes Classifier (NBC), and Multi-Layer Perceptron (MLP) are trained on the selected features with stratified 10-fold cross-validation to classify retinal images as normal or AMD. The system’s performance is evaluated based on accuracy, error, recall, specificity, precision, and F1-score. Classifiers are trained and tested on three feature sets: texture, color, and a combination of both. The proposed system achieves excellent results with texture features and the SVM classifier, attaining accuracies of 98.89% and 95.43% on the STARE and ODIR datasets, respectively.}, }
@article {pmid41527550, year = {2026}, author = {Wu, P and Lin, M and Chen, Q and Chew, EY and Lu, Z and Peng, Y and Dong, H}, title = {AMD-Mamba: A Phenotype-Aware Multi-modal Framework for Robust AMD Prognosis.}, journal = {Machine learning in medical imaging. MLMI (Workshop)}, volume = {16241}, number = {}, pages = {150-160}, pmid = {41527550}, support = {R21 EY035296/EY/NEI NIH HHS/United States ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, making effective prognosis crucial for timely intervention. In this work, we propose AMD-Mamba, a novel multi-modal framework for AMD prognosis, and further develop a new AMD biomarker. This framework integrates color fundus images with genetic variants and socio-demographic variables. At its core, AMD-Mamba introduces an innovative metric learning strategy that leverages AMD severity scale score as prior knowledge. This strategy allows the model to learn richer feature representations by aligning learned features with clinical phenotypes, thereby improving the capability of conventional prognosis methods in capturing disease progression patterns. In addition, unlike existing models that use traditional CNN backbones and focus primarily on local information, such as the presence of drusen, AMD-Mamba applies Vision Mamba and simultaneously fuses local and long-range global information, such as vascular changes. Furthermore, we enhance prediction performance through multi-scale fusion, combining image information with clinical variables at different resolutions. We evaluate AMD-Mamba on the AREDS dataset, which includes 45,818 color fundus photographs, 52 genetic variants, and 3 socio-demographic variables from 2,741 subjects. Our experimental results demonstrate that our proposed biomarker is one of the most significant biomarkers for the progression of AMD. Notably, combining this biomarker with other existing variables yields promising improvements in detecting high-risk AMD patients at early stages. These findings highlight the potential of our multi-modal framework to facilitate more precise and proactive management of AMD.}, }
@article {pmid41528844, year = {2026}, author = {Wang, SK and Li, J and Nair, S and Kosaraju, R and Chen, Y and Zhang, Y and Kundaje, A and Liu, Y and Wang, N and Chang, HY}, title = {Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate causal variants in macular degeneration.}, journal = {Cell reports}, volume = {45}, number = {1}, pages = {116814}, pmid = {41528844}, issn = {2211-1247}, support = {RM1 HG007735/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/genetics/pathology ; *Choroid/metabolism/pathology ; *Enhancer Elements, Genetic/genetics ; *Single-Cell Analysis/methods ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss worldwide. Genome-wide association studies (GWASs) of AMD have identified dozens of risk loci that may house disease targets. However, variants at these loci are largely noncoding, making it difficult to assess their function and whether they are causal. Here, we present a single-cell gene expression and chromatin accessibility atlas of human retinal pigment epithelium (RPE) and choroid to systematically analyze both coding and noncoding variants implicated in AMD. We employ HiChIP and activity-by-contact modeling to map enhancers in these tissues and predict cell and gene targets of risk variants. We further perform allele-specific self-transcribing active regulatory region sequencing (STARR-seq) to functionally test variant activity in RPE cells, including in the context of complement activation. Our work nominates pathogenic variants and mechanisms in AMD and offers a rich and accessible resource for studying diseases of the RPE and choroid.}, }
@article {pmid41529041, year = {2026}, author = {Helmy, YA and Rahman, NK and Rahman, KT and Groppe, M and Bindra, MS and Latasiewicz, M}, title = {Comparison of intravitreal and subretinal tPA for acute submacular haemorrhage: A retrospective study.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721251413662}, doi = {10.1177/11206721251413662}, pmid = {41529041}, issn = {1724-6016}, abstract = {PurposeThis study compares the anatomical and functional outcomes of two treatments for acute submacular haemorrhage (SMH): pars plana vitrectomy with subretinal recombinant tissue plasminogen activator (tPA) and gas tamponade versus intravitreal tPA and gas injection.MethodsA retrospective single-centre study was conducted of patients treated for acute SMH at Buckinghamshire Healthcare NHS Trust between January 2016 and December 2022. Patients received either intravitreal tPA and gas ± anti-VEGF (Group A) or pars plana vitrectomy with subretinal tPA and gas tamponade ± anti-VEGF (Group B). The primary outcome was anatomical success, defined as displacement of haemorrhage from the fovea. Secondary outcomes were visual acuity (VA) improvement, central foveal thickness (CFT) reduction, and complication rates.ResultsEighty eyes from 73 patients (mean age: 79.8 ± 11.5 years; 57.5% female) were analysed, with 53 eyes in Group A and 27 in Group B. Anatomical success was achieved in 71.6% of Group A and 77.8% of Group B. VA improved in 66% of Group A and 63% of Group B. CFT decreased by over 50% in both groups. No statistically significant differences were found between the two treatment groups and in anatomical or functional improvement.ConclusionIn this real-world study, both approaches effectively displaced SMH and improved vision with comparable outcomes, suggesting that treatment selection may be best determined by patient-specific and logistical factors.}, }
@article {pmid41529093, year = {2026}, author = {Maatouk, CM and Hyman, MJ and Shah, A and Smith, SR and Yehia, M and Moir, J and Gonnah, R and Flores, A and Hariprasad, S and Skondra, D}, title = {Association Between Metformin and Other Diabetic Medications and Five-year Onset of New Neovascular Age-related Macular Degeneration Diagnosis.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {57}, number = {2}, pages = {102-111}, doi = {10.3928/23258160-20251110-01}, pmid = {41529093}, issn = {2325-8179}, mesh = {Humans ; *Metformin/therapeutic use ; Male ; Female ; *Hypoglycemic Agents/therapeutic use ; Aged ; Case-Control Studies ; Middle Aged ; *Wet Macular Degeneration/diagnosis/epidemiology ; *Diabetic Retinopathy/drug therapy/complications ; Retrospective Studies ; Follow-Up Studies ; Aged, 80 and over ; Time Factors ; }, abstract = {BACKGROUND AND OBJECTIVE: Neovascular age-related macular degeneration (nAMD) is a sight-threatening condition with growing prevalence, but few therapies exist to prevent its development. This study investigates whether metformin reduces the odds of new nAMD diagnosis.<br><br>PATIENTS AND METHODS: This was a case-control study using a nationwide insurance claims database of patients ages 55 and older with newly diagnosed nAMD from January 2008 to December 2019. Multivariable conditional logistic regression was utilized to determine how various exposures impacted the odds of new nAMD diagnosis.<br><br>RESULTS: Among 55,080 cases with new nAMD diagnosis and 55,066 matched controls, any metformin exposure reduced 5-year odds of new nAMD diagnosis compared to individuals not on metformin (odds ratio [OR]: 0.94; 95% CI: 0.90 to 0.99). Insulin and sulfonylurea exposures were also protective. These findings were consistent in subgroup analyses of patients with diabetes without diabetic retinopathy.<br><br>CONCLUSION: Metformin may reduce the 5-year odds of developing nAMD, particularly in diabetic patients without diabetic retinopathy.}, }
@article {pmid41529750, year = {2026}, author = {Arokia Vijaya Anand, M and Yang, CJ and Wang, WL and Yao, CH and Lai, JY}, title = {Marine-derived polysaccharides enhance the drug delivery mechanism in the management of ocular diseases: A review.}, journal = {International journal of biological macromolecules}, volume = {340}, number = {Pt 2}, pages = {150199}, doi = {10.1016/j.ijbiomac.2026.150199}, pmid = {41529750}, issn = {1879-0003}, mesh = {Humans ; *Polysaccharides/chemistry/therapeutic use/pharmacology ; *Eye Diseases/drug therapy ; *Drug Delivery Systems/methods ; *Aquatic Organisms/chemistry ; Animals ; *Drug Carriers/chemistry ; Drug Liberation ; Nanoparticles/chemistry ; }, abstract = {Ocular drug delivery remains significantly challenging due to complex anatomical and physiological barriers, poor bioavailability, and inefficient drug absorption. These limitations highlight the requirement for advanced delivery systems to overcome the ocular barrier and enable efficacious therapeutic outcomes. This review explores the potential of marine-derived polysaccharides as innovative carriers for ocular applications, emphasizing their potential as drug-delivery mechanisms to enhance drug retention, permeation, and bioavailability through advanced nanoplatforms. Polysaccharides such as κ-carrageenan, agarose, alginate, chitosan, hyaluronic acid, heparan sulfate, and chondroitin sulfate possess physicochemical, biocompatible, biodegradable, and mucoadhesive properties, making them ideal materials for ocular drug delivery. Notably, marine-derived polysaccharides have been reported to significantly improve ocular delivery performance, achieving up to a 3-fold increase in corneal permeability, higher drug accumulation in the aqueous humor (>47% vs. ∼20%), and approximately 3.6-3.8-fold enhancement in precorneal retention, while also enabling intelligent systems such as pH- and light-responsive drug release. These polymers have been engineered into various delivery platforms, including nanoparticles, micelles, dendrimers, nanosuspensions, hydrogels, and implants. Such systems promote sustained (long-acting), targeted (site-specific), and intelligent (stimuli-responsive) drug release, thereby significantly enhancing precorneal retention and therapeutic efficacy. These approaches are particularly relevant for treating various corneal diseases, including glaucoma, diabetic retinopathy, ocular inflammation, and age-related macular degeneration. The article also emphasizes the potential of emerging strategies to transform ocular drug delivery by offering customizable, stimuli-responsive, and patient-friendly therapeutic options. However, further in-depth research is crucial to optimize formulations, evaluate long-term safety, and address regulatory challenges for successful clinical translation.}, }
@article {pmid41531643, year = {2025}, author = {Das, D and Chawla, B and Lomi, N and Grover, S and Narayan, A}, title = {AI in the Shadows: Unveiling the Strengths and Blind Spots of Medios AI Retinal Screening in Cancer Care.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e99002}, pmid = {41531643}, issn = {2168-8184}, abstract = {Introduction Artificial intelligence (AI) is increasingly being integrated into ophthalmic diagnostics, offering potential for efficient screening of common retinal diseases. The Medios AI system by Remidio (Singapore, Singapore), designed for use with a smartphone-based fundus camera, claims to detect diabetic retinopathy (DR), age-related macular degeneration (ARMD), and glaucoma. However, its performance in complex clinical settings such as ocular oncology remains underexplored. This study aims to evaluate both the diagnostic capabilities and limitations of the Medios AI system when applied to a diverse cohort of oncology patients. Materials and methods An observational study was conducted over three months in an ocular oncology clinic. Ninety-eight cancer patients (196 eyes) underwent fundus photography using the Remidio smartphone-based fundus imaging system. The images were analyzed using the Medios AI algorithm. AI-generated findings were compared with clinical evaluations by an experienced ophthalmologist to identify diagnostic concordance and discrepancies. Additional attention was paid to the system's imaging capabilities, including its ability to capture wide-field or montage images. Result The AI system accurately identified glaucomatous cupping in three patients, flagged two cases of DR, and detected signs of ARMD in two patients-all consistent with clinical examination. However, eight patients with leukemic retinopathy were incorrectly flagged as having DR, revealing a lack of specificity in distinguishing vascular retinal pathologies. The system also failed to detect optic atrophy, a critical neuro-ophthalmic finding in oncology patients. A technical limitation was also noted: the inability of the Remidio system to generate montage or wide-field images, restricting visualization of the peripheral retina. Conclusion While the Medios AI system demonstrates promise in identifying common retinal pathologies such as DR, ARMD, and glaucoma, its limitations are significant in the oncology context. The inability to distinguish similar hemorrhagic retinopathies, failure to detect optic nerve atrophy, and lack of wide-field imaging capabilities underscore the need for cautious implementation. Integration of AI tools must be accompanied by expert clinical oversight, especially in specialized settings where retinal presentations are complex and atypical.}, }
@article {pmid41532690, year = {2026}, author = {Wagner, M and Leutloff, CJ and Rauscher, FG}, title = {A Simulation Procedure for Stereological Correction of Early AMD Lesion Sizes Observed in Single OCT-B-Scans.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {1}, pages = {21}, pmid = {41532690}, issn = {2164-2591}, mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Macular Degeneration/diagnostic imaging/pathology ; Aged ; Female ; Male ; Computer Simulation ; Aged, 80 and over ; Middle Aged ; }, abstract = {PURPOSE: Early lesions caused by age-related macular degeneration (AMD) are imaged by optical coherence tomography (OCT) in unprecedented detail. Most probably, however, the sampling plane of an OCT scan meets a given lesion noncentrally, and the observed sizes of its diameter, cross-sectional area, and volume must be stereologically corrected.<br><br>METHODS: Stereological corrections are obtained by a simulation procedure, which is applied to the leading scans in a consecutive sample of 100 early AMD participants.<br><br>RESULTS: Mean corrections for lesion diameter, cross-sectional area and volume amount to +9.1%, +32.0%, and +46.6%, respectively. After correction, AMD stage classifications with respect to the 125-&#xb5;m diameter cutpoint had to be changed for seven participants.<br><br>CONCLUSIONS: Simulation results confirm that for lesions pictured and measured in OCT scans - regardless of the accuracy of OCT imaging - stereological correction of observed sizes is compelling and unavoidable.<br><br>TRANSLATIONAL RELEVANCE: Categorial AMD classifications based on observed OCT data must be reexaminated after stereological correction.}, }
@article {pmid41533007, year = {2026}, author = {Li, J and Wang, T and Lu, W and Jishkariani, D and Tsourkas, A and Kaja, S and Vining, KH and Thussananutiyakul, J and Spence, A and Nair, RM and Dunaief, JL and Mitchell, CH}, title = {PLGA nanoparticles restore acidic pH and degradative function to compromised lysosomes with Cy3-labeling providing enhanced tracking to lysosomes.}, journal = {American journal of physiology. Cell physiology}, volume = {330}, number = {2}, pages = {C509-C523}, doi = {10.1152/ajpcell.00494.2025}, pmid = {41533007}, issn = {1522-1563}, support = {EY001538//HHS | NIH | National Eye Institute (NEI)/ ; //Research to Protect Blindness/ ; //Richard A Perritt MD Charitable Foundation/ ; EY013434//HHS | NIH | National Eye Institute (NEI)/ ; //This work was partially supported by the Collaborative Research Grant (KV) from the Institute of Regenerative Medicine at the University of Pennsylvania&amp;&#xa0;and the REgeneration and ReSToration of Function/ ; //Illinois Society for the Prevention of Blindness (ISPB)/ ; R01 EY013434/EY/NEI NIH HHS/United States ; EY015537//HHS | NIH | National Eye Institute (NEI)/ ; //Dr. John P. and Therese E. Mulcahy Endowed Professorship in Ophthalmology/ ; //Penn Undergraduate Research Mentoring Program (PURM)/ ; R01 EY015537/EY/NEI NIH HHS/United States ; //Eversight/ ; }, mesh = {*Lysosomes/metabolism/drug effects ; *Nanoparticles/chemistry/metabolism ; *Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; Humans ; Hydrogen-Ion Concentration ; *Carbocyanines/chemistry/metabolism ; Retinal Pigment Epithelium/metabolism/drug effects ; Induced Pluripotent Stem Cells/metabolism/drug effects ; Cell Line ; }, abstract = {Lysosomal dysfunction and elevated lysosomal pH are hallmark features of age-related neurodegenerative diseases including age-related macular degeneration (AMD), Alzheimer's disease (AD), and Parkinson's disease (PD). Restoring lysosomal acidity is important for maintaining enzymatic degradation, preventing protein aggregation, and reducing cellular waste accumulation in degenerating tissues. Acidic nanoparticles represent a promising therapeutic strategy to normalize lysosomal pH; however, accurate monitoring of their delivery, retention, and dosage is critical for rigorous evaluation. To address this, we developed fluorescently labeled poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles conjugated with Cyanine3 amine (Cy3). Nanoparticle uptake was systematically optimized, achieving over 90% delivery to lysosomes of induced pluripotent stem cell-derived retinal pigment epithelial (iPS-RPE) cells, although uptake rates varied among adjacent cells. Once internalized, nanoparticles demonstrated remarkable stability, with no detectable change in concentration, distribution, or size for at least 28 days. iPS-RPE cells exhibited higher nanoparticle internalization compared with the ARPE-19 cell line and optic nerve head astrocytes. The capacity of the nanoparticles to restore function to stressed lysosomes was confirmed by their ability to reacidify lysosomes, restore cathepsin B activity, and increase the levels of active cathepsin D. The nanoparticles also reduced the levels of LC3II in astrocytes treated with chloroquine, indicating that they can also restore autophagy rates. In summary, this study demonstrates the value of Cy3 labeling for enhanced nanoparticle tracking to lysosomes. The findings also identify PLGA nanoparticles as powerful tools for restoring degradative lysosomal function and autophagy in cells undergoing lysosomal stress.NEW &amp; NOTEWORTHY Tools that restore acidic pH in compromised lysosomes can enhance autophagy and waste clearance in degenerative disorders characterized by excessive accumulation. Here, we describe the synthesis of lysosome-targeted nanoparticles composed of poly(d,l-lactide-co-glycolide) (PLGA) polymers covalently bound to the fluorescent dye Cyanine3 amine (Cy3). These Cy3-PLGA nanoparticles enable precise tracking of lysosomal delivery and demonstrate sustained long-term retention within lysosomes, supporting their potential for future applications aimed at restoring lysosomal pH in aging and degenerating diseases.}, }
@article {pmid41533847, year = {2026}, author = {Miladinovic, A and Biscontin, A and Ajcevic, M and Kresevic, S and Accardo, A and Tognetto, D and Inferrera, L}, title = {Neurosymbolic AI Framework for Explainable Retinal Disease Classification From OCT Images.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {1}, pages = {6}, pmid = {41533847}, issn = {2164-2591}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Diseases/classification/diagnostic imaging/diagnosis ; *Neural Networks, Computer ; Retrospective Studies ; Deep Learning ; }, abstract = {PURPOSE: Accurate classification of retinal diseases such as dry age-related macular degeneration, wet AMD, epiretinal membrane, full-thickness macular hole (MH), lamellar MH, and central serous chorioretinopathy (CSC) is essential for effective treatment and clinical decision-making. Traditional deep learning models, however, often struggle with imbalanced datasets and lack interpretability, limiting their translational applicability in ophthalmology.<br><br>METHODS: We propose a neurosymbolic framework that integrates a convolutional neural network (CNN) with a symbolic reasoning layer based on expert-defined clinical rules. A total of 10,846 optical coherence tomography images were retrospectively collected and categorized into seven diagnostic classes: dry AMD, wet AMD, epiretinal membrane, full-thickness MH, lamellar MH, central serous chorioretinopathy, and healthy retinas.<br><br>RESULTS: Our neurosymbolic model achieved macro-precision 0.83, recall 0.82, and F1 0.81, on internal dataset, having slightly better performance than the CNN (0.64/0.83/0.68). On the external dataset, it retained superior performance, macro-precision 0.85, recall 0.79, F1 0.78, versus the CNN (0.73/0.64/0.59).<br><br>CONCLUSIONS: Our hybrid neurosymbolic framework introduces a unified paradigm that couples symbolic reasoning with a conventional CNN, improving diagnostic performance while delivering transparent, clinically interpretable decisions. It is particularly effective for rare and complex conditions that often challenge end-to-end deep learning models.<br><br>TRANSLATIONAL RELEVANCE: By integrating symbolic clinical logic with visual pattern recognition, the neurosymbolic model fosters trust in artificial intelligence-assisted diagnostics and supports precise, explainable decision-making in retinal care.}, }
@article {pmid41533856, year = {2026}, author = {Owsley, C and McGwin, G and Gao, L and Clark, ME and Gooden, L and Thomas, TN and Goerdt, L and Curcio, CA}, title = {Natural History of Visual Function Changes Over Three Years in Normal Aging and in Early and Intermediate Age-Related Macular Degeneration: ALSTAR2.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {1}, pages = {16}, pmid = {41533856}, issn = {2164-2591}, support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Macular Degeneration/physiopathology ; Aged ; *Visual Acuity/physiology ; Female ; Male ; Contrast Sensitivity/physiology ; *Aging/physiology ; Middle Aged ; Dark Adaptation/physiology ; Aged, 80 and over ; }, abstract = {PURPOSE: The purpose of this study was to evaluate change in visual functions over 3 years in normal macular health, and early and intermediate age-related macular degeneration (AMD) including tests of rod-, cone-, and mixed rod-cone-mediated visions; and to evaluate whether visual function change over 3 years meets the minimal clinically important difference (MCID), defined as meaningful to patients in everyday life.<br><br>METHODS: Eight visual functions were evaluated at baseline and 3-year follow-up (acuity, low luminance acuity, photopic and mesopic contrast sensitivity, mesopic and scotopic light sensitivity, and rod-mediated dark adaptation [RMDA] at 5 degrees and 12 degrees). The Age-Related Eye Disease Study (AREDS) 9-step classification system defined AMD severity.<br><br>RESULTS: In normal aging and intermediate AMD, 6 of 8 visual functions had statistically significant worsening over 3 years; mesopic contrast sensitivity and mesopic light sensitivity, respectively, showed no change. In early AMD, five of eight visual functions showed worsening over time, with photopic and mesopic contrast sensitivity and scotopic sensitivity unchanged. The largest percentage of eyes in each group meeting MCID was RMDA at 5 degrees or 12 degrees (38%-55%). The lowest percentage of eyes meeting MCID was visual acuity and photopic contrast sensitivity (0%-10%).<br><br>CONCLUSIONS: Whereas most visual functions evaluated have statistically significant worsening over 3 years in normal aging to intermediate eyes, the percentage of eyes reaching MCID was low for most visual functions except RMDA, which met MCID for almost half the eyes.<br><br>TRANSLATIONAL RELEVANCE: The natural history of change in visual function over time in normal aging to intermediate AMD should be characterized in terms of MCID, not only statistical significance.}, }
@article {pmid41533868, year = {2025}, author = {Guo, S and Gao, L and Cao, D and Huang, H and Ye, D and Lin, J and Meng, J and Xue, J and Li, Z and Li, J and Cheng, H}, title = {The Prevalence of Malnutrition and Early-Stage Age-Related Macular Degeneration: Using Three Nutritional Scoring Systems.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {12}, pages = {25}, pmid = {41533868}, issn = {2164-2591}, mesh = {Humans ; *Macular Degeneration/epidemiology/diagnosis ; Female ; Male ; Aged ; *Malnutrition/epidemiology/diagnosis/complications ; Prevalence ; *Nutritional Status ; Middle Aged ; *Nutrition Assessment ; Aged, 80 and over ; Choroid/pathology/blood supply/diagnostic imaging ; }, abstract = {PURPOSE: To investigate the interrelationships among malnutrition, choroidal parameters, and early-stage age-related macular degeneration (AMD), particularly the reticular pseudodrusen (RPD) phenotype, and to assess the predictive value of three nutritional scores.<br><br>METHODS: A total of 177 eyes were included in the study, categorized into control (n = 54), AMD (n = 55), and AMD-RPD (n = 68) groups based on fundus features. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score, Geriatric Nutritional Risk Index (GNRI), and Prognostic Nutritional Index (PNI). Choroidal vascular index (CVI) and choroidal thickness (ChT) were measured.<br><br>RESULTS: Nutritional scores indicated a progressive decline in nutritional status from control to AMD to AMD-RPD. Compared with the control group, both AMD and AMD-RPD individuals had significantly worse CONUT, GNRI, and PNI scores (all P &#x2264; 0.01). Compared with the AMD group, AMD-RPD had significantly lower GNRI and PNI scores (both P < 0.001). CVI was positively correlated with GNRI (r = 0.308, P < 0.001) and PNI (r = 0.284, P < 0.001). The predictive value of all three nutritional scores for both AMD and AMD-RPD was demonstrated, with GNRI and PNI showing utility in differentiating RPD from AMD.<br><br>CONCLUSIONS: Malnutrition is associated with early-stage AMD phenotypes and choroidal vascular abnormalities may underlie this link. GNRI and PNI may help identify high-risk RPD individuals and support early nutritional assessment and intervention.<br><br>TRANSLATIONAL RELEVANCE: Integrating these nutritional scores may enhance collaboration between ophthalmologists and dietitians, enabling better detection and management of AMD and RPD in clinical practice.}, }
@article {pmid41533899, year = {2026}, author = {Yasuda, H and Nakamura, S and Shirakawa, A and Kuse, Y and Shimazawa, M}, title = {Inhibition of Pathological Mitochondrial Fission in Retinal Pigment Epithelium Mitigates Choroidal Neovascularization.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {1}, pages = {4}, pmid = {41533899}, issn = {1552-5783}, mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology/prevention &amp; control/drug therapy ; *Mitochondrial Dynamics/drug effects/physiology ; Mice, Inbred C57BL ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Mice ; *Quinazolinones/pharmacology ; Disease Models, Animal ; Blotting, Western ; Fluorescein Angiography ; *Mitochondria/metabolism ; Cells, Cultured ; Dynamins/metabolism ; Male ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {PURPOSE: Mitochondria are highly dynamic organelles that continuously undergo fission and fusion, and their dysfunction is associated with various age-related disorders. This study aimed to elucidate the role of mitochondrial fission in the development of choroidal neovascularization (CNV), a hallmark of neovascular age-related macular degeneration (AMD), and to evaluate the therapeutic potential of its pharmacological inhibition.<br><br>METHODS: The murine CNV model was created by laser photocoagulation using C57BL/6J mice. Expression changes of mitochondrial fission-related protein during CNV development were examined using western blotting and immunofluorescence. To assess the effectiveness of pharmacological inhibition of mitochondrial fission, the effects of mitochondrial division inhibitor-1 (Mdivi-1) and mitochondrial fusion promoter (M1) were evaluated by CNV area measurement, fluorescein angiography, and western blot analysis. The pro-angiogenic mechanisms associated with mitochondrial fission were further investigated in RPE cells cultured under hypoxic condition.<br><br>RESULTS: In a murine laser-induced CNV model, mitochondrial fission-related proteins increased in the retinal pigment epithelium (RPE)-choroid complex, and the high expression of phosphorylated dynamin-related protein 1 (DRP1) was observed in RPE cells surrounding the CNV lesion. Additionally, intravitreal injection of Mdivi-1 or M1 suppressed CNV formation, vascular leakage, and pro-angiogenic factor production. In RPE cells exposed to hypoxia, DRP1-mediated mitochondrial fission was rapidly activated, accompanied by increased mitochondrial reactive oxygen species production. Moreover, inhibition of mitochondrial fission suppressed mitochondrial bioenergetic dysfunction and the upregulation of vascular endothelial growth factor.<br><br>CONCLUSIONS: These findings support that pharmacological inhibition of activated mitochondrial fission could serve as a potential therapeutic approach for neovascular AMD.}, }
@article {pmid41533907, year = {2026}, author = {Veernala, I and Cuamatzi-Castelan, AS and Rajesh, A and Gong, J and D'Souza, GJ and Lavine, JA}, title = {Levodopa Suppresses Choroidal Neovascularization Through a Tyrosinase-Dependent Dual Mechanism.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {1}, pages = {8}, pmid = {41533907}, issn = {1552-5783}, mesh = {Animals ; *Levodopa/pharmacology/therapeutic use ; *Choroidal Neovascularization/drug therapy/metabolism/prevention &amp; control/pathology ; Mice ; *Monophenol Monooxygenase/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Dopamine D2/agonists/metabolism ; Choroid/drug effects ; Dopamine Agonists/pharmacology ; Signal Transduction ; }, abstract = {PURPOSE: Levodopa (L-DOPA), a precursor for melanin and dopamine, has been linked to reduced intravitreal injection burden and delayed onset of neovascular age-related macular degeneration (AMD). Further, L-DOPA and dopamine receptor D2 (DRD2) agonists inhibit laser-induced choroidal neovascularization (CNV). However, the contributions of endogenous versus exogenous L-DOPA signaling, their effects in alternative CNV models, and the contributions of DRD2 versus GPR143, the receptor for L-DOPA, signaling remain unresolved.<br><br>METHODS: Choroidal sprouting assays (CSA) were performed using wild-type (WT) and tyrosinase-mutant (Tyr-/-) mice with and without dopamine pathway agonists and antagonists. CNV number and area were measured in pigmented Vldlr-/- and albino Vldlr-/-Tyr-/- mice with and without L-DOPA or the DRD2 agonist quinpirole.<br><br>RESULTS: Endogenous L-DOPA deficiency (Tyr-/-) did not affect CSA sprouting or CNV in Vldlr-/- mice. Exogenous L-DOPA suppressed angiogenesis ex vivo in both WT and Tyr-/- choroidal explants in a dose-dependent manner. In vivo, L-DOPA reduced CNV lesion number, lesion area, and macrophage infiltration in albino but not pigmented Vldlr-/- mice. Dopamine and quinpirole produced modest anti-angiogenic effects, and eticlopride partially reversed L-DOPA inhibition in choroidal explants. Quinpirole suppressed CNV lesion number, lesion area, and macrophage infiltration in pigmented Vldlr-/- mice.<br><br>CONCLUSIONS: Our findings show that L-DOPA's anti-angiogenic effects are exogenous, more effective in tyrosinase-mutant mice, and mediated by both the DRD2 and non-DRD2 pathways, potentially GPR143. The saturation of GPR143 signaling in pigmented eyes provides a mechanistic basis for reduced responsiveness, highlighting the importance of pigmentation biology in the development of L-DOPA-based therapeutics.}, }
@article {pmid41533916, year = {2026}, author = {Lyu, A and Mungalsingh, MA and Silva, AE and Khan, S and Labreche, T and Leat, SJ and Woo, GC and Woo, S and Thompson, B and Cheong, AMY}, title = {Transcranial Direct Current Stimulation Does Not Enhance Perceptual Learning of Chinese Character Reading in Adults With Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {1}, pages = {16}, pmid = {41533916}, issn = {1552-5783}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Contrast Sensitivity/physiology ; *Learning/physiology ; *Macular Degeneration/physiopathology/therapy ; *Reading ; *Transcranial Direct Current Stimulation/methods ; Visual Acuity/physiology ; Visual Cortex/physiology ; *Visual Perception/physiology ; Language ; }, abstract = {PURPOSE: Macular degeneration impairs central vision, compelling patients to use their peripheral vision for reading, which is difficult due to reduced spatial resolution and crowding. Although perceptual learning improves reading, single-session anodal transcranial direct current stimulation (a-tDCS) over the visual cortex has shown inconsistent outcomes, with transient improvements observed in English reading but no benefit for Chinese reading in macular degeneration patients. This randomized controlled trial investigated whether combining multi-session a-tDCS with perceptual learning enhances Chinese reading performance in these patients compared to sham stimulation.<br><br>METHODS: Twenty Chinese-reading patients with macular degeneration (39-90 years old) were randomized to receive either active (n = 10) or sham (n = 10) a-tDCS during six sessions of rapid serial visual presentation (RSVP) reading training. Trained outcomes (RSVP reading) and untrained functions (sentence reading, crowding, contrast sensitivity, and visual acuity) were compared at baseline, 1 day, and 1 month post-training.<br><br>RESULTS: Perceptual learning significantly improved RSVP reading speed (P < 0.001) in both groups, with effects lasting at least a month. No additive effect of active versus sham a-tDCS was observed (group &#xd7; time P = 0.99). Transfer effects to untrained functions were limited to visual acuity and critical print size for sentence reading.<br><br>CONCLUSIONS: Perceptual learning enhances Chinese reading performance in individuals with macular degeneration, but a-tDCS confers no additional benefit. This contrasts with previous results where non-invasive brain stimulation enhanced English reading in macular degeneration. The results emphasize the need for more refined neuromodulation strategies for improving logographic reading.}, }
@article {pmid41533927, year = {2025}, author = {Li, Q and Liu, D and Zhang, M}, title = {Obstructive Sleep Apnea Accelerates Progression of Intermediate Age-Related Macular Degeneration: A Three-Year Prospective Cohort Study.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {59}, pmid = {41533927}, issn = {1552-5783}, mesh = {Humans ; Female ; Male ; Disease Progression ; *Sleep Apnea, Obstructive/complications/physiopathology/diagnosis ; Prospective Studies ; Aged ; Middle Aged ; Visual Acuity/physiology ; Follow-Up Studies ; Polysomnography ; *Macular Degeneration/diagnosis/physiopathology ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/diagnosis/physiopathology ; Risk Factors ; Geographic Atrophy/diagnosis ; Fluorescein Angiography ; }, abstract = {PURPOSE: Obstructive sleep apnea (OSA) and age-related macular degeneration (AMD) share pathophysiological mechanisms involving oxidative stress and inflammation. We investigated whether OSA accelerates AMD progression in patients with intermediate AMD.<br><br>METHODS: This prospective cohort study enrolled 470 patients aged &#x2265;50 years with intermediate AMD and age-matched healthy controls. After baseline polysomnography and multimodal retinal imaging, 470 participants were enrolled and stratified into AMD+OSA (n = 185), AMD-noOSA (n = 185), and healthy controls (n = 100). Of these, 391 completed the 36-month follow-up (AMD+OSA n = 153; AMD-noOSA n = 158; controls n = 80). The primary endpoint was composite AMD progression (central geographic atrophy, neovascular AMD, or &#x2265;15-letter vision loss) over 36 months. Secondary endpoints included changes in visual acuity, drusen volume, and geographic atrophy area.<br><br>RESULTS: Of 391 participants completing follow-up (83.2% retention), the AMD+OSA group showed significantly higher progression rates. The primary endpoint occurred in 31.4% (48/153) of AMD+OSA versus 15.2% (24/158) of AMD-noOSA patients (P = 0.002). Visual acuity worsened by 0.15 versus 0.06 logarithm of the minimum angle of resolution (P < 0.001), and drusen volume increased by 0.05 versus 0.02 mm3 (P < 0.001), respectively. Cox regression revealed a dose-dependent relationship: mild OSA (hazard ratio [HR] = 1.45; 95% confidence interval [CI], 0.95-2.20; P = 0.08), moderate OSA (HR = 2.10; 95% CI, 1.35-3.28; P = 0.001), and severe OSA (HR = 2.80; 95% CI, 1.75-4.47; P < 0.001) versus no OSA.<br><br>CONCLUSIONS: OSA is an independent, dose-dependent risk factor for accelerated AMD progression. Screening and treating OSA in patients with intermediate AMD may represent a novel strategy to preserve vision.}, }
@article {pmid41533930, year = {2025}, author = {Kato, N and Haruta, M and Arai, R and Nagae, A and Sato, K and Furushima, K and Yoshida, S}, title = {Association of Molar Dose and Early Retinochoroidal Blood Flow Changes After Intravitreal Anti-Vascular Endothelial Growth Factor Therapy.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {56}, pmid = {41533930}, issn = {1552-5783}, mesh = {Humans ; Intravitreal Injections ; Retrospective Studies ; Recombinant Fusion Proteins/administration &amp; dosage ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Female ; Male ; *Choroid/blood supply ; *Angiogenesis Inhibitors/administration &amp; dosage ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Regional Blood Flow/physiology/drug effects ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Aged, 80 and over ; *Retinal Vessels/physiopathology/physiology ; Dose-Response Relationship, Drug ; Laser-Doppler Flowmetry ; *Wet Macular Degeneration/drug therapy/physiopathology ; Fluorescein Angiography ; Middle Aged ; Blood Flow Velocity ; Follow-Up Studies ; Visual Acuity ; Tomography, Optical Coherence ; }, abstract = {PURPOSE: The purpose of this study was to evaluate short-term intraocular blood flow changes post-intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in patients with neovascular age-related macular degeneration (nAMD), compare reductions across 4 agents (brolucizumab, faricimab, aflibercept 2 mg, and aflibercept 8 mg), and examine correlations between each agent's molar dose and the magnitude of 30-minute blood flow change.<br><br>METHODS: This retrospective series included 61 eyes with nAMD (15 treated with brolucizumab, 15 with faricimab, 15 with aflibercept 2 mg, and 16 with aflibercept 8 mg). Laser speckle flowgraphy quantified mean blur rate (MBR) at the optic nerve head vessels (ONH MBR-vessel) and choroid (CHOR MBR) before and 30 minutes post-injection. Percent changes (%ONH MBR-vessel, %CHOR MBR) were compared among groups, and correlations with molar dose were assessed.<br><br>RESULTS: In the aflibercept 8 mg group, the mean percent changes were -11.2% &#xb1; 11.2% for ONH MBR-vessel (P = 0.001) and -13.7% &#xb1; 7.5% for CHOR MBR (P < 0.001). Pairwise comparisons showed no significant differences in %ONH MBR-vessel between aflibercept 8 mg and other agents. The reduction in %CHOR MBR was significantly greater with aflibercept 8 mg than with aflibercept 2 mg (P = 0.019). Molar dose was not significantly correlated with %ONH MBR-vessel, whereas %CHOR MBR showed a significant negative association with molar dose (Spearman &#x3c1; = -0.395, P = 0.002).<br><br>CONCLUSIONS: Aflibercept 8 mg produced a significant 30-minute reduction in ocular blood flow. Choroidal flow reduction was greater than with aflibercept 2 mg and negatively correlated with molar dose, suggesting a concentration-dependent hemodynamic effect.}, }
@article {pmid41533943, year = {2025}, author = {Kramer, A and Rinsky, B and Elbaz-Hayoun, S and Khateb, S and Jaouni, T and Jaskoll, S and Tiosano, L and Durst, R and Chowers, I}, title = {Altered High-Density Lipoprotein Expression Pattern in the Aqueous Humor From Eyes With Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {73}, pmid = {41533943}, issn = {1552-5783}, mesh = {Humans ; *Aqueous Humor/metabolism ; Male ; Female ; Aged ; *Lipoproteins, HDL/metabolism ; Proteomics/methods ; Chromatography, Liquid ; Aged, 80 and over ; Tandem Mass Spectrometry ; *Wet Macular Degeneration/metabolism ; Middle Aged ; *Macular Degeneration/metabolism ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is associated with altered protein expression in the aqueous humor (AH). We aim to perform an unbiased proteomic analysis of the AH to identify proteomic signatures characterizing the disease's neovascular AMD (nAMD) and non-neovascular AMD (nnAMD) stages.<br><br>METHODS: AH samples were collected from eyes with nAMD (n = 39), nnAMD (n = 30), and healthy control eyes (n = 36). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the AH proteome; differentially expressed proteins underwent functional analysis. Serum high-density lipoprotein cholesterol (HDL-C) levels were correlated with AH high-density lipoprotein (HDL) pathway proteins.<br><br>RESULTS: Seventeen proteins were upregulated and five were downregulated in nAMD eyes compared with healthy controls. Enriched pathways include the fibrinogen complex, the complement alternate, the spherical HDL particle, and the serine protease inhibitor. Forty-six proteins were upregulated in nAMD versus nnAMD, whereas nine were downregulated. Enriched pathways included the spherical HDL particle, peptidase S1A, membrane attack complex, Sushi domain, and complement alternate pathway. No differentially expressed proteins were found between nnAMD and control eyes. Upregulated proteins associated with the spherical HDL particle pathway in nAMD, including apolipoprotein A-I, apolipoprotein A-II, and paraoxonase 1, exhibited a negative correlation with serum HDL-C levels (r = -0.43, P = 0.012; r = -0.37, P = 0.031; and r = -0.52, P = 0.002, respectively).<br><br>CONCLUSIONS: HDL-associated proteins exhibit increased expression in AH of nAMD eyes, independent of serum HDL-C levels. These findings suggest that serum HDL-C may not accurately reflect ocular HDL particle levels, highlighting the role of retinal lipid dysregulation in nAMD.}, }
@article {pmid41534822, year = {2026}, author = {Zahran, L and Elnabawy, RH}, title = {Key optogenetic advances in retinal prostheses: A comparative narrative review.}, journal = {Brain research}, volume = {1874}, number = {}, pages = {150166}, doi = {10.1016/j.brainres.2026.150166}, pmid = {41534822}, issn = {1872-6240}, mesh = {*Optogenetics/methods ; Humans ; *Visual Prosthesis/trends ; Retinal Ganglion Cells/physiology ; Animals ; Retina ; Retinitis Pigmentosa/therapy ; }, abstract = {This narrative review examines optogenetic strategies for retinal prostheses, which represent an advanced step in vision restoration, particularly for patients with retinitis pigmentosa and age-related macular degeneration. This review highlights the use of optogenetic stimulation to target high-density retinal ganglion cells (RGCs), focusing on developments like the FlexLED device. Opsins such as ChR2, ReaChR, and ChrimsonR, engineered for light sensitivity and faster responses, are critical for enhancing vision restoration. Combining optogenetic and electrical stimulation improves the reproducibility and specificity of RGC responses. Neuroimaging techniques like adaptive optics scanning laser ophthalmoscopy (AOSLO) help monitor cell activity, aiding in the development of visual repair methods. However, challenges remain in improving opsin sensitivity, gene delivery techniques, and ensuring long-term efficacy of retinal responses in patients. This review emphasizes the potential of optogenetic retinal prostheses to offer lasting, effective vision rehabilitation, significantly improving the quality of life for patients. This narrative review emphasizes that further research is needed to overcome current obstacles, such as improving opsin sensitivity and gene delivery techniques, to ensure long-term, effective vision restoration in patients.}, }
@article {pmid41535097, year = {2026}, author = {Carlà, MM and Crincoli, E and Catania, F and De Luca, L and Giannuzzi, F and Boselli, F and Gambini, G and Mateo, C and Rizzo, S}, title = {Advanced analysis of leading large language models for diagnostic accuracy in retinal imaging.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-327634}, pmid = {41535097}, issn = {1468-2079}, abstract = {BACKGROUND/AIMS: To evaluate and compare the diagnostic capabilities of advanced large language models (LLMs) in interpreting ophthalmological fundus images across diverse pathologies.<br><br>METHODS: We evaluated eight leading multimodal LLMs (GPT-4.5, Claude 3.7 Sonnet, Grok-2, Deepseek Cognition V2, Qwen2 72B, Gemini 2.0 Pro, Llama 3 405B and Mixtral 8&#xd7;22B) on their ability to interpret 100 fundus images representing various ophthalmological conditions. Performance was assessed using validated charts for diagnostic accuracy, specificity, sensitivity, consistency, relevance and explanation quality.<br><br>RESULTS: GPT-4.5 achieved the highest overall diagnostic accuracy (65.0%), followed by Gemini 2.0 Pro (63.0%). All models showed varied performance across pathology categories, with rhegmatogenous pathologies being most accurately identified (Gemini 2.0 Pro: 81.3%, GPT-4.5: 75.0%) and myopic maculopathy (mean accuracy 21.8%) being particularly challenging. The remaining models performed significantly worse: Deepseek Cognition V2 (52.0%), Claude 3.7 Sonnet (52.0%), Qwen2 72B (49.0%), Llama 3 405B (48.0%), Grok-2 (47.0%) and Mixtral 8&#xd7;22B (46.0%). Lower-performing models frequently declined to provide diagnoses, with refusal rates from 8.0% (Claude 3.7 Sonnet) to 19.0% (Mixtral 8&#xd7;22B).<br><br>CONCLUSION: Current LLMs show promising but limited capabilities in ophthalmological image interpretation. While performance on common conditions like retinal detachments and age-related macular degeneration is moderately good, significant challenges remain with rare conditions, myopic pathologies and complex vascular disorders. The competitive performance between GPT-4.5 and Gemini 2.0 Pro, with each excelling in different pathology categories, suggests that leveraging their complementary strengths might offer improved diagnostic support.}, }
@article {pmid41535412, year = {2026}, author = {García Cruz, MC and Flores Márquez, A and Morilla Ortega, A and Moreno Gutiérrez, J&#xc1; and Barranco Rodríguez, M and Escarramán Reyes, J and García Casares, N and Chinchurreta Capote, A}, title = {Resilience and vision-related quality of life in advanced age-related macular degeneration: a brief clinical report.}, journal = {Eye (London, England)}, volume = {40}, number = {5}, pages = {733-734}, pmid = {41535412}, issn = {1476-5454}, }
@article {pmid41536214, year = {2026}, author = {Wu, J and Su, B and Fan, Z and Zhan, H}, title = {Genetically predicted high-density lipoprotein traits and pan-disease risk: a systematic review.}, journal = {Epidemiologic reviews}, volume = {48}, number = {1}, pages = {}, doi = {10.1093/epirev/mxag001}, pmid = {41536214}, issn = {1478-6729}, mesh = {Humans ; *Lipoproteins, HDL/genetics/blood ; Mendelian Randomization Analysis ; Biomarkers/blood ; Risk Factors ; }, abstract = {High-density lipoprotein (HDL) is a highly heterogeneous lipoprotein with multiple physiological functions. However, observational studies present conflicting evidence regarding its association with various diseases. This review systematically summarizes evidence from Mendelian randomization (MR) studies to investigate the causal relationships between HDL-related biomarkers and a wide spectrum of disease outcomes. We systematically searched multiple databases up to November 2024. The causal relationship between HDL and 158 diseases was studied. Findings reveal that the role of HDL is highly disease-specific. Genetically predicted higher HDL levels are protective against most circulatory and digestive system diseases. Conversely, however, they are associated with an increased risk of certain conditions, including breast cancer, intracerebral hemorrhage, and age-related macular degeneration. The MR analyses revealed inconsistent and sometimes conflicting findings for several disease outcomes, notably Alzheimer's disease. This review underscores the context-dependent nature of HDL's effects, which may be driven by factors like HDL particle heterogeneity and functional transformation into a pro-inflammatory state. Future research should move beyond concentration-based metrics to focus on HDL functionality and precise subtyping to fully understand its role in disease etiology.}, }
@article {pmid41536240, year = {2026}, author = {Němec, P and Vysloužilová, D and Hejsek, L and Němčanský, J and Studnička, J}, title = {Best Practices for Age-Related Macular Degeneration (AMD) Therapy.}, journal = {Ceska a slovenska oftalmologie : casopis Ceske oftalmologicke spolecnosti a Slovenske oftalmologicke spolecnosti}, volume = {82}, number = {Ahead of Print}, pages = {1-9}, doi = {10.31348/2026/2}, pmid = {41536240}, issn = {1211-9059}, mesh = {Humans ; *Macular Degeneration/diagnosis/therapy/classification ; }, abstract = {Age-related macular degeneration is one of the leading causes of severe loss of sight in developed countries. Diagnostic procedures have developed dramatically in recent years, and modern imaging methods have contributed to improved options for population screening, targeted diagnostics, and monitoring of the treatment process. At the same time, new treatment options have also been developing rapidly. The recommended procedures summarize the current knowledge with the aim of unifying procedures for the diagnosis, classification, and treatment of age-related macular degeneration (AMD).}, }
@article {pmid41537428, year = {2026}, author = {Lucenteforte, E and Ng, SM and Saulle, R and Hoad, G and Schillinger, R and Virgili, G}, title = {Anti-vascular endothelial growth factor (anti-VEGF) agents for neovascular age-related macular degeneration (nAMD): a network meta-analysis.}, journal = {The Cochrane database of systematic reviews}, volume = {1}, number = {1}, pages = {CD016298}, pmid = {41537428}, issn = {1469-493X}, mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use/adverse effects ; Antibodies, Monoclonal, Humanized/therapeutic use ; Bevacizumab/therapeutic use ; *Biosimilar Pharmaceuticals/therapeutic use ; *Macular Degeneration/drug therapy ; Network Meta-Analysis as Topic ; Randomized Controlled Trials as Topic ; Ranibizumab/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; }, abstract = {This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the comparative efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) agents and their biosimilars for people with neovascular age-related macular degeneration (nAMD), and provide a relative ranking of interventions using network meta-analysis (NMA) methods, considering differences in treatment intensity.}, }
@article {pmid41537758, year = {2026}, author = {Cheung, R and Trinh, M and Duong, A and Chen, S and Ng, D and Schiller, G and Hodge, C and Nivison-Smith, L}, title = {Prognostic Ability of Automated RPE Sinuosity for Late AMD Supersedes Qualitative Outer Retinal Band Assessment.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {1}, pages = {33}, pmid = {41537758}, issn = {1552-5783}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/pathology ; Female ; Male ; Aged ; Prognosis ; *Macular Degeneration/diagnosis ; Disease Progression ; Follow-Up Studies ; Aged, 80 and over ; Middle Aged ; Visual Acuity ; }, abstract = {PURPOSE: Outer retinal band integrity strongly predicts late age-related macular degeneration (AMD), however, it is often assessed subjectively and vulnerable to intergrader variability. This study quantifies retinal pigment epithelium (RPE) sinuosity from automated segmentations of a commercially available optical coherence tomography (OCT) and its ability to predict late AMD.<br><br>METHODS: Consecutive patients with intermediate AMD who progressed to late disease (n = 69) or remained stable (n = 198) were recruited. Outer retinal band integrity was measured quantitatively using RPE sinuosity, calculated as the ratio of RPE:RPE-fit line length across macular B-scans. RPE sinuosity was measured in the foveal B-scan alongside the mean, maximum, and median values across the five central B-scans. The RPE and ellipsoid zone (EZ) continuity was graded qualitatively, as well as other AMD biomarkers currently used for prognostication. Adjusted odds ratios for progression were calculated for each variable.<br><br>RESULTS: Mean follow-up time was 3.15 years (1.93 years). Pigmentary abnormalities (P = 0.001), subretinal drusenoid deposits (SDDs; P > 0.0001), drusen volume (P = 0.01), and late AMD in the fellow eye (P = 0.001) were present in a higher proportion of progressor than stable eyes at baseline. Median RPE sinuosity was the strongest predictor of progression within 5 years (2.52 [1.14-5.55]) and across the study period (2.35 [1.25-4.43]). No qualitative measures could predict late AMD within any time frame.<br><br>CONCLUSIONS: RPE sinuosity outperformed qualitative outer retinal band integrity assessments for late AMD prediction and is a reliable, repeatable evaluation method. Verifying these results using different OCT devices in a prospective cohort is needed to determine whether the feature can enhance late AMD risk models and improve clinical management.}, }
@article {pmid41538072, year = {2026}, author = {Zong, Y and Liu, J and Yang, M and Zhang, J and Zou, Y and Ye, Z and Deng, J and Gu, W and Du, J and Ohno-Matsui, K and Kamoi, K}, title = {Advances in microneedle Technology for Treatment of retinal degenerative diseases: a narrative review.}, journal = {Biomedical microdevices}, volume = {28}, number = {1}, pages = {5}, pmid = {41538072}, issn = {1572-8781}, mesh = {Humans ; *Needles ; Animals ; *Retinal Degeneration/drug therapy/therapy ; *Drug Delivery Systems/instrumentation ; }, abstract = {Retinal degenerative diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR), present significant therapeutic challenges due to the complex anatomical and physiological barriers of the posterior eye. Conventional drug delivery methods, particularly intravitreal injections, are often limited by their invasiveness, rapid drug clearance, and burden on patient compliance. Microneedle technology has emerged as a paradigm-modifying approach for ocular drug delivery, offering a minimally invasive platform to bypass barriers like the blood-retinal barrier while targeting specific ocular tissues. This narrative review provides a critical overview of the latest advancements in microneedle technology for treating retinal degeneration, evaluating diverse configurations-including solid, hollow, dissolvable, coated, and hydrogel-forming designs-and their efficacy in facilitating suprachoroidal, intravitreal, and subretinal administration. Recent clinical trials highlighted in this review demonstrate promising results regarding safety, delivery efficiency, and patient acceptability. However, the translation from bench to bedside still faces hurdles in scale-up production, regulatory standardization, and long-term stability assessment. We discuss these technological challenges and explore future developments, such as the integration of smart materials and personalized approaches, emphasizing the potential of microneedle systems to revolutionize treatment paradigms through precise, controlled delivery to the posterior eye segments.}, }
@article {pmid41538667, year = {2025}, author = {Soares, TS and Cristino, ADS and Silva, AF and Santos, LRD}, title = {Optical coherence tomography angiography for the diagnosis of choroidal neovascularization in age-related macular degeneration: a systematic review.}, journal = {Einstein (Sao Paulo, Brazil)}, volume = {23}, number = {}, pages = {eRW1521}, pmid = {41538667}, issn = {2317-6385}, mesh = {Humans ; *Choroidal Neovascularization/diagnostic imaging ; *Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Sensitivity and Specificity ; *Macular Degeneration/diagnostic imaging/complications ; Aged ; Middle Aged ; Reproducibility of Results ; }, abstract = {OBJECTIVE: To evaluate the diagnostic accuracy of optical coherence tomography angiography for the identification of choroidal neovascularization in age-related macular degeneration.<br><br>METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations. A literature search of the PubMed/MEDLINE, Scientific Electronic Library Online (SciELO), EMBASE, Cochrane Library, CAPES Periodicals, and LILACS scientific databases was conducted to identify relevant full-text articles published in English and Portuguese from January 2012 to January 2025. To comprehensively evaluate the effectiveness and the performance of optical coherence tomography angiography in terms of sensitivity and specificity, fundus fluorescein angiography (the gold standard for detecting choroidal neovascularization) was used as the comparator. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) 2 tool was used to assess methodological quality and risk of bias.<br><br>RESULTS: Eleven articles were included in the systematic review. The patients' mean age ranged from 58.5 to 79.7 years. The sensitivity ranged from 50.0% to 94.0%, and the specificity ranged from 67.6% to 100.0%. The risk of bias was low, and the methodological quality of the studies was good, suggesting that optical coherence tomography angiography holds promise for the diagnosis of choroidal neovascularization.<br><br>CONCLUSION: Optical coherence tomography angiography exhibited high sensitivity and specificity, demonstrating its potential for the detection of choroidal neovascularization in patients with age-related macular degeneration. However, current scientific evidence suggests that optical coherence tomography angiography is not superior to fundus fluorescein angiography and should not be used as a substitute. Extended and affordable protocols to analyze different subtypes of choroidal neovascularization and the performance of optical coherence tomography angiography devices should be evaluated.<br><br>CRD420251046669.}, }
@article {pmid41539007, year = {2026}, author = {Cohen, BA and Fhima, J and Meisel, M and Meital, B and Nakayama, LF and Berkowitz, E and Behar, JA}, title = {Ophthalmology foundation models for clinically significant age macular degeneration detection.}, journal = {Physiological measurement}, volume = {47}, number = {3}, pages = {}, doi = {10.1088/1361-6579/ae3936}, pmid = {41539007}, issn = {1361-6579}, mesh = {*Macular Degeneration/diagnostic imaging/diagnosis ; Humans ; *Ophthalmology ; Supervised Machine Learning ; }, abstract = {Objective. Self-supervised learning (SSL) has enabled vision transformers (ViTs) to learn robust representations from large-scale natural image datasets, enhancing their generalization across domains. In retinal imaging, foundation models pretrained on either natural or ophthalmic data have shown promise, but the benefits of in-domain pretraining remain uncertain.Approach. To investigate this, we benchmark six SSL-pretrained ViTs on seven digital fundus image (DFI) datasets totaling 70 000 expert-annotated images for the task of moderate-to-late age-related macular degeneration (AMD) identification.Main results. Our results show that DINOv2, pretrained on natural images, shows similar performance than domain-specific models. These findings highlight the value of foundation models in improving AMD identification, and challenge the assumption that in-domain pretraining is necessary.Significance. We present our model AMDNet, which performs state-of-the-art out-of-domain AUROCs on six public datasets. Furthermore, we release BRAMD, an open-access dataset (n = 587) of DFIs with AMD labels from Brazil. Project page:www.aimlab-technion.com/lirot-ai.}, }
@article {pmid41542493, year = {2026}, author = {Shang, P and Hoang, J and Hong, E and Geng, Z and Ambrosino, H and Abnoosian, E and Zhu, X and Ma, M and Wei-Navarro, NA and Webber, B and Qu, J and Montezuma, SR and Agbaga, MP and Dutton, JR and Ferrington, DA}, title = {Complement Factor H (Y402H) polymorphism for age-related macular degeneration alters retinal lipids.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.06.697989}, pmid = {41542493}, issn = {2692-8205}, abstract = {Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is associated with multiple risk factors and involves death of the retinal pigment epithelium (RPE). We investigated how the Y402H polymorphism of Complement Factor H (CFH) and cigarette smoke extract (CSE), major AMD genetic and environmental risks, affect lipid metabolism in RPE differentiated from induced pluripotent stem cells (iPSC-RPE) that were derived from human donors genotyped for low-risk (LR) or high-risk (HR) CFH. Results from discovery-based (lipidomics, proteomics) and targeted (mitochondrial fatty acid oxidation (FAO)) assays found significant genotype-dependent differences under basal conditions include higher free fatty acids and cholesterol esters in HR cells. CSE induced differences in proteins regulating lipid handling, lipolysis, and inflammation. Lower FAO in HR cells was observed in multiple donors and pairs of parent/isogenic edited lines compared with LR lines. CSE induced lipid accumulation, lipid composition remodeling, and upregulation of proteins involved in lipid synthesis/hydrolysis, production of bioactive lipid mediators, and metabolism of ceramide and cholesterol. These results elucidate putative mechanisms driving pathology in RPE harboring CFH Y402H.}, }
@article {pmid41543675, year = {2026}, author = {El Alili, M and van de Laar, CJ and de Greeff, JPF and Vromans, JGF and van Asten, F and Bosmans, JE}, title = {Budget Impact of Faricimab in Neovascular Age-Related Macular Degeneration in the Netherlands: A Systematic Review and Meta-Analysis of Injection Count.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {2}, pages = {591-639}, pmid = {41543675}, issn = {2193-8245}, abstract = {INTRODUCTION: Frequent anti-vascular endothelial growth factor (anti-VEGF) injections for the treatment of neovascular age-related macular degeneration (nAMD) burden patients and healthcare systems. Faricimab may reduce this burden, but robust data are lacking. This study aimed to systematically quantify the injection frequency reduction with faricimab compared to anti-VEGF agents and estimate Dutch budget impact.<br><br>METHODS: A systematic review of studies on patients with nAMD switching to faricimab was conducted in PubMed. A hybrid approach using artificial intelligence (NotebookLM) and manual verification was employed for data extraction and risk of bias assessment. A random-effects meta-analysis determined the pooled mean difference in annual injections. A budget impact analysis estimated direct medical costs (drug and administration costs) over a 1-year time horizon using Dutch data.<br><br>RESULTS: A meta-analysis of 19 real-world studies (2231 patients) was conducted. Patients switched to faricimab for persistent fluid or to extend treatment intervals, resulting in a significant mean reduction of 2.65 injections in the first year (from 9.70 to 7.05; 95% confidence interval -&#x2009;3.36 to -&#x2009;1.93). The base-case analysis projected annual savings of approximately &#x20ac;79&#xa0;million, corresponding to 96,235 fewer injections nationwide. Scenario analyses showed that substantial savings (&#x20ac;16 to &#x20ac;75&#xa0;million) can be achieved when using faricimab in second- and third-line settings, although replacing first-line bevacizumab would increase costs.<br><br>CONCLUSIONS: Switching patients to faricimab reduced the injection frequency by two to three injections in the first year. Although evidence certainty was limited by statistical heterogeneity, the reduction was consistent across studies. Although replacing first-line bevacizumab increases costs, substantial savings are achievable in later lines. Strategic positioning of faricimab in the second-line yields significantly higher savings compared to third-line use, and could significantly lower the clinical, patient, and economic burden of nAMD care in the Netherlands. These findings provide quantified, real-world evidence to inform Dutch clinical practice and healthcare policy.}, }
@article {pmid41543898, year = {2026}, author = {Singh, KK and Jin, Y and Hu, MW and Palazzo, I and Cano, M and Hoang, T and Bhutto, I and Wang, S and Sinha, D and Blackshaw, S and Qian, J and Handa, JT}, title = {Molecular underpinnings of induced degenerative heterogeneity in the retinal pigment epithelium.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {3}, pages = {e2505412123}, pmid = {41543898}, issn = {1091-6490}, support = {EY033765//HHS | NIH | National Eye Institute (NEI)/ ; EY031594//HHS | NIH | National Eye Institute (NEI)/ ; EY035805//HHS | NIH | National Eye Institute (NEI)/ ; EY031594//HHS | NIH | National Eye Institute (NEI)/ ; EY036173//HHS | NIH | National Eye Institute (NEI)/ ; EY031779//HHS | NIH | National Eye Institute (NEI)/ ; EY001765//HHS | NIH | National Eye Institute (NEI)/ ; Stein award//Research to Prevent Blindness (RPB)/ ; EY034571//HHS | NIH | National Eye Institute (NEI)/ ; M2020166//BrightFocus Foundation (BFF)/ ; None//Maryland Stem Cell Research Fund (MSCRF)/ ; None//Foundation Fighting Blindness (FFB)/ ; None//Edward N. and Della L. Thome Memorial Foundation (Thome Memorial Foundation)/ ; }, mesh = {Animals ; *Retinal Pigment Epithelium/pathology/metabolism/drug effects ; Mice ; *Macular Degeneration/pathology/genetics/metabolism ; Humans ; Aging/genetics/pathology ; Epigenesis, Genetic ; Mice, Inbred C57BL ; Male ; Cigarette Smoking/adverse effects ; Female ; }, abstract = {Cigarette smoking induces epigenetic changes that can cause degenerative heterogeneity with aging and disease. In disease such as age-related macular degeneration (AMD), the leading worldwide cause of blindness among the elderly, retinal pigment epithelial (RPE) cell heterogeneity is a key change. Since smoking is a powerful risk factor for AMD, we hypothesized that smoke induces epigenetic-mediated degenerative RPE heterogeneity. We administered cigarette smoke condensate (CSC) to young and aged mice. Using snRNA-seq and single nuclear ATAC sequencing, we identified distinct healthy and dedifferentiated RPE clusters in both aged vehicle- and young CSC-treated mice. Dedifferentiated RPE had globally decreased chromatin accessibility and expression of genes linked to "hallmarks of aging." Notably, young, dedifferentiated RPE also exhibited a compensatory upregulation of hallmarks of aging-related genes including mitochondrial function and proteostasis while aged dedifferentiated RPE did not, which decreased their survival following CSC treatment, as experimentally verified with TUNEL labeling. Similar populations of dedifferentiated and healthy RPE were identified both in mice exposed to cigarette smoke for 4 mo and in macular RPE from a donor who smoked and another with early AMD, but not from a nonsmoker donor. Degenerative cellular heterogeneity that includes an abnormal cluster can jeopardize cell survival and represents a hallmark of ocular aging.}, }
@article {pmid41544798, year = {2026}, author = {Zhang, M and Ge, Y and Wang, Z and Li, H and Wang, G and Zhang, Y and Wang, X and Hou, H and Meng, L and Wei, L and Meng, D and Wang, L and Sheng, HY and Yin, Y and Mortadza, SAS and Roger, S and Li, J and Ren, F and Jiang, LH}, title = {Insights into the role of the mechanosensitive Piezo1 channel and signaling mechanisms in CNS functions and diseases.}, journal = {Neuroscience and biobehavioral reviews}, volume = {183}, number = {}, pages = {106562}, doi = {10.1016/j.neubiorev.2026.106562}, pmid = {41544798}, issn = {1873-7528}, mesh = {Humans ; *Ion Channels/metabolism ; Animals ; *Central Nervous System/metabolism ; *Central Nervous System Diseases/metabolism ; *Mechanotransduction, Cellular/physiology ; *Signal Transduction/physiology ; Neurodegenerative Diseases/metabolism ; }, abstract = {The mechanosensitive Piezo1 channel is widely distributed in the central nervous system (CNS), expressed by neurons, astrocytes, oligodendrocytes, microglia, neural stem and progenitor cells, retinal ganglion and photoreceptor cells and, moreover, neurovascular and lymphatic endothelial cells, implicating an important role for the Piezo1 channel in the CNS physiology and disease. Indeed, recent studies have disclosed that the Piezo1 channel plays a vital part in mediating or modulating numerous CNS functions, ranging from brain development, synapse function, neurogenesis, axonal (re)generation, axonal pathfinding, astrocyte-neuron communication, axonal myelination, immune response, brain vasculature modelling to cerebrospinal fluid drainage. There is also increasing evidence to indicate critical engagement of the Piezo1 channel in the pathogenesis and progression of multiple debilitating CNS conditions, exemplified by spinal cord injury, stroke and related ischemia/reperfusion brain damage, neurodegenerative diseases, and age-related macular degeneration. Here, we provide a comprehensive overview of the current understanding and highlight the unanswered questions regarding the roles and mechanisms of the Piezo1 channel in CNS functions and diseases, presenting the Piezo1 channel as an attractive therapeutic target to intervene CNS damage and diseases.}, }
@article {pmid41545331, year = {2026}, author = {Polasek, TM and Paneliya, KJ and Lin, T and Mata, NL and Wang, I and Scholl, HP and Lin, J}, title = {Effects of Gastric Acid Suppression, Cytochrome P4503A Inhibition and Induction, and Food on the Pharmacokinetics of Tinlarebant in Healthy Adults.}, journal = {Clinical pharmacology in drug development}, volume = {15}, number = {1}, pages = {e70009}, doi = {10.1002/cpdd.70009}, pmid = {41545331}, issn = {2160-7648}, support = {//Belite Bio Inc/ ; }, mesh = {Humans ; Male ; Adult ; Female ; *Cytochrome P-450 CYP3A Inhibitors/pharmacology/administration &amp; dosage/adverse effects ; *Food-Drug Interactions ; Young Adult ; Middle Aged ; Healthy Volunteers ; *Omeprazole/pharmacology/administration &amp; dosage ; Cytochrome P-450 CYP3A/metabolism ; Area Under Curve ; *Itraconazole/pharmacology/administration &amp; dosage ; Rifampin/pharmacology/administration &amp; dosage ; *Cytochrome P-450 CYP3A Inducers/pharmacology/administration &amp; dosage/adverse effects ; *Proton Pump Inhibitors/pharmacology/administration &amp; dosage ; Drug Interactions ; Administration, Oral ; Adolescent ; }, abstract = {Tinlarebant is an oral retinol binding protein 4 antagonist in clinical development for geographic atrophy, an advanced stage of dry age-related macular degeneration, and Stargardt disease, an inherited juvenile-onset macular degeneration. A randomized, open-label, two-period, interaction study in healthy adults was conducted in four parts to determine the effects of gastric acid suppression (omeprazole 40 mg QD), cytochrome P4503A (CYP3A) inhibition (itraconazole 200 mg BD) and induction (rifampin 600 mg QD), and food on the pharmacokinetics of tinlarebant (5 mg single dose). The effects on tinlarebant exposure were quantified by geometric least squares (GLS) mean Cmax and AUCinf ratios, where GLS mean Cmax or AUCinf with potential perpetrator is divided by GLS mean Cmax or AUCinf without potential perpetrator. Steady-state dosing of omeprazole had no effect on tinlarebant exposure (Cmax ratio = 1.16 and AUCinf ratio = 1.03). The Cmax and AUCinf ratios of tinlarebant following itraconazole dosing were 1.29 and 2.42, respectively. Rifampin co-administration decreased tinlarebant Cmax and AUCinf ratios to 0.53 and 0.19, respectively. Compared with the fasting state, taking tinlarebant with food gave Cmax and AUCinf ratios in the range 1.08-1.22. No unexpected safety signals occurred and tinlarebant was well tolerated in all participants. These data show that the pharmacokinetics of tinlarebant is not significantly altered by gastric acid suppression or food. Dosing patients with tinlarebant and strong CYP3A inhibitors is unlikely to compromise safety based on its pharmacokinetic-pharmacodynamic relationships, but tinlarebant should be contraindicated with strong CYP3A inducers due to potential treatment failure.}, }
@article {pmid41545508, year = {2026}, author = {Jang, B and Lee, CH and Kim, SJ and Yoon, CK and Park, UC and Choi, J and Lee, EK and Kim, YG}, title = {Artificial intelligence based prediction of first recurrence in neovascular age related macular degeneration with validation by 19 experts.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {4440}, pmid = {41545508}, issn = {2045-2322}, mesh = {Humans ; *Artificial Intelligence ; Female ; Aged ; Male ; Recurrence ; Tomography, Optical Coherence ; *Macular Degeneration/drug therapy/diagnosis ; ROC Curve ; Aged, 80 and over ; Ophthalmologists ; Middle Aged ; Algorithms ; }, abstract = {This study aimed to investigate the value and difference in predictive performance between ophthalmologists and a previously developed and validated artificial intelligence (AI) model, and to evaluate how AI assistance influences expert decision-making in reliably assessing recurrence prediction of neovascular age-related macular degeneration (nAMD) after anti-vascular endothelial growth factor (VEGF) treatment. 19 experts (nine retinal specialist ophthalmologists and ten non-retinal specialist ophthalmologists) predicted the first recurrence of nAMD within three months based on optical coherence tomography (OCT) images and clinical information. Predictions were made in five sessions with increasing information availability. The AI model used in this study had been developed and validated in our earlier work, and it predicted recurrence using baseline and after the loading phase OCT images. We compared the area under the receiver operating characteristic curve (AUROC), Fleiss' kappa, and Delong's test between expert groups and the AI algorithm. The study included 149 eyes of 130 patients. The AI model achieved an AUROC of 0.744 (95% confidence interval, 0.665-0.822). Expert performance improved across sessions, with AUROCs ranging from 0.562 ± 0.034 to 0.679 ± 0.049. No significant differences were observed between expert groups based on experience or subspecialty. AI-supported decisions showed slightly improved performance in predicting nAMD recurrence compared to human experts, regardless of clinical experience. These results suggest the potential of AI-assistance in predicting recurrence and optimizing treatment strategies for nAMD, which could significantly improve patient counseling and management. This study also highlights the novel contribution of evaluating the impact of AI assistance on ophthalmologists' decision-making in nAMD recurrence prediction.}, }
@article {pmid41545709, year = {2026}, author = {Gale, R and Awad, MH and Bailey, C and Cackett, P and Chhabra, R and Downey, L and Ghanchi, F and Kotagiri, A and Narendran, N and Pearce, I and Peto, T and Sivaprasad, S and Younis, S and Napier, J and Gilbert, R and Ismat, S}, title = {Aflibercept 8 mg treat-and-extend pathway for the treatment of neovascular age-related macular degeneration: guidance from a UK expert panel.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41545709}, issn = {1476-5454}, abstract = {BACKGROUND/OBJECTIVES: Therapies with robust visual outcomes and reduced patient and healthcare system treatment burden are needed amidst the rising incidence of neovascular age-related macular degeneration (nAMD). Aflibercept 8 mg is an additional treatment option with demonstrated potential for extended dosing intervals of up to 24 weeks. The objective of this publication is to introduce a clinical care pathway, developed by expert consensus of experienced UK clinicians, to support best practice with aflibercept 8 mg in nAMD.<br><br>METHODS: A structured, face-to-face roundtable meeting of 13 UK retina specialists was held on 8 October 2024, organised and funded by Bayer. The expert panel reached consensus following review of key clinical trial data and consideration of current NHS clinical practice to provide guidance on the use of intravitreal aflibercept 8&#x2009;mg in nAMD.<br><br>RESULTS: The panel provided recommendations for an aflibercept 8&#x2009;mg treat-and-extend pathway for both treatment-na&#xef;ve and previously treated patients with nAMD. Criteria were developed to guide dosing interval extension, reduction or maintenance based on visual acuity and optical coherence tomography imaging. More detailed guidance includes considerations for switching treatments to or from aflibercept 8&#x2009;mg, monitoring, and discontinuing treatment.<br><br>CONCLUSIONS: Aflibercept 8&#x2009;mg may offer opportunities for longer treatment intervals and reduced patient and clinic burden compared with first-generation agents. The proposed treatment pathway is practical and accounts for variability in healthcare structures and capacity pressures, providing clinicians with flexibility in implementing these recommendations while addressing patient needs.}, }
@article {pmid41545711, year = {2026}, author = {Bailey, C and Lange, C and Munk, MR and Lanzetta, P and Oubraham, H and Machewitz, T and Allmeier, H and Zhang, X and Morgan-Warren, P and Hasanbasic, Z and Chaudhary, V and , }, title = {Infographic: SPECTRUM: study design of the global real-world study of aflibercept 8 mg in the treatment of neovascular age-related macular degeneration and diabetic macular edema.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41433-025-04140-2}, pmid = {41545711}, issn = {1476-5454}, }
@article {pmid41546875, year = {2026}, author = {Zhang, Y and Gupta, P and Fenwick, E and Man, R and Wong, CMJ and Tan, ACS and Cheung, CMG and Colega, MT and Chong, MF and Lai, JS and Lamoureux, EL}, title = {The Association of Dietary Patterns with Age-Related Macular Degeneration in a Multiethnic Older Singaporean Population.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {}, number = {}, pages = {1-10}, pmid = {41546875}, issn = {1423-0267}, abstract = {INTRODUCTION: The associations of dietary patterns and age-related macular degeneration (AMD) have been reported using mostly Western and Japanese populations and evidence in multiethnic Asian populations, with potentially different dietary patterns, is lacking. In this study, we aimed to identify dietary patterns in a multiethnic older Singaporean population and examine their associations with AMD.<br><br>METHODS: This was a cross-sectional analysis of the Population Health and Eye Disease Profile in Elderly Singaporeans (PIONEER) study. Dietary intake was assessed using a 110-item interviewer-administered food frequency questionnaire validated in a Singaporean population. Presence and stage of AMD were categorized using fundus photographs and an established AMD classification. Dietary patterns were generated by applying exploratory factor analysis, and their associations with presence of AMD and stage of AMD were evaluated using adjusted logistic regression models and adjusted multinomial logistic regression models, respectively.<br><br>RESULTS: Of 1,480 Chinese, Malay, and Indian individuals aged &#x2265;60 years (mean 71.3 &#xb1; 7.7), age-standardized prevalence of any, early, and late AMD were 7.1%, 4.8%, and 2.2%. Three dietary patterns were generated: "snacks, fried foods, and refined carbohydrates"; "poultry, meat, and Fish"; and "wholemeal bread, legumes, and nuts." After adjusting for covariates, higher "snacks, fried foods, and refined carbohydrates" pattern scores were associated with higher odds of any AMD (OR = 1.41, 95% CI: 1.02-1.96) and early AMD (OR = 1.63, 95% CI: 1.12-2.37). "Snacks, fried foods, and refined carbohydrates" pattern scores in the highest quartile were associated with higher odds of any AMD (OR = 2.18, 95% CI: 1.01-4.72), compared to the lowest quartile.<br><br>CONCLUSION: Only the "snacks, fried foods, and refined carbohydrates" pattern was associated with AMD in this multiethnic older Singaporean population. These findings may inform the development of dietary guidelines in Singapore for more targeted AMD management, although prospective, longitudinal data are needed.}, }
@article {pmid41547437, year = {2026}, author = {Torres-Villaros, H and Albou, J and Fajnkuchen, F and Couturier, A and Giocanti-Aurégan, A and Massin, P}, title = {Telemedicine-based diabetic retinopathy screening in patients over 70 Years: a French cohort study within the OPHDIAT network.}, journal = {Diabetes &amp; metabolism}, volume = {52}, number = {2}, pages = {101728}, doi = {10.1016/j.diabet.2026.101728}, pmid = {41547437}, issn = {1878-1780}, mesh = {Humans ; *Diabetic Retinopathy/diagnosis/epidemiology ; Aged ; *Telemedicine ; Male ; Female ; Middle Aged ; France/epidemiology ; Adult ; Cohort Studies ; *Mass Screening/methods ; Adolescent ; Young Adult ; }, abstract = {AIM: To assess the outcomes of teleophthalmology-based diabetic retinopathy (DR) screening in individuals over 70 years within the OPHDIAT network and to compare them with those of patients aged 18-69 years.<br><br>METHODS: A cohort of 16,459 diabetic patients, without known DR or with mild non-proliferative DR (NPDR), screened in 2024 in 32 OPHDIAT centers, was included and divided into two groups: < 70 years (n = 13,639) and &#x2265; 70 years (n = 2,820). Two non-mydriatic retinal photographs per eye were analyzed by certified ophthalmologists.<br><br>RESULTS: Among patients aged &#x2265;70 years, 21.3% (95% CI: 19.8-22.8) had any DR, and 6.1% (95% CI: 5.2-6.9) were referred to an ophthalmologist for moderate NPDR or a more severe form of the disease, including suspected macular edema. These proportions did not significantly differ from those found in patients < 70 years: 21.9% (95% CI: 21.2-22.6) and 6.1% (95% CI:5.6-6.5), respectively. Severe NPDR or proliferative DR were rare in both groups (1.0%, 95% CI: 0.6-1.4% vs. 1.7%, 95% CI: 1.5-1.9%, P < 0.001). The proportion of ungradable images was higher in the group &#x2265;70 year (14.4%, 95% CI:13.1-15.7% vs. 6.1%, 95% CI: 5.7-6.5%, P < 0.001), particularly in phakic eyes, although 80% of patients had interpretable images for both eyes. Pupil dilation significantly improved image quality in this group. Screening also allowed detecting other ocular disorders, including age-related macular degeneration and glaucoma, which were more common in the group &#x2265; 70 years (2.1%, 95% CI: 1.5-2.6% vs. 0.6%, 95% CI: 0.4-0.7% P < 0.001).<br><br>CONCLUSION: Teleophthalmology-based DR screening appeared feasible and clinically relevant in patients aged &#x2265;70 years, allowing identifying patients requiring ophthalmologic evaluation, while also detecting other age-related ocular diseases. Pupil dilation is recommended to optimize image quality in this population.}, }
@article {pmid41548484, year = {2026}, author = {Pan, JQ and Chen, JH and Pan, XB}, title = {Alpha-difluoromethylornithine suppresses angiogenesis via the FLI1-CLEC14A-VEGFC pathway in retinal endothelial cells.}, journal = {Biochemical and biophysical research communications}, volume = {800}, number = {}, pages = {153251}, doi = {10.1016/j.bbrc.2026.153251}, pmid = {41548484}, issn = {1090-2104}, mesh = {Humans ; Animals ; *Endothelial Cells/drug effects/metabolism ; *Lectins, C-Type/metabolism/genetics ; *Proto-Oncogene Protein c-fli-1/metabolism/genetics ; *Vascular Endothelial Growth Factor C/metabolism/genetics ; *Retina/drug effects/metabolism/cytology ; Mice ; Signal Transduction/drug effects ; *Neovascularization, Pathologic/metabolism/drug therapy ; Mice, Inbred C57BL ; Angiogenesis ; }, abstract = {Pathological angiogenesis is a leading cause of vision loss in blinding disorders such as age-related macular degeneration, in which anti-VEGF therapies are widely used, yet their limitations necessitate new therapeutic strategies. This study explores the molecular mechanisms through which alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, suppresses angiogenesis in human retinal microvascular endothelial cells (HRMECs). Transcriptome sequencing revealed that DFMO significantly reduced tube formation and downregulated 3839 genes, including C-type lectin domain-containing 14A (CLEC14A) and vascular endothelial growth factor C (VEGFC), both of which are implicated in angiogenic processes. Functional assays demonstrated that CLEC14A knockdown decreased VEGFC expression and impaired angiogenesis, whereas CLEC14A overexpression alleviated DFMO-induced downregulation of VEGFC. Moreover, bioinformatic analyses and dual-luciferase reporter assays identified Friend leukemia virus integration 1 (FLI1) as a direct transcriptional activator of CLEC14A. Knockdown of FLI1, but not STAT3, reduced CLEC14A expression, confirming the critical regulatory role of FLI1. In vivo studies confirmed upregulation of the FLI1-CLEC14A-VEGFC axis in the retina of a mouse model of choroidal neovascularization. In conclusion, these findings reveal that DFMO suppresses retinal angiogenesis via the FLI1-CLEC14A-VEGFC axis. This study provides new insights into the transcriptional regulation of angiogenesis and suggests potential molecular targets for treating neovascular retinal diseases.}, }
@article {pmid41548710, year = {2026}, author = {Lin, V and Lee, W and Kang, EY and Liu, PK and Wang, NK}, title = {Outer retinal tubulation associated with photoreceptor degeneration.}, journal = {Progress in retinal and eye research}, volume = {111}, number = {}, pages = {101435}, pmid = {41548710}, issn = {1873-1635}, support = {K99 EY036930/EY/NEI NIH HHS/United States ; R01 EY031354/EY/NEI NIH HHS/United States ; R21 EY037007/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Tomography, Optical Coherence/methods ; *Retinal Degeneration/pathology/diagnosis ; *Retinal Pigment Epithelium/pathology ; Ophthalmoscopy/methods ; Animals ; *Photoreceptor Cells, Vertebrate/pathology ; }, abstract = {Outer retinal tubulation (ORT) is a distinct structural manifestation of chronic photoreceptor degeneration, observed across a broad spectrum of retinal diseases. Initially described histologically as rosette-like formations, ORT has gained clinical relevance with the advent of high-resolution imaging modalities such as spectral-domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AO-SLO), which enable in vivo visualization of its tubular architecture. ORT arises from sustained photoreceptor and retinal pigment epithelium (RPE) injury, leading to the reorganization of surviving cones ensheathed by gliotic Müller cell processes. This review integrates historical, histological, and imaging data to elucidate ORT's cellular composition, formation mechanisms, and disease-specific patterns. We introduce a novel etiological classification of ORT, categorized as degenerative, fibrotic, or edematous ORT according to predominant pathogenic drivers, to facilitate cross-disease comparison and prognostic stratification. Clinically, ORT serves as a non-exudative biomarker of chronic retinal injury, aiding differential diagnosis and informing treatment strategies. In age-related macular degeneration, ORT is associated with subretinal fibrosis and poor visual outcomes; in geographic atrophy, it may signal slower lesion progression. In inherited retinal dystrophies, ORT reflects genotype-specific vulnerabilities and residual photoreceptor survival, with implications for therapeutic targeting. As imaging technologies advance, ORT offers promise as a structural marker of disease chronicity, photoreceptor resilience, and Müller cell plasticity, enhancing diagnostic precision and supporting its role as a meaningful endpoint in clinical trials.}, }
@article {pmid41548795, year = {2026}, author = {Rinaldi, M and Cennamo, G and Fioretto, G and Passaro, ML and De Falco, F and Bertocchi, M and Marotta, M and Chiosi, F and Calabro, F and Strianese, D and Costagliola, C}, title = {Scleral iontophoresis for targeted lutein delivery in intermediate stage dry AMD: Is this a new frontier in age macular degeneration?.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {57}, number = {}, pages = {105356}, doi = {10.1016/j.pdpdt.2026.105356}, pmid = {41548795}, issn = {1873-1597}, mesh = {Humans ; *Iontophoresis/methods ; Aged ; *Lutein/administration &amp; dosage ; Female ; Male ; Pilot Projects ; Prospective Studies ; Sclera/drug effects ; *Macular Degeneration/drug therapy ; Middle Aged ; Visual Acuity/drug effects ; Aged, 80 and over ; }, abstract = {OBJECTIVES: To evaluate the retinal morphofunctional changes in patients with stage 2 age-related macular degeneration (AMD) following scleral iontophoresis for lutein delivery, and to assess its safety.<br><br>METHODS: In this prospective, non-randomized, single-arm pilot study, 30 stage 2 AMD patients (mean age 71.6 &#xb1; 10.88 years) received scleral iontophoresis with a liquid lutein formulation. Comprehensive ophthalmologic assessments-including best-corrected visual acuity (BCVA), macular pigment optical density (MPOD) via one-wavelength reflectometry, and microperimetry (mean sensitivity, mean defect, and fixation stability measured as BCEA)-were performed at baseline and at 6 months. Adverse events were monitored, and ocular surface health was assessed using the Ocular Surface Disease Index (OSDI).<br><br>RESULTS: At 6 months, MPOD significantly increased from 0.169 &#xb1; 0.06 to 0.180 &#xb1; 0.075 density units (p = 0.0313). Mean sensitivity improved from 7.26 &#xb1; 5.13 dB to 8.18 &#xb1; 4.57 dB (p = 0.0179), and mean defect improved from -11.48 &#xb1; 4.90 dB to -10.27 &#xb1; 3.76 dB (p = 0.0207). Fixation stability, as measured by BCEA at 3 standard deviations, significantly decreased (p = 0.0107). No significant change was observed in BCVA, and OSDI scores remained stable. No adverse events were reported.<br><br>CONCLUSIONS: Scleral iontophoresis of lutein is a safe and promising technique to enhance local MPOD and retinal sensitivity in intermediate AMD patients. Further studies with larger cohorts are warranted to confirm these preliminary findings.}, }
@article {pmid41551980, year = {2026}, author = {Xu, J and Cai, T and Li, J and Ge-Zhang, S and Jiang, Z and Cao, M}, title = {Hydrogel-encapsulated antioxidant nanotherapeutics against age-related macular degeneration (AMD) oxidative damage.}, journal = {International journal of pharmaceutics: X}, volume = {11}, number = {}, pages = {100477}, pmid = {41551980}, issn = {2590-1567}, abstract = {Age-related macular degeneration (AMD) is still the main cause of irreversible vision loss, and the current intravitreal injections is limited by frequent administration and short retinal residence time. This review summarizes the latest progress of hydrogel-nanocarrier hybrid systems, aiming at prolonging ophthalmic drug delivery and supporting retinal tissue. We summarized the pathogenesis of AMD, focusing on oxidative stress and degeneration of retinal pigment epithelium (RPE), and investigated inorganic and organic nano-platforms endowed with antioxidant, anti-inflammatory and anti-angiogenesis functions. The design strategy of embedding nanoparticles into injectable or stimulus-responsive hydrogels is discussed. However, challenges remain, including long-term biocompatibility, inflammatory response to degradation products and potential tissue accumulation. Finally, it is emphasized to accelerate clinical translation through comprehensive long-term in vivo safety evaluation, quantitative optimization of release kinetics, standardized evaluation scheme and development of extensible manufacturing process. It is worth noting that this review mainly emphasizes inorganic nanoparticles and extracellular vesicles, but does not discuss other mature organic nanocarriers in detail. These carriers have been widely studied and emphasized by many other reviews.}, }
@article {pmid41552651, year = {2026}, author = {Prasad, M and Vitale, S and Agrón, E and Arunachalam, T and Chew, EY}, title = {Changes in Vision-Related Quality of Life before and after Geographic Atrophy Development in Age-Related Eye Disease Study Participants.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {101022}, pmid = {41552651}, issn = {2666-9145}, abstract = {OBJECTIVE: To examine for change in vision-related quality of life before and after geographic atrophy (GA) development.<br><br>DESIGN: A post hoc analysis of a prospective randomized clinical trial.<br><br>PARTICIPANTS: Age-Related Eye Disease Study (AREDS) participants with &#x2265;2 study visits 1 year apart at which they completed the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) and age-related macular degeneration (AMD) severity gradings available at the VFQ visits.<br><br>METHODS: A masked reading center assessed AMD severity using annual color fundus photographs. Regression spline models with random effects for time and eye-within-participant (SAS 9.4) were used to compare the rate of change in quality of life (difference in slope for each of the 4 quality of life measures) before and after development of GA (with separate models for GA subtypes: central GA [CGA], noncentral GA [NCGA], and any GA). Models were adjusted for age and visual acuity. If neovascular AMD developed after a GA outcome, we censored the subsequent observations.<br><br>MAIN OUTCOME MEASURES: Outcomes included the VFQ composite score calculated as an average score of nonmissing answered items. The method of successive dichotomizations was used to estimate person measures for the overall NEI VFQ-25 and for 2 derived subscales: visual functioning and social-emotional functioning.<br><br>RESULTS: Among AREDS participants with NEI VFQ-25 data available, 358 eyes (298 participants) developed any GA. None of the quality of life measures differed significantly pre- and post-CGA. Rasch-calibrated subscale score for visual function and composite scores declined more quickly after NCGA (difference in slope [post minus pre]: -0.10 logit/yr [95% confidence interval: -0.18, -0.01], P = 0.03; -0.78 points/yr [95% confidence interval: -1.47, -0.08], P = 0.03, respectively) and after any GA (-0.09 logit/yr [95% confidence interval: -0.16, -0.01], P = 0.02; -0.68 points/yr [95% confidence interval: -1.29, -0.07], P = 0.03, respectively).<br><br>CONCLUSIONS: We observed worsening quality of life after development of NCGA and any GA in AREDS participants across several quality of life measures. Development of CGA was not associated with any significant changes in the quality of life measures, possibly due to the smaller sample size and limited power. Our findings highlight the importance of examining the relationship between GA subtypes and different indices of quality of life.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41552657, year = {2026}, author = {Leng, T and Leung, EH and Mukkamala, SK and Taban, MR and Havilio, M and Nahen, K and Mohan, N and Benyamini, G and Keenan, TDL}, title = {Longitudinal Validation of the Artificial Intelligence Algorithm in Home OCT for Age-Related Macular Degeneration-Report 3.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100907}, pmid = {41552657}, issn = {2666-9145}, support = {P30 EY026877/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE: Longitudinal validation of the artificial intelligence-based Notal OCT Analyzer (NOA) for identification of clinically significant changes in the trajectories of retinal total hypo-reflective volume (TRO) from daily home OCT (HOCT) self-imaging in eyes with age-related macular degeneration.<br><br>DESIGN: Post hoc analysis of the HOCT Fluid Visualization Agreement Study.<br><br>PARTICIPANTS: Three hundred seventeen eyes of 180 participants who self-imaged daily using the HOCT for 5 weeks.<br><br>METHODS: For each eye study, the ground truth of TRO stability or change was defined by human experts grading the 5-week time series of HOCT volume scans. The TRO trajectory of the 5 weeks was plotted separately for each study eye by NOA. Three approaches to identifying the optimal threshold (OT) for a clinically significant change in TRO were pursued: (1) personalized approach based on the reference change value methodology used in laboratory medicine; (2) optimized uniform approach; (3) uniform approach commonly used of 10 volume units (VU). The personalized approach comprised TRO curve-fitting to evaluate the change in amplitude (signal) and within-subject variations (noise), followed by receiver operating characteristic analysis of the signal-to-noise ratio (SNR) to identify the OT for determination of a clinically significant change in TRO.<br><br>MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC); sensitivity, specificity, and accuracy at the OT.<br><br>RESULTS: Of the 296 trajectories analyzed, 107 (36.1%) were classified as changing and the remaining 189 (63.9%) as stable. The personalized approach had an AUROC of 0.9811 (with 99.1% sensitivity, 89.4% specificity, and 94.2% accuracy), at OT of SNR = 2.42. The optimized uniform approach had an AUROC of 0.9687 (with 94.4% sensitivity, 89.4% specificity, and 91.9% accuracy), at OT of 3.88 VU. The 10 VU uniform approach had 76.6% sensitivity, 94.7% specificity, and 85.7% accuracy.<br><br>CONCLUSIONS: The NOA-generated trajectories permitted highly accurate determination of TRO change vs. stability, with favorable SNR. The personalized approach had higher sensitivity in detecting TRO change at 99.1% than the uniform approaches. Notal OCT analyzer and its trajectories were a reliable tool for identifying clinically relevant changes in retinal fluid status by the quality standards of laboratory medicine.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41552660, year = {2026}, author = {Sun, J and Shen, M and Chen, J and Wu, Y and Zhou, Y and Feng, J and Cheng, Y and Jia, H and Yang, X and Gong, Y and Liu, Y and Wang, H and Wang, RK and Rosenfeld, PJ and Li, T and Wang, F and Sun, X}, title = {Intravitreal Gene Therapy with LX102-C01 in Neovascular Age-Related Macular Degeneration: A Phase I Dose-Escalation Study of 12-Month Safety and Efficacy Outcomes.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100970}, pmid = {41552660}, issn = {2666-9145}, support = {R01 AG060942/AG/NIA NIH HHS/United States ; R01 EY028753/EY/NEI NIH HHS/United States ; R01 EY030564/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE: To assess the safety, tolerability, and preliminary efficacy of a single intravitreal injection of LX102-C01 in eyes with neovascular age-related macular degeneration (nAMD) followed up to 52 weeks.<br><br>DESIGN: Open-label, single-center, dose-escalation investigator-initiated trial (NCT05831007) with 2 cohorts (3E10 vector genome [vg] and 1E11 vg per eye).<br><br>SUBJECTS: Eyes with choroidal neovascularization secondary to nAMD, subretinal or intraretinal fluid, and a history of >2 anti-VEGF treatments in the past 6 months with a good response.<br><br>METHODS: All patients received 1 injection of aflibercept 2 weeks before LX102-C01. Dose escalation started with 3E10 vg and increased to 1E11 vg per eye. Visual acuity, anatomy, and adverse events (AEs) were assessed. Macular choroidal thickness (CT) and vascularity were measured using a 6 &#xd7; 6 mm scan on swept-source OCT angiography imaging.<br><br>MAIN OUTCOME MEASURES: The primary endpoint was AEs at 1 year. The secondary endpoints were best-corrected visual acuity (BCVA), central subfield thickness (CST), and incidence of rescue treatment. Exploratory endpoints included the macular hypoautofluorescent area, CT, and choroidal vascularity index (CVI).<br><br>RESULTS: Six eyes of 6 patients were included. There were no LX102-C01-related nonocular AEs. All LX102-C01-related ocular AEs were mild, predominantly anterior inflammation. There was no evidence of vasculitis, retinitis, choroiditis, vascular occlusions, or endophthalmitis. Two eyes from 2 patients developed recurrent subretinal fluid or hemorrhages that did not meet rescue criteria and resolved spontaneously after 1 to 2 months. All patients were free of rescue anti-VEGF treatments till the latest visit. Compared to baseline, BCVA maintained and CST decreased up to 12 months in both cohorts. The area of hypo-autofluorescence remained stable in both groups. The mean choroidal thickness (MCT) decreased from 162.1 &#x3bc;m to 147.1 &#x3bc;m (P = 0.03), but the CVI measurement showed no significant change (P = 0.6) up to 12 months. Changes in the MCT and CVI showed no statistically significant differences compared with the control group receiving standard aflibercept treatment.<br><br>CONCLUSIONS: LX102-C01 showed a favorable safety profile and potential efficacy in this preliminary 52-week study, with no observed macular atrophy, suggesting short-term tolerability of gene therapy associated anti-VEGF expression.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41553279, year = {2026}, author = {Nguyen, VP and Jeong, J and Zhe, J and Zheng, M and Lee, J and Tran, K and Wei, Z and Lee, CH and Paulus, YM}, title = {Silicon Nanoneedle Patches for Painless, Sustained Treatment of Macular Degeneration.}, journal = {ACS biomaterials science &amp; engineering}, volume = {12}, number = {2}, pages = {1269-1285}, doi = {10.1021/acsbiomaterials.5c01783}, pmid = {41553279}, issn = {2373-9878}, mesh = {*Silicon/chemistry ; Animals ; Rabbits ; *Macular Degeneration/drug therapy/pathology ; *Bevacizumab/administration &amp; dosage/therapeutic use/chemistry ; *Choroidal Neovascularization/drug therapy/pathology ; Drug Delivery Systems ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Delayed-Action Preparations/chemistry ; Humans ; }, abstract = {Choroidal neovascularization (CNV) represents a major cause of vision loss in various retinal diseases such as age-related macular degeneration (AMD). Current treatment involves frequent, often monthly, eye injections. The development of minimally invasive, long-term, painless, and effective ocular drug delivery systems is crucial for advancing the treatment of AMD. This study explores a novel method that integrates controllably bioresorbable silicon nanoneedles loaded with bevacizumab (Si NNs-Bev) on a tear-soluble subconjunctival patch for sustained, 1 year ocular drug delivery. The Si NNs-Bev embed into the sclera in a minimally invasive manner, undergoing controlled degradation over one year. This approach facilitates the sustained release of therapeutic agents, enhancing treatment efficacy and reducing treatment burden. Si NNs-Bev for the treatment of CNV are validated in a rabbit model of AMD. The SiNN-Bev patch achieved a sustained therapeutic effect on CNV regression, with a mean reduction of 82% by 4 months that is persistent for at least 1 year with minimal recurrence, which is consistent with the localized drug delivery mechanism facilitated by the transscleral microneedles. These preliminary findings underscore the potential of SiNNs as a platform technology for long-term, sustained ocular therapeutics.}, }
@article {pmid41553889, year = {2026}, author = {Lachinov, D and Pinetz, T and Bogunovic, H}, title = {PINN-EM: Physics-Guided Disease Progression Model of Geographic Atrophy.}, journal = {IEEE transactions on bio-medical engineering}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TBME.2026.3655164}, pmid = {41553889}, issn = {1558-2531}, abstract = {OBJECTIVE: To construct a personalizable spatio-temporal disease progression model of patients with a late dry form of Age-Related Macular Degeneration (AMD), known as Geographic Atrophy (GA).<br><br>METHODS: From a series of retinal optical coherence tomography (OCT) scans, we infer the coefficients for the parametrized partial differential equation (PDE), such that the parametrized PDE best describes the observed imaging data. Acting as a soft constraint, the recovered PDE helps to extrapolate an implicit neural representation (INR) of the GA segmentation map progression. To enable efficient training, we propose an iterative method - PINN-EM, designed to recover coefficients of non-linear PDEs. At each iteration, the method decouples the problem into PDE coefficients fitting and data fitting steps, resembling Expectation Maximization algorithm.<br><br>RESULTS: We extensively tested the proposed method in large-scale experiments using the open-source PDEBench benchmark to validate its performance. Furthermore, we applied the method to the challenging problem of GA progression modeling, where patients exhibit a high variance in GA growth patterns and speed. The proposed spatio-temporal disease progression model outperformed the baselines, even outperforming posterior knowledge models in Dice score for newly affected growth areas.<br><br>CONCLUSION: We demonstrated that the proposed spatio-temporal disease progression model fitted with introduced PINN-EM outperforms existing baselines in synthetic and real clinical applications, highlighting the extrapolation capabilities of the INR models.<br><br>SIGNIFICANCE: The proposed spatio-temporal disease progression model and PINN-EM fitting procedure can be applied across diverse domains facing the challenge of fitting parametrized PDE to the empirical datasets.}, }
@article {pmid41554422, year = {2026}, author = {Kong, L and Qi, S and Han, X and Zhang, J and Zhang, L and Li, D and Jiang, Q and Zhang, S and Zhao, C}, title = {Integrated proteomic profiling of aqueous humor reveals CDC42/RHOA-mediated pathogenic mechanisms in nAMD and PDR.}, journal = {Experimental eye research}, volume = {264}, number = {}, pages = {110871}, doi = {10.1016/j.exer.2026.110871}, pmid = {41554422}, issn = {1096-0007}, mesh = {*Aqueous Humor/metabolism ; Humans ; *Proteomics/methods ; *cdc42 GTP-Binding Protein/metabolism ; Male ; *Diabetic Retinopathy/metabolism ; *rhoA GTP-Binding Protein/metabolism ; Female ; Aged ; *Wet Macular Degeneration/metabolism ; Middle Aged ; }, abstract = {Neovascular age-related macular degeneration (nAMD) and proliferative diabetic retinopathy (PDR), though clinically distinct, are both sight-threatening ocular disorders driven by pathological neovascularization. However, their shared molecular mechanisms remain poorly characterized. In this study, we performed DIA quantitative proteomic analysis of aqueous humor (AH) from patients with nAMD, PDR, and control. A total of 3186 proteins were identified, in which 877 and 1017 differentially expressed proteins (DEPs) were detected in the nAMD and PDR groups, respectively, compared to control group. Functional enrichment analysis revealed significant involvement of inflammatory and metabolic pathways in both diseases. Notably, the persistent upregulation of cell division cycle 42 (CDC42) and ras homolog family member A (RHOA) in nAMD and PDR, combined with their established role in cytoskeletal remodeling, suggests their significant involvement in pathological angiogenesis. These findings offer novel perspectives on shared pathogenic pathways in neovascular ocular disorders and suggest potential therapeutic targets for further investigation.}, }
@article {pmid41556037, year = {2025}, author = {Kaganovski, A and Rostomian, N and Shrier, E}, title = {Massive Submacular Hemorrhage Following Intravitreal Faricimab Injection for Neovascular Age-Related Macular Degeneration.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e99652}, pmid = {41556037}, issn = {2168-8184}, abstract = {We report a case of massive submacular hemorrhage (SMH) in a patient with neovascular age-related macular degeneration (AMD) occurring three days after intravitreal faricimab injection. While faricimab has demonstrated a favorable safety profile and lower hemorrhagic events compared to other anti-vascular endothelial growth factor agents, SMH, in specific, is not listed among the significant adverse events in available clinical trial safety data or in postmarketing pharmacovigilance analyses. This case highlights a new severe hemorrhagic complication that can cause permanent visual damage related to faricimab even in well-monitored patients.}, }
@article {pmid41557066, year = {2026}, author = {Lee, WA and Tsai, DH and Shao, SC and Lai, EC}, title = {Intraocular inflammation incidence and real-world safety of intravitreal faricimab treatment across retinal indications.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {41557066}, issn = {1432-1912}, abstract = {This multi-institutional real-world study evaluated the incidence of intraocular inflammation (IOI) following faricimab treatment across major retinal diseases. The study reviewed records of adults treated with faricimab between January 2022 and April 2025 and classified them into four disease cohorts: neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and polypoidal choroidal vasculopathy (PCV). Patients with a recent history of IOI were excluded. In total, 7784 patients were analyzed, including 4085 with nAMD, 1456 with DME, 1057 with RVO, and 1166 with PCV. Mean ages varied by disease group, ranging from 65.5 years in DME to 75.6 years in nAMD, and more than half of all patients had prior intravitreal anti-VEGF therapy. Within 180 days of treatment initiation, the incidence of new-onset IOI was 0.54% with nAMD, 1.24% with DME, 1.23% with RVO, and 1.03% with PCV. Overall, IOI risk ranged from approximately 0.5 to 1.2%, with higher rates observed among patients with DME and RVO. These findings highlight the importance of ongoing pharmacovigilance as newer retinal therapeutics enter clinical practice, and they provide timely evidence to support safety monitoring in real-world ophthalmology settings.}, }
@article {pmid41557187, year = {2026}, author = {Sonntag, SR and Fries, S and Gniesmer, S and Grisanti, S and Miura, Y}, title = {Fluorescence lifetime imaging ophthalmoscopy (FLIO) of patients with neovascular age-related macular degeneration before and after treatment with intravitreal ranibizumab.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41557187}, issn = {1435-702X}, abstract = {PURPOSE: Neovascular age-related macular degeneration (AMD) is a leading cause of severe vision loss worldwide. Although intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections improve outcomes, frequent treatments are burdensome and responses vary. This study investigates changes in macular fluorescence lifetime before and after anti-VEGF therapy using fluorescence lifetime imaging ophthalmoscopy (FLIO), and explores FLIO parameters as potential biomarkers for treatment response.<br><br>METHODS: Twenty patients with neovascular AMD underwent FLIO imaging (excitation: 473&#xa0;nm; emission: short spectral channel [SSC]: 498-560&#xa0;nm; long spectral channel [LSC]: 560-720&#xa0;nm) and macular OCT before and 4-6 weeks after ranibizumab injection. Fluorescence lifetime components (mean &#x3c4;m, short &#x3c4;1, long &#x3c4;2), retinal thickness (RT), and best-corrected visual acuity (BCVA, logMAR) were compared. Analysis focused on central (C), inner ring (IR), and outer ring (OR) regions of the ETDRS grid. Spearman correlation was used to assess relationships between parameter changes.<br><br>RESULTS: Changes in FLIO parameters post-treatment varied individually without a consistent trend. However, statistically significant correlations were found between changes in BCVA (&#x2206;logMAR) and changes in &#x3c4;1 in the central area (p&#x2009;=&#x2009;0.030) as well as &#x3c4;2 in the inner ring (p&#x2009;=&#x2009;0.040) in the SSC, with greater BCVA improvement associated with shorter fluorescence lifetimes. No significant correlation was observed between RT and BCVA.<br><br>CONCLUSION: FLIO parameters correlated with visual acuity changes, while retinal thickness did not. This suggests that FLIO may capture treatment-induced alterations beyond structural changes, potentially reflecting metabolic processes. FLIO may therefore serve as a valuable adjunct tool for monitoring anti-VEGF therapy response in neovascular AMD.}, }
@article {pmid41557492, year = {2026}, author = {Rosli, AH and Abdul-Aziz, CB and Siti-Azrin, AH and Zunaina, E}, title = {Evaluation of IL-6 and TNF-α in Tears and Serum in Age-Related Macular Degeneration.}, journal = {Tropical medicine &amp; international health : TM &amp; IH}, volume = {}, number = {}, pages = {}, doi = {10.1111/tmi.70089}, pmid = {41557492}, issn = {1365-3156}, support = {//Malaysian Society of Ophthalmology/ ; }, abstract = {OBJECTIVE: The purpose of this study was to assess the levels of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in the tears and serum of patients with age-related macular degeneration, as well as to identify the factors associated with IL-6 and TNF-α levels in tears.<br><br>METHODS: This was a comparative, cross-sectional study involving age-related macular degeneration patients and a control group. Tear samples were collected using Schirmer paper strips, while 3&#x2009;mL of blood was obtained from each patient. IL-6 and TNF-&#x3b1; levels in tears and serum were measured using a commercial human enzyme-linked immunosorbent assay (ELISA) kit. The study analysed the effects of duration of age-related macular degeneration, disease stage, and smoking status on IL-6 and TNF-&#x3b1; levels in tears, aiming to determine their associations.<br><br>RESULTS: A total of 142 patients were recruited for this study, including 56 patients with early age-related macular degeneration, 56 patients with late neovascular age-related macular degeneration, and 30 patients in the control group. Age-related macular degeneration patients exhibited significantly higher mean levels of IL-6 in both tears and serum, as well as TNF-&#x3b1; in serum, compared to the control group, both before and after adjusting for covariates (21.97&#x2009;&#xb1;&#x2009;10.95 vs. 16.06&#x2009;&#xb1;&#x2009;10.00&#x2009;pg/mL, p&#x2009;=&#x2009;0.008 and p&#x2009;=&#x2009;0.014; 12.00&#x2009;&#xb1;&#x2009;6.04 vs. 8.53&#x2009;&#xb1;&#x2009;4.13&#x2009;pg/mL, p&#x2009;=&#x2009;0.004 and p&#x2009;=&#x2009;0.004; 18.58&#x2009;&#xb1;&#x2009;7.90 vs. 13.61&#x2009;&#xb1;&#x2009;4.86&#x2009;pg/mL, p&#x2009;=&#x2009;0.001 and p&#x2009;=&#x2009;0.004, respectively). Within the age-related macular degeneration group, the mean IL-6 level in serum was significantly higher in patients with late neovascular age-related macular degeneration compared to those with early age-related macular degeneration (13.89&#x2009;&#xb1;&#x2009;6.08 vs. 10.11&#x2009;&#xb1;&#x2009;5.41&#x2009;pg/mL, p&#x2009;=&#x2009;0.001). The levels of IL-6 and TNF-&#x3b1; in tears were not associated with the duration of age-related macular degeneration, the stages of age-related macular degeneration, or smoking status.<br><br>CONCLUSION: There are significantly higher levels of IL-6 in both tears and serum, whereas tears and serum TNF-&#x3b1; serve as non-specific biomarkers for age-related macular degeneration. This study could serve as a basis for future research.}, }
@article {pmid41559451, year = {2026}, author = {Dai, Y and Liang, G and Xu, J and Wang, J and Yang, C}, title = {Inflammatory cytokines are not associated with early age-related macular degeneration: a two-sample Mendelian randomisation study.}, journal = {Eye (London, England)}, volume = {40}, number = {5}, pages = {715-732}, pmid = {41559451}, issn = {1476-5454}, mesh = {Humans ; *Mendelian Randomization Analysis/methods ; *Cytokines/genetics/metabolism ; *Polymorphism, Single Nucleotide ; *Macular Degeneration/genetics/metabolism ; Genome-Wide Association Study ; }, abstract = {BACKGROUND/OBJECTIVES: Observational research indicated a potential relationship between inflammatory cytokines and early age-related macular degeneration (AMD), but causal associations remain unclear.<br><br>SUBJECTS/METHODS: Using summary data from genome-wide association studies (GWAS) of 41 different inflammatory cytokines and AMD (including early and late stages), we employed a two-sample Mendelian randomisation (MR) design. Analytical methods including inverse variance weighted (IVW), weighted median, weighted mode and MR-Egger were conducted to detect the causal associations. 'mRnd' online analysis tool was used to evaluate the statistical power of MR estimates. MR-Egger, MR pleiotropy residual sum and outlier (MR-PRESO), Cochran's Q and leave-one-out method were applied for sensitivity analysis.<br><br>RESULTS: Our study selected 452 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for following analysis. The IVW results showed that inflammatory cytokines, such as IL-10, GCSF, SCF, IL-1ra, SCGFb and MIG were causally associated with AMD, and MIG, SCGFb and Dry AMD were causally related, while IL-1ra, GCSF and Bngf were causally related to Wet AMD. Interestingly, however, our results suggest no strong causal effect between other inflammatory cytokines and AMD. The analysis results did not reveal horizontal pleiotropy or heterogeneity, and the results are considered robust. The approved drugs or kinase inhibitors predicted by DsigDB to be druggable were obtained mainly from target genes such as ALK, F12 and HTR7.<br><br>CONCLUSIONS: Our MR study suggested that specific inflammatory cytokines may have an impact on overall AMD, but no causal relationship was observed with early AMD. The relationship between them needs further study.}, }
@article {pmid41560351, year = {2026}, author = {Bai, J and Li, S and Wang, A and Wang, B and Wan, Z and Li, JJ and Zhou, Y and Jia, R and Jin, H and Gao, P and Ding, X}, title = {Prosaposin is a dual-action therapeutic target for vascular stabilization and neuroprotection.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2026.01.015}, pmid = {41560351}, issn = {1525-0024}, abstract = {The disruption of vascular homeostasis is a key pathological feature of fundus abnormal vascular diseases, including wet age-related macular degeneration, diabetic macular edema, and retinal vein occlusion. While anti-vascular endothelial growth factor therapies are widely used, many patients exhibit limited or suboptimal responses. Through proteomic analysis of 173 aqueous humor samples from fundus abnormal vascular disease patients, followed by validation in an independent cohort of 70 samples, this study identifies prosaposin as a potential therapeutic candidate. In vitro, prosaposin mitigated endothelial dysfunction and reduced vascular permeability, while in vivo, it demonstrated anti-angiogenic and anti-inflammatory effects comparable to aflibercept, effectively reducing vascular leakage and retinal edema. Additionally, prosaposin provided neuroprotection by preserving photoreceptor cells. These findings highlight the dual role of prosaposin in maintaining vascular homeostasis and protecting neural tissues, suggesting its potential as an alternative treatment for patients unresponsive to anti-vascular endothelial growth factor therapies.}, }
@article {pmid41561667, year = {2026}, author = {Nunziata, A and Bianco, L and Antropoli, A and Arrigo, A and Bandello, F and Mansour, AM and Battaglia Parodi, M}, title = {ABCA4-associated retinopathy complicated by didanosine-associated retinal toxicity.}, journal = {American journal of ophthalmology case reports}, volume = {41}, number = {}, pages = {102509}, pmid = {41561667}, issn = {2451-9936}, abstract = {PURPOSE: To describe a rare case of severe central and peripheral chorioretinal atrophy in a patient with ABCA4-associated retinopathy and prior didanosine exposure.<br><br>OBSERVATIONS: A 66-year-old man with a 20-year history of Stargardt disease and HIV/AIDS treated with didanosine for almost ten years in the late '90s presented with progressive bilateral visual loss and color desaturation. Best-corrected visual acuity was 20/400 in both eyes. Multimodal imaging revealed extensive retinal pigment epithelium and choroidal atrophy involving both the macula and mid-periphery, with macular thinning and structural damage confirmed on optical coherence tomography. The peripheral atrophy pattern was consistent with known didanosine toxicity, while the macular degeneration was typical of ABCA4-associated disease. Genetic testing identified three heterozygous ABCA4 variants: one pathogenic nonsense mutation, one likely pathogenic missense mutation, and one variant of uncertain significance. Segregation analysis was not possible due to lack of parental samples.<br><br>CONCLUSIONS AND IMPORTANCE: This case suggests that prior mitochondrial-toxic drug exposure may exacerbate the course of inherited retinal dystrophies, producing unusually severe panretinal degeneration. Clinicians should review medication history in patients with inherited retinal diseases and consider long-term retinal monitoring even years after discontinuing potentially toxic agents.}, }
@article {pmid41563466, year = {2026}, author = {Ueffing, M and Lange, C and Schlunck, G and Wolf, J}, title = {[Liquid biopsy proteomics in ophthalmology : A clinical and scientific perspective].}, journal = {Die Ophthalmologie}, volume = {123}, number = {3}, pages = {169-177}, pmid = {41563466}, issn = {2731-7218}, mesh = {Humans ; *Proteomics/methods ; Liquid Biopsy/methods ; *Aqueous Humor/metabolism/chemistry ; *Eye Diseases/diagnosis/pathology/metabolism ; *Eye Proteins/analysis ; *Ophthalmology/trends/methods ; }, abstract = {BACKGROUND: For many patients with age-related macular degeneration, diabetic retinopathy and other partially monogenetic retinal diseases as well as for tumors of the eye that are relatively rare but are usually associated with profound consequences for affected patients, there is still no effective treatment available. Metastatic melanoma, for example, remains poorly predictable with respect to disease progression, response to treatment and outcome. This illustrates the urgent need for a deeper molecular understanding of the disease with the goal to develop novel therapeutic strategies. Liquid biopsies of the aqueous humor represent a promising possibility for molecular analyses in the eyes of patients.<br><br>OBJECTIVE: A&#xa0;clinical and scientific perspective with respect to potential fields of applications of liquid biopsy proteomics in ophthalmology is presented.<br><br>MATERIAL AND METHODS: A systematic literature search was carried out in PubMed and the personal experiences of the authors are presented.<br><br>RESULTS AND CONCLUSION: Aqueous humor proteomics offer a&#xa0;plethora of potential applications in ophthalmology and could become a&#xa0;key factor in personalized ophthalmology. Potential areas of application include the selection of treatment based on the activated biological signalling pathways, the selection of patients for clinical trials as well as the diagnostics, prognosis estimation and monitoring of the response to treatment. In addition, it can be a&#xa0;valuable component of multimodal diagnostics and enable insights into neurodegenerative diseases, such as Alzheimer's or Parkinson's disease.}, }
@article {pmid41564179, year = {2026}, author = {Becker, S and L'Ecuyer Morison, Z and Allen, J and Saeid, S and Sturgis, L and Adderley, A and Koskelainen, A and Vinberg, F}, title = {Healing of ischemic injury in the retina.}, journal = {Science advances}, volume = {12}, number = {4}, pages = {eadx7204}, pmid = {41564179}, issn = {2375-2548}, support = {R43 EY037154/EY/NEI NIH HHS/United States ; T32 EY024234/EY/NEI NIH HHS/United States ; R01 EY031706/EY/NEI NIH HHS/United States ; P30 EY014800/EY/NEI NIH HHS/United States ; P30 EY008098/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Retina/pathology/drug effects/metabolism ; *Reperfusion Injury/pathology ; Mice ; *Ischemia/pathology ; Disease Models, Animal ; Oxidative Stress ; Neuroprotective Agents/pharmacology ; }, abstract = {Neuro- and retinal degenerative diseases, including Alzheimer's, stroke, age-related macular degeneration, and central retinal artery occlusion, rob millions of their independence. Studying these diseases in human retinas has been hindered by the rapid loss of neuronal activity after death. While some CNS activity has been restored postmortem, synchronized neuronal transmission beyond 30 min has remained elusive. We overcome this barrier by reviving and sustaining light signal transmission in human retinas recovered up to 4 hours after death and stored for up to 48 hours. We also introduce infrared-based ex vivo imaging for precise sampling, a closed perfusion system for drug testing, and an ex vivo ischemia-reperfusion model in mouse and human retina. This platform enables testing of neuroprotective and neurotoxic effects of drugs targeting oxidative stress and glutamate excitotoxicity. Our advances question the irreversibility of ischemic injury, support preclinical studies in vision restoration, offer insights into treating CNS ischemia, and pave the way for human donor eye transplantation.}, }
@article {pmid41565848, year = {2026}, author = {Irodi, A and Faes, L and Fu, DJ}, title = {Infographic: Efficacy and safety evaluation of multiwavelength photobiomodulation in nonexudative age-related macular degeneration using the Lumithera Valeda Light Delivery System: 13-month results from the LIGHTSITE III trial.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41565848}, issn = {1476-5454}, }
@article {pmid41565850, year = {2026}, author = {Yu, S and Jones, IL and Maunz, A and Bachmeier, I and Albrecht, T and Ebneter, A and Gliem, M and Staurenghi, G and Sadda, SR and Chakravarthy, U and Fauser, S}, title = {Correction: Artificial intelligence-based analysis of retinal fluid volume dynamics in neovascular age-related macular degeneration and association with vision and atrophy.}, journal = {Eye (London, England)}, volume = {40}, number = {4}, pages = {568}, doi = {10.1038/s41433-025-04232-z}, pmid = {41565850}, issn = {1476-5454}, }
@article {pmid41566404, year = {2026}, author = {Lizińczyk, AM and Pankiewicz, JE and Cullina, WL and Franco, LA and Sullivan, PM and Sadowski, MJ}, title = {APOE genotype differentially modulates prion pathology in a mouse model.}, journal = {Acta neuropathologica communications}, volume = {14}, number = {1}, pages = {29}, pmid = {41566404}, issn = {2051-5960}, support = {R01 AG067478/AG/NIA NIH HHS/United States ; RF1 AG088226/AG/NIA NIH HHS/United States ; R01 AG0758401/AG/NIA NIH HHS/United States ; }, abstract = {UNLABELLED: APOE polymorphism affects the risk of occurrence and the rate of progression in several neurodegenerative diseases including Alzheimer’s disease, primary tauopathies, α-synucleinopathy, and age-related macular degeneration, but its role in prionoses remains unestablished. Using APOE targeted replacement (TR) mice, we investigated how APOE genotype affects key neurodegenerative mechanisms involved in prion pathology. Male and female ε2/ε2, ε3/ε3, and ε4/ε4 APOE-TR mice were inoculated with 22L mouse-adapted scrapie strain or normal brain homogenate and monitored with behavioral testing from 10-week post inoculation (wpi.) onward. Mice were euthanized at 23 wpi. when all prion-infected animals were symptomatic, and their brains were analyzed for multiple neuropathological, biochemical, and transcriptomic metrics. ε4/ε422L mice featured the shortest disease latency time, the worst neurological score, and the highest load of spongiform lesions. ε2/ε222L mice performed significantly better than ε4/ε422L mice but significantly worse than ε3/ε322L animals. Numerous aspects of PrP proteinopathy were exacerbated in the presence of the ε4 allele including increased PrP[Sc] accumulation, reduced PrP solubility, and increased PrP oligomerization. These metrics were comparable between ε2/ε222L and ε3/ε322L mice. Prion pathology significantly increased brain apolipoprotein (apo) E levels, with the greatest increase in ε4/ε422L mice. All apoE isoforms formed complexes with conformationally altered PrP, but this interaction was the strongest in ε4/ε422L mice. ε4/ε422L mice had the highest load of reactive microglia and astrocytes and upregulation of transcriptomic markers typical of neurodegenerative microglia and astrocytes, followed by ε2/ε222L, with ε3/ε322L having the lowest. Thus, APOE polymorphism differentially regulates the progression of prion pathology attributable to two ε4-affected mechanisms: increased conversion and accumulation of PrP[Sc] and worsened prion-associated neuroinflammation. Though less severely than ε4, the ε2 allele also increased the inflammatory response, rendering disease outcome worse relative to the ε3 allele. Our findings suggest both ε4 and ε2 alleles are disadvantageous determinants in prion pathology.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-025-02207-5.}, }
@article {pmid41567054, year = {2026}, author = {Prod'hom, S and Massa, H and Thumann, G and Malclès, A}, title = {[Ophthalmology : what's new in 2025].}, journal = {Revue medicale suisse}, volume = {22}, number = {946}, pages = {170-173}, doi = {10.53738/REVMED.2026.22.946.48124}, pmid = {41567054}, issn = {1660-9379}, mesh = {Humans ; Macular Degeneration/drug therapy/therapy ; Quality of Life ; Presbyopia/therapy/drug therapy ; *Ophthalmology/trends ; Graves Ophthalmopathy/drug therapy/therapy ; Antibodies, Monoclonal, Humanized/therapeutic use ; }, abstract = {Presbyopia, atrophic age-related macular degeneration, and thyroid eye disease are ophthalmic conditions that can significantly affect patients' vision and quality of life. In this article, we present the most recent therapeutic innovations for their management, including the myotic eye drop aceclidine for presbyopia, complement inhibitors (pegcetacoplan, avacincaptad pegol) to slow the progression of atrophic AMD, and teprotumumab, an anti-IGF1-R antibody, to reduce proptosis and diplopia in thyroid eye disease.}, }
@article {pmid41567568, year = {2026}, author = {Patel, HP and Robbins, CB and Karl, JJ and Weng, P and Vajzovic, L and Fekrat, S}, title = {Corrigendum to "Oral Antithrombotic Medication Is Associated with Improved Visual Outcomes in Eyes with Submacular Hemorrhage from Wet Age-Related Macular Degeneration" [Ophthalmology Science. 2025;5:100796].}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100976}, doi = {10.1016/j.xops.2025.100976}, pmid = {41567568}, issn = {2666-9145}, abstract = {[This corrects the article DOI: 10.1016/j.xops.2025.100796.].}, }
@article {pmid41569039, year = {2026}, author = {Guénot, J and Verghese, P}, title = {Cue combination for depth perception in macular degeneration: Motion parallax augments disparity.}, journal = {Journal of vision}, volume = {26}, number = {1}, pages = {11}, pmid = {41569039}, issn = {1534-7362}, support = {R01 EY027390/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Depth Perception/physiology ; Male ; Female ; *Cues ; *Macular Degeneration/physiopathology ; *Motion Perception/physiology ; *Vision Disparity/physiology ; Aged ; Middle Aged ; *Vision, Binocular/physiology ; Scotoma/physiopathology ; Sensory Thresholds/physiology ; Photic Stimulation/methods ; Aged, 80 and over ; Visual Fields/physiology ; }, abstract = {In macular degeneration (MD), depth perception from binocular disparity is impacted in regions with vision loss in either eye, but monocular cues like motion parallax remain available. This study investigates whether combining motion parallax with disparity improves depth perception and compensates for the loss of depth due to central field loss (CFL). Eleven MD participants and 19 controls viewed a horizontal sine-wave corrugation in depth, defined by disparity and/or motion parallax, judging which half-cycle appeared farther away in depth. We measured thresholds for each cue alone and for the two cues combined. In MD participants, cue integration benefits depended on scotoma characteristics. Disparity performance correlated strongly with the size of the stereoblind zone, while motion parallax thresholds showed no significant relation, suggesting preservation despite CFL. MD participants with extensive stereoblind zones showed elevated thresholds for both single cues compared to controls but demonstrated optimal integration when disparity was added to motion parallax. Those with small stereoblind zones achieved control-like thresholds and exhibited optimal or better than predicted integration. However, asymmetric patterns emerged with suboptimal performance when motion parallax was added to threshold disparity. Controls with simulated scotomas maintained stable integration, contrasting with variable patterns in MD. Our results show that individuals with CFL retain significant capacity for depth cue integration, contingent upon residual binocular disparity. Thus, motion parallax emerges as a valuable compensatory cue to improve depth perception in individuals with MD.}, }
@article {pmid41571973, year = {2026}, author = {Mimura, T and Noma, H}, title = {Regional association between PM2.5 exposure and anti-VEGF treatment demand for age-related macular degeneration: a nationwide ecological study in Japan.}, journal = {Environmental science and pollution research international}, volume = {33}, number = {4}, pages = {1416-1429}, pmid = {41571973}, issn = {1614-7499}, mesh = {*Macular Degeneration/drug therapy ; Humans ; *Particulate Matter ; Japan ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Air Pollution ; Intravitreal Injections ; Ranibizumab/therapeutic use ; Air Pollutants ; Aged ; *Environmental Exposure ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness in aging populations, and intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are the mainstay of its treatment. Recently, environmental air pollution has been proposed as a potential risk factor for ocular diseases. However, few nationwide studies have examined the association between demand for anti-VEGF therapy and environmental factors.<br><br>OBJECTIVE: This study aimed to investigate the relationship between intravitreal anti-VEGF treatment volume and air pollution indicators across all prefectures in Japan using a nationwide database.<br><br>METHODS: Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), we extracted data for the fiscal year 2020 on the number of intravitreal brolucizumab injections administered to AMD patients, as well as the total number of anti-VEGF intravitreal injections (including brolucizumab, ranibizumab, and aflibercept) for macular diseases across 48 prefectures. Brolucizumab was approved only for AMD during this year, allowing us to use its usage as a proxy for AMD cases. Environmental data, including average annual concentrations of PM2.5 (&#x3bc;g/m[3]), sulfur oxides (SOX), nitrogen oxides (NOX), and particulate matter dust (PMD; m[3]N/h), were obtained from the Ministry of the Environment. We then analyzed the correlation between anti-VEGF injection volumes per 10,000 persons aged 60 and older and air pollution indicators for each prefecture.<br><br>RESULTS: A strong positive correlation was observed between the number of brolucizumab injections (AMD-specific indicator) and total anti-VEGF injections (non-specific indicator) (r&#x2009;=&#x2009;0.82, p&#x2009;<&#x2009;0.001). Both were significantly correlated with PM2.5 concentrations (brolucizumab: r&#x2009;=&#x2009;0.25, p&#x2009;=&#x2009;0.045; total anti-VEGF: r&#x2009;=&#x2009;0.37, p&#x2009;=&#x2009;0.005). In contrast, no significant correlations were found with SOX (brolucizumab: r&#x2009;=&#x2009;-0.28, p&#x2009;=&#x2009;0.969; total anti-VEGF: r&#x2009;=&#x2009;-0.13, p&#x2009;=&#x2009;0.802), NOX (r&#x2009;=&#x2009;-0.06, p&#x2009;=&#x2009;0.656; r&#x2009;=&#x2009;0.11, p&#x2009;=&#x2009;0.224), or PMD (r&#x2009;=&#x2009;0.03, p&#x2009;=&#x2009;0.430; r&#x2009;=&#x2009;0.14, p&#x2009;=&#x2009;0.180). Moreover, PM2.5 showed no meaningful correlations with SOX, NOX, or PMD.<br><br>CONCLUSION: This nationwide analysis revealed a significant association between regional PM2.5 levels and the use of anti-VEGF intravitreal injections for macular diseases. No such relationship was observed for SOX, NOX, or PMD. These findings suggest that PM2.5 may contribute to the regional demand for AMD treatment, highlighting the need for further investigation into the impact of air pollution on ocular health.}, }
@article {pmid41572339, year = {2026}, author = {Wang, Y and Ma, H and Ge, J and Chen, K and Chen, K and Ye, H and Pan, X and Wang, X and Xia, J and Shen, J and Cheng, T and Cui, H and Sheng, Y}, title = {Senescence-induced endothelial-to-mesenchymal transition accelerates the subretinal fibrosis in neovascualr age-related macular degeneration.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {251}, pmid = {41572339}, issn = {1479-5876}, support = {82401265//National Natural Science Foundation of China/ ; SDCX-ZG-202503121//Postdoctoral Innovation Project of Shandong Province/ ; }, mesh = {Animals ; *Cellular Senescence/genetics/drug effects ; Fibrosis ; Mice, Inbred C57BL ; *Macular Degeneration/pathology/genetics ; Humans ; Endothelial Cells/pathology/metabolism/drug effects ; *Epithelial-Mesenchymal Transition ; *Retina/pathology ; Mice ; Rats ; Rats, Inbred BN ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Male ; Choroidal Neovascularization/pathology ; }, abstract = {BACKGROUND: Subretinal fibrosis remains the severe vision loss in neovascular age-related macular degeneration (nAMD), yet effective treatments are still deficient. Cellular senescence and endothelial-to-mesenchymal transition (EndMT) have been implicated in nAMD pathogenesis.<br><br>METHODS: We analyzed single-cell RNA sequencing data to investigate the role of senescent choriocapillary endothelial cells (CapECs) in subretinal fibrosis. In vitro assays were performed to validate the link between senescence and EndMT. We utilized Brown-Norway rats and INK-ATTAC mice with laser-induced subretinal fibrosis to evaluate the therapeutic effects of senolytic treatment (dasatinib plus quercetin, D&#x2009;+&#x2009;Q) or selective clearance of p16[INK4A]-positive cells. Additionally, young (2-3 months) and old (18 months) C57BL/6J mice were compared to assess the influence of aging on EndMT and fibrosis.<br><br>RESULTS: Our results revealed that CapECs in nAMD exhibited elevated SenMayo gene set variation analysis (GSVA) scores, and upregulated differentially expressed genes (DEGs) were enriched in senescence and mesenchymal transition pathways. A higher proportion of senescence-like CapECs (17.68%) was observed in nAMD, which also showed increased mesenchymal scores and TGFB1 expression. Senescent endothelial cells in laser-induced fibrotic models and bleomycin/doxorubicin-treated human umbilical vein endothelial cells underwent enhanced EndMT. Early intervention with D&#x2009;+&#x2009;Q or removal of p16[INK4A]-positive cells markedly reduced subretinal fibrosis and restored retinal function. Furthermore, endothelial cells from old mice exhibited heightened EndMT and more severe subretinal fibrosis compared to those from young mice.<br><br>CONCLUSIONS: The accumulation of senescent endothelial cells promotes subretinal fibrosis via EndMT in nAMD. Targeting these cells represents a promising therapeutic strategy for mitigating fibrosis-associated vision loss.}, }
@article {pmid41572720, year = {2026}, author = {Jo, Y and Gouya, C and Mieler, WF and Kang-Mieler, JJ}, title = {Advancements and challenges in ophthalmic microneedles to treat eye diseases.}, journal = {Drug delivery}, volume = {33}, number = {1}, pages = {2617688}, pmid = {41572720}, issn = {1521-0464}, mesh = {Humans ; *Needles ; *Drug Delivery Systems/methods/instrumentation ; *Eye Diseases/drug therapy ; Administration, Ophthalmic ; Animals ; }, abstract = {By 2050, more than 61 million people worldwide are expected to lose their vision due to conditions like age-related macular degeneration, glaucoma, diabetic retinopathy, and uveitis (Bourne et al. 2021). This anticipated rise highlights the urgent need for more effective treatment options. While progress continues in developing new pharmacological agents, treating ocular diseases with these therapies remains particularly challenging due to the eye's unique and complex anatomy. This is largely due to the limitations of current drug delivery methods, including systemic administration, topical delivery application, transscleral/periocular drug delivery, and intravitreal injections, which are associated with low bioavailability, side effects, and rapid drug clearance. Given these challenges, microneedles have emerged as a promising alternative. Their minimally invasive nature and ability to precisely target the anterior and posterior segments make them well suited for enhancing therapeutic outcomes while reducing systemic exposure and potential side effects, as well as improving patient adherence (Kang-Mieler et al. 2017; Gadziński et al. 2022). The purpose of this review is to discuss recent advancements, key challenges, and strategies for microneedle-based ocular drug delivery systems, with an emphasis on their potential to treat both anterior and posterior eye diseases.}, }
@article {pmid41572870, year = {2026}, author = {Wu, J and Shan, S and Zhou, J and Li, Y and Ke, Q and Zhu, L and Rudan, I and Song, P and , }, title = {National, regional, and provincial prevalence of age-related macular degeneration in China in 2020: an updated systematic review and modelling study.}, journal = {Journal of global health}, volume = {16}, number = {}, pages = {04062}, pmid = {41572870}, issn = {2047-2986}, mesh = {Humans ; China/epidemiology ; *Macular Degeneration/epidemiology ; Prevalence ; Aged ; Aged, 80 and over ; Middle Aged ; Adult ; Male ; Female ; }, abstract = {BACKGROUND: The burden of age-related macular degeneration (AMD) has steadily increased in recent decades. We aimed to estimate the prevalence of AMD, including its subtypes, among individuals aged 40-89 years in China.<br><br>METHODS: We conducted an updated literature search in the CNKI, Wanfang, Chinese Science and Technology Journal Database, PubMed, Embase, and MEDLINE for studies published between 27 June 2016 and 30 July 2024 that reported on the prevalence of AMD in China. We also included data from the 2017 China AMD Study. We utilised a multi-level mixed-effects meta-regression model to estimate age- and sex-specific prevalence of any AMD and its subtypes at the national level. For any AMD, we additionally conducted random-effects meta-analyses to pool odds ratios for associated factors, after which we incorporated these estimates into an associated factor-based model to estimate prevalence at regional and provincial levels.<br><br>RESULTS: We included 40 articles, of which 24 contributed data for modelling analysis. The estimated national prevalence in China in 2020 was 4.70% (95% CI&#x2009;=&#x2009;3.40, 6.46) for any AMD, 4.06% (95% CI&#x2009;=&#x2009;2.92, 5.60) for early AMD, and 0.64% (95% CI&#x2009;=&#x2009;0.48, 0.86) for late AMD, including 0.30% (95% CI&#x2009;=&#x2009;0.25, 0.37) for geographic atrophy and 0.34% (95% CI&#x2009;=&#x2009;0.23, 0.49) for neovascular AMD. These corresponded to 32.42 million cases (95% CI&#x2009;=&#x2009;23.43, 44.54) with any AMD, 28.00 million (95% CI&#x2009;=&#x2009;20.15, 38.61) with early AMD, 4.42 million (95% CI&#x2009;=&#x2009;3.28, 5.93) with late AMD, 2.09 million (95% CI&#x2009;=&#x2009;1.71, 2.52) with geographic atrophy, and 2.33 million (95% CI&#x2009;=&#x2009;1.57, 3.41) with neovascular AMD. Regionally, the highest prevalence and number of cases was observed in Southwest China (5.95%; 95% CI&#x2009;=&#x2009;4.48, 7.81) and South Central China (10.68 million; 95% CI&#x2009;=&#x2009;7.60, 14.82), respectively. At the provincial level, Hainan and Guangdong exhibited the highest prevalence (7.64%; 95% CI&#x2009;=&#x2009;4.61, 12.22) and the largest number of individuals affected (3.50 million; 95% CI&#x2009;=&#x2009;2.34, 5.13), respectively.<br><br>CONCLUSIONS: We observed a substantial burden of AMD in Mainland China, with variations across subtypes, regions, and provinces. These findings underscore a need for targeted public health strategies to address AMD in the context of ageing.<br><br>REGISTRATION: PROSPERO: CRD420251080685.}, }
@article {pmid41573440, year = {2025}, author = {Mangrio, SM and Faisal, S and Malik, Z and Naeem, A and Saeed, U}, title = {Unilateral Ptosis and Bulbar Symptoms as the Initial Presentation of Late-Onset Acetylcholine Receptor Antibody-Positive Myasthenia Gravis Mimicking Acute Ischemic Stroke in an 82-Year-Old Man.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e99832}, pmid = {41573440}, issn = {2168-8184}, abstract = {Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. In older adults, it may present with bulbar and ocular symptoms that resemble acute stroke. Ocular myasthenia is typically asymmetric and often bilateral; persistent unilateral ptosis in this context can be misleading. An 82-year-old man with type 2 diabetes mellitus, chronic kidney disease, cataracts, and macular degeneration presented with a two-week history of fatigable dysphagia, slurred speech, and new-onset unilateral left ptosis. Symptoms were worse towards the end of the day. He denied diplopia and limb weakness. On examination, he was alert with marked left ptosis, mild left facial weakness, and normal limb strength and gait. A working diagnosis of ischemic stroke was made. Computed tomography of the head, magnetic resonance imaging of the brain with magnetic resonance angiography, and carotid Doppler ultrasound showed no acute vascular pathology. Speech and language therapy assessment demonstrated moderately dysarthric but functional speech and a safe swallow using compensatory strategies. ENT review was arranged as a safety assessment to exclude structural lesions or throat pathology in view of his recent swallowing difficulty, sensation of food sticking on the left side, and intermittent nasal speech later in the day; flexible nasal endoscopy was normal. Neurology review noted fluctuating bulbar symptoms with isolated unilateral ptosis, normal extraocular movements, and a normal limb examination, raising suspicion for myasthenia gravis. Pyridostigmine was started with rapid improvement in ptosis, speech, and swallowing. By the following day, both eyes were open, and he was seen reading, although transient recurrence of ptosis was observed during reassessment, consistent with fatiguability. Computed tomography of the chest excluded thymoma. During brief withdrawal of pyridostigmine for neurophysiology, unilateral ptosis and dysphagia recurred. Nerve conduction studies and limited single-fibre electromyography were non-diagnostic. Subsequent serology confirmed positive acetylcholine receptor antibodies (13.8) and negative anti-MuSK antibodies. He was treated with pyridostigmine and oral prednisolone with gastric and bone protection and close monitoring of glycaemic control. At follow-up, he remained asymptomatic, with full resolution of unilateral ptosis and bulbar symptoms. Persistent unilateral ptosis with fluctuating bulbar symptoms in an elderly patient, normal neuroimaging, and preserved limb strength should prompt consideration of myasthenia gravis despite an initial stroke pathway. As most cases classically present before the age of 50-60 years, this presentation in an 82-year-old man also illustrates very late-onset acetylcholine receptor antibody-positive disease. This case highlights that unilateral ocular involvement does not exclude myasthenia gravis and that close attention to fatigability and symptom evolution can prevent misdiagnosis and support timely, appropriate treatment.}, }
@article {pmid41576663, year = {2026}, author = {Liu, W and Wang, L and Jiang, S}, title = {FGF21 protects retinal pigment epithelium from sodium iodate-induced injury: Association with inhibition of ferroptosis and the NRF2/GPX4 pathway.}, journal = {Experimental eye research}, volume = {265}, number = {}, pages = {110883}, doi = {10.1016/j.exer.2026.110883}, pmid = {41576663}, issn = {1096-0007}, mesh = {*Ferroptosis/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; *Iodates/toxicity ; *Fibroblast Growth Factors/pharmacology ; Animals ; *NF-E2-Related Factor 2/metabolism ; Mice ; *Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; Humans ; Mice, Inbred C57BL ; Disease Models, Animal ; Macular Degeneration/metabolism/prevention &amp; control ; Signal Transduction ; Lipid Peroxidation ; Cell Line ; Blotting, Western ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness, with retinal pigment epithelium (RPE) cell death representing a central pathological event. Ferroptosis, an iron-dependent form of regulated cell death, has recently been implicated in RPE degeneration. Although fibroblast growth factor 21 (FGF21) has demonstrated cytoprotective effects in various contexts, its specific role and mechanism in RPE protection, particularly concerning ferroptosis, remain unexplored. This study investigated the protective effect of FGF21 against sodium iodate (NaIO3)-induced damage and its underlying mechanism, with a focus on ferroptosis. In vitro, NaIO3 treatment induced significant injury in ARPE-19 cells, which was effectively rescued by FGF21 co-treatment. The protective efficacy of FGF21 was comparable to that of the specific ferroptosis inhibitor Ferrostatin-1. Mechanistically, FGF21 alleviated intracellular iron overload in ARPE-19 cells by modulating the expression of iron regulators (CD71 and FPN1), reduced lipid peroxidation, and restored glutathione levels. Mechanistic exploration revealed that FGF21 treatment was associated with the upregulation of NRF2 and HO-1 and, crucially, with the attenuation of GPX4 downregulation. In a NaIO3-induced mouse model of retinal degeneration, FGF21 administration significantly preserved retinal structure, as evidenced by the maintained outer nuclear layer and total retinal thickness in optical coherence tomography (OCT) and histological analyses. Consistent with the cellular findings, FGF21 upregulated GPX4, NRF2, and HO-1 protein expression in retinal tissues. Our findings demonstrate that FGF21 protects ARPE-19 cells and the retina from NaIO3-induced damage. Its protective profile is closely associated with the mitigation of key ferroptosis hallmarks and correlates with the modulation of the NRF2/GPX4 antioxidant axis. This study provides novel insights and important preclinical evidence supporting further investigation into FGF21 as a potential therapeutic agent for ferroptosis-related retinal degenerative diseases.}, }
@article {pmid41577329, year = {2026}, author = {Lee, J and Han, M and Wang, K and Butler, LR and Sinclair, DA}, title = {Epigenetic reprogramming for ocular aging and disease: Mechanisms, biomarkers, and the road to the clinic.}, journal = {Progress in retinal and eye research}, volume = {111}, number = {}, pages = {101442}, doi = {10.1016/j.preteyeres.2026.101442}, pmid = {41577329}, issn = {1873-1635}, mesh = {Humans ; *Epigenesis, Genetic/physiology ; *Aging/genetics/physiology ; Animals ; Biomarkers/metabolism ; *Cellular Reprogramming ; DNA Methylation ; }, abstract = {The eye's visual function relies on retinal neural cells that are long-lived, post-mitotic, and possess minimal regenerative capacity. These combined properties render them exceptionally vulnerable to the cumulative damage that drives age-related functional decline. Accumulating evidence now implicates epigenetic alterations, such as aberrant DNA methylation and histone modifications, not merely as correlates of aging but as fundamental drivers of aging and disease. These changes disrupt the stable gene expression programs required to maintain cellular identity and function, thereby contributing to the pathogenesis of irreversible blinding diseases like glaucoma and age-related macular degeneration (AMD). Unlike immutable genetic mutations, the reversible nature of these epigenetic marks offers a novel therapeutic paradigm. Epigenetic reprogramming, a strategy involving the transient expression of Yamanaka factors or chemical cocktails, provides a powerful means to reset this dysregulated epigenetic landscape and restore cells to a more youthful state. Compelling preclinical studies have validated this approach by demonstrating vision restoration in models of optic neuropathy through the rejuvenation of damaged and aged neurons. This review provides a comprehensive overview of ocular aging from an epigenetic perspective, examines the promise and potential concerns of epigenetic reprogramming, and discusses the future of rejuvenation therapies in ophthalmology.}, }
@article {pmid41577331, year = {2026}, author = {Chung, YC and Alhelaly, M and Nittala, MG and Velaga, SB and He, Y and Haines, JL and Pericak-Vance, MA and Stambolian, D and Sadda, SR}, title = {OCT Risk Factors for Progression to Late-Stage Age-Related Macular Degeneration in the Amish Eye Study.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.01.010}, pmid = {41577331}, issn = {2468-6530}, abstract = {PURPOSE: To characterize the prevalence of some critical OCT biomarkers-including cuticular drusen and acquired vitelliform lesions (AVLs)-and to identify their relative risk for progression to late age-related macular degeneration (AMD) over 2 years in subjects with early or intermediate AMD in the Amish Eye Study.<br><br>DESIGN: Prospective, observational, longitudinal, population-based cohort study.<br><br>PARTICIPANTS: This study included 276 eyes from 171 subjects with early or intermediate AMD at baseline who completed the 2-year follow-up.<br><br>METHODS: Baseline OCT scans were evaluated for the presence of cuticular drusen, AVLs, subretinal drusenoid deposits (SDDs), high drusen volume (defined as &#x2265;0.2 mm[3] within the central 5 mm), intraretinal hyperreflective foci (IHRF), hyporeflective drusen cores (hDCs), thick/thin double-layer sign (DLS), and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA). Subfoveal choroidal thickness (SFCT) was also measured.<br><br>MAIN OUTCOME MEASURES: Incidence of late AMD (geographic atrophy or macular neovascularization) at 2 years as determined by multimodal imaging (OCT, color fundus photography, and confocal fundus autofluorescence).<br><br>RESULTS: By 2 years of follow-up, 26 eyes (10.7%) progressed to late AMD. The most prevalent baseline features in this cohort, in descending order, were cuticular drusen (52.3%), IHRF (17.3%), hDC (16.0%), thin DLS (11.9%), SDD (8.2%), iRORA (7.8%), AVL (7.0%), and high drusen volume (2.5%). The mean SFCT was 243.23 &#xb1; 75.45 &#x3bc;m. Univariate analysis demonstrated that the presence of thick DLS, iRORA, AVL, SDD, IHRF, hDC, and SFCT was associated with an increased risk of progression. In multivariate regression, only the presence of iRORA (odds ratio [OR], 29.60; 95% confidence interval [CI], 6.86-127.84; P < 0.001) and AVL (OR, 15.90; 95% CI, 3.24-78.00; P < 0.001) remained significant, whereas the presence of IHRF showed borderline significance (OR, 4.71; 95% CI, 1.00-22.16; P = 0.050).<br><br>CONCLUSIONS: In this cohort, the presence of iRORA and AVL was independently associated with progression to late AMD over 2 years. Although cuticular drusen were highly prevalent, their presence, as assessed in this study, was not significantly associated with an increased risk of progression to late AMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41578078, year = {2026}, author = {Bansal, M and Singh, P and Mehta, RK and Laul, RS and Rana, P and Shah, U and Vohra, R and Desai, S and Bhomaj, S and Patwardhan, S and Manoher, JM and Sapar, A and Parwal, S and Amabde, AK and Shroff, R and Natesh, S and Biswas, RK and D, LR and Sinha, BP and C K, M and Patel, E and Kamble, A and Bhende, P and Patil, S and Shah, A and Narula, R and Kumari, B and Bathula, L and Kirtane, S and Darji, B and Doshi, M and Parmar, D}, title = {A Phase III Randomized Trial Comparing Efficacy, Safety, and Immunogenicity of ZRC-3285 vs. Eylea[®] in Patients with Wet Age-Related Macular Degeneration.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {2}, pages = {803-816}, pmid = {41578078}, issn = {2193-8245}, abstract = {INTRODUCTION: This study aims to evaluate the efficacy, safety, and immunogenicity of ZRC-3285 (aflibercept biosimilar) with Eylea[®] (aflibercept) in patients with neovascular (wet) age-related macular degeneration (nAMD).<br><br>METHODS: This phase&#xa0;III, multicenter, double-blind study was conducted across 27 sites in India and randomized (2:1) patients with nAMD into either the test aflibercept (ZRC-3285, Zydus Lifesciences Ltd.) or Eylea[&#xae;] (Regeneron Pharmaceuticals, Inc.) groups. All 184 enrolled patients (122 and 62 in the ZRC-3285 and Eylea[&#xae;] groups, respectively) were included in the modified intend-to-treat (mITT) population. ZRC-3285 or Eylea[&#xae;] was administered by intravitreal injection at a dose of 2&#xa0;mg (0.05&#xa0;mL) on days&#xa0;1, 29, and 57. The primary objective was to assess non-inferiority of ZRC-3285 versus Eylea[&#xae;] in treating nAMD and was evaluated by determining the proportion of patients who lose fewer than 15 letters from baseline visual acuity over 12&#xa0;weeks using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Secondary objectives included comparison of additional efficacy outcomes, immunogenicity, and safety.<br><br>RESULTS: Over 12&#xa0;weeks, all patients in the ZRC-3285 (122, 100%) and Eylea[&#xae;] (62, 100%) groups showed loss of fewer than 15 letters, demonstrating non-inferiority [95% confidence interval (CI) not evaluable (NE); p&#x2009;=&#x2009;NE)] of ZRC-3285 to Eylea[&#xae;]. The proportion of patients who gained more than 15 letters in best corrected visual acuity (BCVA) over 12&#xa0;weeks and the mean changes in BCVA, choroidal neovascularization (CNV), and central retinal thickness (CRT) were similar in both arms.<br><br>CONCLUSION: Efficacy, immunogenicity, and safety profiles of ZRC-3285 were found to be similar to those of Eylea[&#xae;].<br><br>TRIAL REGISTRATION: Clinical trial Registry of India (CTRI): CTRI/2023/09/057655 [Registered on 14/09/2023].}, }
@article {pmid41578358, year = {2026}, author = {Pellegrini, M and Adamo, GG and Cartabellotta, A and Talli, PM and Crisafulli, S and Parmeggiani, F and Mura, M}, title = {Add-on implantation of the smaller-incision new generation implantable miniature telescope (SING IMT™) in pseudophakic eyes.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {28}, pmid = {41578358}, issn = {2056-9920}, abstract = {BACKGROUND: To describe a novel surgical technique for add-on sulcus implantation of the Smaller-Incision New Generation Implantable Miniature Telescope (SING IMT™) in pseudophakic eyes with end-stage age-related macular degeneration (AMD).<br><br>METHODS: Two pseudophakic patients with bilateral end-stage AMD underwent add-on SING IMT&#x2122; implantation in the ciliary sulcus. Pre- and postoperative evaluations included best-corrected distance visual acuity (BCDVA), anterior segment OCT (AS-OCT), corneal endothelial cell counts, and subjective visual function assessments, with follow-up to 6 months.<br><br>RESULTS: Both surgeries were uneventful. The devices remained stable and well-centered with no significant inflammation, corneal decompensation, or intraocular pressure elevation. BCDVA improved by 3&#x2013;4 ETDRS lines, and both patients reported improved daily visual function. Corneal endothelial loss was <&#x2009;5% at 6 months.<br><br>CONCLUSIONS: Add-on sulcus implantation of the SING IMT&#x2122; in pseudophakic eyes is surgically feasible and well tolerated, expanding the potential indications of this visual rehabilitation device to a broader AMD population.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40942-025-00797-9.}, }
@article {pmid41581044, year = {2026}, author = {Ranga, D and Kaur, S and Nallabelli, N and Sharma, SP and Tigari, B and Dogra, M and Katoch, D and Sharma, SK and Singh, R and Singh, N}, title = {Impact of age-related maculopathy susceptibility 2, high-temperature requirement A serine peptidase 1, and complement factor H genetic variants on clinical phenotypes of age-related macular degeneration.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {2}, pages = {279-285}, pmid = {41581044}, issn = {1998-3689}, mesh = {Humans ; *High-Temperature Requirement A Serine Peptidase 1/genetics/metabolism ; *Complement Factor H/genetics/metabolism ; Male ; Female ; *Polymorphism, Single Nucleotide ; Tomography, Optical Coherence ; Aged ; Phenotype ; *Macular Degeneration/genetics/diagnosis/epidemiology/metabolism ; Fluorescein Angiography ; Genotype ; *Proteins/genetics/metabolism ; India/epidemiology ; Middle Aged ; *Genetic Predisposition to Disease ; *DNA/genetics ; Fundus Oculi ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly. This study investigated the association of single-nucleotide polymorphisms (SNPs) in ARMS2, HTRA1, and CFH with AMD and its clinical phenotypes and systemic cytokine profiles in a North Indian population.<br><br>METHOD: A total of 113 AMD patients and 99 controls were genotyped using TaqMan assays. All patients underwent detailed ophthalmic evaluations, including optical coherence tomography (OCT), fundus photography, and angiography-based imaging. Serum cytokine levels were quantified using bead-based multiplex immunoassay and analyzed via flow cytometry. Statistical analyses were performed using SPSS v23.0, employing t-tests, ANOVA, and Mann-Whitney U tests.<br><br>RESULTS: Significant associations were observed between AMD and control for risk alleles in ARMS2 (36.3% vs 10.1%, P = 0.001), HTRA1 (37.2% vs 33.3%, P = 0.003), and CFH (27.4% vs 13.1%, P = 0.001). Genotype-phenotype correlations revealed that heterozygous and homozygous risk genotypes were significantly associated with hallmark AMD features such as pigment epithelial detachment (PED), choroidal neovascular membrane (CNVM), large drusen, and retinal pigment epithelium (RPE) atrophy. Cytokine profiling showed significantly reduced levels of erythropoietin (EPO) in AMD patients and granulocyte colony-stimulating factor (G-CSF) in controls (P = 0.044 and P = 0.023).<br><br>CONCLUSION: This study establishes novel genotype-phenotype correlations for ARMS2, HTRA1, and CFH SNPs in a North Indian cohort, linking heterozygous/homozygous risk alleles to distinct AMD clinical features. Reduced EPO and G-CSF levels suggest impaired neuroprotective/anti-inflammatory mechanisms, revealing dual pathways in AMD pathogenesis. By integrating these findings with global data, future efforts can deepen our understanding of AMD's complex etiology and improve patient outcomes worldwide.}, }
@article {pmid41581636, year = {2026}, author = {Wu, F and Xu, K and Zhao, Y and Wang, W and Yang, H and Li, Y and Zheng, G and Li, Z and Xia, Y and Liu, Y and Wu, H and Bai, S}, title = {Associations of Cardiovascular-Kidney-Metabolic Syndrome With Age-Related Macular Degeneration Risk.}, journal = {American journal of ophthalmology}, volume = {285}, number = {}, pages = {1-7}, doi = {10.1016/j.ajo.2026.01.023}, pmid = {41581636}, issn = {1879-1891}, abstract = {PURPOSE: No study has explored the longitudinal association between cardiovascular-kidney-metabolic (CKM) syndrome and age-related macular degeneration (AMD). We aimed to investigate the associations between CKM syndrome, genetic predisposition, and AMD risk.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: A total of 319,638 participants from the UK Biobank who did not have AMD at baseline.<br><br>METHODS: CKM syndrome was diagnosed based on the presence of chronic kidney disease, cardiovascular disease, and metabolic risk factors. We categorized participants into stages 0 to 4 according to their CKM syndrome status. A genetic risk score was used to estimate genetic predisposition to AMD. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident AMD.<br><br>MAIN OUTCOME MEASURES: AMD incidence.<br><br>RESULTS: During a median follow-up of 12.5 years, 4982 AMD cases were identified. After multivariable adjustment, the HRs (95% CIs) for AMD were 1.15 (1.02-1.30), 1.25 (1.13-1.38), 1.22 (1.08-1.38), and 1.48 (1.30-1.68) for participants in CKM stage 1, 2, 3, and 4, respectively, compared to those in CKM stage 0. No significant interaction between genetic predisposition and CKM syndrome was observed (P for interaction = .06). Joint analyses showed that compared to those with CKM stage 0 and low genetic predisposition, individuals with CKM stage 4 and high genetic predisposition exhibited the highest risk of AMD (HR = 2.67, 95% CI: 2.22-3.33).<br><br>CONCLUSIONS: Poor CKM health was positively associated with AMD risk, independent of genetic predisposition.}, }
@article {pmid41582022, year = {2026}, author = {Wang, L and Liu, H and Liu, C}, title = {Comment on "A deep learning approach for the screening of referable age-related macular degeneration - Model development and external validation".}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jfma.2026.01.049}, pmid = {41582022}, issn = {0929-6646}, }
@article {pmid41582115, year = {2026}, author = {Kose, H and Ozkan, B and Kanli, A and Karabas, LV and Akpinar, G and Kasap, M and Sumer, F}, title = {Correction: Evaluation of protein profile in vitreous samples of patients with naive age-related macular degeneration using proteomic approaches.}, journal = {BMC geriatrics}, volume = {26}, number = {1}, pages = {100}, pmid = {41582115}, issn = {1471-2318}, }
@article {pmid41582270, year = {2026}, author = {Fukuda, Y and Sakurada, Y and Kotoda, Y and Kikushima, W and Kashiwagi, K}, title = {Two year outcomes of as needed brolucizumab therapy in exudative age related macular degeneration with or without pachychoroid phenotype.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {6183}, pmid = {41582270}, issn = {2045-2322}, mesh = {Humans ; Female ; Male ; Aged ; Phenotype ; Treatment Outcome ; Visual Acuity/drug effects ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; *Macular Degeneration/drug therapy/pathology ; Aged, 80 and over ; Follow-Up Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; }, abstract = {Brolucizumab is a second-generation vascular endothelial growth factor (VEGF) inhibitor. To date, there have been no reports comparing treatment outcomes between exudative age-related macular degeneration with or without the pachychoroid phenotype using a second-generation VEGF inhibitor. The present study compared two-year as-needed brolucizumab treatment outcomes in patients with and without pachychoroid phenotypes. Sixty-six eyes completed two years of follow-up, and 14 and 52 eyes were classified into the pachychoroid and non-pachychoroid phenotypes, respectively. At 24 months, best-corrected visual acuity (BCVA) significantly improved in both groups, from 0.30 ± 0.29 to 0.12 ± 0.21 in the pachychoroid phenotype and 0.43 ± 0.36 to 0.31 ± 0.37 in the non-pachychoroid phenotype (p = 0.014 and 0.0013, respectively). At the 24-month follow-up, there were significantly fewer eyes requiring retreatment in the pachychoroid phenotype than in the non-pachychoroid phenotype (50% vs. 83%, p = 0.03). Although the number of additional injections was comparable between the two groups in the first 12 months (1.2 ± 1.4 vs. 1.7 ± 1.6, p = 0.29), the number of additional injections was significantly lower in the pachychoroid phenotype than in the non-pachychoroid phenotype (1.5 ± 2.4 vs. 3.2 ± 2.6, p = 0.0098) in the second 12 months. In the 24-month as-needed brolucizumab treatment group, the response to the pachychoroid phenotype was favorable, with significant BCVA improvement and fewer additional injections, particularly in the second 12 months.}, }
@article {pmid41582411, year = {2026}, author = {}, title = {Highlighting Eye Health for National Age-Related Macular Degeneration Awareness Month.}, journal = {Nursing}, volume = {56}, number = {2}, pages = {63}, doi = {10.1097/NSG.0000000000000329}, pmid = {41582411}, issn = {1538-8689}, }
@article {pmid41584094, year = {2026}, author = {Hunt, PW and Olshen, AB and Murad, N and Ambayec, GC and Sezgin, E and Schneider, MF and Jabs, DA}, title = {Erratum to "Plasma Proteomic Markers of Interleukin-1β Pathway Associated with Incident Age-Related Macular Degeneration in Persons with AIDS" [Ophthalmol Sci. 2025;5:100794].}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100974}, doi = {10.1016/j.xops.2025.100974}, pmid = {41584094}, issn = {2666-9145}, abstract = {[This corrects the article DOI: 10.1016/j.xops.2025.100794.].}, }
@article {pmid41584096, year = {2026}, author = {Chakravarthy, U and Csincsik, L and Teo, KYC and Munk, MR and Grewal, DS and Guymer, RH and Jaffe, GJ and Peto, T and Sadda, SR and Staurenghi, G and Cheung, CMG and , }, title = {Standardization of Imaging Criteria for Detecting Macular Fibrosis in Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {101027}, pmid = {41584096}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate conventional imaging modalities for detecting fibrosis in neovascular age-related macular degeneration (nAMD) and to develop a standardized diagnostic workflow.<br><br>DESIGN: Systematic discussion and grading exercise assessing multiple imaging modalities.<br><br>PARTICIPANTS: Retina specialists from the International Fibrosis Consensus workgroup and members of the International Retinal Imaging Society.<br><br>METHODS: An international panel assessed the advantages and limitations of 5 imaging modalities-color fundus photography (CFP), fluorescein angiography (FA), spectral domain OCT (SD-OCT), near-infrared reflectance, and fundus autofluorescence-for detecting fibrosis in nAMD. A structured debate was followed by 2 online, masked image grading surveys. Sensitivity, specificity, and predictive accuracy of each modality, alone and in combination, were determined. Intergrader agreement was calculated. Imaging features were also correlated with histology in a nonhuman primate laser model. Based on consensus discussions at 2 in-person meetings and survey results, a 2-step diagnostic approach using SD-OCT as the primary modality was proposed.<br><br>MAIN OUTCOME MEASURES: Recommendation for a standardized approach for diagnosing fibrosis in eyes with nAMD.<br><br>RESULTS: Among the 5 modalities, SD-OCT was considered essential by all workgroup members. Hyperreflective material on OCT was unanimously identified as a key indicator of fibrosis. However, its limited specificity was acknowledged. In 2 masked grading exercises, SD-OCT showed the highest sensitivity (0.88 and 0.84) but only moderate specificity (0.56 and 0.57). The area under the curve (AUC) for SD-OCT was 0.72 and 0.70. A 2-step strategy combining SD-OCT with CFP or FA improved diagnostic accuracy. Hyperreflective material was defined as material with reflectivity equal to or greater than normal retinal pigment epithelium (RPE), well-defined margins, RPE disruption, and a laminated appearance. Corresponding CFP findings included well-defined yellow/white/gray subretinal lesions, and FA findings included early blocked fluorescence and late staining. This 2-step approach increased AUC to 0.85, with sensitivity of 0.83 and specificity of 0.87.<br><br>CONCLUSIONS: The study establishes a 2-step approach using OCT as the primary modality in clinical studies for the detection of fibrosis.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41584098, year = {2026}, author = {Weng, CY and Blinder, KJ and Hall, EF and Rosenthal, WN}, title = {Personalizing Personalized Medicine: The Pursuit of Optimal Thresholds in the Home OCT Artificial Intelligence Algorithm for Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {101017}, pmid = {41584098}, issn = {2666-9145}, }
@article {pmid41585411, year = {2026}, author = {Sun, Y and Huang, J and Zhang, Z and Chen, Z and Li, Z and Wu, F and Wang, Z and Wu, T and Yi, G and Meng, F and Wu, S}, title = {Protective Effects of Bone Mineral Density on Age-Related Macular Degeneration: A Mendelian Randomization Study.}, journal = {International journal of endocrinology}, volume = {2026}, number = {}, pages = {6619808}, pmid = {41585411}, issn = {1687-8337}, abstract = {INTRODUCTION: Observational studies have established the connection between a decrease in bone mineral density (BMD) and an increased susceptibility to age-related macular degeneration (AMD). However, the cause-and-effect link of this correlation remains uncertain. This study employed Mendelian randomization (MR) methods to examine the causality between BMDs and AMD.<br><br>MATERIALS AND METHODS: The GEnetic Factors for OSteoporosis (GEFOS) Consortium, UK Biobank, and FinnGen Biobank offered summary statistics for BMD and AMD. We adopted an array of quality control procedures to screen for eligible instrumental single nucleotide polymorphisms (SNPs). The inverse variance weighting (IVW) algorithm was the most trustworthy approach in MR analyses. Furthermore, we employed additional analytical methods such as MR-Egger and weighted median (WM) for confirming the soundness of the present MR outcomes.<br><br>RESULTS: The findings indicated that genetically predicted total body BMD (TB-BMD, IVW: OR&#x2009;=&#x2009;0.772, 95% CI&#x2009;=&#x2009;0.642-0.928, p = 0.006), lumbar spine BMD (LS-BMD, IVW: OR&#x2009;=&#x2009;0.739, 95% CI&#x2009;=&#x2009;0.583-0.937, p = 0.013), femoral neck (FN-BMD, WM: OR&#x2009;=&#x2009;0.626, 95% CI&#x2009;=&#x2009;0.432-0.906, p = 0.013), and TB-BMD (age over 60, MR-Egger, OR&#x2009;=&#x2009;0.383, 95% CI&#x2009;=&#x2009;0.163-0.902, p = 0.041) were associated with lower odds of wet AMD. No significant causal relationship can be found between other BMDs and Wet-AMD, or between BMDs and Dry-AMD.<br><br>CONCLUSION: Our MR analysis supported the causal correlation between genetically predicted BMD and Wet-AMD. As to Dry-AMD, it was not causally related to BMD. Our study complemented the evidence from previous observational surveys and emphasized the extraordinary importance of monitoring BMD for preventing and treating AMD.}, }
@article {pmid41587414, year = {2026}, author = {Ramulu, S and Sindal, MD and Thotakura, M and Vaidya, MV and Venkatesh, R and Ramulu, PY}, title = {Patients with age-related macular degeneration face impairment in activities of daily living.}, journal = {Clinical &amp; experimental optometry}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/08164622.2026.2616034}, pmid = {41587414}, issn = {1444-0938}, abstract = {CLINICAL RELEVANCE: Age-related macular degeneration can lead to significant visual impairment in older individuals. These can significantly impact their day-to-day life, and understanding these limitations is crucial for healthcare providers.<br><br>BACKGROUND: The aim of this work is to determine impairment of activities of daily living secondary to visual impairment caused by age-related macular degeneration in a South Indian population.<br><br>METHODS: In this prospective cross-sectional study, the instrumental activities of daily living questionnaire was administered to participants with uniocular or binocular visual impairment due to age-related macular degeneration, and controls who did not have any significant ocular or retinal pathology.<br><br>RESULTS: The study recruited 90 participants in each arm, where those with age-related macular degeneration were older. More participants with age-related macular degeneration (92.2%) had impairment with one or more activities of daily living as compared to controls (55.6%,p&#x2009;<&#x2009;0.001). The age-related macular degeneration group faced a median of 4 (IQR 2-8) impairments and could perform 53.3% with difficulty, 39.4% with assistance and 7.3% activities could not be completed. In the age-related macular degeneration group, those with unilateral disease had 8.95-fold (p&#x2009;<&#x2009;0.001) greater level of impairment, while those with bilateral disease has a 10.72-fold (p&#x2009;=&#x2009;0.001) greater level of impairment as compared to controls.<br><br>CONCLUSION: Visual impairment due to age-related macular degeneration has a significant impact on activities of daily living. The patients often need assistance in completing their activities. Care in age-related macular degeneration needs to involve rehabilitation and help in carrying out daily activities in addition to treatment for visual benefits.}, }
@article {pmid41587655, year = {2026}, author = {Faurite, C and Michaud, C and Olivier, P and Gallice, M and Chiquet, C and Soler, V and Berry, I and Cottereau, BR and Peyrin, C}, title = {Enhancing peripheral scene recognition through spatial frequency training: Behavioral evidence from macular degeneration and healthy aging.}, journal = {Neuropsychologia}, volume = {223}, number = {}, pages = {109377}, doi = {10.1016/j.neuropsychologia.2026.109377}, pmid = {41587655}, issn = {1873-3514}, mesh = {Humans ; Male ; Female ; *Macular Degeneration/rehabilitation/physiopathology/psychology/complications ; Aged ; Middle Aged ; *Healthy Aging/physiology/psychology ; Photic Stimulation ; *Pattern Recognition, Visual/physiology ; Aged, 80 and over ; *Recognition, Psychology/physiology ; *Space Perception/physiology ; *Aging ; }, abstract = {Macular degeneration (MD) causes central vision loss and leads to long-term reorganization of visual functions. Central vision loss in MD severely reduces access to high spatial frequencies (HSF) that convey fine visual details, while low spatial frequencies (LSF) remain relatively accessible through peripheral vision and may support compensatory processing. This study investigated whether repeated training in categorizing filtered scenes improves peripheral scene recognition by enhancing spatial frequency processing. Ten MD patients and ten age- and gender-matched controls performed a scene categorization task (indoor vs. outdoor) using LSF or HSF images. Both groups completed a 12-session training protocol: patients performed the task at their preferred retinal location (PRL), and controls fixated with their fovea and viewed stimuli through an individualized artificial scotoma matched to their paired patient. Before training, MD patients showed a marked deficit for HSF scenes compared to controls, and a milder deficit for LSF scenes. After training, patients exhibited a significant improvement in categorizing LSF scenes, and an improvement specifically limited to HSF outdoor scenes, suggesting enhanced use of preserved peripheral information and partial compensation for the HSF deficit. Older controls also showed reduced performance for HSF scenes in peripheral vision, and similarly benefited from training. These results highlight the potential of perceptual training to enhance peripheral visual processing in MD patients, particularly by leveraging coarse visual cues. They support the idea that such protocols may be beneficial not only for visual rehabilitation in MD but also for preserving visual-cognitive functions in normal aging.}, }
@article {pmid41590921, year = {2026}, author = {Lopukhova, EA and Idrisova, GM and Mukhamadeev, TR and Voronkov, GS and Kutluyarov, RV and Topolskaya, EP}, title = {A Hierarchical Deep Learning Architecture for Diagnosing Retinal Diseases Using Cross-Modal OCT to Fundus Translation in the Lack of Paired Data.}, journal = {Journal of imaging}, volume = {12}, number = {1}, pages = {}, pmid = {41590921}, issn = {2313-433X}, abstract = {The paper focuses on automated diagnosis of retinal diseases, particularly Age-related Macular Degeneration (AMD) and diabetic retinopathy (DR), using optical coherence tomography (OCT), while addressing three key challenges: disease comorbidity, severe class imbalance, and the lack of strictly paired OCT and fundus data. We propose a hierarchical modular deep learning system designed for multi-label OCT screening with conditional routing to specialized staging modules. To enable DR staging when fundus images are unavailable, we use cross-modal alignment between OCT and fundus representations. This approach involves training a latent bridge that projects OCT embeddings into the fundus feature space. We enhance clinical reliability through per-class threshold calibration and implement quality control checks for OCT-only DR staging. Experiments demonstrate robust multi-label performance (macro-F1 =0.989±0.006 after per-class threshold calibration) and reliable calibration (ECE =2.1±0.4%), and OCT-only DR staging is feasible in 96.1% of cases that meet the quality control criterion.}, }
@article {pmid41591569, year = {2026}, author = {Heidari, Z and Mirghorbani, M and Abounoori, M and Ebrahimibesheli, K and Tabarestani, M and Khabazkhoob, M and Yousefi, S and Modjtahedi, BS}, title = {Vitreoretinal disease detection using artificial intelligence: a systematic review and meta-analysis.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {77}, pmid = {41591569}, issn = {1573-2630}, mesh = {Humans ; *Artificial Intelligence ; *Retinal Diseases/diagnosis ; *Vitreous Body/diagnostic imaging/pathology ; }, abstract = {INTRODUCTION: Early detection of vitreoretinal diseases (VRDs) is critical for preventing vision loss, and currently relies on the examination and interpretation of multimodal imaging techniques. Artificial intelligence (AI) is emerging as a powerful tool to detect abnormalities in vitreoretinal morphology and ideally detect changes at earlier stages to allow for intervention. This meta-analysis evaluates and summarizes the diagnostic performance of AI models in the detection of VRDs using retinal imaging systems.<br><br>METHODS: This study was registered in PROSPERO (CRD42023450207). A comprehensive electronic search of PubMed/MEDLINE, EMBASE, and Web of Science was conducted by three independent reviewers up to August 2023. Study validity was assessed using the QUADAS-2 tool, which evaluates risk of bias across four domains and applicability concerns across three domains. Eligible articles were categorized into nine VRD subgroups-age related macular degeneration, diabetic retinopathy, retinal vascular diseases, retinal dystrophies, Cystoid macular edema, vitreoretinal interface disorders, retinal detachment, Central serous chorioretinopathy, and myopic retinopathy-and included in the meta-analysis. Pooled estimates of accuracy (PEA), sensitivity (PESen), and specificity (PESpe) were calculated for all selected studies.<br><br>RESULTS: A total of 195 studies were included in the final analysis, yielding an overall PEA of 95.76% (95% CI: 95.0-96.47), PESen of 91.94% (95% CI: 90.72-93.08) and PESpe of 96.09% (95% CI: 95.27-96.79). In the subgroup analysis, most AI models had a PEA&#x2009;>&#x2009;90%, especially convolutional neural networks (CNN), followed by support vector machine (SVM) and random forest (RF).<br><br>CONCLUSIONS: AI diagnostic tools, particularly CNNs, have demonstrated robust performance in VRDs detection. However, results from studies with limited generalizability should be applied cautiously in real-world settings. Further exploration of emerging models, such as large language models (LLMs), is recommended.}, }
@article {pmid41592857, year = {2026}, author = {Wang, Z and Xu, C and Wang, L and Qiang, W and Li, Y and Li, D and Xu, F and Zhang, Y and Jiang, J and Li, Z}, title = {Evaluating reasoning large language models with human-like thinking in ophthalmic question answering.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {1}, pages = {}, pmid = {41592857}, issn = {2397-3269}, mesh = {Humans ; *Ophthalmology/education ; *Thinking/physiology ; *Language ; *Educational Measurement/methods ; Large Language Models ; }, abstract = {OBJECTIVES: To evaluate the performance of reasoning large language models (LLMs) with human-like thinking in ophthalmic question answering.<br><br>METHODS: We evaluated two state-of-the-art open-source reasoning LLMs (DeepSeek-R1 and QwQ-32B) and one conventional non-reasoning LLM (LLaMA-3.3-70B-Instruct) models on ophthalmology questions, assessing not only answer accuracy (ACC) but also the quality of their reasoning processes. First, we curated MedQA-Eye, a dataset of 967 ophthalmology questions across 10 subspecialties, 3 scenarios, 5 medical entities and 3 languages. Second, we proposed a novel framework considering human thinking patterns essential to medical practice to evaluate the thinking performance of reasoning LLMs on MedQA-Eye.<br><br>RESULTS: DeepSeek-R1 demonstrated superior overall ACC (90.59%, 95% CI 88.59% to 92.27%) to LLaMA-3.3-70B-Instruct (87.90%, 95%&#x2009;CI 85.69% to 89.81%, p=0.015) and QwQ-32B (84.28%, 95%&#x2009;CI 81.85% to 86.44%, p<0.001) with performance varying across subspecialties. Analysis of reasoning LLMs revealed incorrect logical inference as the primary point of failure, accounting for 93.41%-94.74% of incorrectly answered questions. We further quantified semantic uncertainty in reasoning LLM thinking as a predictor of answer reliability. DeepSeek-R1 exhibited lower semantic uncertainty (1.04&#xb1;3.63) compared with QwQ-32B (4.31&#xb1;40.70), p<0.001.<br><br>CONCLUSION: Reasoning LLMs demonstrated superior performance in ophthalmology question answering, with DeepSeek-R1 achieving the highest ACC. Our findings demonstrate that reasoning LLM can better simulate human-like thinking processes compared with conventional non-reasoning LLM, suggesting its potential for more trustworthy LLM systems in ophthalmology.}, }
@article {pmid41593166, year = {2026}, author = {Lee, JH and Lee, SY and Jang, B and Kim, YG and Yoon, CK and Park, UC and Park, KH and Lee, EK}, title = {OCT biomarkers as predictors of treatment interval in neovascular age-related macular degeneration treated with intravitreal aflibercept using a treat-and-extend regimen.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {6504}, pmid = {41593166}, issn = {2045-2322}, abstract = {Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in older adults. Treat-and-extend (T&amp;E) regimen for anti-vascular endothelial growth factor therapy are widely used to individualize treatment, yet substantial variability exists in achievable treatment intervals, and reliable baseline predictors remain unclear. This study investigates the association between baseline optical coherence tomography (OCT) biomarkers and treatment interval in eyes with nAMD treated with intravitreal aflibercept using a T&amp;E regimen in real-world clinical settings. This retrospective study analyzed 174 treatment-naïve eyes with nAMD of 167 patients from an initial screening of 536 eyes of 333 patients. Baseline OCT biomarkers were evaluated. Subretinal fluid, intraretinal fluid, and pigment epithelial detachments were automatically quantified using convolutional neural network-based segmentation algorithms. Correlations between OCT measurements and < q12 weeks intervals at 52 weeks were analyzed. Of the 174 eyes included, 78 (44.8%) were treated at intervals < q12 weeks at 12 months. Retinal angiomatous proliferation (RAP) (odds ratio [OR], 2.896; 95% confidence interval [CI], 1.045 − 8.022; p = 0.041), absence of intra/subretinal hemorrhage (OR, 0.381; 95% CI, 0.165 − 0.880; p = 0.024), and longer disruption of external limiting membrane (ELM) (OR, 1.094; 95% CI, 1.018 − 1.176; p = 0.014) and ellipsoid zone (EZ) (OR, 1.066; 95% CI, 1.011 − 1.124; p = 0.018) were significantly associated with < q12 weeks interval, whereas quantitative fluid measurements were not significantly associated with dosing interval. Baseline structural OCT biomarkers were associated with treatment interval requirements in nAMD managed with a T&amp;E regimen, suggesting their potential value for early identification of patients likely to require more intensive treatment.}, }
@article {pmid41594154, year = {2026}, author = {Yoon, T and Kang, D}, title = {Efficient Ensemble Learning with Curriculum-Based Masked Autoencoders for Retinal OCT Classification.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {2}, pages = {}, pmid = {41594154}, issn = {2075-4418}, support = {RS-2023-00249104//National Research Foundation of Korea (NRF) through a grant funded by the Korean government (MSIT)/ ; }, abstract = {Background/Objectives: Retinal optical coherence tomography (OCT) is essential for diagnosing ocular diseases, yet developing high-performing multiclass classifiers remains challenging due to limited labeled data and the computational cost of self-supervised pretraining. This study aims to address these limitations by introducing a curriculum-based self-supervised framework to improve representation learning and reduce computational burden for OCT classification. Methods: Two ensemble strategies were developed using progressive masked autoencoder (MAE) pretraining. We refer to this curriculum-based MAE framework as CurriMAE (curriculum-based masked autoencoder). CurriMAE-Soup merges multiple curriculum-aware pretrained checkpoints using weight averaging, producing a single model for fine-tuning and inference. CurriMAE-Greedy selects top-performing fine-tuned models from different pretraining stages and ensembles their predictions. Both approaches rely on one curriculum-guided MAE pretraining run, avoiding repeated training with fixed masking ratios. Experiments were conducted on two publicly available retinal OCT datasets, the Kermany dataset for self-supervised pretraining and the OCTDL dataset for downstream evaluation. The OCTDL dataset comprises seven clinically relevant retinal classes, including normal retina, age-related macular degeneration (AMD), diabetic macular edema (DME), epiretinal membrane (ERM), retinal vein occlusion (RVO), retinal artery occlusion (RAO), and vitreomacular interface disease (VID) and the proposed methods were compared against standard MAE variants and supervised baselines including ResNet-34 and ViT-S. Results: Both CurriMAE methods outperformed standard MAE models and supervised baselines. CurriMAE-Greedy achieved the highest performance with an area under the receiver operating characteristic curve (AUC) of 0.995 and accuracy of 93.32%, while CurriMAE-Soup provided competitive accuracy with substantially lower inference complexity. Compared with MAE models trained at fixed masking ratios, the proposed methods improved accuracy while requiring fewer pretraining runs and reduced model storage for inference. Conclusions: The proposed curriculum-based self-supervised ensemble framework offers an effective and resource-efficient solution for multiclass retinal OCT classification. By integrating progressive masking with snapshot-based model fusion, CurriMAE methods provide high performance with reduced computational cost, supporting their potential for real-world ophthalmic imaging applications where labeled data and computational resources are limited.}, }
@article {pmid41594936, year = {2026}, author = {Zhang, YY and Sun, QF and Bai, W and Yao, J}, title = {Retinal Astrocytes: Key Coordinators of Developmental Angiogenesis and Neurovascular Homeostasis in Health and Disease.}, journal = {Biology}, volume = {15}, number = {2}, pages = {}, pmid = {41594936}, issn = {2079-7737}, support = {82271107//National Natural Science Foundation of China/ ; K2023060//Jiangsu Provincial Health Commission Medical Research Key Project/ ; JX10414318//Postgraduate Research and Practice Innovation Program of Jiangsu Province/ ; }, abstract = {Retinal astrocytes reside mainly in the nerve fiber layer and are central to shaping retinal vessels and maintaining neurovascular balance. Derived from the optic nerve head, they spread across the inner retina to form a meshwork that both supports and instructs the emerging superficial vascular plexus. Immature astrocytes supply vascular endothelial growth factor-A(VEGF-A) to guide endothelial sprouting, while signals from growing vessels promote astrocyte maturation and strengthen the blood-retinal barrier. In disorders such as diabetic retinopathy and neovascular age-related macular degeneration, these cells show marked plasticity. Reactive astrogliosis can sustain VEGF and inflammation, favoring fragile, leaky neovessels, whereas alternative astrocyte states help reinforce barrier function and release anti-angiogenic factors. Located at the core of the neurovascular unit, astrocytes communicate continuously with endothelial cells, pericytes and neurons. This review integrates data from single-cell profiling and advanced imaging to outline astrocyte development, morphology and key signaling pathways (VEGF, PDGF, Wnt/Norrin, Eph/ephrin), and considers how tuning astrocyte polarization might be exploited to preserve retinal vascular integrity.}, }
@article {pmid41598159, year = {2025}, author = {Kudasiewicz-Kardaszewska, A and Ozimek, MA and Urbański, T and Jamontt, K and Tkaczenko, A and Bonińska, K and Cisiecki, S}, title = {Combined Pharmacological and Pneumatic Displacement Therapy for Sub-Macular Haemorrhage Secondary to Age-Related Macular Degeneration: A Case Series and Review of the Literature.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {1}, pages = {}, pmid = {41598159}, issn = {2075-1729}, abstract = {PURPOSE: We aimed to present the clinical outcomes of a combined pharmacological and gas-assisted treatment for sub-macular haemorrhage secondary to neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This retrospective case series included ten eyes with sub-macular haemorrhage (SMH) treated between January 2024 and September 2025. All patients received intravitreal alteplase (100 &#xb5;g) and C3F8 gas, followed by aflibercept (2 mg or 8 mg) within a treat-and-extend regimen. BCVA- and OCT-based anatomical changes were recorded at baseline, 7-14 days, 1 month, 3 months, and 6 months. BCVA changes were analysed using repeated-measures testing.<br><br>RESULTS: Mean BCVA improved from 0.99 &#xb1; 0.21 logMAR at baseline to 0.89 &#xb1; 0.20 at 7-14 days, 0.80 &#xb1; 0.20 at 1 month, 0.60 &#xb1; 0.18 at 3 months, and 0.53 &#xb1; 0.20 at 6 months (p < 0.05 for overall change). Eight eyes (80 percent) showed restoration of foveal contour, while two developed foveal atrophy. No major adverse events occurred.<br><br>CONCLUSION: Combined intravitreal alteplase and C3F8, followed by aflibercept, may provide favourable short-term visual and anatomical improvement in SMH secondary to nAMD. Early intervention appears beneficial, but larger controlled studies are needed to confirm these findings.}, }
@article {pmid41598179, year = {2025}, author = {Li, B and Addo, EK and Chang, FY and Guo, S and Awuni, M and Conway, E and Ying, J and Ramos, D and Bernstein, PS}, title = {Retinal Carotenoid Supplementation Increases HDL Cholesterol in Humans and Mice.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {1}, pages = {}, pmid = {41598179}, issn = {2075-1729}, support = {EY-11600, EY-14800//NIH grants EY-11600, EY-14800, by the BrightFocus Foundation, and by unrestricted departmental funds from Research to Prevent Blindness/ ; }, abstract = {Carotenoid supplementation may reduce the risk of age-related macular degeneration (AMD). These retinal nutrients are hydrophobic molecules obtained from the diet that are transported to the retina through high-density lipoprotein (HDL) complexes. HDL cholesterol is a recognized biomarker for AMD risk. This study examined the effect of carotenoid supplementation on circulating HDL cholesterol levels. Serum lipid profiles were measured in 20 participants from the Lutein and Zeaxanthin in Pregnancy (L-ZIP) trial, which enrolled 40 pregnant women. In addition to standard prenatal supplements, half received 10 mg of lutein and 2 mg of zeaxanthin daily from the first trimester, and half received a placebo. Carotenoid supplementation significantly increased HDL cholesterol in the third trimester, with no changes in total cholesterol, LDL cholesterol, or triglycerides (TG) across trimesters. To further evaluate individual carotenoids, serum lipids were analyzed in macular pigment transgenic mice fed lutein, zeaxanthin, or β-carotene for one month. All three carotenoids significantly increased HDL cholesterol and reduced TG levels, with the effect ranking as zeaxanthin > lutein > β-carotene. These findings suggest that carotenoid supplementation modulates the serum lipid profile-elevating HDL cholesterol and lowering TG-which may contribute to protection against AMD and other lipid-associated diseases.}, }
@article {pmid41598388, year = {2026}, author = {Ongun, GT and Yağcı, R}, title = {The Effect of Intravitreal Ranibizumab Injection on Retinal Nerve Fiber Layer Thickness and Optic Disc Parameters.}, journal = {Journal of clinical medicine}, volume = {15}, number = {2}, pages = {}, pmid = {41598388}, issn = {2077-0383}, abstract = {Objectives: To evaluate the effects of intravitreal ranibizumab on retinal nerve fiber layer (RNFL) thickness and optic disc parameters in patients treated for exudative age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Methods: This retrospective study analyzed the clinical records of 60 patients who received intravitreal ranibizumab injections for macular edema secondary to AMD, DME, or RVO between October 2014 and January 2016. All patients received intravitreal ranibizumab at a dose of 0.5 mg. Best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were recorded at baseline and during follow-up. RNFL thickness and optic disc parameters were assessed using optical coherence tomography (OCT) and Heidelberg Retina Tomograph III (HRT-3). Measurements were obtained before treatment and at 1 week, 1 month, 3 months, and 6 months after injection. Comparisons were performed within and between disease groups. Results: Of the 60 patients, 31 (51.7%) had DME, 20 (33.3%) had AMD, and 9 (15.0%) had RVO. Best-corrected visual acuity improved significantly during the follow-up period. Mean RNFL thickness measured by OCT showed a significant reduction in the DME and RVO groups (p = 0.0001 and p = 0.043, respectively). In contrast, no significant changes in RNFL thickness were detected using HRT-3, and no consistent alterations in other optic disc parameters were observed. Changes in optic disc parameters varied among disease groups. Conclusions: Intravitreal ranibizumab treatment was associated with a reduction in mean RNFL thickness measured by OCT in patients with DME and RVO during a six-month follow-up period, whereas no corresponding RNFL thinning was detected using HRT-3 in any disease group. The observed optic disc parameter changes appeared to be disease specific. Given the absence of untreated control eyes and the exclusion of patients with glaucoma, these findings apply only to non-glaucomatous eyes and should not be extrapolated to patients with glaucoma. Further prospective studies with larger cohorts, appropriate control groups, and longer follow-up durations are warranted to clarify the long-term effects of anti-VEGF therapy on the optic nerve.}, }
@article {pmid41598408, year = {2026}, author = {Sarna, M and Waszczykowska, A}, title = {Submacular Hemorrhage Management: Evolving Strategies from Pharmacologic Displacement to Surgical Intervention.}, journal = {Journal of clinical medicine}, volume = {15}, number = {2}, pages = {}, pmid = {41598408}, issn = {2077-0383}, support = {no//Medical University of Lodz/ ; }, abstract = {Background: Submacular hemorrhage (SMH) is a vision-threatening condition most associated with neovascular age-related macular degeneration (nAMD), although it may also arise from polypoidal choroidal vasculopathy, pathological myopia, retinal vascular diseases, trauma, and systemic factors. Rapid management is essential because subretinal blood induces photoreceptor toxicity, clot organization, and fibroglial scarring, leading to irreversible visual loss. The choice and urgency of treatment depend on hemorrhage size, duration, and underlying pathology, and the patient's surgical risk category, which can influence the invasiveness of the selected procedure. This review aims to provide an updated synthesis of recent advances in the surgical and pharmacological management of SMH, focusing on evidence from the past five years and comparing outcomes across major interventional approaches. Methods: A narrative review of 27 recent clinical and multicentre studies was conducted. The included literature evaluated pneumatic displacement (PD), pars plana vitrectomy (PPV), subretinal or intravitreal recombinant tissue plasminogen activator (rtPA), anti-VEGF therapy, and hybrid techniques. Studies were analyzed about indications, surgical methods, timing of intervention, anatomical and functional outcomes, and complication and patient risk stratification. Results: Outcomes varied depending on the size and duration of hemorrhage, as well as the activity of underlying macular neovascularization. PD with intravitreal rtPA was reported as effective for small and recent SMH. PPV combined with subretinal rtPA, filtered air, and anti-VEGF therapy demonstrated favorable displacement and visual outcomes in medium to large hemorrhages or those associated with active nAMD. Hybrid techniques further improved clot mobilization in selected cases. Across studies, delayed intervention beyond 14 days correlated with reduced visual recovery due to blood organization and photoreceptor loss. Potential risks, including recurrent bleeding and rtPA-associated toxicity, were reported but varied across studies. Conclusions: Management should be individualized, considering hemorrhage characteristics and surgical risk. Laser therapy, including PDT, may serve as an adjunct in the perioperative or postoperative period, particularly in PCV patients. Early, tailored intervention typically yields the best functional outcomes.}, }
@article {pmid41599848, year = {2026}, author = {Abouhish, H and Shalaby, L and Elzayat, O and Peddireddy, N and Tawfik, A}, title = {Modulating One-Carbon Metabolism with B-Vitamins to Protect the Retinal Barrier and Prevent Retinal Degeneration.}, journal = {Nutrients}, volume = {18}, number = {2}, pages = {}, pmid = {41599848}, issn = {2072-6643}, mesh = {Animals ; *Retinal Degeneration/prevention &amp; control/etiology ; Mice, Inbred C57BL ; *Vitamin B 12 Deficiency/blood ; Homocysteine/blood ; Vitamin B 12/administration &amp; dosage/blood/pharmacology ; Mice ; *Vitamin B Complex/pharmacology/administration &amp; dosage ; *Blood-Retinal Barrier/drug effects/metabolism ; *Carbon/metabolism ; Disease Models, Animal ; Male ; Cystathionine beta-Synthase/genetics ; Vitamin B 6/administration &amp; dosage ; }, abstract = {BACKGROUND/OBJECTIVES: Vitamin B12 deficiency is increasingly recognized as a contributor in both vascular and neurodegenerative aging-related disorders. Its deficiency disrupts one-carbon metabolism, leading to impaired homocysteine (Hcy) cycling. Elevated Hcy is a well-established risk factor for vascular dysfunction. Previously, we established that elevated Hcy contributes to aging retinal diseases and plays a central role in blood retinal barrier (BRB) dysfunction. Building on this foundation, the present study examines how B-vitamin deficiency disrupts one-carbon metabolism and whether restoring these vitamins can serve as a preventive or therapeutic strategy. Since B-vitamins (B6, B9, and B12) are crucial cofactors in the metabolism of Hcy, we investigated how dietary changes in these vitamins affect serum Hcy levels and retinal vascular integrity in mice.<br><br>METHODS: C57BL/6- Wild-type (WT) and cbs[+/-] mice (Cystathionine Beta-Synthase heterozygotes, common mouse model for elevated Hcy) were fed specially formulated diets, which contained different levels of B-vitamins (normal, deficient (B-Vit (-)) or enriched (B-Vit (+)). Initially, two groups of mice were placed on either a normal or a deficient diet. After 12-16 weeks, the success of the diet regimes was confirmed by observing serum B12 deficiency in the B-Vit (-) group, along with elevated Hcy levels. Subsequently, a subgroup of the B-Vit (-) mice was switched to an enriched diet. The BRB integrity was evaluated in living mice using fluorescein angiography (FA), optical coherence tomography (OCT), and in the perfused mice retinas with Western blot analysis of leaked retinal albumin and tight junction proteins (occludin and ZO-1) levels.<br><br>RESULTS: The B-vitamin deficiency caused significant drop in serum vitamin B12 and an increase in plasma Hcy, leading to vascular leakage, altered retinal thickness, choroidal neovascular changes, increased retinal albumin leak, and decreased tight junction protein expression, indicating BRB disruption, which was restored with B-vitamin supplementation.<br><br>CONCLUSIONS: a long-term deficiency of vitamins B6, B9, and B12 can lead to disruptions in the BRB. However, supplementation with these B-vitamins has the potential to reverse these effects and help maintain the integrity of BRB. This under-score the significance of one-carbon metabolism for retinal health and suggests that ensuring adequate levels of B-vitamins may aid in preventing aging retinal diseases with BRB disruption such as diabetic retinopathy and age-related macular degeneration.}, }
@article {pmid41601821, year = {2025}, author = {Zhang, S and Zhang, X and Wang, Z and Shi, W and Ren, Z and Wang, Y and Jia, Q and Li, Y and Guo, Y and Li, Z}, title = {Multimodal imaging for early drusen detection: RM-SLO as a promising imaging approach.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1703332}, pmid = {41601821}, issn = {2296-858X}, abstract = {PURPOSE: This study aimed to evaluate the diagnostic performance of retro-mode scanning laser ophthalmoscopy (RM-SLO) in detecting drusen compared to conventional multimodal imaging. Additionally, it sought to explore the imaging characteristics of RM-SLO for early age-related macular degeneration (AMD).<br><br>METHODS: In this cross-sectional study, 192 patients (263 eyes) were examined using color fundus photography (CFP), optical coherence tomography (OCT), fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), and RM-SLO. Three retinal specialists independently reviewed all images for the presence of drusen. Detection rates across modalities were compared using Cochran's Q-test, and imaging characteristics of hard and soft drusen were described.<br><br>RESULTS: RM-SLO detected drusen in 102 eyes (38.78%). This detection rate was significantly higher compared to other methods such as OCT (22.05%), CFP (8.37%), FFA (5.32%), and FAF (4.18%) (all p&#x202f;<&#x202f;0.0001 vs. RM-SLO). OCT was superior to CFP, FAF, and FFA (p&#x202f;<&#x202f;0.0001); CFP had statistically significant differences from FFA and FAF (p&#x202f;=&#x202f;0.039; p&#x202f;=&#x202f;0.001). While FFA did not reveal any statistically significant differences from FAF (p&#x202f;=&#x202f;0.453). RM-SLO provided a clear pseudo-three-dimensional visualization, enabling the identification of both hard and soft drusen, including small lesions that were not captured by other modalities.<br><br>CONCLUSION: RM-SLO demonstrates superior sensitivity and imaging clarity for drusen detection compared to conventional multimodal approaches. Its ability to visualize small and morphologically distinct drusen highlights its potential as a promising tool for early AMD screening and clinical management.}, }
@article {pmid41601834, year = {2025}, author = {Jiang, L and Jiang, X and Shi, X and Hu, X and Song, C and Yang, W and Tong, Y}, title = {Educational performance of TikTok short videos for age related macular degeneration and its link to user engagement.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1751545}, pmid = {41601834}, issn = {2296-858X}, abstract = {BACKGROUND: To systematically evaluate the information quality, reliability, and content characteristics of short videos related to age-related macular degeneration on the Chinese mainland version of TikTok, filling the research gap in this field and providing references for ophthalmic health education and platform information governance.<br><br>METHODS: This cross-sectional study was conducted on October 15, 2025, by searching the keyword "" on TikTok. The top 200 videos under "comprehensive ranking" were screened, and 196 videos meeting the eligibility criteria were ultimately included. Content integrity was evaluated following the American Academy of Ophthalmology guidelines and the Goobie framework. Video quality was assessed using the DISCERN instrument and the PEMAT-A/V tool. Statistical analyses were performed in IBM SPSS Statistics 27.0, with inter-rater reliability measured by the intraclass correlation coefficient. Differences among groups and associations between variables were examined using ANOVA and correlation analysis.<br><br>RESULTS: The overall quality of the included videos was moderate, with a median DISCERN tool score of 48.00 and a median Overall quality score of 3.00. The Understandability score was relatively high (median 84.62%), whereas the Actionability score was lower (median 75.00%). Videos uploaded by the Non-Profit group showed the highest quality (mean DISCERN tool score 59.13 &#xb1; 2.50), followed by the Medical group. The Non-Medical and For-Profit groups demonstrated the lowest quality, with statistically significant differences among groups (P < 0.05). Quality metrics were moderately positively correlated with user engagement metrics. The correlation coefficients between reliability and engagement were r = 0.48-0.54 (P < 0.05). Video duration showed a mild positive correlation with both quality and engagement (r = 0.23-0.30, P < 0.05). Inter-rater reliability was good (intraclass correlation coefficient = 0.839-0.947, P < 0.001).<br><br>CONCLUSION: Age-related macular degeneration videos on TikTok showed moderate overall quality, with content emphasizing clinical concerns but neglecting basic knowledge. Information quality varied by uploader source, with non-profit organizations and medical professionals providing most high-quality content. Higher-quality videos tended to receive greater user engagement, suggesting that platform algorithms may preferentially spread better educational material. These findings provide empirical support for improving science communication on this disease and strengthening information quality management on digital platforms.}, }
@article {pmid41602785, year = {2026}, author = {Khorrami-Nejad, M and Naroo, SA and Oklla, A and Narooie-Noori, F}, title = {Blue-light-filtering spectacle lenses in managing vision-related symptoms: an updated review.}, journal = {Therapeutic advances in ophthalmology}, volume = {18}, number = {}, pages = {25158414251412798}, pmid = {41602785}, issn = {2515-8414}, abstract = {Blue light, emitted by natural and artificial sources such as digital screens, has raised concerns regarding its impact on ocular health, visual comfort, and circadian rhythms. Prolonged exposure has been linked to digital eye strain (DES), visual fatigue, potential retinal damage, and sleep disturbances. Blue-light-filtering spectacle lenses have been developed to mitigate these effects by reducing short-wavelength blue light transmission, but their efficacy remains debated. Studies indicate that these lenses have minimal or no significant impact on contrast sensitivity, color discrimination, and task performance, with visual outcomes comparable to standard lenses. While some research suggests minor benefits in reducing DES and visual fatigue in specific populations, most studies report no significant differences. This highlights the multifactorial nature of DES. Experimental evidence supports the potential for blue-light-filtering spectacle lenses to reduce oxidative stress and phototoxicity in retinal cells, which may offer protection against retinal damage and age-related macular degeneration (ARMD). Additionally, these lenses show promise in neurological and psychological domains, including reduced migraine frequency, alleviation of mania symptoms, and improved sleep quality through circadian rhythm regulation. However, subjective sleep improvements are often not supported by objective measures. In summary, blue-light-filtering spectacle lenses may provide benefits in retinal protection, sleep regulation, and neurological health. However, their effectiveness in reducing visual fatigue, enhancing task performance, and preventing ARMD remains inconclusive. Further research with standardized methodologies and larger sample sizes is needed to clarify their clinical and everyday utility.}, }
@article {pmid41603251, year = {2026}, author = {Li, M and Yue, Y and Wu, S and He, X and Song, J and Ma, S and Zhang, H and Xu, C and Chen, S and Huang, Y and Xie, S and Yan, H}, title = {DNA Nanoflower LYTACs Enable Efficient VEGF Degradation and Verteporfin Loading for Combined Therapy of Wet Age-Related Macular Degeneration.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {13}, number = {16}, pages = {e15852}, doi = {10.1002/advs.202515852}, pmid = {41603251}, issn = {2198-3844}, support = {82330031//National Natural Science Foundation of China/ ; 32270892//National Natural Science Foundation of China/ ; TJYXZDXK-3-004A//Tianjin Key Medical Discipline Construction Project/ ; }, mesh = {*Verteporfin/pharmacology/therapeutic use/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/metabolism ; Animals ; *Wet Macular Degeneration/drug therapy/metabolism ; Humans ; *Photochemotherapy/methods ; Photosensitizing Agents/pharmacology ; Choroidal Neovascularization/drug therapy ; *DNA ; Mice ; Lysosomes/metabolism ; Aptamers, Nucleotide ; }, abstract = {Wet age-related macular degeneration (wAMD), characterized by pathological choroidal neovascularization (CNV), is a leading cause of irreversible vision loss in the elderly. The current standard treatment-anti-vascular endothelial growth factor (VEGF) therapy-effectively manages neovascularization in many patients. However, some experience suboptimal responses, and frequent intravitreal injections raise safety concerns. Photodynamic therapy is another effective option for treating wAMD, but it can lead to an increase in reactive VEGF after the procedure, resulting in CNV recurrence. In response to these challenges, we propose an integrated approach that combines a DNA nanoflower VEGF degrader with photodynamic therapy. The DNA nanoflower consists of numerous aptamer-based lysosome-targeted chimaera (LYTAC) units, which drive extracellular VEGF in the lesion area to the lysosome for degradation. Simultaneously, the DNA nanoflower acts as a carrier for verteporfin (VER), a clinically used photosensitizer. The resulting nanoflower, named NF@VER, generates reactive oxygen species under near-infrared light to induce endothelial cell death. These combined effects on endothelial cells effectively block VEGF-induced CNV in vivo, without causing noticeable side effects. Overall, this innovative approach presents a precise and effective strategy for treating wAMD, reducing the risk of VEGF reactivation-induced CNV recurrence, and minimizing the systemic side effects associated with photodynamic therapy.}, }
@article {pmid41603341, year = {2026}, author = {Wang, S and Wang, C and Hong, H and Tang, C and Yu, J and Wang, Q}, title = {An integrative multi-omics study reveals glutamine metabolism dysregulation connecting Alzheimer's disease and age-related macular degeneration.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {110}, number = {2}, pages = {795-809}, doi = {10.1177/13872877261418263}, pmid = {41603341}, issn = {1875-8908}, mesh = {*Alzheimer Disease/metabolism/genetics ; *Glutamine/metabolism ; Animals ; Humans ; Mice ; Metabolomics/methods ; *Macular Degeneration/metabolism/genetics ; Mice, Transgenic ; Mendelian Randomization Analysis ; Male ; Gene Expression Profiling ; Female ; Multiomics ; }, abstract = {BackgroundAlzheimer's disease (AD) and age-related macular degeneration (AMD) are two common neurodegenerative diseases with many similar pathological features, but their shared metabolic characteristics have not been fully elucidated.ObjectiveThis study aims to explore the shared metabolic pathways between AD and AMD using an integrated multi-omics strategy.MethodsWe incorporated Mendelian randomization (MR), bulk and single-cell transcriptomics, and targeted metabolomics to investigate the metabolic links.ResultsThrough MR, we found elevated genetically inferred glutamine concentrations were correlated with a lower likelihood of AD but a higher likelihood of AMD. Using transcriptomic profiling, we detected 19 common differentially expressed genes associated with glutamine and glutamate metabolism, such as GLS. Analysis of single-cell RNA sequencing data revealed that GLS displays distinct cell-type expression patterns. Targeted metabolomic profiling in APP/PS1 mice at 5 months of age provided additional evidence for alterations in glutamine metabolism. The degree of metabolic changes in the eyes was higher than that in the cortex and hippocampus, and the prominent eyes may be an early indicator of neurodegenerative metabolic dysfunction.ConclusionsOverall, these findings suggest that glutamine metabolism disorders represent a convergent mechanism between AD and AMD. Our findings shed light on the overlapping metabolic pathways linking AD and AMD, underscoring the value of ocular biomarkers as promising tools for early disease detection.}, }
@article {pmid41603556, year = {2026}, author = {Owsley, C and Gao, L and Gooden, L and Thomas, TN and Pu, J and Crosson, JN and Curcio, CA and McGwin, G and Kwon, M}, title = {Preserved Contrast Sensitivity in Early and Intermediate Age-Related Macular Degeneration and Marked Loss in Late Stage: ALSTAR2.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {1}, pages = {58}, pmid = {41603556}, issn = {1552-5783}, support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Aged ; *Contrast Sensitivity/physiology ; Female ; Male ; Cross-Sectional Studies ; Visual Acuity/physiology ; Aged, 80 and over ; Middle Aged ; Disease Progression ; *Macular Degeneration/physiopathology ; *Wet Macular Degeneration/physiopathology ; *Geographic Atrophy/physiopathology ; }, abstract = {PURPOSE: To cross-sectionally compare parameters from the quick contrast sensitivity function (qCSF)-area under the log CSF (AULCSF) and sensitivity at each spatial frequency-in older eyes with normal macular health and early, intermediate, and late AMD. Our purpose was to determine whether qCSF could be a promising functional outcome measure in interventions designed to slow AMD progression from aging to late AMD.<br><br>METHODS: qCSF contrast sensitivity was measured at 1.0 to 18 cycles per degree (cyc/deg). Models evaluated the impact of diagnostic group on the AULCSF and individual spatial frequencies, adjusting for age and lens status. The AREDS nine-step classification system defined AMD presence and severity.<br><br>RESULTS: Eight hundred twenty-three eyes were studied: 383 normal macular health, 203 early AMD, 208 intermediate AMD, and 29 late AMD (23 geographic atrophy, six neovascular AMD). AULCSF decreased with increasing AMD severity; this was mostly attributable to the late AMD eyes having lower AULCSF than other groups. Late AMD eyes had significantly worse sensitivity at 1 and 1.5&#xa0;cyc/deg compared to all other groups, with other groups having similar sensitivity. At frequencies near or just beyond the CSF peak (3-12&#xa0;cyc/deg), late AMD eyes again had the worst sensitivity, with intermediate AMD eyes having slightly worse sensitivity than early AMD eyes. There were no group differences at 18&#xa0;cyc/deg.<br><br>CONCLUSIONS: The qCSF will be most useful in trials studying the transition from intermediate AMD to late-stage AMD, rather than in studying the transition from aging to early and intermediate AMD.}, }
@article {pmid41604455, year = {2026}, author = {Oshima, Y and Nagidi, Y and Moorthy, ME and Heier, J and Matsubara, JA and Hardin, J and Flajnik, M and Vogel, BE}, title = {TEP-1, a glial thioester protein is required for cilia organization and intraflagellar transport in ensheathed sensory neurons in Caenorhabditis elegans.}, journal = {Molecular biology of the cell}, volume = {37}, number = {3}, pages = {ar24}, pmid = {41604455}, issn = {1939-4586}, support = {R35 GM145312/GM/NIGMS NIH HHS/United States ; }, mesh = {*Caenorhabditis elegans/metabolism/cytology/genetics ; Animals ; *Caenorhabditis elegans Proteins/metabolism/genetics ; *Cilia/metabolism/ultrastructure ; *Neuroglia/metabolism ; Humans ; *Sensory Receptor Cells/metabolism ; }, abstract = {Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by progressive degeneration of retinal photoreceptors. Traditional disease models suggest that defective repression of thioester protein C3 activity by complement factor H (CFH) is a major contributor to pathogenesis in AMD and a related disease, early-onset drusen maculopathy (EODM). Our previous study identified novel functions for human CFH and Caenorhabditis elegans CFH-1 in the maintenance of inversin compartment integrity in photoreceptors and mechanosensory neurons, indicating that CFH has a novel, evolutionarily conserved role in cilia compartment organization that is distinct from its established function in alternative complement pathway regulation. Here, we investigate the C. elegans thioester protein TEP-1, an ancestral relative of C3 and other members of the AMCOM family (C4, C5, CD109, and alpha-2-macroglobulin). TEP-1 localizes to select glial cell surfaces and regulates inversin compartment organization and intraflagellar transport (IFT) within the cilia of ensheathed sensory neurons. In addition to revealing a novel role for an AMCOM family member in sensory neuron structure and protein transport, the localization of C3 and CFH on human photoreceptors provides support for noncanonical models of AMD and EODM pathogenesis in which defects in cilia structure and protein transport contribute directly to the progressive photoreceptor dysfunction that characterizes these diseases.}, }
@article {pmid41607454, year = {2026}, author = {Walia, S and Morya, AK}, title = {Psychiatric disorders linked to visual impairment: A review of mental health challenges and interventions across age groups.}, journal = {World journal of psychiatry}, volume = {16}, number = {1}, pages = {111118}, pmid = {41607454}, issn = {2220-3206}, abstract = {The intersection of visual impairment and mental health has profound effects on quality of life and warrants attention from healthcare providers, educators, and policymakers. With 20 million children under the age of 14 affected globally, older adults also experience significant psychological impact including depression, anxiety, and cognitive impairment. The implications of vision-related challenges extend far beyond mere sight. Depression and anxiety, exacerbated by social isolation and reduced physical activity, underscore the need for comprehensive interventions that address both medical and psychosocial dimensions. By recognizing the profound impact of ocular morbidities like strabismus, myopia, glaucoma, and age-related macular degeneration on mental health and investing in effective treatments and inclusive practices, society can pave the way for a healthier, more equitable future for affected individuals. There is evidence that myopic children experience a higher prevalence of depressive symptoms compared to their normal peers, and interventions like the correction of strabismus can enhance psychological outcome - demonstrating the value of an integrated management approach.}, }
@article {pmid41612003, year = {2026}, author = {Bartolomeo, N and Kalyvianakis, KK and Schuetz, YP and Nascimbeni, AC and Castro, DG and Crozat, B and Barry, MP and Ambresin, A}, title = {Early Outcomes of Intravitreal Aflibercept 8 mg in Eyes Previously Treated with Aflibercept 2 mg for Neovascular Age-Related Macular Degeneration with AI-Based Biomarker Quantification.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {2}, pages = {831-842}, pmid = {41612003}, issn = {2193-8245}, abstract = {INTRODUCTION: To evaluate the early outcomes of aflibercept 8 mg (afl8) treatment in patients with neovascular age-related macular degeneration (nAMD) previously treated with aflibercept 2 mg (afl2).<br><br>METHODS: A retrospective, observational, monocentric Swiss study. Patients with nAMD who had received&#x2009;&#x2265;&#x2009;3 consecutive afl2 injections and switched to afl8 because of persistent or recurrent fluids, or to extend treatment intervals, were included in the study. All patients started a loading phase of 3-monthly afl8 injections, followed by a treat-and-extend regimen. Outcome measures included changes in best-corrected visual acuity (BCVA), maximal pigment epithelial detachment (PED) height, central subfield thickness (CST), optical coherence tomography (OCT) biomarkers quantified using artificial intelligence, and treatment intervals until month 6.<br><br>RESULTS: Fifty-two eyes of 44 patients who concluded the loading phase were included in this analysis. Mean age was 80.2&#x2009;&#xb1;&#x2009;8.5&#xa0;years; 73% of patients were females. At month 6, BCVA was unchanged, PED and CST height experienced a significant decrease by - 18.5&#x2009;&#xb1;&#x2009;12.9&#xa0;&#x3bc;m (p&#x2009;=&#x2009;0.0005) and - 14.0&#x2009;&#xb1;&#x2009;3.5&#xa0;&#x3bc;m (p&#x2009;=&#x2009;0.0042), respectively. Volumes of intraretinal fluid (IRF), subretinal fluid (SRF), and PED decreased (IRF: 4.4&#x2009;&#xb1;&#x2009;15.6-3.8 nl; SRF: 15.7&#x2009;&#xb1;&#x2009;35.7-10.3&#x2009;&#xb1;&#x2009;34.0 nl; PED: 268.2&#x2009;&#xb1;&#x2009;423.2-252.2&#x2009;&#xb1;&#x2009;484.1 nl). Mean treatment intervals increased by 1.7&#x2009;&#xb1;&#x2009;0.5&#xa0;weeks from the last assigned interval and by 0.6&#x2009;&#xb1;&#x2009;0.2&#xa0;weeks from previous maximal fluid-free intervals after switching (p&#x2009;=&#x2009;0.0005 and p&#x2009;=&#x2009;0.18, respectively). One mild vitritis was observed and resolved with vitrectomy and topical drops without decreased visual acuity.<br><br>CONCLUSION: Our real-world study supports the potential short-term benefits of afl8 in improving anatomical and durability outcomes in patients with recurrent nAMD. These findings also highlight the added value of data-driven evaluations. Long-term studies are needed to confirm the effectiveness and durability of afl8 in this population.}, }
@article {pmid41613191, year = {2025}, author = {Shanidze, NM and Velisar, A}, title = {Cancellation of the vestibulo-ocular reflex during smooth pursuit in patients with maculopathy.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1632527}, pmid = {41613191}, issn = {1664-2295}, support = {K99 EY026994/EY/NEI NIH HHS/United States ; R00 EY026994/EY/NEI NIH HHS/United States ; R01 EY036172/EY/NEI NIH HHS/United States ; }, abstract = {INTRODUCTION: Macular degeneration is associated with loss of central vision, including the fovea. Central visual field loss is associated with impaired smooth pursuit eye movements, and the associated scotoma can lead to target disappearance which may or may not be transient. While smooth pursuit in and of itself does not require a foveal position signal, suppression of the vestibuloocular reflex (VOR) needed during combined eye and head pursuit relies on the fovea for appropriate calibration. Prior work has shown that target extinction during, or even at the beginning of the trial does not affect the dynamics of the eye or head responses necessary for pursuit. These findings suggest that the potential disappearance of the target into the scotoma during pursuit can be overcome, particularly when both eye and head movements are used. The objective of this study was to test the hypothesis that head-unrestrained smooth pursuit deficits in CFL are at least partially related to individuals' inability to cancel their VOR.<br><br>METHODS: We performed a secondary analysis of a previously published data set of head restrained and unrestrained pursuit of a 10 &#xb0;/s target in 7 individuals with maculopathy (56-89 years) and 7 age-matched controls (61-78 years). We used a two-parameter linear regression model to quantify the eye-only pursuit (Kfix) and VOR (Kv) contributions to determine whether participants were able to effectively cancel the VOR to improve pursuit gain.<br><br>RESULTS: We observed reduced pursuit velocities in the head-unrestrained versus restrained smooth pursuit condition (Kfix < 1), particularly in the control group (CFL: Kfix = 0.90 &#xb1; 0.16; Control: Kfix = 0.74 &#xb1; 0.08). For VOR cancellation, Kv estimates did not deviate from -1 for either of our groups (CFL: Kv = -0.92 &#xb1; 0.09; Control: Kv = -0.98 &#xb1; 0.20), suggesting complete cancellation of the VOR during head-unrestrained pursuit. For the self-generated VOR experiment, participants in both groups had similar, near-one VOR gains (CFL: GainVOR = -1.00 &#xb1; 0.05; Control: GainVOR = -1.03 &#xb1; 0.02).<br><br>DISCUSSION: We confirmed that VOR responses to actively generated head movements were similarly intact in both groups. Our analyses of the pursuit data indicate that, regardless of visual function older adults attenuate eye-driven pursuit when the head is unrestrained (as compared to the restrained condition), and those with CFL fail to exploit residual VOR cancellation, helping to explain their persistent gaze-tracking deficits.}, }
@article {pmid41613944, year = {2025}, author = {Marmorstein, AD and Scruggs, BA and Knudsen, T and Hill, M and Kopp, FN and Trncic, E and Korda, D and Atherton, E and Berger, A and Finnemann, SC and Gandhi, J and Iezzi, R}, title = {Degradable fibrin hydrogels for transplantation of iPSC-derived retinal pigment epithelial cell monolayers.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1739620}, pmid = {41613944}, issn = {2296-634X}, abstract = {Death or dysfunction of retinal pigment epithelium (RPE) cells occurs in age-related macular degeneration (AMD) and certain inherited retinal dystrophies (IRDs). Induced-pluripotent stem cell (iPSC) derived-RPE have been used in early-stage clinical trials to treat AMD and IRDs by injecting them as a cell suspension or monolayers. While RPE transplant shows therapeutic potential, issues ranging from failure to repopulate the entire treatment area, clumping and monolayer folding, and a foreign body response to the support have been reported. We've shown that RPE can be grown on high concentration (>30 mg/mL) degradable fibrin hydrogels, and that cell free fibrin hydrogels implanted in the subretinal space degrade without causing inflammation. Here we describe manufacture and surgical implantation of degradable fibrin hydrogels carrying iPSC-RPE into a porcine model of geographic atrophy (GA). Large (15.25 × 58.42 × 0.2 mm) fibrin gel blanks were produced by injection molding, and iPSC-RPE were grown on their surface. Using a mechanical punch, the blank was subdivided into 1.5 × 5.0 × 0.2 mm doses, which fit a custom tool used for storage and surgical placement. Following aseptic packaging, RPE and gels were stable at 37 °C for at least 7 weeks. When transplanted into a pig model of GA, the fibrin scaffold degraded in <1 month and the iPSC-RPE provided partial rescue from GA as assessed by preservation of photoreceptors and blood flow in the choriocapillaris. We conclude that iPSC-RPE delivered on degradable fibrin hydrogels represent a potentially safe and effective approach to RPE transplantation.}, }
@article {pmid41615526, year = {2026}, author = {Ciarmatori, N and Cartabellotta, A and Adamo, GG and Biffi, C and Talli, PM and Pellegrini, M and Mura, M}, title = {Bilateral implantation of extended depth of focus intraocular lens in patients with early or intermediate age-related macular degeneration.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {87}, pmid = {41615526}, issn = {1573-2630}, support = {Investigator Initiated Trial Grant (IIT#75441181)//Alcon/ ; }, mesh = {Humans ; Male ; Female ; Prospective Studies ; *Visual Acuity/physiology ; Aged ; *Lenses, Intraocular ; *Macular Degeneration/complications/surgery/physiopathology/diagnosis ; *Vision, Binocular/physiology ; *Depth Perception/physiology ; *Lens Implantation, Intraocular/methods ; Patient Satisfaction ; Aged, 80 and over ; Prosthesis Design ; Middle Aged ; Follow-Up Studies ; Refraction, Ocular/physiology ; *Phacoemulsification/methods ; }, abstract = {PURPOSE: To evaluate the visual outcomes, dysphotopsia profile, and patient satisfaction following bilateral implantation of the AcrySof IQ Vivity intraocular lens (IOL) in patients with early or intermediate age-related macular degeneration (AMD).<br><br>METHODS: Prospective, single-center study. 24 patients (48 eyes) with bilateral cataract and early or intermediate AMD who underwent bilateral implantation of the AcrySof IQ Vivity IOL. The primary outcome was monocular corrected distance visual acuity (mCDVA). Secondary endpoints were distance-corrected and unaided monocular and binocular visual acuity at 4&#xa0;m, 66&#xa0;cm, and 40&#xa0;cm, monocular defocus curve, subjective dysphotopsia (McAlinden QoV questionnaire) and haloes perception (Aston Halometer), visual function (Catquest-9SF), and spectacle independence (IOLSAT).<br><br>RESULTS: At 3&#xa0;months postoperatively, mCDVA improved significantly from 0.30 to 0.00 logMAR (p&#x2009;<&#x2009;0.001). Binocular uncorrected distance and intermediate visual acuities of&#x2009;&#x2264;&#x2009;0.2 logMAR were achieved by 23 (95.8%) and 17 (70.8%) patients, respectively. The defocus curve showed visual acuity of 0.2 logMAR across a range of&#x2009;+&#x2009;1.40 D to -1.72 D. Bothersome dysphotopsias significantly decreased, with QoV scores improving from 58.5 (IQR: 26.1-66.5) to 0.00 (IQR: 0.00-14.3) (p&#x2009;<&#x2009;0.05). The mean halo eccentricity was 0.50&#x2009;&#xb1;&#x2009;0.08 degrees. Spectacle independence was reported by 22 (91.7%), 20 (83.3%), and 13 (54.2%) patients for distance, intermediate, and near tasks, respectively. Overall, 22 (91.7%) patients reported postoperative satisfaction.<br><br>CONCLUSION: The AcrySof IQ Vivity IOL demonstrated favourable outcomes in patients with early or intermediate AMD, offering a meaningful range of spectacle-free vision with minimal photic phenomena.}, }
@article {pmid41617934, year = {2026}, author = {Bo, N and Ding, Y}, title = {Estimation of the interpretable heterogeneous treatment effect with causal subgroup discovery in survival outcomes.}, journal = {Lifetime data analysis}, volume = {32}, number = {1}, pages = {11}, pmid = {41617934}, issn = {1572-9249}, support = {R01GM141076/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Macular Degeneration/drug therapy/genetics ; Treatment Outcome ; Survival Analysis ; Computer Simulation ; Precision Medicine/methods ; Randomized Controlled Trials as Topic ; Antioxidants/therapeutic use ; Treatment Effect Heterogeneity ; }, abstract = {Estimating heterogeneous treatment effects (HTE) for survival outcomes has gained increasing attention in precision medicine, as it captures variations in treatment efficacy among patients or subgroups. However, most existing methods conduct post-hoc subgroup identifications rather than simultaneously estimating HTE and identifying causal subgroups. In this paper, we propose an interpretable HTE estimation framework that integrates meta-learners with tree-based methods to estimate the conditional average treatment effect (CATE) for survival outcomes and identify predictive subgroups simultaneously. We evaluated the performance of our method through extensive simulation studies. We also demonstrated its application in a large randomized controlled trial (RCT) for age-related macular degeneration (AMD), a progressive polygenic eye disease, to estimate the HTE of an antioxidant and mineral supplement on time-to-AMD progression and to identify genetically defined subgroups with enhanced treatment effects. Our method offers a direct interpretation of the estimated HTE and provides evidence to support precision healthcare.}, }
@article {pmid41617984, year = {2026}, author = {Bailey, C and Lange, C and Chaudhary, V and Lanzetta, P and Oubraham, H and Kirchner, M and Machewitz, T and Allmeier, H and Zhang, X and Hasanbasic, Z and Munk, MR and , }, title = {SPECTRUM: early clinical experience from the first global real-world study of aflibercept 8 mg in patients with neovascular age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {40}, number = {5}, pages = {735-738}, pmid = {41617984}, issn = {1476-5454}, }
@article {pmid41618563, year = {2026}, author = {Cui, M and Cheng, SY and Liang, J and McGowan, J and Xu, M and Xu, G and Luo, L and Wu, J and Harman, CD and Jacobson, AL and Kapeller, LE and Mayes, MA and Namkung, S and Sharma, T and Leland, TB and Zhang, F and Yip, M and Rossmiller, B and Xue, T and Chen, X and Boonying, W and Lotun, A and Wang, D and Su, Q and Xie, J and Wei, Y and Rothstein, AM and Gregory-Ksander, MS and Komaromy, A and Tian, B and Lin, H and Punzo, C and Tai, PWL and Gao, G}, title = {Modification of the VP1u region boosts transduction of adeno-associated virus vectors for ocular gene therapy.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, pmid = {41618563}, issn = {1525-0024}, support = {UH3 HL147367/HL/NHLBI NIH HHS/United States ; UG3 HL147367/HL/NHLBI NIH HHS/United States ; R01 HL097088/HL/NHLBI NIH HHS/United States ; P01 HL131471/HL/NHLBI NIH HHS/United States ; U19 AI149646/AI/NIAID NIH HHS/United States ; R21 AI183080/AI/NIAID NIH HHS/United States ; R01 AI121135/AI/NIAID NIH HHS/United States ; R01 NS076991/NS/NINDS NIH HHS/United States ; R01 HL152723/HL/NHLBI NIH HHS/United States ; }, abstract = {Adeno-associated virus (AAV) capsids that can confer efficient and safe gene therapy of the retina remain unmet needs. In this study, we isolated a library of natural capsids from human tissues and identified two variants that conferred strong transduction of retinal tissues following intravitreal injections into mice and non-human primates. Interestingly, the defining amino acids among the two variants are located within the luminal VP1 unique (VP1u) region of the capsid. Combining these defining residues into a single capsid (AAV2.MC1) had an additive effect. We demonstrated that the MC1 modification enhances intracellular trafficking and nuclear entry. Importantly, we provide proof of concept that the AAV2.MC1 capsid can deliver an anti-vascular endothelial growth factor (VEGF) transgene to treat wet age-related macular degeneration. Finally, we demonstrate that the modification can also be grafted onto other AAV serotypes to boost baseline transduction. These findings open up new avenues for capsid modification through targeted alterations of the VP1u region.}, }
@article {pmid41619168, year = {2026}, author = {Raczynska, D and Ernest, J and Baumane, K and Sagong, M and Akiyama, K and Rauschning, W and Vajas, A and Nowosielska, A and Dusova, J and Majtánová, N and Oleksy, P and Kuneva, I and Resch, M and Lange, N and Briede, E and Bajdik, B and Jeong, A and Kozub, B and Papp, A}, title = {Therapeutic Equivalence of Eyluxvi (Aflibercept) to Eylea in Neovascular Age-Related Macular Degeneration: ALTERA Trial (Randomized).}, journal = {Ophthalmology and therapy}, volume = {15}, number = {2}, pages = {887-899}, pmid = {41619168}, issn = {2193-8245}, abstract = {INTRODUCTION: This study aimed to evaluate the efficacy and safety of Eyluxvi, an aflibercept biosimilar, compared with reference Eylea in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This phase&#xa0;3, multicenter, randomized, double-masked, parallel-group study enrolled 431 patients at 79 sites across 12 countries. Patients were randomized 1:1 to receive intravitreal Eyluxvi or Eylea (2&#xa0;mg) every 4&#xa0;weeks through week&#xa0;12, then every 8&#xa0;weeks through week&#xa0;48. The primary endpoint was change from baseline in best corrected visual acuity (BCVA) at week&#xa0;8.<br><br>RESULTS: The week&#xa0;8 least-squares mean BCVA change was 5.771 letters with Eyluxvi vs 7.863 letters with Eylea (difference -&#x2009;2.092 [95% confidence interval (CI) -&#x2009;3.431 to -&#x2009;0.753]). This equivalence was maintained through week&#xa0;52. Week&#xa0;52 adjusted mean changes were comparable for central subfield thickness (CST) (difference -&#x2009;4.742&#xa0;&#x3bc;m [95%&#xa0;CI -&#x2009;22.006 to 12.521]) and choroidal neovascularization (CNV) area (difference 0.233&#xa0;mm[2] [95%&#xa0;CI -&#x2009;0.724 to 1.191]). Safety profiles and immunogenicity were similar between groups.<br><br>CONCLUSION: This study demonstrated therapeutic equivalence between Eyluxvi and Eylea in nAMD treatment, with comparable anatomical outcomes and safety profiles. These findings support the development of Eyluxvi as an aflibercept biosimilar, potentially increasing treatment accessibility for patients with nAMD.<br><br>TRIAL REGISTRATION: EudraCT Identifier 2021-004530-11.}, }
@article {pmid41619249, year = {2026}, author = {Hiles, JD and Deri, O and Sishtla, K and Bear, JC and Cockcroft, JK and Opara, EI and Al-Kinani, AA and Alany, RG and Corson, TW and Schwikkard, SL}, title = {Sulphur Analogues of Homoisoflavonoids as Potential Treatments for Neovascular Eye Diseases.}, journal = {ChemMedChem}, volume = {21}, number = {2}, pages = {e202500824}, pmid = {41619249}, issn = {1860-7187}, support = {R01EY025641/MH/NIMH NIH HHS/United States ; RGPIN-2025-04563//Retina Research Foundation, Canada Foundation for Innovation, and Natural Sciences and Engineering Research Council/ ; }, mesh = {Humans ; *Angiogenesis Inhibitors/chemistry/pharmacology/chemical synthesis ; Cell Proliferation/drug effects ; *Isoflavones/chemistry/pharmacology/chemical synthesis ; Endothelial Cells/drug effects ; Structure-Activity Relationship ; Cell Line ; *Sulfur/chemistry/pharmacology ; Molecular Structure ; *Neovascularization, Pathologic/drug therapy ; Dose-Response Relationship, Drug ; Cyclooxygenase 2/metabolism ; }, abstract = {Treatment of neovascular eye diseases like age-related macular degeneration require a compound that is not toxic to ocular cells, that can reduce inflammation and inhibit angiogenesis. Homoisoflavonoids, naturally occurring compounds isolated primarily from the Hyacinthaceae sub-family of plants, have shown promise as anti-inflammatories and inhibitors of angiogenesis. A series of sulphur analogues, (3-benzylidene thiochroman-4-ones), were synthesised via a three-step procedure. These compounds were evaluated for selectivity towards endothelial cells over non-endothelial cells and their ability to inhibit COX-II over COX-I.Their potential anti-angiogenic activity was assessed using the Matrigel tube formation assay. (3Z)-3-[(3-bromophenyl)methylidene]-6-methoxy-2,3-dihydro-4H-1-benzothiopyran-4-one (10) was most active with respect to anti-proliferation against human retinal endothelial cells (HREC cells) (GI50 3.07 μM). All demonstrated selectivity with all GI50 values against retinal pigment epithelial cell line ARPE-19 >100 µM, with the exception of (3Z)-6-bromo-3-[(4-nitrophenyl)methylidene]-2,3-dihydro-4H-1-benzothiopyran-4-one (12), which was not toxic to either. (3Z)-3-[(3-bromophenyl)methylidene]-6-methoxy-2,3-dihydro-4H-1-benzothiopyran-4-one (10) showed significant reduction in angiogenesis properties in a Matrigel-based tube formation assay (38.79%, 5 µM, 56.41%, 10 µM). (3Z)-6-bromo-3-[(3-bromophenyl)methylidene]-2,3-dihydro-4H-1-benzothiopyran-4-one (7) was found to be the most active against COX-II with inhibition of 22.7 % (4.35 nM). The 3-benzylidene thiochroman-4-ones show promise as antiangiogenic agents, but limited selectivity to COX-II over COX-I.}, }
@article {pmid41620512, year = {2026}, author = {Alqassab, AIM and Luque-Nieto, M&#xc1; and Mohammed, MA}, title = {Identification of multiple ocular diseases using a hybrid quantum convolutional neural network with fundus images.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {6798}, pmid = {41620512}, issn = {2045-2322}, support = {PID2023-146540OB-C43//Ministerio de Ciencia e Innovaci&#xf3;n/ ; }, mesh = {Humans ; *Neural Networks, Computer ; *Fundus Oculi ; *Eye Diseases/diagnosis/diagnostic imaging ; Diabetic Retinopathy/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Convolutional Neural Networks ; }, abstract = {Ocular diseases remain a major cause of vision impairment globally, making early and accurate diagnosis essential. This study presents a novel diagnostic model for identifying seven common ocular conditions age-related macular degeneration, glaucoma, hypertension, diabetic retinopathy, myopia, cataracts, and other pathologies using clinical fundus images. To improve image quality, Anisotropic Diffusion Filtering and Wavelet Transform are applied for hue and contrast enhancement. Data imbalance is addressed through targeted augmentation techniques. The core of the model is a hybrid Quantum Convolutional Neural Network (QCNN), which integrates quantum convolutional pooling into a classical CNN architecture to boost feature extraction and classification. Evaluated on the OIA-ODIR dataset, the proposed model outperformed benchmarks such as Fundus-DeepNet, Inception-v4, VGG16 with SGD, and ResNet-101. It achieved 94% classification accuracy, along with substantial gains in precision, recall, and F1-score. These results confirm the model's effectiveness and its potential for supporting early, multi-disease ocular diagnosis in clinical settings.}, }
@article {pmid41620804, year = {2026}, author = {Li, K and Tang, J and Zhang, Z and Li, X and Zheng, Y and Jiang, D and Sun, J}, title = {Global burden and cross-country inequalities of age-related eye diseases from 1990 to 2021: a comprehensive analysis of temporal trends and socioeconomic disparities.}, journal = {Eye and vision (London, England)}, volume = {13}, number = {1}, pages = {4}, pmid = {41620804}, issn = {2326-0254}, support = {LMS26F020026//Natural Science Foundation of Zhejiang Province/ ; }, abstract = {BACKGROUND: Age-related eye diseases (AREDs) are leading causes of visual impairment worldwide. With global population aging, understanding their epidemiological trends and socioeconomic disparities is crucial for public health planning and equitable resource allocation.<br><br>METHODS: We conducted a secondary epidemiological analysis of AREDs using data from the Global Burden of Disease (GBD) Study 2021. We evaluated years lived with disability (YLDs) and age-standardized YLD rates (ASYR) and conducted trend analysis using Joinpoint regression. Cross-country inequalities were assessed using the slope index of inequality (SII) and concentration index, with correlation and regression analyses examining associations with the socio-demographic index (SDI).<br><br>RESULTS: Global YLDs for AREDs increased from 78.503 to 100.006, while ASYR decreased from 112.815 to 92.803 per 100,000 populations between 1990 and 2021. Despite a global increase in the relative burden of glaucoma, both absolute and relative inequalities for age-related macular degeneration (AMD) and cataracts decreased. Low-SDI countries showed slight improvements in reducing these inequalities. The SII for AREDs improved in lower-SDI countries between 1990 and 2021, with reductions in AMD (from&#x2009;-&#x2009;9.250 to&#x2009;-&#x2009;6.033), cataract (from&#x2009;-&#x2009;258.131 to&#x2009;-&#x2009;173.762), and glaucoma (from&#x2009;-&#x2009;21.090 to&#x2009;-&#x2009;20.064). The concentration index for AMD and cataract decreased from&#x2009;-&#x2009;0.167 and&#x2009;-&#x2009;0.335 in 1990 to&#x2009;-&#x2009;0.129 and&#x2009;-&#x2009;0.272 in 2021, respectively, while the concentration index for glaucoma increased from&#x2009;-&#x2009;0.208 to&#x2009;-&#x2009;0.263, Regional disparities in the AREDs burden were evident, with most regions showing improved inequality in lower-SDI countries as reflected in both the SII and concentration index.<br><br>CONCLUSIONS: Despite global improvements in the relative burden of AREDs, significant socioeconomic and geographical inequalities persist, particularly in low-SDI regions. Targeted public health strategies and strengthened eye care systems are urgently needed to address these disparities and achieve equitable eye health outcomes worldwide.}, }
@article {pmid41621805, year = {2026}, author = {Sarraf, D and Corvi, F and Rosenfeld, PJ and Ach, T and Blodi, B and Bottoni, F and Cozzi, M and Chakravarthy, U and Chew, EY and Csaky, K and Cukras, C and Curcio, CA and Ferris, FL and Freund, KB and Grunwald, J and Guymer, RH and Holz, FG and Jaffe, GJ and Liakopoulos, S and Lim, TH and Monés, JM and Owsley, C and Pagliarini, S and Pauleikhoff, D and Schmitz-Valckenberg, S and Spaide, RF and Sparrow, J and Tadayoni, R and Tufail, A and Viola, F and Fraser, S and Staurenghi, G and Sadda, SR}, title = {Standardizing Measurement of Complete Retinal Pigment Epithelial and Outer Retinal Atrophy-Classification of Atrophy Meeting Report 8.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.01.017}, pmid = {41621805}, issn = {2468-6530}, abstract = {PURPOSE: To highlight the role of en face OCT in the measurement of choroidal hypertransmission defects (hyperTDs) in complete retinal pigment epithelial and outer retinal atrophy (cRORA), and to refine the definition of retinal pigment epithelium (RPE)-related alterations associated with cRORA.<br><br>DESIGN: Consensus meeting.<br><br>PARTICIPANTS: Panel of retina specialists, including retinal imaging experts, reading center leaders, and retinal histologists.<br><br>METHODS: As part of the Classification of Atrophy Meeting (CAM) program, an international group of experts analyzed and discussed the role of en face OCT in the assessment of cRORA. A structured study was conducted, consisting of an exercise to assess en face OCT cases, reviewed jointly during the eighth CAM meeting, and to explore the utility of this advanced tool for disease staging and progression. Additionally, definitions previously applied to RPE abnormalities were discussed and refined leading to modifications. The current report summarizes the methods used during the consensus meeting and the outcomes achieved as pertains to the application of en face OCT for cRORA grading and simplification of the RPE assessment criteria.<br><br>MAIN OUTCOME MEASURES: Defining the role of en face OCT in the detection and quantification of hyperTDs, improving classification of cRORA, and refining the terminology related to RPE alterations to enhance grading consistency.<br><br>RESULTS: During the consensus case discussions, high levels of agreement were achieved for hyperTD detection using en face OCT. The CAM group affirmed the role of en face OCT as a critical adjunct to traditional B-scan analysis, for more precise measurement of the area of cRORA lesions and for distinguishing threshold cRORA from smaller incomplete retinal pigment epithelial and outer retinal atrophy lesions. Additionally, merger of RPE attenuation and RPE disruption into a unified category termed "abnormal RPE band" significantly reduced interreader variability, leading to greater consistency among graders.<br><br>CONCLUSIONS: The integration of en face OCT with cross sectional B-scan imaging enhances the accurate classification and area measurement of early atrophic alterations in age-related macular degeneration, improving diagnostic consistency and lesion assessment. The consensus panel's adoption of the abnormal RPE band term as a unified category for RPE abnormalities may reduce confusion regarding the definition of RPE degeneration and has the potential to improve interreader variability.<br><br>FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid41621806, year = {2026}, author = {Xiao, JF and Hyman, MJ and Moir, J and Yehia, M and Hariprasad, S and Flores, A and Skondra, D}, title = {Association of Metformin Use and New-Onset International Classification of Diseases Coding of Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.01.019}, pmid = {41621806}, issn = {2468-6530}, abstract = {PURPOSE: To investigate whether metformin use is associated with decreased odds of new-onset International Classification of Diseases (ICD) coding of neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Case-control study.<br><br>PARTICIPANTS: A total of 22,205 cases with new-onset ICD coding of nAMD and 22,126 matched controls without age-related macular degeneration (AMD) were identified in the Merative MarketScan Research Databases between 2008 and 2017. A subgroup of patients diagnosed with diabetes included 6664 cases and 5513 controls.<br><br>METHODS: Cases with new-onset ICD coding of nAMD were propensity score matched to controls without AMD. Multivariable conditional logistic regression analyzed the association between new-onset ICD coding of nAMD and metformin use controlling for: (1) AMD risk factors, including diabetes, diabetic retinopathy, hyperlipidemia, obesity, and smoking; (2) exposures to other antidiabetic medications, including insulin, sulfonylureas, glitazones, meglitinides, other diabetic medications, and statins; and (3) the number of antidiabetic medications.<br><br>MAIN OUTCOME MEASURES: Adjusted odds ratios (aORs) of new-onset ICD coding of nAMD for any metformin use and cumulative 2-year metformin dose in grams.<br><br>RESULTS: Any metformin use was associated with decreased adjusted odds of new-onset nAMD (aOR, 0.84; 95% confidence interval [CI], 0.74-0.95). In an exploratory dosing analysis, associations across cumulative-dose categories were heterogeneous, with the largest magnitude in the middose range (between 271 and 600 g; aOR, 0.73; 95% CI, 0.63-0.85); because adherence cannot be verified from claims, dose-response findings are interpreted as hypothesis-generating. These associations persisted among diabetic patients (any metformin use: aOR, 0.83; 95% CI, 0.72-0.94; 271 to 600 g: aOR, 0.72; 95% CI, 0.61-0.85; >1080 g: aOR, 0.85; 95% CI, 0.72-0.999). Any metformin use in diabetic patients without retinopathy was associated with decreased odds of new-onset ICD nAMD (aOR, 0.79; 95% CI, 0.69-0.92); however, this association was absent in diabetic patients with retinopathy.<br><br>CONCLUSIONS: In this claims-based analysis, metformin use was associated with lower odds of incident ICD-coded nAMD, and an exploratory dosing analysis suggests a low-to-moderate cumulative dose may be associated with the greatest decrease. These associations persisted among diabetic patients without retinopathy. Causal inference is limited by the observational design, potential diagnostic misclassification, imperfect exposure measurement, and residual confounding. Replication with validated case definitions, active-comparator new-user designs, and adjudicated outcomes is warranted.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41622023, year = {2026}, author = {Hart, KM and Ayton, LN and Wu, Z}, title = {Developing age-related macular degeneration recommendations for clinical optometrists via a modified Delphi study.}, journal = {Clinical &amp; experimental optometry}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/08164622.2025.2610977}, pmid = {41622023}, issn = {1444-0938}, abstract = {CLINICAL RELEVANCE: Clear, evidence-based guidelines support optometrists in diagnosing and managing age-related macular degeneration, a leading cause of vision loss in older adults. This condition is an increasing focus of clinical care due to expanding treatment options and evolving imaging technologies.<br><br>BACKGROUND: Clinical practice guidelines support consistent, evidence-based care in optometry and play a critical role in guiding the diagnosis and management of chronic eye diseases. This paper discusses the methodological approach used to develop age-related macular degeneration guidelines, emphasising the modified Delphi approach used to refine and formally establish recommendations.<br><br>METHODS: Recommendations were developed from a literature review and draft guideline. An expert working group of optometrists (n&#x2009;=&#x2009;9) participated in a three-round Delphi process, rating their agreement with the draft recommendations using a 6-point Likert scale across two survey rounds, followed by a virtual meeting to discuss and re-vote on unclear or contentious items. Quantitative and qualitative measures during the first two rounds of the Delphi survey guided recommendation refinement and inclusion for discussion in round 3. Consensus for inclusion was defined as a mean score &#x2265;5 and &#x2265;80% agreement.<br><br>RESULTS: Out of 37 initial recommendations, 25 (68%) were accepted and included in the final guideline. Consensus was achieved for recommendations concerning clinical classification, assessment and management strategies. Round 3 discussions helped resolve uncertainties and refine recommendations wording, particularly regarding nutritional supplements and clinical biomarkers for progression. Adoption of the Delphi approach demonstrated the value of both quantitative and qualitative feedback.<br><br>CONCLUSION: The feasibility and value of using a modified Delphi method to develop optometric clinical practice guidelines is demonstrated. The process supported the inclusion or exclusion of recommendations in a systematic way with the final guideline offering contemporary, practice-relevant guidance for the diagnosis and management of age-related macular degeneration.}, }
@article {pmid41622390, year = {2026}, author = {Chen, X and Shi, W and Zhu, Y and Li, K and Xia, Y and Wu, H and Hu, T and Qin, C and Wei, W}, title = {PF protects retinal pigment epithelial cells from oxidative injury by enhancing mitophagy through a CUL3-dependent AMPK/ULK1 pathway.}, journal = {Archives of pharmacal research}, volume = {49}, number = {2}, pages = {242-261}, pmid = {41622390}, issn = {1976-3786}, support = {QN202414//Jiangsu Provincial Administration of Traditional Chinese Medicine/ ; GSPYY2023009//Jiangsu Provincial Administration of Traditional Chinese Medicine/ ; }, mesh = {*Mitophagy/drug effects ; *Autophagy-Related Protein-1 Homolog/metabolism ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; *Oxidative Stress/drug effects ; Humans ; Animals ; *AMP-Activated Protein Kinases/metabolism ; Protein Serine-Threonine Kinases/metabolism ; *Cullin Proteins/metabolism ; Signal Transduction/drug effects ; Mice ; AMP-Activated Protein Kinase Kinases ; Hydrogen Peroxide ; Cell Line ; Mice, Inbred C57BL ; *Intracellular Signaling Peptides and Proteins/metabolism ; Dose-Response Relationship, Drug ; Male ; }, abstract = {Mitophagy dysfunction is a critical contributor to retinal pigment epithelial (RPE) cell damage during the progression of retinal degenerative diseases, including age-related macular degeneration (AMD). In this study, we investigated the effects of paeoniflorin (PF) on mitophagy in RPE cells, with a particular focus on the CUL3/LKB1/AMPK/ULK1 signaling pathway. ARPE-19 cells were treated with different concentrations of PF to evaluate cytotoxicity, and its protective effects were further examined in H2O2-induced oxidative stress models in vitro and in sodium iodate (NaIO3)-induced RPE injury models in vivo. Protein levels of CUL3, apoptosis-related factors, mitophagy markers, and components of the LKB1/AMPK/ULK1 pathway were assessed by western blotting, and mitophagy was visualized using MitoTracker labeling. Cycloheximide (CHX) and coimmunoprecipitation (Co-IP) assays were performed to analyze the interaction between CUL3 and LKB1. PF treatment enhanced mitophagy in H2O2-stimulated ARPE-19 cells, whereas Parkin knockdown markedly attenuated this effect. In oxidatively damaged cells, PF promoted AMPK and ULK1 phosphorylation, increased mitophagy-associated protein expression, and alleviated mitochondrial dysfunction; these protective effects were abolished by pharmacological inhibition of AMPK or ULK1. In addition, CUL3 overexpression significantly attenuated PF-induced mitophagy activation and reduced PF-associated phosphorylation of LKB1, AMPK, and ULK1. Mechanistically, PF downregulated CUL3 expression, while CUL3 promoted the ubiquitination and degradation of LKB1. Silencing CUL3 induced mitophagy in H2O2-treated cells, whereas concurrent knockdown of CUL3 and LKB1 abolished this effect. In vivo, PF mitigated RPE cell loss, enhanced mitophagy, and activated the CUL3/LKB1/AMPK/ULK1 signaling pathway in the retinal tissues of NaIO3-induced mice. Collectively, these findings indicate that PF protects against RPE injury in an NaIO3-induced AMD-like model by downregulating CUL3 expression and activating LKB1/AMPK/ULK1-mediated mitophagy.}, }
@article {pmid41622479, year = {2026}, author = {Løkken, JFT and Moe, MC and Sæther, EM and Jørstad, &#xd8;K}, title = {Beyond drug price: A comparison of overall costs of anti-vascular endothelial growth factor therapy alternatives for neovascular age-related macular degeneration in Norway.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70069}, pmid = {41622479}, issn = {1755-3768}, support = {//Bayer Norway/ ; }, abstract = {PURPOSE: Norwegian guidelines designate off-label Avastin as the first-line intravitreal therapy for neovascular age-related macular degeneration (nAMD) because of its well-documented clinical efficacy and low price. However, this overlooks non-drug costs, which increase with injection frequency. We evaluated whether newer, longer-acting agents offer greater long-term cost-efficiency by reducing total costs despite higher drug prices in a Norwegian setting.<br><br>METHODS: We developed a 2-year cost-minimization model that included pharmaceutical, consultation and administrative and patient-related costs in Norway; the pharmaceutical cost component incorporated the routine practice of splitting vials into prefilled syringes in hospital pharmacies. The model compared four nAMD monotherapies, Avastin, Eylea 2&#x2009;mg, Eylea 8&#x2009;mg and Vabysmo, as well as the common practice of switching treatment-resistant patients from Avastin to Eylea 2&#x2009;mg. We derived injection frequencies from clinical trials (for monotherapies) or observational data (for switching) and conducted one-way sensitivity analyses to identify key cost drivers.<br><br>RESULTS: Over 2&#x2009;years, the switching regimen had the highest per-patient cost (146&#x2009;722 NOK), followed by Eylea 2&#x2009;mg (100&#x2009;481 NOK), Vabysmo (93&#x2009;207 NOK), Avastin (86&#x2009;262 NOK) and Eylea 8&#x2009;mg (68&#x2009;738 NOK). Avastin had the lowest drug cost, but its high injection frequency increased non-drug costs. Sensitivity analyses showed that injection frequency strongly influenced total costs for high-priced drugs, while patient time had a substantial impact for Avastin.<br><br>CONCLUSION: In our model, longer-acting agents reduced injection frequency and decreased overall treatment costs. These findings suggest that adopting longer-acting monotherapy could improve cost-efficiency in long-term nAMD management in Norway.}, }
@article {pmid41624137, year = {2025}, author = {Rusciano, D and Bagnoli, P}, title = {The controversial role of nutraceuticals vs. drugs in proliferative retinopathies.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1727089}, pmid = {41624137}, issn = {1662-4548}, abstract = {Neovascular eye diseases, notably age-related macular degeneration and diabetic retinopathy, remain major causes of vision loss despite advances in pharmacological management. The proliferation of abnormal retinal blood vessels leads to the loss of retinal cells and progressive visual dysfunction. Anti-VEGF therapies have revolutionized treatment; however, their efficacy is incomplete, they require repeated administration, and resistance or suboptimal responses are not uncommon. These limitations have stimulated interest in additional therapeutic approaches, both inspired by preclinical research and aimed at improving the management of systemic conditions that contribute to neovascular pathologies. Beyond conventional pharmacology, nutraceuticals have attracted attention for their proposed mechanisms-enhancement of antioxidant defenses, modulation of inflammatory cascades, and potential interference with angiogenic signaling-which provide a molecular rationale for their application in ocular disease. This review critically examines the dual landscape of current pharmacological strategies and nutraceutical approaches, analyzing how the latter might enhance retinal resilience and vascular stability in the early stages of disease. The novelty of this work lies in juxtaposing the mechanistic underpinnings of nutraceuticals with the clinical shortcomings of anti-VEGF therapy, thereby identifying opportunities for integrative therapeutic perspectives. Nevertheless, nutraceuticals cannot replace pharmacological treatment in advanced disease; rather, they may offer incremental benefits in early-stage or high-risk patients, contingent upon timely preventive diagnosis. Until more robust clinical evidence and regulatory oversight are established, nutraceuticals should be regarded as adjunctive components within personalized care models-supporting, but not substituting for, established pharmacological interventions.}, }
@article {pmid41626424, year = {2026}, author = {Mukherjee, S and Wu, D and Emde, LV and Vance, E and Ji, M and Emamverdi, M and De Silva, T and Thavikulwat, AT and Kalpathy-Cramer, J and Domalpally, A and Cukras, CA and Keenan, TDL}, title = {ReticularNet: Automated Pixel-Level Segmentation of Reticular Pseudodrusen on Near-Infrared Reflectance Images by Deep Learning.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {101038}, pmid = {41626424}, issn = {2666-9145}, abstract = {OBJECTIVE: Reticular pseudodrusen (RPD) represent an important biomarker in age-related macular degeneration (AMD) but are difficult to grade and often assessed only for presence or absence, without quantitative or spatial analysis of RPD burden. The objective was to develop and validate a deep learning model for pixel-level RPD grading on near-infrared reflectance (NIR) images, which are commonly acquired in clinical practice and the most accurate en face detection modality.<br><br>DESIGN: Deep learning model development study.<br><br>PARTICIPANTS: Five hundred eight images of 117 eyes (70 participants) with or without RPD, over a wide range of AMD severities.<br><br>METHODS: The ground truth grading pipeline comprised reading center multimodal grading for RPD presence and NIR annotation with RPD contours, followed by pixel-level NIR annotation of all individual RPD lesions. The data set was split 80:20 into training and test sets. A DeepLabv3-ResNet-18 segmentation deep learning model ("ReticularNet") was trained to perform pixel-level grading of RPD on NIR images. Its performance was compared with that of 4 ophthalmologists.<br><br>MAIN OUTCOME MEASURES: Dice similarity coefficient (DSC); intraclass correlation coefficient (ICC) for RPD lesion number, pixel area, and contour area.<br><br>RESULTS: For pixel-level grading, ReticularNet achieved a mean DSC of 0.36 (standard deviation 0.16). This was significantly higher than the mean DSC of each ophthalmologist (0.03, 0.13, 0.19, and 0.23; P &#x2264; 0.02 for each) and of all ophthalmologists together (P < 0.0001). ReticularNet had ICCs of 0.44 (lesion number), 0.56 (pixel area), and 0.61 (contour area), with no significant underestimation or overestimation (P &#x2265; 0.24). These values were numerically higher than the ICCs of each ophthalmologist, who had ICC ranges of -0.08 to 0.23, -0.05 to 0.40, and -0.09 to 0.58, respectively, and significant underestimation in almost all cases. For all 3 parameters, ReticularNet's ICC was significantly higher than that of all specialists considered together (P &#x2264; 0.02).<br><br>CONCLUSIONS: ReticularNet achieved automated pixel-level grading of RPD on NIR images. Its grading was superior to that of 4 ophthalmologists, across a variety of metrics. We are making the code/models available for research use. Improved access to quantitative and spatial RPD grading should lead to improved understanding of these lesions as important biomarkers of retinal disease.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41626425, year = {2026}, author = {Chen, ZJ and Yu, J and Ho, M and Ng, DSC and Brelen, ME and Young, AL and Yam, JCS and Tham, CC and Pang, CP and Chen, LJ}, title = {The CFH-CFHR5 Locus in Wet Age-Related Macular Degeneration, Polypoidal Choroidal Vasculopathy, and Central Serous Chorioretinopathy.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {101043}, pmid = {41626425}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the effects of haplotype-tagging single nucleotide polymorphisms (SNPs) in the complement factor H-complement factor H related 5 (CFH-CFHR5) locus on neovascular age-related macular degeneration (nAMD), polypoidal choroidal vasculopathy (PCV), and chronic central serous chorioretinopathy (cCSCR) in Chinese patients.<br><br>DESIGN: Case-control genetic association study.<br><br>PARTICIPANTS: A total of 846 patients (341 nAMD, 288 PCV, and 217 cCSCR including 43 with secondary macular neovascularization [MNV]) and 632 healthy Chinese controls.<br><br>METHODS: A total of 17 candidate SNPs were initially selected from the CFH-CFHR5 region; after excluding 5 SNPs that deviated from Hardy-Weinberg equilibrium, 12 SNPs were retained for the final analysis. Association analyses included logistic regression adjusted for age and sex and haplotype-based analysis using Haploview. Study-wide significance threshold was set at P < 0.0042 for allelic tests (Bonferroni-corrected for 12 SNPs) and at P < 0.05 for haplotype tests (adjusted using 10 000 permutations).<br><br>MAIN OUTCOME MEASURES: Associations between individual SNPs and haplotypes in the CFH-CFHR5 locus with nAMD, PCV, and cCSCR (with or without MNV), respectively.<br><br>RESULTS: The tagging SNP, rs12144939, for the CFHR3/1 deletion was significantly associated with nAMD (odds ratio [OR] = 0.37, P = 0.0031). Notably, we identified 3 candidate variants showing novel associations with PCV, including rs12144939 (OR = 0.29, P = 6.29 &#xd7; 10[-4]), rs423641 in CFHR1 (OR = 0.74, P = 0.0038), and rs10922152 in CFHR5 (OR = 1.55, P = 0.0031). No SNP in this locus was associated with cCSCR without MNV, whereas CFH rs529825 was nominally associated with cCSCR with MNV (OR = 0.47, P = 0.0047). Similar patterns of haplotype associations were observed across the 3 maculopathies. Notably, the haplotype A-T-C-G spanning CFHR4, CFHR2, and CFHR5 (OR = 1.81, permutation P = 0.0099) and haplotype G-A-G within CFHR5 (OR = 1.56, permutation P = 0.025) were specifically associated with PCV.<br><br>CONCLUSIONS: This study validates the association of the CFHR3/1 deletion (tagged by rs12144939) with nAMD. Furthermore, we reveal a novel genetic architecture for PCV within the CFH-CFHR5 locus, characterized by associations at rs12144939, rs423641 (CFHR1), and rs10922152 (CFHR5), as well as risk haplotypes unique to PCV. These findings underscore the critical role of CFH-related genes in PCV and provide new insights into its genetic mechanisms.<br><br>FINANCIAL DISCLOSURES: The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid41626488, year = {2026}, author = {Wang, Y and Chen, S and Cao, Y and Wen, X and Fu, C and Liang, J and Luo, Q and Liu, Q}, title = {Molecular Dynamics and Experimental Validation of Natural Products from Chuanxiong Rhizoma as VEGFR2 Inhibitors for nAMD Therapy.}, journal = {ACS omega}, volume = {11}, number = {3}, pages = {3949-3964}, pmid = {41626488}, issn = {2470-1343}, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly worldwide. Neovascular AMD (nAMD) is a significant subtype of AMD, responsible for the blindness of over 90% of patients with AMD. The hallmark of nAMD is choroidal angiogenesis dysregulation, a condition that can result in severe inflammation, leakage, and bleeding, ultimately leading to a precipitous decline in visual acuity. Inhibition of the vascular endothelial growth factor (VEGF) pathway has been proven to be an effective therapeutic strategy for this disease. Intraocular injection of anti-VEGF macromolecule drugs is a clinical therapy for this disease, but it has shortcomings, such as severe side effects, high cost, long treatment cycle, and complex administration methods. Consequently, the identification of novel small-molecule drugs and the development of innovative delivery mechanisms are of paramount importance for the treatment of this condition. Chuanxiong Rhizoma (CX), a type of traditional Chinese medicine (TCM), has been employed in the treatment of vascular-related diseases. Contemporary pharmacological research has demonstrated that CX contains a substantial quantity of natural compounds that exhibit anti-VEGF activity. In this study, we employed molecular simulation docking and molecular dynamics (MD) to examine the anti-VEGFR2 effects of 10 natural compounds derived from CX. Sorafenib was selected as the reference ligand, which is a marketed VEGFR2 inhibitor for cancer treatment. As a DFG-out inhibitor, sorafenib stabilizes the inactive conformation of the kinase by binding to an allosteric site near the ATP-binding pocket. In our research, natural products exhibiting a strong binding affinity were identified using computer-simulated docking technology and detailed binding sites were predicted. The findings of the research indicate that apigenin exhibits the strongest affinity for the VEGFR2 receptor with the formation of three hydrogen bonds. The molecular docking results indicate that the CYS919 and ASP1046 amino acid residues of VEGFR2 are the primary groups that form hydrogen bonds with the ligands. Furthermore, the AutoQSAR module of Schrödinger Suite predicted apigenin to have the highest predicted pIC50 value among the ten candidate compounds, suggesting its potential for significant VEGFR2 inhibitory activity. A subsequent MD simulation revealed that the binding of apigenin to the protein was more stable, and the conformation was stronger. According to the ADMET prediction results, apigenin is characterized by low toxicity. To ascertain the capacity of apigenin to impede the proliferation of choroidal angiogenesis, the choroid sprouting assay was utilized as a methodological framework. An in vitro experiment demonstrated that apigenin can significantly inhibit the growth of choroidal vessels in a dose-dependent manner. The present study was conducted with the objective of assessing the potential of natural products in the treatment of nAMD. In addition, the study offered valuable insights for the development of new natural agents.}, }
@article {pmid41627332, year = {2026}, author = {Kado Abdalkader, R and Kawakami, S and Takashima, Y and Fujita, T}, title = {Development of a 3D-printed microfluidic chip for retinal organoid-endothelial co-culture.}, journal = {Lab on a chip}, volume = {26}, number = {4}, pages = {965-975}, doi = {10.1039/d5lc00939a}, pmid = {41627332}, issn = {1473-0189}, mesh = {Coculture Techniques/instrumentation ; Humans ; *Organoids/cytology/metabolism ; *Printing, Three-Dimensional ; *Lab-On-A-Chip Devices ; *Endothelial Cells/cytology/metabolism ; *Retina/cytology ; Induced Pluripotent Stem Cells/cytology ; Retinal Pigment Epithelium/cytology ; }, abstract = {Pathological angiogenesis, such as that observed in wet age-related macular degeneration (AMD), is difficult to reproduce in vitro using human-relevant models. Although organ-on-chip (OoC) systems incorporating retinal pigment epithelium (RPE) and endothelial barriers have been reported, models integrating human retinal organoids with vascular networks remain limited. Here, we present a fully 3D-printed microfluidic platform for co-culture of human induced pluripotent stem cell (hiPSC)-derived retinal organoids containing intrinsic RPE regions with endothelial cells. The device, fabricated from flexible thermoplastic polyurethane (TPU) on a transparent polyvinyl chloride (PVC) substrate, supports three-dimensional co-culture within a fibrin-Matrigel matrix. In this system, endothelial cells formed organized vascular networks that localized around RPE-associated regions of retinal organoids without direct tissue invasion. Organoid-endothelial co-culture resulted in increased VEGF secretion, while exogenous VEGF further enhanced endothelial localization near RPE regions without affecting organoid growth. Functional assays using fluorescent dextran and rhodamine-labeled liposomal nanoparticles demonstrated spatially restricted and time-dependent transport along vascularized regions adjacent to the organoid interface. This retinal organoid-on-chip provides a simple and robust in vitro platform for studying retinal-vascular interactions and vascular-mediated transport processes.}, }
@article {pmid41627545, year = {2026}, author = {Cheng, X and Zeng, X and Liu, S and Liu, C and Liu, Y and Xu, G}, title = {Shared diagnostic biomarkers and diagnostic models of age-related macular degeneration and systemic lupus erythematosus.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {95}, pmid = {41627545}, issn = {1573-2630}, support = {U2267220//Yulong Liu/ ; }, mesh = {Humans ; *Lupus Erythematosus, Systemic/diagnosis/genetics/metabolism ; *Macular Degeneration/diagnosis/genetics/metabolism ; *Biomarkers/metabolism ; Gene Expression Profiling ; Mendelian Randomization Analysis ; }, abstract = {PURPOSE: This study aimed to investigate the potential link between age-related macular degeneration (AMD) and systemic lupus erythematosus (SLE), exploring whether AMD may share underlying autoimmune mechanisms with SLE. The objective was to identify shared core genes and potential diagnostic biomarkers for both diseases.<br><br>METHODS: We utilized GEO datasets to develop diagnostic models and performed differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and three machine learning techniques-LASSO regression, random forest (RF), and support vector machine recursive feature elimination (SVM-RFE)-to identify common key genes between AMD and SLE. Mendelian randomization analysis was conducted to validate the potential causal relationship between AMD and the identified essential genes. Single-cell RNA sequencing data were analyzed to explore the expression patterns of shared biomarkers at the cellular level. The expression level of the identified biomarker was validated using reverse transcription quantitative polymerase chain reaction and Western blotting.<br><br>RESULTS: Several shared core genes were identified as associated with both AMD and SLE. The Mendelian randomization study confirmed a potential correlation between AMD and these essential genes. Single-cell transcriptomic analysis revealed distinct expression profiles of these markers across relevant cell types, supporting their role in disease pathology.<br><br>CONCLUSION: Our findings suggest that AMD and SLE share key genetic features, supporting the hypothesis that AMD may have an autoimmune component. These shared genes hold promise as potential therapeutic targets and diagnostic biomarkers for both diseases.}, }
@article {pmid41629364, year = {2026}, author = {Spörri, L and Studer, JM and Kreuzer, M and Rotzetter, J and Schärer, D and Largiadèr, CR and Jaggi, D and Zinkernagel, MS and Zysset-Burri, DC}, title = {Linking the microbiome to the complement system in geographic atrophy.}, journal = {NPJ genomic medicine}, volume = {11}, number = {1}, pages = {}, pmid = {41629364}, issn = {2056-7944}, support = {CF10000044-EPFL SCR0237812//Foundation Bertarelli Catalyst Fund, EPFL (Ecole Polytechnique F&#xe9;d&#xe9;rale de Lausanne), Lausanne, Switzerland/ ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss in the aged population with the late stage geographic atrophy (GA). Risk factors for AMD include age, genetic variants in the complement system, nutritional factors, and alterations in the gut microbiome (GM). To identify taxonomic and functional differences in the microbiome associated to disease pathophysiology and genetic risk factors, this study investigated the GM and the ocular surface microbiome (OSM) of GA patients compared to healthy controls by whole-metagenome shotgun sequencing. 16 AMD-associated SNPs were genotyped from blood samples using TaqMan assays and Sanger sequencing. While GA patients showed differences in the GM, and altered metabolic pathways including inosine 5'-phosphate degradation, NAD salvage, and ketogenesis, no alterations in the OSM were found. Genetic analysis associated SNP rs1061170 in the complement factor H gene with GA. These findings suggest that microbial alterations may contribute to GA through inflammation and oxidative stress.Registry: ClinicalTrials.gov, NCT02438111, Registration date: 28 April 2015, and NCT04658238, Registration date: 01 December 2020.}, }
@article {pmid41629572, year = {2026}, author = {Kindo, H and Hosokawa, MM and Ouchi, C and Matoba, R and Morita, T and Hayashi, J and Morizane, Y}, title = {Real-world six-month outcomes after switching from aflibercept 2 mg to aflibercept 8 mg for neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {41629572}, issn = {1613-2246}, abstract = {PURPOSE: To investigate 6-month outcomes in eyes with neovascular age-related macular degeneration (nAMD) switched from intravitreal aflibercept 2 mg to intravitreal aflibercept 8 mg.<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: We reviewed records of consecutive nAMD eyes switched from aflibercept 2 mg to 8 mg. In eyes continuing aflibercept 8 mg, best-corrected visual acuity (BCVA), treatment intervals, and anatomical/exudative parameters were evaluated at 6 months. In eyes that could not continue, reasons for discontinuation were examined.<br><br>RESULTS: Forty-four eyes from 44 patients were included. At 6 months, 35 eyes (79.5%) continued and 9 (20.5%) discontinued aflibercept 8 mg. Discontinuing eyes had significantly shorter pre-switch treatment intervals and more frequent prior therapies than continuing eyes. In the continuation group, BCVA remained stable (median 0.05 to 0.00 logMAR, P = 0.351), while the treatment interval was significantly extended (median 7.0 to 9.0 weeks, P < 0.001). Central retinal thickness and pigment epithelial detachment height decreased significantly (P = 0.035 and P = 0.021, respectively). The proportion of eyes with subretinal fluid significantly decreased from 74.3 to 37.1% (P = 0.003). Of the discontinuations, 4 were due to worsening exudation and 5 to inability to extend to &#x2265;8 weeks as required by labeling. No intraocular inflammation or serious adverse events occurred.<br><br>CONCLUSIONS: Switching to aflibercept 8&#x202f;mg achieved anatomical improvements and longer treatment intervals in ~80% of nAMD cases, suggesting it may be a useful alternative to aflibercept 2 mg. However, continuation may be difficult in refractory cases requiring frequent injections before switching.}, }
@article {pmid41630010, year = {2026}, author = {Cassavia Junior, ASF and Bellanda, V and Audi, LO and Barbosa, GCS and Caravelas, RAM and Volpe, GJ and Moreira, HT and Schmidt, A and Jorge, R}, title = {Assessing the prevalence of extensive macular atrophy with pseudodrusen-like appearance in patients with rheumatic fever-associated valvular heart disease: a cross-sectional study.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {31}, pmid = {41630010}, issn = {2056-9920}, abstract = {BACKGROUND: Extensive macular atrophy with pseudodrusen-like appearance (EMAP) is a rare retinal disorder characterized by bilateral macular atrophy and subretinal drusenoid deposits (SDDs), typically occurring earlier and progressing faster than age-related macular degeneration. A possible association between EMAP and rheumatic fever (RF) has been proposed, but its prevalence in this population remains unclear.<br><br>METHODS: In this cross-sectional study, 118 patients (236 eyes) with valvular disease secondary to RF were prospectively screened at a tertiary cardiology clinic. EMAP was defined by vertically predominant macular atrophy with SDDs and exclusion of alternative diagnoses. Multimodal imaging included spectral-domain optical coherence tomography and fundus autofluorescence. Demographic, clinical, and cardiologic parameters were descriptively analyzed between patients with and without EMAP, and compared between those with and without SDDs using appropriate statistical tests.<br><br>RESULTS: Two patients (1.69%; 95% confidence interval [CI], 0.47&#x2013;5.97%) met diagnostic criteria for EMAP. Both were women aged 62 and 73 years, with RF onset during childhood and long disease duration (54 and 62 years). SDDs were identified in 12 patients (10.17%; 95% CI, 5.91&#x2013;16.94%), including both EMAP cases. Patients with SDDs were significantly older (p&#x2009;=&#x2009;0.007), had longer RF duration (p&#x2009;=&#x2009;0.032), and received a greater cumulative benzathine penicillin prophylaxis burden (p&#x2009;=&#x2009;0.029).<br><br>CONCLUSIONS: EMAP is uncommon among patients with RF-associated valvular disease, suggesting that additional genetic or environmental factors may be necessary for disease manifestation. The prevalence of SDDs highlights potential subclinical retinal involvement associated with chronic systemic inflammation in this patient population.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40942-026-00805-6.}, }
@article {pmid41630283, year = {2026}, author = {Chen, J and Chen, T and Zhao, C and Bao, Z and Liu, H}, title = {Mendelian randomization study of causality between 35 blood and urine biomarkers and age-related eye diseases.}, journal = {Medicine}, volume = {105}, number = {5}, pages = {e47286}, pmid = {41630283}, issn = {1536-5964}, mesh = {Humans ; Mendelian Randomization Analysis ; *Biomarkers/urine/blood ; Macular Degeneration/urine/genetics/blood ; Cataract/urine/genetics/blood ; *Eye Diseases/urine/blood/genetics ; Glaucoma/urine/genetics/blood ; Diabetic Retinopathy/urine/genetics/blood ; Causality ; }, abstract = {Age-related eye diseases (AREDs) are a group of age-related visual degenerative diseases characterized by insidious and gradual onset. Identification of biomarkers associated with the early stage of AREDs is particularly important to delay its progression. This study aimed to evaluate the causal relationship between 35 blood and urine biomarkers and AREDs, thereby providing new insights into disease mechanisms and potential therapeutic targets. Two-sample Mendelian randomization (MR) was used to clarify the causal relationship between blood and urine biomarkers and AREDs. We classified AREDs into 4 types: age-related cataract (SC), age-related macular degeneration, glaucoma, and diabetic retinopathy. Inverse variance weighting method was used as the main analysis method, Cochran Q test, MR-Egger intercept, and leave-one-out test were used to investigate whether there was heterogeneity and pleiotropy of MR results. And the results were corrected by false discovery rate. Through MR analysis, this study provides the first systematic genetic evidence regarding the associations between blood and urine biomarkers and 4 AREDs. Specifically, our findings suggest a causal effect of 1 biomarker on SC, support causal roles of 3 biomarkers in age-related macular degeneration, and indicate causal relationships for 3 biomarkers with diabetic retinopathy. The reliability of these results was bolstered by a series of sensitivity analyses. This study strengthened the link between specific blood and urine biomarkers and the risk of AREDs. It has enhanced our understanding of the pathogenesis of AREDs and may guide the development of targeted prevention, diagnosis, and treatment strategies.}, }
@article {pmid41631247, year = {2026}, author = {Hsiao, YJ and Li, H and Xue, CC and Chong, CCY and Zhu, E and Yuan, Q and Yu, M and Cheung, CMG and Fan, Q and Sabanayagam, C and Tham, YC and Cheng, CY}, title = {Chronic Kidney Disease as a Risk Factor for Age-Related Macular Degeneration: A Prospective Cohort and Mendelian Randomization Analyses.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {101036}, pmid = {41631247}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate shared genetic influences and investigate the association of chronic kidney disease (CKD) with the risk for advanced age-related macular degeneration (AMD).<br><br>DESIGN: Prospective cohort study and 2-sample Mendelian randomization (MR) analyses.<br><br>PARTICIPANTS: Data from 430 016 participants in the UK Biobank cohort and summary statistics from the largest publicly available genome-wide association studies on estimated glomerular filtration rate (eGFR) (n = 1 004 040) and advanced AMD (n = 33 976; 16 144 cases) were analyzed.<br><br>METHODS: Cox regression models were used to assess the association between CKD and incident AMD, adjusting for demographic, lifestyle, and clinical covariates. For MR analyses, we used the random-effects inverse-variance weighted model as the primary model, supported by 5 additional MR models for sensitivity analyses. A causal relationship was considered significant if P < 0.05 in the primary model and in &#x2265;2 sensitivity models, with all MR models showing a consistent effect direction. Colocalization analysis was performed to further identify shared genetic loci linking CKD and AMD.<br><br>MAIN OUTCOME MEASURES: Causal associations between eGFR and advanced AMD.<br><br>RESULTS: In the UK Biobank, baseline CKD was significantly associated with an increased risk of incident AMD (hazard ratio, 1.12; 95% confidence interval [CI], 1.01-1.25; P = 0.035) over a 10-year follow-up. Mendelian randomization analyses also demonstrated causality between lower eGFR and higher risk of advanced AMD (odds ratio, 2.03; 95% CI, 1.01-4.08; P = 0.048). Colocalization analysis indicated that the apolipoprotein E gene may contribute to this causality (rs56131196; colocalization posterior probability = 1.00, P = 2.29 x 10[-33] for AMD; P = 2.29 x 10[-13] for eGFR).<br><br>CONCLUSIONS: Both prospective cohort and MR analyses support causality between CKD and AMD, highlighting the need for AMD screening among patients with CKD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41632207, year = {2026}, author = {Nimmo, J and Bright, M and Yang, Z and Nicholls, LE and Morgan, BP and Daskoulidou, N and Zelek, WM}, title = {Complement in brain and eye disease: shared mechanisms, convergent pathologies, and common therapeutic opportunities.}, journal = {Mammalian genome : official journal of the International Mammalian Genome Society}, volume = {37}, number = {1}, pages = {33}, pmid = {41632207}, issn = {1432-1777}, abstract = {The brain and eye share striking anatomical, physiological, and immunological similarities. Both are protected by specialised vascular barriers, the blood-brain barrier (BBB) and blood-retinal barrier (BRB) respectively, that maintain homeostasis through tightly regulated cellular and molecular mechanisms. Increasing evidence implicates complement dysregulation as a key driver of neurodegeneration in both organs, contributing to disorders such as Alzheimer’s disease (AD), and age-related macular degeneration (AMD). Genetic and molecular studies highlight overlapping mechanisms, with variants in complement regulators influencing susceptibility to both retinal and brain pathologies. Locally synthesised complement components modulate glial activation, vascular integrity, and synaptic remodelling at both sites and, when dysregulated, contribute to chronic inflammation, synapse loss and neuronal degradation. Despite these shared pathways, therapeutic development has progressed asymmetrically; several complement therapeutics are already in the clinic for AMD and other ocular pathologies, while none are yet in use for brain diseases. This is in part a consequence of the accessibility of the eye where complement targeted drugs can be directly delivered and impact on pathology monitored, difficult in the brain. Lessons learned from the eye, including local delivery to overcome challenges of barrier penetration, may help accelerate development of complement therapeutics for the brain. Here we present a brief perspective that integrates current understanding of complement-mediated mechanisms across brain and eye, emphasising clues from convergent pathophysiology and ocular translational successes.}, }
@article {pmid41632222, year = {2026}, author = {Kim, JY and Lee, J and Oh, SB and Kim, C and Park, YH}, title = {α-Crystallins and vascular endothelial growth factor in aqueous humor of patients with neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {41632222}, issn = {1613-2246}, support = {ZC23TISI0770//Seoul St. Mary's Hospital, Catholic University of Korea/ ; RS-2023-00253065//National Research Foundation/ ; }, abstract = {PURPOSE: This study investigated aqueous humor (AH) levels of α-crystallins and vascular endothelial growth factor (VEGF) in patients with neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Prospective study.<br><br>METHODS: AH samples were collected from treatment-na&#xef;ve phakic nAMD patients before the first and third anti-VEGF injections and from cataract patients without retinal disease as controls. &#x3b1;B-crystallin, &#x3b1;A-crystallin, and VEGF levels were quantified using enzyme-linked immunosorbent assay. Patients were classified as good responders (achieved remission) or poor responders (persistent intraretinal or subretinal fluid) according to response after three consecutive monthly anti-VEGF injections.<br><br>RESULTS: A total of 28 eyes from 24 nAMD patients and 27 eyes from 23 controls were analyzed. nAMD showed higher &#x3b1;B-crystallin and VEGF, but similar &#x3b1;A-crystallin levels versus controls (P < 0.001, P = 0.002, and P = 0.721, respectively). In nAMD eyes, after two anti-VEGF injections, &#x3b1;B-crystallin and &#x3b1;A-crystallin remained unchanged, whereas VEGF decreased (P = 0.057, P = 0.182, and P = 0.017, respectively). Among nAMD eyes, 20 eyes from 18 patients were good responders and 8 from 6 were poor responders. Good responders demonstrated reductions in &#x3b1;B-crystallin and VEGF (P = 0.016 and P = 0.002, respectively), whereas poor responders showed no significant changes (P = 0.249 and P = 0.075, respectively). In untreated nAMD eyes, &#x3b1;B-crystallin and VEGF levels showed a positive correlation (P = 0.010).<br><br>CONCLUSION: In nAMD, AH &#x3b1;B-crystallin levels were elevated compared with controls. Among good responders to anti-VEGF therapy, &#x3b1;B-crystallin levels decreased. Moreover, &#x3b1;B-crystallin levels showed a positive correlation with VEGF.}, }
@article {pmid41632743, year = {2026}, author = {Belloni Baroni, L and Toto, L and Formenti, F and Passamonti, M and Quarta, A and Ruggeri, ML and Aloia, R and Di Nicola, M and Mastropasqua, R}, title = {Long-Term Follow-Up of Faricimab Intravitreal Injections in Naïve Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmic research}, volume = {69}, number = {1}, pages = {74-82}, pmid = {41632743}, issn = {1423-0259}, mesh = {Humans ; Intravitreal Injections ; Female ; Male ; Follow-Up Studies ; *Visual Acuity/physiology ; Tomography, Optical Coherence ; Aged ; Fluorescein Angiography ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; Middle Aged ; Time Factors ; Treatment Outcome ; Fundus Oculi ; Prospective Studies ; Antibodies, Bispecific ; }, abstract = {INTRODUCTION: The aim of the study was to evaluate functional and anatomical changes at the 44-week follow-up in patients with naïve neovascular age-related macular degeneration (nAMD) treated with faricimab intravitreal injections (IVIs).<br><br>METHODS: Fifty-four eyes of 54 patients with na&#xef;ve active macular neovascularization and nAMD were enrolled at the Ophthalmology Clinic of University "G. d'Annunzio," Chieti-Pescara, Italy. All patients were scheduled for faricimab IVI. Each patient underwent complete ophthalmic examination including best-corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) charts and optical coherence tomography. All measurements were evaluated at baseline, at week 20 and then according to fixed retreatment interval up to week 44. Fluorescein angiography and indocyanine green angiography were also performed at baseline. Main outcome measures were changes in BCVA, central macular thickness (CMT), subfoveal choroidal thickness (SFCT), intraretinal fluid presence, subfoveal subretinal fluid presence and thickness, the presence of pigment epithelial detachments (PEDs), and its maximum height (PED-MH).<br><br>RESULTS: BCVA improved and CMT reduced significantly from baseline to week 44 (p = 0.002 and p = 0.020, respectively) in the overall sample with a higher significant improvement from baseline to week 20 (p < 0.001 for both parameters) and no additional significant improvement from week 20 to week 44 in the overall sample (p = 0.348 and p = 0.146, respectively). At week 20, 72.3% of patients were in the Q12/Q16 interval. Patients in the Q8 interval showed significant improvement in BCVA (p < 0.001) and significant reduction of CMT (p = 0.008) from baseline to week 44, respectively. PED-MH as well showed a significant reduction from baseline to week 44 (p < 0.001). Patients in the Q12 interval showed significant improvement in BCVA (p = 0.030) and significant reduction of CMT, SFCT, and PED-MH from baseline to week 36 (p < 0.001). Patients in the Q16 interval showed significant reduction of BCVA during follow-up (p = 0.026). CMT, SFCT, and PED-MH were significantly reduced from baseline to week 44 (p < 0.001).<br><br>CONCLUSION: Faricimab showed efficacy in the treatment of na&#xef;ve nAMD patients with an improvement of many anatomical and functional parameters at 44 weeks, allowing the maintenance of a treatment regimen for most patients equal to or greater than 12 weeks.}, }
@article {pmid41633199, year = {2026}, author = {Hayashi, K and Kobayashi, M and Mori, K and Nakagawa, Y and Watanabe, B and Masuya, T and Ashimori, A and Higashijima, F and Yoshimoto, T and Morita, T and Murai, T and Kirihara-Kojima, S and Kimura, K}, title = {A novel prohibitin inhibitor acts as a dual inhibitor of angiogenesis and fibrosis.}, journal = {Biochemical and biophysical research communications}, volume = {805}, number = {}, pages = {153386}, doi = {10.1016/j.bbrc.2026.153386}, pmid = {41633199}, issn = {1090-2104}, mesh = {Prohibitins ; *Repressor Proteins/antagonists &amp; inhibitors/metabolism/genetics ; Animals ; Humans ; *Choroidal Neovascularization/drug therapy/pathology/metabolism ; Fibrosis ; Mice ; *Angiogenesis Inhibitors/pharmacology ; Mice, Inbred C57BL ; Cells, Cultured ; Endothelial Cells/drug effects ; Human Umbilical Vein Endothelial Cells/drug effects ; *Neovascularization, Pathologic/drug therapy ; Mitochondria/drug effects/metabolism ; Angiogenesis ; }, abstract = {We previously showed that the benzoylphenylurea derivative BPU17 inhibits epithelial-mesenchymal transition and acts as an antifibrotic agent. This compound acts as a prohibitin (PHB) inhibitor by directly binding to PHB1. This binding disrupts the interaction between PHB1 and PHB2, leading to mild mitochondrial dysfunction. Here, we investigated the effect of BPU17 on angiogenesis using primary cultures of human vascular and microvascular endothelial cells, as well as a mouse model of choroidal neovascularization (CNV). A series of studies has shown that BPU17 inhibits angiogenesis both in vitro and in vivo. The molecular mechanism is that BPU17 inhibits serum response factor (SRF)/CArG box-mediated transcription by repressing the expression of SRF and its cofactor myocardin-related transcription factors (MRTF-A and -B [MRTF]). This defect causes the downregulation of adaptor and cell adhesion molecules such as vinculin and integrins, leading to the inhibition of angiogenesis. This inhibitory effect is closely associated with mild mitochondrial dysfunction, and siRNA-mediated knockdown of PHB1 similarly inhibits angiogenesis. Given that age-related inflammatory responses and subsequent choroidal neovascularization (CNV) contribute to the development of neovascular age-related macular degeneration (nAMD), this novel PHB inhibitor holds promise as a treatment for nAMD through its dual inhibitory effects on angiogenesis and fibrosis.}, }
@article {pmid41633707, year = {2026}, author = {Patel, SS and Boyer, DS and Loewenstein, A and Clark, J and Zhu, L and Tang, J and Desai, D}, title = {Safety and tolerability of avacincaptad pegol in combination with ranibizumab in treatment-naïve patients with neovascular age-related macular degeneration: results from a phase 1 and phase 2a study.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {1}, pages = {}, pmid = {41633707}, issn = {2397-3269}, mesh = {Humans ; *Ranibizumab/administration &amp; dosage/adverse effects/pharmacokinetics ; Male ; Female ; Aged ; Intravitreal Injections ; *Visual Acuity ; Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Drug Therapy, Combination ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Polyethylene Glycols/administration &amp; dosage/pharmacokinetics/adverse effects ; Aged, 80 and over ; Treatment Outcome ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Dose-Response Relationship, Drug ; Tomography, Optical Coherence ; }, abstract = {OBJECTIVE: To assess the safety and tolerability of avacincaptad pegol (ACP), a Food and Drug Administration-approved therapy for geographic atrophy, administered in combination with ranibizumab, an approved therapy for neovascular age-related macular degeneration (nAMD), in patients with nAMD.<br><br>METHODS: The phase 1 study (NCT00709527) was a two-part, ascending-dose and parallel-group, open-label trial that assessed the safety, tolerability and pharmacokinetic profile of monthly intravitreal injections of ACP (0.03, 0.3, 1, 2, 3&#x2009;mg) in combination with ranibizumab (0.5&#x2009;mg) on the same day in treatment-na&#xef;ve patients with nAMD (n=43 patients received a maximum of 6 injections). The phase 2a study (NCT03362190) was an open-label trial assessing the 6-month safety of intravitreal injections of ACP administered in combination with ranibizumab in treatment-na&#xef;ve patients with nAMD (n=64). Patients received either ACP 2&#x2009;mg or 4&#x2009;mg either 14 days or 1&#x2009;month apart, given on the same day or 2&#x2009;days after ranibizumab. Primary outcome measures were safety and tolerability.<br><br>RESULTS: During the phase 1 study, there were no dose-limiting toxicities at any dose level. In both studies, ocular treatment-emergent adverse events were mostly mild or moderate, with the most reported events related to the injection procedure. There were no clinically significant increases in intraocular pressure or cumulative increases with multiple injections over time. There were no safety issues identified through measurement of visual acuity.<br><br>CONCLUSIONS: Coadministration of ACP and ranibizumab in treatment-na&#xef;ve patients with nAMD was well tolerated across different dosing regimens with no new safety issues based on results from two independent studies.}, }
@article {pmid41633708, year = {2026}, author = {Romdhoniyyah, DF and Alshukri, A and Parry, DG and Harding, S and Beare, NAV}, title = {Metformin and incidence of age-related macular degeneration in people with diabetes: a population-based 5-year case-control study.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {1}, pages = {}, pmid = {41633708}, issn = {2397-3269}, mesh = {Humans ; *Metformin/therapeutic use ; *Macular Degeneration/epidemiology/diagnosis/prevention &amp; control ; Male ; Female ; Incidence ; *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology ; Aged ; Case-Control Studies ; Middle Aged ; *Hypoglycemic Agents/therapeutic use ; Disease Progression ; *Diabetic Retinopathy/drug therapy/diagnosis/epidemiology ; Follow-Up Studies ; }, abstract = {OBJECTIVE: Metformin has been identified as a potential treatment for age-related macular degeneration (AMD). Photographic screening for diabetic retinopathy provides an opportunity to conduct a case-control study with systematic AMD grading. We aimed to investigate associations between metformin use and incidence and progression of AMD at different grades.<br><br>METHODS AND ANALYSIS: We randomly sampled 2600 participants from 10&#x2009;336 people aged &#x2265;50 years with diabetes who attended retinopathy screening in 2011 (baseline) and were enrolled to the Individualised Screening for Diabetic Retinopathy study. 2545 of these participants had type 2 diabetes and gradable fundus photographs at baseline, which were graded using modified age related eye disease study grading. We used data including those on metformin prescription from general practitioner records. We used multivariate logistic regression to investigate associations between metformin and incidence or progression of early, intermediate and late AMD.<br><br>RESULTS: Of 2545 participants, 2089 attended and had gradable fundus images on year 5. Metformin was associated with reduced incidence of intermediate AMD by 5 years after adjusting for confounders (complete record OR 0.63, 95%&#x2009;CI 0.43 to 0.92, p=0.02). In univariate analysis, metformin was associated with reduced incidence of late AMD (OR 0.43, 95% CI 0.21 to 0.88, p=0.02) but this did not remain significant after adjusting for age and sex. The numbers progressing to late AMD were small. There was no association between metformin and the incidence of early AMD.<br><br>CONCLUSION: We have found a significant association between metformin use and reduction in incidence of intermediate AMD by 37% in people with diabetes over 5 years. Previous epidemiological studies of metformin and AMD have used secondary data on AMD. In this observational study, there were baseline differences between groups, although significant findings remained after adjusting for important confounders. Given metformin's anti-ageing therapeutic effects, the reduction in risk is plausible and warrants prospective clinical trials.}, }
@article {pmid41634481, year = {2026}, author = {Cheung, CMG and Kikushima, W and Teo, KYC}, title = {Initial Experiences of Switching to Aflibercept 8 mg for Neovascular Age-Related Macular Degeneration and Polypoidal Chorodal Vasculopathy in an Asian Population.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {3}, pages = {1057-1068}, pmid = {41634481}, issn = {2193-8245}, support = {NMRC/LCG23 May/0032//National Medical Research Council Singapore Open Fund Large Collaborative Grant/ ; 24-Jan-0005//STaR/ ; }, abstract = {INTRODUCTION: Recent advances in the development of antivascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (nAMD) include the approval of aflibercept 8 mg, which delivers four times the previously commercially available dose. A longer durability of aflibercept 8 mg compared with 2 mg was reported in the clinical trial results. However, there are limited data in patients switching to aflibercept 8 mg from other agents in clinical practice. This study reports the initial real-world experience of consecutive patients switched to aflibercept 8 mg.<br><br>METHODS: Consecutive eyes with previously treated nAMD receiving aflibercept 8&#xa0;mg switched from other agents were retrospectively reviewed. Patients were switched either owing to suboptimal control of disease activity (efficacy group) or to potentially extend treatment intervals (durability group). The main outcome measures included change in optical coherence tomography (OCT)-based anatomical parameters, including central subfield thickness (CST) and presence of subretinal fluid (SRF), intraretinal fluid (IRF), and pigment epithelial detachment (PED) before and after switching. In addition, quantification of OCT biomarkers was performed using the RetinAI Discovery algorithm.<br><br>RESULTS: A total of 30 eyes from 29 patients were identified. Among the 25 eyes in the efficacy group, 20 eyes remained on aflibercept 8&#xa0;mg through to the last follow-up visit. Median CST showed a significant reduction from 291 (275-301) &#xb5;m to 279 (269-289) &#xb5;m (p&#x2009;=&#x2009;0.02). Volumetric analysis showed a significant reduction in SRF volume, a small nonsignificant increase in IRF volume, and a trend toward reduction in PED volume. The five eyes in the durability group had no SRF, IRF, or hemorrhage at the time of switching and remained stable during the follow-up period.<br><br>CONCLUSIONS: These results provide early experience of aflibercept 8&#xa0;mg in a clinical cohort in hard-to-treat patients. The current analysis demonstrated favorable anatomical outcomes after switching in most patients, with no safety signals.}, }
@article {pmid41634482, year = {2026}, author = {Grimaldi, G and Bartolomeo, N and Garweg, JG and Pfister, IB and Schild, C and Peyla, A and Tillmann, A and De Oliveira Figueiredo, EC and Spitznagel, T and Kitay, AM and Gabathuler, F and Zweifel, S and Kurz-Levin, MM and Ebneter, A and Somfai, GM and Eandi, CM and Munk, MR and Ambresin, A and Menghini, M}, title = {One-Year Real-World Outcomes of Aflibercept 8 mg in Treatment-Naïve Neovascular Age-Related Macular Degeneration: A Swiss Retina Research Network Report.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {3}, pages = {1069-1082}, pmid = {41634482}, issn = {2193-8245}, abstract = {INTRODUCTION: This study reports the 1-year efficacy of aflibercept 8 mg (afl8) in a real-world cohort of treatment-naïve patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: An observational, retrospective case series from nine centers of the Swiss Retina Research Network including treatment-na&#xef;ve eyes with nAMD started on intravitreal afl8. Changes in visual acuity (VA), macular thickness, pigment epithelial detachment (PED) height, and retinal fluids were evaluated over 12&#xa0;months and compared with baseline. Treatment intervals and safety data were recorded along with subgroup analyses based on macular neovascularization type, loading-phase completion, and treatment regimen.<br><br>RESULTS: A total of 91 eyes met the inclusion criteria. After 1 year of treatment, VA changed by&#x2009;+&#x2009;1.0&#x2009;&#xb1;&#x2009;13.2 letters (p&#x2009;=&#x2009;0.018), mean CST changed by -110.0&#x2009;&#xb1;&#x2009;130.9&#xa0;&#xb5;m (p&#x2009;<&#x2009;0.001), and mean PED height changed by -71.2&#x2009;&#xb1;&#x2009;104.8&#xa0;&#xb5;m (p&#x2009;<&#x2009;0.001). After 12&#xa0;months, 66.2% of eyes demonstrated a complete absence of macular fluids. Mean treatment interval was 13.9&#x2009;&#xb1;&#x2009;7.9&#xa0;weeks, with 56.1% of eyes being extended to&#x2009;&#x2265;&#x2009;12&#xa0;weeks with an anatomy-driven approach. No functional or anatomical differences were observed between eyes receiving a clean loading phase and in terms of different macular neovascularization (MNV) subtypes. Two adverse events were observed.<br><br>CONCLUSIONS: The first 1-year real-world experience with afl8 in patients with nAMD revealed a robust anatomical response but only a variable and limited visual gain over 12&#xa0;months due to a ceiling effect. Our findings confirm the fast and sustained macular drying reported from clinical trials, allowing for extended treatment intervals without compromising safety and efficacy.}, }
@article {pmid41636066, year = {2026}, author = {Lei, Y and Yang, J and Li, Y and Xiao, B and Lai, D and Qiu, Q}, title = {Radiotherapy for Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.}, journal = {Current eye research}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/02713683.2026.2621179}, pmid = {41636066}, issn = {1460-2202}, abstract = {PURPOSE: Anti-vascular endothelial growth factor (anti-VEGF) drugs have limitations in the treatment of neovascular age-related macular degeneration (nAMD). This study aims to evaluate the efficacy and safety of radiotherapy combined with anti-VEGF therapy versus anti-VEGF monotherapy in the treatment of nAMD.Methods: This systematic review and meta-analysis (PROSPERO registration number: CRD420251010811) searched PubMed, Embase, Cochrane, Web of Science, LILACS, ISRCTN registry, and ClinicalTrials.gov up to February 25, 2025. Two radiotherapy modalities were analyzed: epimacular brachytherapy (EBM) and stereotactic radiotherapy (SRT). The primary outcome was the proportion of participants who lost more than 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 12 and 24 months. A total of four studies were included, yielding 7 articles for meta-analysis.<br><br>RESULTS: For EBM combined with anti-VEGF therapy, compared with anti-VEGF monotherapy, there was a higher risk of losing more than 15 ETDRS letters at 12 months (relative risk [RR] 2.36, 95% confidence interval [CI] 1.49-3.74) and 24 months (RR 2.39, 95% CI 1.68-3.39). The difference in best-corrected visual acuity (BCVA) was 0.10 logarithm of the minimum angle of resolution (logMAR) (95% CI 0.05-0.15) at 12 months and 0.17 logMAR (95% CI 0.13-0.21) at 24 months. For SRT combined with anti-VEGF therapy, there was a greater risk of losing more than 15 ETDRS letters at 24 months (RR 1.75, 95% CI 1.12-2.74) compared with anti-VEGF monotherapy; however, the SRT group required 2.10 fewer ranibizumab injections than the sham-irradiation group (mean difference [MD] -2.10, 95% CI -2.97 to -1.22).<br><br>CONCLUSION: Epimacular brachytherapy (EBM) combined with anti-VEGF therapy may worsen patient outcomes and increase the risk of adverse events. In contrast, stereotactic radiotherapy (SRT) combined with anti-VEGF therapy does not improve visual acuity but can reduce the frequency of anti-VEGF injections, potentially alleviating the treatment burden for patients with nAMD.}, }
@article {pmid41636413, year = {2026}, author = {Cinque, F and Pas, JAAH and de Breuk, A and Heesterbeek, T and Klaver, CCW and Hoyng, CB and Lechanteur, YTE and van Heugten, CM}, title = {Visual Acuity Provides a More Meaningful Measure of Vision-Related Functioning Than Mesopic Microperimetry in Age-Related Macular Degeneration Patients: A Cross-Sectional Study.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {2}, pages = {5}, pmid = {41636413}, issn = {2164-2591}, mesh = {Humans ; Cross-Sectional Studies ; *Visual Acuity/physiology ; Female ; Male ; *Visual Field Tests/methods ; Aged ; *Macular Degeneration/physiopathology/diagnosis ; *Visual Fields/physiology ; *Mesopic Vision/physiology ; Aged, 80 and over ; Middle Aged ; Retina/physiopathology ; Surveys and Questionnaires ; }, abstract = {PURPOSE: Mesopic microperimetry is a promising tool to evaluate retinal function in clinical trials. Although visual function (VF), the ability to perform vision-related tasks, relates strongly to visual acuity (VA) in patients with age-related macular degeneration, the relationship between mesopic microperimetry and VF remains unclear.<br><br>METHODS: A cross-sectional study in patients with age-related macular degeneration was performed. VF was measured by questionnaire using a subset of the National Eye Institute 25-Item Visual Function Questionnaire. The macular integrity assessment microperimeter, was used with a 4-2 staircase strategy with a 10&#xb0; diameter circular grid containing 37 loci. Three interpretations of the retinal sensitivity data were calculated: the mean of the 37 thresholds (mean sensitivity [MS]), the percent-reduced threshold (PRT), and the log-transformed candela mean (MS cd log). MS, PRT, and MS cd log were tested via stepwise hierarchical linear regression and R2.<br><br>RESULTS: We analyzed data from 102 patients (64 females [61%]; mean age, 71.8 &#xb1; 11.2 years). VF was explained best by VA (MS; R2 VA = 0.38, MS cd log; R2 VA = 0.38, PRT; R2 VA = 0.39). All retinal sensitivities contributed significantly to total R2. In the MS cd log model (total adjusted R2 = 0.52) the combined contribution of variance explained by VA and MS cd log was 46% (partial adjusted R2 = 0.46).<br><br>CONCLUSIONS: Mesopic microperimetry is associated with VF but VA provides a more meaningful estimation of this same construct. These results suggest that VA provides stronger evidence of clinical efficacy.<br><br>TRANSLATIONAL RELEVANCE: This study relates functional tests to daily vision-related functioning.}, }
@article {pmid41636834, year = {2026}, author = {Mesfin, Y and Salvi, A and Arnal, L and Langlotz, C and Mahajan, V and Ludwig, CA}, title = {Shaping the future of myopia: artificial intelligence for vitreoretinal complications of high and pathologic myopia.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41636834}, issn = {1435-702X}, support = {E. Matilda Ziegler Foundation for the Blind//E. Matilda Ziegler Foundation for the Blind/ ; NEI P30-EY026877//Stanford P30 Vision Research Core Grant/ ; K23EY035741//National Eye Institute K23 Grant/ ; Research to Prevent Blindness, Inc//Research to Prevent Blindness, Inc/ ; }, abstract = {PURPOSE: The global impact of myopia extends far beyond individual ocular health, posing significant challenges to healthcare systems worldwide. Artificial intelligence (AI), particularly deep learning (DL) applied to ophthalmic imaging, offers a promising strategy to ease constraints posed by the myopia epidemic by detecting subtle structural changes early. Here we describe the current literature on AI for detecting retinal sequelae of myopia, including retinal detachments (RD), myopic macular degeneration (MMD), and myopic traction maculopathy (MTM), with attention to imaging modality and model task (classification vs. segmentation).<br><br>METHODS: A literature search was conducted to identify studies using DL to detect RD, MMD, and MTM across ophthalmic imaging modalities (including OCT and fundus photography, and where available fluorescein angiography and ultrasonography).<br><br>RESULTS/FINDINGS: We reviewed 28 studies that piloted DL models usingclassification and/or segmentation approaches for RD (10 studies), MMD (12 studies), and MTM (6 studies). Reported performance for RD ranged from area under the curve (AUC) 86-100%, accuracy 79.3-98.9%, sensitivity 77.1-97.6%, and specificity 79.7-100%. For MMD, performance ranged from AUC 86-100%, accuracy 85.3-99.8%, sensitivity 37.1-97.8%, and specificity 91.5-99.9%. For MTM, performance ranged from AUC 93.8-99.7%, accuracy 94.3-99.3%, sensitivity 74.5-98.4%, and specificity 84.8-99.7%. Across studies, there was substantial heterogeneity in case definitions, datasets, and evaluation methods, and external validation was inconsistently reported. Many earlier studies used CNN-based architectures, while more recent work increasingly incorporates transformer-based backbones and pretrained or foundation models.<br><br>CONCLUSION: Researchers have demonstrated excellent results for developing DL models that accurately classify and segment retinal pathologies associated with myopia. However, despite strong performance, additional work is needed to translate these models into clinical use, including robust external validation, calibration for clinical decision-making, and prospective evaluation, particularly for longitudinal prognostication of incident complications in pathologic myopia.}, }
@article {pmid41638110, year = {2026}, author = {Amin, R and Kaiser, PK}, title = {Tyrosine kinase inhibitors for wet age-related macular degeneration: The current developmental landscape.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {393}, number = {3}, pages = {103803}, doi = {10.1016/j.jpet.2026.103803}, pmid = {41638110}, issn = {1521-0103}, abstract = {Age-related macular degeneration (AMD) is a leading cause of permanent vision loss in older patients worldwide. The neovascular (wet) AMD is characterized by abnormal choroidal neovascularization driven by vascular endothelial growth factor (VEGF), platelet-derived growth factor, and Tie2 signaling pathways, leading to retinal damage and progressive vision decline. Current standard-of-care anti-VEGF therapies aim to limit choroidal neovascularization through extracellular targeting of cytokines involved in the VEGF signaling pathway implicated in angiogenesis. Although these existing therapies can be effective, many patients face a high treatment burden of multiple intraocular injections, which can negatively impact compliance, safety, and long-term efficacy. Tyrosine kinase inhibitors (TKIs) aim to address these limitations by offering longer durability, broad-spectrum targeting of angiogenic pathways, and a reduction in treatment burden through intracellular targeting of angiogenic pathways. With multiple pharmaceutical TKI candidates advancing through clinical trials and showing promising data, this class of drugs could lead to a shift in future treatment options for patients with wet AMD. Despite the progress TKIs have made, there have yet to be any candidates approved for wet AMD treatment. Much of the existing evidence is from early-phase and short-term studies, and questions remain about long-term efficacy and safety compared to current standard-of-care anti-VEGF therapies. Nevertheless, with multiple candidates advancing through phase III clinical trials, TKIs have the potential to emerge as a next-generation treatment class that may transform the wet AMD therapeutic landscape. SIGNIFICANCE STATEMENT: Given the chronic nature of wet age-related macular degeneration and the limitations of current anti-vascular endothelial growth factor therapies, tyrosine kinase inhibitors have emerged as a promising class of anti-angiogenic agents. This review highlights the recent clinical developments in this evolving therapeutic landscape.}, }
@article {pmid41638748, year = {2026}, author = {Vougioukalou, S and Read, SM and Csontos, JK and Jones, A and Jaber, A and Sharma, A and Balaskas, K}, title = {Comparing community-based monitoring to hospital-based care of patients with quiescent age-related macular degeneration: a qualitative study of patient and practitioner perspectives on acceptability and access.}, journal = {BMJ open}, volume = {16}, number = {2}, pages = {e101379}, pmid = {41638748}, issn = {2044-6055}, mesh = {Humans ; Qualitative Research ; Female ; Aged ; Male ; *Macular Degeneration/therapy ; *Community Health Services ; *Patient Acceptance of Health Care ; *Attitude of Health Personnel ; *Health Services Accessibility ; Aged, 80 and over ; Middle Aged ; Patient Satisfaction ; Hospitals ; }, abstract = {OBJECTIVES: This process evaluation explores patient and healthcare professional acceptability of community-based monitoring versus hospital-based care for patients with quiescent neovascular age-related macular degeneration (QnAMD).<br><br>DESIGN: Qualitative process evaluation was conducted as part of a randomised controlled trial.<br><br>SETTING: Six hospitals and six community-based practices.<br><br>PARTICIPANTS: 25 patients and 16 healthcare professionals (ophthalmologists and optometrists). This approach helped differentiate between common issues and those specific to community-based monitoring.<br><br>INTERVENTION: The Quality-Assured Follow-Up of QnAMD by non-medical practitioners trial aimed to examine whether non-medical practitioners follow-up patients with QnAMD in the community in a safe and clinically and cost-effective way. The process evaluation aimed to examine whether the intervention was acceptable by patients and professionals. The process evaluation was based on interviews which contained open-ended questions focused on patient experience and confidence in community-based care, issues concerning the practicalities of the organisation and management of the clinic, and resources including IT and digital equipment. The theory of acceptability framework was used to interpret the findings.<br><br>RESULTS: Patients reported positively on the experience of receiving QnAMD services in the community and highlighted staff professionalism and clear communication. Key themes were the proximity of care provision for patients, IT interoperability and the real-world costs of running the service. Some patients randomised to the hospital showed preference for the intervention to take place in the hospital, mediated mainly by prior experience of hospital care and travel distance. The location of the clinic and transport routes affected the experience of attending appointments, with strong preference expressed for proximity to one's home. Inaccessibility due to non-modifiable internal building structures in the community and parking in hospital eye services was reported by a small proportion of patients. Healthcare professionals reported positively about their ability to deliver QnAMD services in community settings but raised concerns about the compatibility of technological infrastructure that facilitates the sharing of optical coherence tomography image and video files. Some optometrists were also concerned about the financial sustainability of the intervention after the end of the trial due to the costs involved in the administration of QnAMD follow-up care.<br><br>CONCLUSIONS: The delivery of QnAMD services in the community by non-medical personnel was broadly accepted by both patients and practitioners. This implies that non-medical practitioners can follow up patients with QnAMD in the community in a safe way. Further research would be needed to establish whether similar results would be obtained during routine practice outside a research project and whether the long-term follow-up for QnAMD would be financially sustainable for independent as well as chain community optometry practices.<br><br>TRIAL REGISTRATION NUMBER: NCT03893474.}, }
@article {pmid41641369, year = {2026}, author = {Wang, N and Luo, L and Yang, X}, title = {The gut-eye axis in age-related macular degeneration: from microbial dysbiosis to targeted intervention strategies.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {251}, number = {}, pages = {10876}, pmid = {41641369}, issn = {1535-3699}, mesh = {Humans ; *Macular Degeneration/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology/complications/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; Prebiotics ; }, abstract = {Age-related macular degeneration (AMD) represents a leading cause of irreversible blindness among the older persons. Characterized by a complex pathogenesis and multiple risk factors, AMD poses substantial challenges for treatment and has emerged as a significant public health concern. The gut microbiota constitutes a vast and dynamically evolving ecosystem, with a healthy microbial community playing an essential role in maintaining host homeostasis through its involvement in digestion and immune defense. However, alterations in microbial composition or function can compromise intestinal barrier integrity, trigger systemic inflammation, and contribute to disease pathogenesis. Evidence now underscores the influence of gut microbiota on the development and progression of AMD. This review examines the mechanisms by which gut microbes may contribute to AMD pathogenesis and evaluates the therapeutic potential of interventions targeting the gut microbiome-including dietary modifications, Pharmacological and Biological Agents, probiotics, prebiotics, and fecal microbiota transplantation-for AMD management.}, }
@article {pmid41641466, year = {2026}, author = {Veerman, D and Cuartas-Vélez, C and Gensheimer, T and van Dorp, T and van der Meer, A and Bosschaart, N}, title = {Label-free assessment of a microfluidic vessel-on-chip model with visible-light optical tomography reveals structural changes in vascular networks.}, journal = {Lab on a chip}, volume = {26}, number = {6}, pages = {1901-1914}, pmid = {41641466}, issn = {1473-0189}, mesh = {Humans ; *Lab-On-A-Chip Devices ; *Tomography, Optical Coherence ; *Light ; *Tomography, Optical/instrumentation ; *Microfluidic Analytical Techniques/instrumentation ; }, abstract = {Microvascular dysfunction is characterized by impaired structure and function of small blood vessels, contributing to disease-related tissue and organ damage, such as in the retina. Optical coherence tomography is a widely used clinical technology to detect, monitor and diagnose disorders of the retina and choroid, such as diabetic retinopathy, macular degeneration, and various inherited retinal diseases. Currently, there are limited experimental platforms that correlate observed changes in clinical metrics with underlying mechanisms of disease progression. Organ-on-chips have the potential to offer a platform for correlative studies. Previous studies have demonstrated that the three-dimensional complexity of the microvasculature can be captured in a vessel-on-chip. Yet, current vessel-on-chip imaging analysis is based on end-point read-outs that provide limited dynamic information and do not have direct correlation with imaging techniques used in the clinic. Therefore, there is a need for clinically relevant, label-free, real-time imaging technologies. In this work, we show that optical coherence tomography can fulfill this need by providing non-invasive, label-free imaging of vascular networks-on-chip. We show that optical coherence tomography can detect and can be used to quantify changes in vascular network structures over multiple days, both during vascular network development and in response to disease-associated conditions. Our results indicate that optical coherence tomography has the potential to become a standard read-out for monitoring dynamic processes in organ-on-chips. In the future, these read-outs may enable the correlation of clinical metrics, thereby providing deeper insights in the pathophysiology of diseases, for example of the retina.}, }
@article {pmid41641772, year = {2026}, author = {Salkar, A and Palanivel, V and Basavarajappa, D and Heng, B and Schulz, A and Gupta, V and Graham, S and Mirzaei, M and You, Y}, title = {Retinal glial cells in glaucoma and age-related retinal diseases: Inflammatory responses, disease transitions, and translational perspectives.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-01905}, pmid = {41641772}, issn = {1673-5374}, abstract = {Microglia, Müller cells, and astrocytes play a crucial role in maintaining retinal structure, homeostasis, and neuronal function. In disease, they undergo reprogramming that drives chronic inflammation and neurodegeneration. Unique to the retina, these glial cells occupy specialized niches and interact closely with the blood-retinal barrier, creating distinct vulnerabilities. We summarized the glial activation mechanisms, shared triggers, including oxidative stress, metabolic dysfunction, aging, and systemic inflammation, as well as key pathways, such as nuclear factor kappa-B, mitogen-activated protein kinase, Janus kinase/signal transducer and activator of transcription, the inflammasome, and the complement system. Disease-specific responses in glaucoma, age-related macular degeneration, diabetic retinopathy, and vascular occlusions were compared, highlighting the heterogeneity of gliosis and its impact on neuronal and vascular pathology. We also discussed emerging human-derived platforms alongside proteomics approaches, highlighting their utility for mechanistic insights and discovering biomarkers. Despite advances, critical gaps remain in understanding glial-glial interactions and in developing robust models focused on glia. Despite these advances, major gaps remain in our understanding of glial-glial communication, state transitions, and their temporal relationship to neurodegeneration. Moreover, the lack of experimental models explicitly designed to interrogate glial biology continues to limit translational progress. Addressing these challenges will be essential to reposition glial cells as central drivers of retinal disease rather than secondary responders. A strategic shift toward glia-centered models, integrative multi-omics analyses, and human-relevant systems holds promise for advancing biomarker discovery and developing targeted therapeutic strategies that aim to modulate glial dysfunction and preserve vision.}, }
@article {pmid41641862, year = {2026}, author = {Chambon, C and Picard, E and Zola, M and Aichedo, S and Lebon, C and Youale, J and Matet, A and Bousquet, E and Ferreira, C and Kowalczuk, L and Théron, L and Behar-Cohen, F}, title = {Proteomic Signature in Men with Central Serous Chorioretinopathy.}, journal = {Journal of proteome research}, volume = {25}, number = {3}, pages = {1761-1774}, doi = {10.1021/acs.jproteome.5c01233}, pmid = {41641862}, issn = {1535-3907}, mesh = {Humans ; Male ; *Proteomics/methods ; *Central Serous Chorioretinopathy/blood/metabolism/pathology ; Middle Aged ; Adult ; Oxidative Stress ; Tandem Mass Spectrometry ; *Proteome ; Case-Control Studies ; Chromatography, Liquid ; Complement Activation ; Complement System Proteins/metabolism/genetics ; Biomarkers/blood ; }, abstract = {To explore systemic contributors to central serous chorioretinopathy (CSCR) pathogenesis, we performed untargeted serum proteomics in 60 male CSCR patients (30 acute, 30 chronic) and 60 age-matched controls using label-free LC-MS/MS with stringent statistical pairing. Among 242 abundant proteins identified, 27 (11.5%) were significantly different in CSCR, converging on pathways of complement activation, coagulation, oxidative stress, immune regulation, and response to external stimuli. Complement cascade components (C1QA, C1S, C3, C4B, C8A/B/G, CFB) were upregulated, while the regulators CFHR1 and CFHR2 were decreased, contrary to age-related macular degeneration. Oxidative stress-related proteins (haptoglobin, hemoglobin subunits, peroxiredoxin-2) were elevated, consistent with prior evidence of systemic redox imbalance in CSCR. Tetranectin (CLEC3B) decreased and attractin (ATRN) increased in CSCR were validated by ELISA. Multiplex immunofluorescence on the human retina localized tetranectin to Müller cells, including the outer limiting membrane, and to the RPE and attractin to photoreceptor segments, retinal pigment epithelium, Bruch's membrane, and the choriocapillaris, supporting potential roles of both proteins at the retina-choroid interface. A distinct systemic proteomic signature in patients with CSCR highlights complement dysregulation, oxidative stress, and stress responses to external stimuli and identifies tetranectin and attractin as candidate biomarkers, which should further be validated in other cohorts.}, }
@article {pmid41642030, year = {2026}, author = {Su, IL and Yeh, KL and Lee, CY and Lin, SC and Chiang, CY and Chen, CJ and Chen, WY and Tseng, CC and Lu, YC and Kuan, YH}, title = {Irigenin Modulates BL-Induced Pyroptosis in Retinal Pigment Epithelial Cells Through p38 MAPK and NFκB Pathways.}, journal = {Journal of biochemical and molecular toxicology}, volume = {40}, number = {2}, pages = {e70723}, pmid = {41642030}, issn = {1099-0461}, support = {NSTC113-2320-B-040-014-MY3//National Science and Technology Council, Taiwan/ ; NCHU-CSMU-11408//National Chung Hsing University and Chung Shan Medical University/ ; R110-030//Ditmanson Medical Foundation Chia-Yi Christian Hospital Research Program/ ; CSMU-TSMH-112-02//Chung Shan Medical University and Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital/ ; }, mesh = {Humans ; *Pyroptosis/drug effects/radiation effects ; *NF-kappa B/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; *p38 Mitogen-Activated Protein Kinases/metabolism ; *Isoflavones/pharmacology ; Cell Line ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Epithelial Cells/metabolism/pathology/drug effects ; Inflammasomes/metabolism ; Signal Transduction/drug effects ; *MAP Kinase Signaling System/drug effects ; }, abstract = {Age-related macular degeneration (AMD), a primary cause of vision loss among older adults, is strongly associated with inflammatory processes. The current study aimed to elucidate the protective effects of irigenin, an isoflavonoid recognized for its anti-inflammatory, antioxidative, antiapoptotic, and anticancer activities, against blue light (BL)-induced damage in N-retinyl-N-retinylidene ethanolamine (A2E)-laden human adult retinal pigment epithelial (A2E-laden ARPE-19) cells. Pretreatment with irigenin markedly mitigated BL-induced cytotoxicity and preserved epithelial barrier function in a concentration-dependent manner. Moreover, irigenin significantly inhibited the expression of proinflammatory cytokines and activation of the nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, as evidenced by decreased expression of NLRP3, ASC, and both full-length and cleaved forms of gasdermin D (GSDMD), along with reduced caspase-1 activity. Further mechanistic analyses indicated that irigenin effectively suppressed the activation of the nuclear factor kappa B (NFκB) signaling pathway, as evidenced by phosphorylation of NFκB and inhibitor of NFκB (IκB)α, and both activation and translocation of NFκB, along with reduced phosphorylation of p38 mitogen-activated protein kinase (MAPK). These findings underscore the potential of irigenin to ameliorate BL-induced retinal pigment epithelial cell damage via modulation of inflammation and pyroptosis pathways, suggesting its therapeutic value for preventing AMD.}, }
@article {pmid41642305, year = {2026}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {How do genetic polymorphisms influence the efficacy of age-related macular degeneration treatments? A systematic review and meta-analysis.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41642305}, issn = {1435-702X}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) has considerable global burden, being a major cause of vision loss. Subsequently, genetic predisposition holds a role in this case by contributing to disease susceptibility. Polymorphisms in genes such as Complement Factor H (CFH) and Age-Related Maculopathy Susceptibility 2 (ARMS2) play a key role as risk factors for AMD. This systematic review and meta-analysis synthesizes existing evidence to investigate and quantify the association between these polymorphisms and the actual risk of AMD. Additionally, the paper sets to unravel the prevalence of high- and low-risk genotypes among AMD patients.<br><br>METHODS: In accordance with PRISMA guidelines, we conducted a systematic search of PubMed, Scopus, Web of Science, EMBASE, and the Cochrane Library databases to identify relevant studies. We included primary studies that involved patients diagnosed with AMD and assessed genetic polymorphisms of CFH (Y402H, rs1061170), ARMS2 (A69S, rs10490924), and we included studies evaluating CFH Y402H and ARMS2 A69S in relation to AMD susceptibility and extracted any available data on anti VEGF treatment response for narrative synthesis. The analytical series considered random effects models to perform the associated meta-analyses. Study heterogeneity was assessed using the I&#xb2; statistic measure as a standard assessment within the studies. The odds ratio (OR) with 95% confidence intervals (CI) was used as the effect measure.<br><br>RESULTS: The literature search obtained 1,420 studies from which 10 satisfied the eligibility criterion. The meta-analysis utilized eight studies. The association between CFH Y402H polymorphism and AMD risk indicated that the risk of AMD among risk allele carriers was OR 2.25 (95% CI: 1.27-4.00, p&#x2009;=&#x2009;0.006). ARMS2 polymorphisms demonstrated a strong genetic association to the risk of AMD with an OR of 4.05 (95% CI: 1.79-9.16, p&#x2009;<&#x2009;0.001). In the second meta-analysis evaluating genotype prevalence, the random-effects model showed an OR of 1.439 (95% CI: 0.929-2.231, p&#x2009;=&#x2009;0.103), suggesting a variable but moderate prevalence of high-risk genotypes among AMD patients (I&#xb2; = 95.7%, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: This meta-analysis confirms the significant association between CFH and ARMS2 polymorphisms and AMD susceptibility, emphasizing their role in disease pathogenesis. The findings highlight the potential for genetic screening in AMD risk assessment and personalized treatment strategies. However, substantial heterogeneity across studies underscores the need for standardized methodologies and further research into gene-environment interactions. Integrating genetic risk assessment into clinical practice may improve early detection and targeted interventions for AMD.}, }
@article {pmid41642581, year = {2026}, author = {Bellanda, V and Schulgit, MJ and Barbosa, GCS and Mohan, N and Arline, A and Bala, S and Kaelber, DC and Srivastava, SK and Sharma, S}, title = {Relative Risk of Neovascular Age-Related Macular Degeneration Following Cataract Surgery.}, journal = {JAMA ophthalmology}, volume = {144}, number = {3}, pages = {281-284}, pmid = {41642581}, issn = {2168-6173}, }
@article {pmid41642651, year = {2026}, author = {Lewis, TR and Castillo, CM and Phan, S and Shores, CR and Hayase, KK and Kim, KY and Ellisman, MH and Alekseev, O and Burns, ME and Arshavsky, VY}, title = {Adam9-deficient retinal pigment epithelium pseudopods maintain photoreceptor outer segment renewal despite subretinal space expansion.}, journal = {The Journal of clinical investigation}, volume = {}, number = {}, pages = {}, doi = {10.1172/JCI196705}, pmid = {41642651}, issn = {1558-8238}, support = {K99 EY033763/EY/NEI NIH HHS/United States ; R00 EY033763/EY/NEI NIH HHS/United States ; }, abstract = {Vision begins in the outer segment compartment of photoreceptor cells, which is constantly renewed through the addition of membrane material at its base and ingestion of mature membranes at its tip by the retinal pigment epithelium (RPE). The close apposition of outer segments to the RPE is believed to be critical for maintaining this renewal process. Yet, in several retinal diseases, expansion of the subretinal space separating photoreceptors from the RPE does not immediately impact photoreceptor functionality. Here, we analyzed outer segment function and renewal in the Adam9 knockout mouse characterized by a major expansion of the subretinal space. Surprisingly, photoreceptor-RPE separation affected neither the sensitivity of photoreceptor light-responses nor the normal rate of outer segment renewal in this mouse prior to the onset of photoreceptor degeneration. The latter is achieved through the formation of elongated RPE "pseudopods" extending across the enlarged subretinal space to ingest outer segment tips. This work suggests that pseudopod formation may underlie the persistence of photoreceptor function in human diseases accompanied by photoreceptor-RPE separation, such as vitelliform macular dystrophy or age-related macular degeneration associated with subretinal drusenoid deposits.}, }
@article {pmid41643859, year = {2026}, author = {Castro-Fernández, DC and Cañizo-Outeriño, A and Cuartero-Martínez, A and Gil-Martinez, M and Mondelo-Garcia, C and González-Barcia, M and Álvarez-Barrios, A and Fernández-Ferreiro, A}, title = {A systematic review on age-related macular degeneration: New insights from multi-omics studies.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.02.001}, pmid = {41643859}, issn = {1879-3304}, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries and a growing global health concern. The multifactorial nature of AMD calls for integrative multi-omics approaches. We summarize studies employing multi-omics in AMD. A comprehensive search in PubMed and Scopus databases identified 561 records with multi-omics criteria, of which duplicates, unrelated and unavailable articles were excluded, resulting in 33 reports. Quality was assessed following the Office of Health Assessment and Translation (OHAT) method, and data was synthesized through standardized evidence tables. Across the reviewed reports, multi-omics approaches were applied to non-clinical and clinical samples, including ocular and systemic fluids. Methodological trends included the widespread use of causal inference approaches (e.g., Mendelian randomization and Bayesian colocalization) and increasing adoption of spatial and single-cell resolution techniques. Converging molecular patterns consistently suggested inflammation, complement activation, angiogenesis, lipid dysregulation, and mitochondrial dysfunction as key processes underlying AMD. Integration of genetic risk with proteomic and metabolomic alterations, enabled the identification of candidate diagnostic and prognostic biomarkers such as carboxyethylpyrrole and PRMT3. Additionally, this review revealed opportunities for personalized medicine in AMD patient stratification, improvement of prediction models, and therapeutic personalization; however, heterogeneity was noted across studies, particularly regarding sample source (systemic vs. ocular), analytical platforms, integration strategies, and ancestry representation. Despite this variability, this review illustrates how integrating multiple omics layers provides a comprehensive and multidimensional understanding of AMD pathology, advancing research towards better diagnosis, prognosis, and therapeutics for these patients.}, }
@article {pmid41646332, year = {2026}, author = {Huang, J and Nittala, MG and Corradetti, G and Chung, YC and Quarta, A and Abbasgholizadeh, R and Soylu, C and Chujo, S and Velaga, SB and Sadda, SR}, title = {Spatial Distribution of Cuticular Drusen and its Association with Category-Specific Progression Risk in Intermediate AMD.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {41646332}, issn = {2693-5015}, support = {R01 EY023164/EY/NEI NIH HHS/United States ; R01 EY030614/EY/NEI NIH HHS/United States ; }, abstract = {OBJECTIVES: To investigate the spatial distribution pattern of cuticular drusen using en face OCT and determine its relationship with 2-year progression of age-related macular degeneration (AMD).<br><br>METHODS: This study included 87 eyes from 57 participants with intermediate AMD and cuticular drusen enrolled in the Amish Eye Study who completed two years of follow-up. Multimodal imaging, including volume spectral-domain OCT, was performed. Density of cuticular drusen was quantified on en face OCT across three Early Treatment Diabetic Retinopathy Study (ETDRS) grid zones using ImageJ. K-means clustering analysis was used to categorize distribution patterns. Firth's penalized logistic regression evaluated association between cuticular drusen distribution categories and progression to late AMD at 2 years.<br><br>RESULTS: Cuticular drusen exhibited a concentric pattern within 6x6mm macular area. Mean (SD) density was highest in central zone (6.14 (3.89) count/mm2). Cluster analysis classified eyes into predominantly central (57.5%), predominantly peripheral (32.2%), and diffuse (10.3%) categories. Over 2 years, 5 eyes progressed to late AMD, 4 of which belonged to predominantly peripheral group. Firth logistic regression demonstrated that predominantly peripheral category had significantly increased risk of AMD progression compared to low-risk groups (predominantly central and diffuse), with an odds ratio of 7.2 (95% CI: 1.2-74.2, p=0.027).<br><br>CONCLUSIONS: The spatial distribution of cuticular drusen exhibits a concentric, centrally-weighted pattern. A predominantly peripheral distribution of cuticular drusen is significantly associated with progression to late AMD over two years. This quantifiable distribution pattern may serve as a novel high-risk biomarker for advanced AMD.}, }
@article {pmid41646411, year = {2026}, author = {Tom, E and Gao, F and Franco, CN and Wong, A and Kemmerer, N and Wang, Z and Xu, Q and Zhuang, Y and Du, SW and Palczewska, G and Palczewski, K and Budin, I and Shi, X and Bonilha, VL and Schöeneberg, J and Wahlin, KJ and Albrecht, LV and Skowronska-Krawczyk, D}, title = {Age-Driven Lipid Remodeling Activates Lysosome-Mediated Plasma Membrane Repair.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {41646411}, issn = {2693-5015}, support = {P30 EY025585/EY/NEI NIH HHS/United States ; F30 EY035146/EY/NEI NIH HHS/United States ; R01 EY009339/EY/NEI NIH HHS/United States ; P30 EY034070/EY/NEI NIH HHS/United States ; T32 GM008620/GM/NIGMS NIH HHS/United States ; T32 EY032448/EY/NEI NIH HHS/United States ; F30 EY033642/EY/NEI NIH HHS/United States ; P30 CA062203/CA/NCI NIH HHS/United States ; U01 EY034594/EY/NEI NIH HHS/United States ; }, abstract = {The abundance and stoichiometry of membrane lipid species vary across a cell's lifespan and metabolic state. In the retinal pigment epithelium (RPE), age-related alterations in lipid composition contribute to vision loss and diseases such as age-related macular degeneration (AMD), yet the molecular drivers of these changes remain unclear. Here, we show that age-dependent remodeling of the composition and biophysical properties of the plasma membrane compromises membrane integrity and function. Remarkably, rather than undergoing cell death, affected cells activate a lysosome-dependent plasma membrane repair program to preserve barrier integrity. While this adaptive response may protect RPE structure under metabolic stress, it also drives spatially polarized release of lysosomal contents that potentially can contribute to extracellular matrix remodeling and sub-RPE deposit formation during aging and AMD. Finally, we demonstrate that supplementation with the direct product of the aging-associated lipid elongase ELOVL2 alleviates these phenotypes, providing direct evidence for a critical role of ELOVL2-mediated PUFA elongation in healthy aging. Taken together, our results propose a model in which age-dependent decline in PUFA elongation disrupts the balance between membrane flexibility and stability, initiating a compensatory cycle of membrane stress and repair.}, }
@article {pmid41646664, year = {2026}, author = {Wang, X and Hoshi, S and Kadomoto, S and Liu, R and Ip, M and Sarraf, D and Sadda, SR and Zhang, Y}, title = {Cuticular Drusen Associated Photoreceptor and RPE Optical Property Perturbation Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {41646664}, support = {R01 EY024378/EY/NEI NIH HHS/United States ; R01 EY034218/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE: To characterize microscopic alteration of photoreceptors and RPE surrounding cuticular drusen in age-related macular degeneration (AMD) using multimodal imaging, including high resolution adaptive optics scanning laser ophthalmoscopy (AOSLO).<br><br>METHODS: Eyes with early to intermediate AMD and predominantly cuticular drusen underwent color fundus photography, infrared reflectance, fundus autofluorescence, optical coherence tomography (OCT), and AOSLO. Cuticular drusen were identified using multimodal imaging and classified into three OCT-defined phenotypes. Cone photoreceptor reflectivity was assessed on AOSLO. A subset of eyes underwent longitudinal AOSLO and OCT imaging.<br><br>RESULT: Nineteen eyes from 12 subjects aged 70.3 &#xb1; 5.8 years were studied. Six eyes had longitudinal follow-up imaging. A total of 3177 cuticular drusen were evaluated and classified into 3 types based on cross sectional OCT imaging. AOSLO revealed corresponding phenotype-dependent cone reflectivity alterations associated with the 3 types of cuticular drusen. Type 1: Maintained cone reflectivity overlying the drusen on a hyporeflective background. Type 2: Cone reflectivity loss overlying the cuticular drusen. Type 3: Cones are predominantly not visible over the cuticular drusen. Lesion diameters were 52.62 &#xb1; 9.38 &#x3bc;m (Type 1), 71.88 &#xb1; 12.39 &#x3bc;m (Type 2), and 124.72 &#xb1; 20.94 &#x3bc;m (Type 3). All lesions were accompanied by hypertransmission in the choroid on OCT. Longitudinal imaging showed that localized outer retinal reflectivity reduction on AOSLO preceded the detection of new cuticular drusen on OCT.<br><br>CONCLUSIONS: Cellular-resolution multimodal imaging demonstrates progressive, phenotype-specific disruption of the photoreceptor-RPE complex associated with cuticular drusen in AMD. Early AOSLO-detected reflectivity changes preceding OCT-visible lesions highlight the sensitivity of adaptive optics imaging for identifying early outer retinal alterations and for advancing understanding of the biogenesis of cuticular drusen.}, }
@article {pmid41646887, year = {2026}, author = {Fabian-Jessing, BK and Askou, AL and Jakobsen, TS and Adsersen, RL and Lindholm, AB and Køllner Bjerre, AK and Alsing, S and Bek, T and Aagaard, L and Corydon, TJ}, title = {AAV-mediated multiple gene therapy combining VEGFA-targeting miR-agshRNAs and PEDF for the suppression of choroidal neovascularization.}, journal = {Molecular therapy. Nucleic acids}, volume = {37}, number = {1}, pages = {102833}, pmid = {41646887}, issn = {2162-2531}, abstract = {Common ophthalmic diseases, including age-related macular degeneration (AMD), generally have a complex pathogenesis involving multiple pathways and varying involvement of specific cell types. This provides a strong rationale for developing novel gene therapy platforms that allow cell-specific up- and down-regulation of multiple targets while contained within standard adeno-associated viral vectors (AAVs). Hence, we engineered a tunable expression cassette with two pri-miR-embedded, Ago2-dependent shRNAs (miR-agshRNAs) units enabling dual target silencing, and intron embedment allowing downstream protein expression. With this platform, we demonstrated additive Vegfa knockdown, concurrent silencing of Vegfa and mTOR, and simultaneous expression of pigment epithelium-derived factor (PEDF) from a single promoter. Following the subretinal injection of AAV5 vectors encoding Vegfa-targeting miR-agshRNAs and PEDF into the murine retina, profound Vegfa suppression and strong PEDF expression were observed. Notably, laser-induced choroidal neovascularization (CNV) was significantly reduced in the therapeutic groups, with the multi-targeting vector achieving the highest level of CNV suppression. Collectively, our data demonstrated robust anti-angiogenic effects of multiple gene therapies, suggesting a "one-and-done" AAV-based delivery of cross-species anti-VEGFA RNAi therapeutics together with PEDF as a valuable tool for the management of neovascular AMD (nAMD) and other complex neovascular ocular diseases.}, }
@article {pmid41648145, year = {2026}, author = {Patel, MK and Piedade, W and Famulski, JK}, title = {Cdhr1a and pcdh15b link photoreceptor outer segments with inner segment calyceal processes revealing a potential mechanism for cone-rod dystrophy.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41648145}, issn = {2692-8205}, support = {P20 GM103436/GM/NIGMS NIH HHS/United States ; }, abstract = {Cone rod dystrophy (CRD) is a macular degeneration disorder characterized by initial cone cell photoreceptor degeneration and subsequently of rod photoreceptors. Mutations in CDHR1, a photoreceptor specific cadherin have been found to be associated with the incidence of cone-rod dystrophy and recapitulated in mouse CDHR1 knockouts. However, the molecular function of CDHR1 remains unknown. CDHR1 has been shown to localize at the leading edge of murine rod nascent outer segment (OS) making junctions to an unknown partner in the inner segment. Using Structured Illumination Microscopy (SIM), we observed that the localization of zebrafish cdhr1a extends from basal nascent OS discs above the periciliary ridge of the inner segment to a considerable length along the OS, akin to calyceal process (CPs). When labeling the CPs using pcdh15b, a CP specific cadherin, we observed that cdhr1a at the leading edge of OS juxtaposes with pcdh15b in the CP. Similar localization patterns were detected in human, macaque, xenopus, ducks, and various rodent PRCs indicating conservation. Importantly, using immunoprecipitation and K652 cell aggregation assays we demonstrate that pcdh15b and cdhr1a can interact and potentially link the OS and CP. To analyze the consequences of OS-CP interactions in CRD, we established a zebrafish cdhr1a mutant line (cdhr1a [fs*146]) and analyzed CRD progression at high temporal resolution. Homozygous cdhr1a [fs*146] mutants begin to exhibit minor cone OS morphology defects starting at 15 dpf (days post fertilization) and severe OS disruption and cell loss by 3 months. Rod OS defects were delayed until 3-6 months. Furthermore, we show that loss of cdhr1a function leads to disorganization and shortening of CPs coinciding with cone outer OS defects which is significantly exacerbated when combined with the loss of pcdh15b. In conclusion, we propose that cdhr1a and pcdh15b function to link cone OSs with CPs to maintain proper OS homeostasis thus revealing a potential novel mechanism for CRD.}, }
@article {pmid41649508, year = {2026}, author = {Muranyi, DS and Molling, J and Hammer, U and Habermann, A and Lehmann, G and Luci, E and Buchwald, C and Hammer, T}, title = {[Real-life data of the IVI interval after switching to faricimab therapy].}, journal = {Die Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41649508}, issn = {2731-7218}, abstract = {BACKGROUND: For neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents currently represents the standard of care. Both treatment intervals and the choice of the optimal agent are critical determinants of therapeutic outcomes.<br><br>OBJECTIVE: This study evaluated the effect of switching from established anti-VEGF agents (ranibizumab, bevacizumab or aflibercept) to faricimab on injection intervals in patients with nAMD or DME.<br><br>MATERIAL AND METHODS: Data were collected in a&#xa0;routine outpatient ophthalmology practice. Inclusion criteria were: (I)&#xa0;treatment according to a&#xa0;treat-and-extend protocol, (II)&#xa0;at least six intravitreal injections prior to switching to faricimab and (III)&#xa0;at least three subsequent faricimab injections. To assess disease-specific effects, patients were stratified into nAMD and DME subgroups.<br><br>RESULTS: A&#xa0;total of 86&#xa0;patients with a&#xa0;mean of 37&#xa0;prior injections were included. The mean injection interval before switching to faricimab was 44&#xa0;days. In the nAMD subgroup (n&#x202f;=&#x2009;74, mean age 72&#xa0;years), the interval significantly increased from 46&#xa0;to 53&#xa0;days (mean difference 7.45 days, p&#x202f;<&#x2009;0.05). In the DME subgroup (n&#x202f;=&#x2009;12, mean age 65&#xa0;years), the interval significantly increased from 42&#xa0;to 57&#xa0;days (mean difference 15.25 days, p&#x202f;<&#x2009;0.05). The effect size was moderate (Cohen's&#xa0;d&#x202f;=&#x2009;0.56) with high statistical power (99.93%).<br><br>CONCLUSION: Switching to faricimab resulted in a&#xa0;significant extension of treatment intervals in both indications, with patients with DME deriving the greatest benefit. Limitations include the small sample size and potential selection bias. These findings suggest an improved benefit-risk profile through reduced injection frequency. Additional real-world data and meta-analyses may help identify biomarkers to further individualize anti-VEGF therapy in the future.}, }
@article {pmid41650065, year = {2026}, author = {Kong, H and Li, J and Lou, J and Zhang, Y and Li, M and Chen, Y and Wang, Y and Tao, T}, title = {A 2-step, 2-sample Mendelian randomization study of gut microbiota, blood metabolites and dry age-related macular degeneration.}, journal = {Medicine}, volume = {105}, number = {6}, pages = {e47527}, pmid = {41650065}, issn = {1536-5964}, support = {Y202148025//Scientific Research Fund of Zhejiang Provincial Education Department/ ; Y202456684//Scientific Research Fund of Zhejiang Provincial Education Department/ ; 2023RC081//Medical Scientific Reasearch Foundation of Zhejiang Province/ ; 2025708925//Medical Scientific Reasearch Foundation of Zhejiang Province/ ; 2024RC-QN-02//Ningbo Health Youth Technical Backbone Talent Development Program/ ; 2023HMJQ25//Zhu Xiu Shan Talent Project of Ningbo No.2 Hospital/ ; }, mesh = {Humans ; Mendelian Randomization Analysis/methods ; *Gastrointestinal Microbiome/genetics ; Genome-Wide Association Study ; *Macular Degeneration/genetics/blood ; Aged ; *Geographic Atrophy/genetics/blood ; }, abstract = {Dry age-related macular degeneration (dAMD) is the leading cause of blindness among elderly people in developed countries. The main objective of this study is to investigate the causal relationship between gut microbiota (GM), blood metabolites, and dAMD among European participants. Based on the genome-wide association analysis database, double sample Mendelian randomization (MR) analysis was performed on GM, blood metabolites, and dAMD. The inverse-variance weighted method is used to estimate the causal relationship between GM, blood metabolites, and dAMD, while multiple methods are employed to eliminate pleiotropy and heterogeneity. A 2-step MR analysis quantitatively assessed the effect of metabolite-mediated GM on dAMD. In MR analysis, 15 GM were found to be associated with increased or decreased risk of dAMD, and 18 blood metabolites were found to be associated with increased or decreased risk of dAMD. Our research also found that the potential association between GM and dAMD may be mediated by blood metabolite levels, specifically, ADpSGEGDFXAEGGGVR levels accounted for 38.9% of the causal pathway from genus Parasutterella to dAMD. Our research findings indicate that certain GM and blood metabolites can affect the onset of dAMD, and increasing the abundance of genus Parasottella can increase the risk of dAMD through the mediation of ADpSGEGDFXAEGGGVR levels.}, }
@article {pmid41650530, year = {2026}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {Comparative effectiveness and safety landscape of anti-VEGF therapies for neovascular age-related macular degeneration: Insights from a systematic review and network meta-analysis.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {196}, number = {}, pages = {118881}, doi = {10.1016/j.biopha.2025.118881}, pmid = {41650530}, issn = {1950-6007}, mesh = {Humans ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage/therapeutic use ; Network Meta-Analysis as Topic ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Treatment Outcome ; Ranibizumab/adverse effects/administration &amp; dosage ; Visual Acuity/drug effects ; Recombinant Fusion Proteins/adverse effects/administration &amp; dosage ; Randomized Controlled Trials as Topic ; Receptors, Vascular Endothelial Growth Factor ; *Macular Degeneration/drug therapy ; Bevacizumab/adverse effects/administration &amp; dosage ; Antibodies, Monoclonal, Humanized ; }, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible vision loss in older adults. Intravitreal anti-vascular endothelial growth factor (VEGF) agents-including Aflibercept, Ranibizumab, Bevacizumab, Brolucizumab, and Faricimab-are the mainstay of therapy. However, their comparative efficacy and safety remain uncertain. This study aimed to compare the visual and systemic outcomes of these agents to inform clinical decision-making.<br><br>METHODS: A systematic search of PubMed, Embase, Scopus, and Web of Science from inception to September 2025 identified randomized controlled trials (RCTs) and observational studies comparing at least two anti-VEGF agents in nAMD. Eligible studies reported outcomes of best-corrected visual acuity (BCVA) change, visual gain &#x2265;&#x202f;15 letters, mortality, or arteriothrombotic events. Risk of bias was assessed using Cochrane Risk of Bias 2 (RoB 2) and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tools. A frequentist network meta-analysis estimated mean differences (MD) and odds ratios (OR) with 95&#x202f;% confidence interval (CI). The protocol was registered in PROSPERO (CRD42025631298).<br><br>RESULTS: Sixteen studies involving 6758 participants (follow-up 3-24 months) met the inclusion criteria. For BCVA improvement, Aflibercept had the highest surface under the cumulative ranking curve (SUCRA) ranking (0.80), although all agents showed similar mean differences that were not statistically significant: aflibercept (MD 0.80; 95&#x202f;% CI -1.20-2.80), Ranibizumab (0.64; -1.87-3.15), Bevacizumab (0.60; -2.02-3.22), Faricimab (2.20; -0.69-5.09), and Brolucizumab (4.20; -5.97-14.36). The larger point estimate for Brolucizumab reflects imprecision rather than superior visual efficacy. Mortality was lowest with Aflibercept (risk ratio (RR) 0.76; 95% CI 0.41-1.55). For arteriothrombotic events, no statistically significant differences were observed between anti-VEGF agents. Comparisons between Aflibercept and Bevacizumab (RR 1.11; 95% CI 0.60-2.07), aflibercept and Ranibizumab (RR 0.77; 95% CI 0.49-1.21), and Bevacizumab and Ranibizumab (RR 0.88; 95% CI 0.60-1.30) showed wide confidence intervals, reflecting substantial imprecision. Certainty of evidence (GRADE) ranged from moderate to low.<br><br>CONCLUSION: All anti-VEGF agents stabilize or improve vision in nAMD. Aflibercept may provide the most favorable efficacy-safety balance, Faricimab offers promising durability, and Brolucizumab demonstrates large visual gains with potential safety concerns. Further head-to-head and long-term real-world studies are needed to optimize individualized treatment strategies.}, }
@article {pmid41653377, year = {2026}, author = {Manders, EA and van Der Wel, V and Schlingemann, R and Hollak, CEM and de Visser, SJ}, title = {Repurposing biosimilars, rethinking costs: a framework for sustainable drug pricing for repurposed bevacizumab for intravitreal injections.}, journal = {The European journal of health economics : HEPAC : health economics in prevention and care}, volume = {}, number = {}, pages = {}, pmid = {41653377}, issn = {1618-7601}, abstract = {Bevacizumab, originally developed by Genentech under the brand name Avastin[®] as an anti-cancer drug, has gained widespread off-label use in ophthalmology due to its similar mechanism of action to other anti-VEGF treatments and its significantly lower cost compared to available on label alternatives for ophthalmological indications. While off-label bevacizumab has been standard in clinical practice for over a decade, recently, a repurposed formulation (brand name: Lytenava[®], Outlook Therapeutics Ltd), developed specifically for vascular retinal conditions, received marketing approval from the European Medicines Agency. This raises questions about what the price for a repurposed formulation should reasonably be, reflecting the efforts to obtain regulatory approval. This paper examines potential cost-based-plus pricing for such a repurposed formulation of bevacizumab using a novel pricing framework across four scenarios. By evaluating the pricing structure through an analysis of critical cost components, including, among others, research and development expenditures, manufacturing costs, and cost-of-capital, the study proposes a price range of €73 to €177 per injection. The explicit breakdown of these cost components provides valuable insights into the economic structure of repurposed biosimilars like bevacizumab, emphasizing how a cost-based-plus pricing model can support more transparent and informed negotiations between pharmaceutical companies and healthcare payers. Ultimately, this approach contributes to the development of pricing strategies that balance affordability for healthcare systems with sustainable returns for manufacturers while fostering the broader development of repurposed treatments. The findings of this paper aim to advance the dialogue on equitable pricing for repurposed therapies.}, }
@article {pmid41654128, year = {2026}, author = {Zhao, J and Montenegro, D and Cheng, S and Kim, HJ and Sparrow, JR}, title = {More insights from Abca4[-/-] mouse models of recessive Stargardt disease.}, journal = {The Journal of biological chemistry}, volume = {302}, number = {3}, pages = {111261}, pmid = {41654128}, issn = {1083-351X}, abstract = {Mutations in the ABC transporter ABCA4 (ABC, subfamily A, member 4) are responsible for recessive Stargardt disease 1 (STGD1), a juvenile form of macular degeneration. In preclinical and clinical studies, it has been shown that deficiency in ABCA4 leads to accelerated formation of the toxic bisretinoid fluorophores that form as the product of nonenzymatic reactions of retinaldehyde with phosphatidylethanolamine (2:1 ratio). Here, by comparing photoreceptor cell viability in albino versus agouti Abca4[-/-] mice and by dark-rearing albino Abca4[-/-] mice, we show that photoreceptor cell degeneration in the Abca4[-/-] mouse is at least partially driven by light. Elevated vitamin A in chow and a high-fat diet reduced photoreceptor cell viability. Phosphatidylethanolamine and N-retinylidiene-phosphatidylethanolamine were reduced, as were steady-state levels of retinoid in light-adapted eyes. As expected, bisretinoids, measured as short-wavelength fundus autofluorescence (AF), were elevated in both pigmented and albino Abca4[-/-] mice. Hyperautofluorescent puncta in fundus AF images colocalized in spectral domain optical coherence tomography scans with aberrant hyper-reflectivity that occupied photoreceptor-attributable bands and extended anteriorly to interrupt the ellipsoid zone and external limiting membrane. In epifluorescence images of Abca4[-/-] retina, retinal pigment epithelium was autofluorescent because of bisretinoid accumulation. Occasionally, AF lesions extended anteriorly from the retinal pigment epithelium to a horizontal band exhibiting less pronounced AF at the level of photoreceptor inner and outer segments. These lesions did not colocalize with IBA1 (ionized calcium-binding adaptor molecule)-labeled microglia. The hyperautofluorescent foci that presented as hyper-reflective lesions in spectral domain optical coherence tomography form in photoreceptor inner segments and are reminiscent of fundus flecks in STGD1.}, }
@article {pmid41654857, year = {2026}, author = {Forte, P and Ferro Desideri, L and Nassisi, M and Milanesi, F and Feo, A and Bagnasco, I and Iglesia, SM and Forte, G and Scandella, D and Roccatagliata, F and Fontana, V and Eandi, CM and Iester, M and Jolly, JK and Zinkernagel, MS and Viola, F and Nicolò, M}, title = {Drusen-specific dark adaptation profiles in intermediate age-related macular degeneration.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {34}, pmid = {41654857}, issn = {2056-9920}, abstract = {AIMS: To investigate the influence of macular drusen phenotypes on dark adaptation (DA) in intermediate age-related macular degeneration (iAMD).<br><br>METHODS: This cross-sectional, multicentric study enrolled 57 eyes of 43 iAMD patients. Drusen were subclassified as cuticular, soft, reticular pseudodrusen (RPD), or combined soft&#x2009;+&#x2009;RPD based on multimodal imaging. Dark adaptometry (AdaptDx; 20-minute test-time) assessed DA function through rod intercept time (RIT), last measured log sensitivity (LMLS; primary outcome) and area under the DA curve (AUDAC; secondary outcome). OCT volumes (30&#xb0;x20&#xb0; field) were analyzed using an AI-enhanced algorithm providing a quantification of chorioretinal layers and pigment epithelium detachments (PED) volumes. Multivariable tobit and linear regression analyzed associations between drusen phenotypes and DA outcomes.<br><br>RESULTS: Drusen phenotype distribution was: cuticular 13 eyes (22.8%), soft 13 eyes (22.8%), isolated RPD 21 eyes (36.8%), and combined soft&#x2009;+&#x2009;RPD 10 eyes (17.5%). Nearly all eyes reaching RIT within the 20-minute test ceiling (10 of 11 eyes) had cuticular drusen, which showed preserved rod function (LMLS: 2.9&#x2009;&#xb1;&#x2009;0.2 log-units; AUDAC: 10.3&#x2009;&#xb1;&#x2009;3.2 log-units&#xb7;min; RIT: 14.9&#x2009;&#xb1;&#x2009;4.5 min) despite presenting the highest PED volumes (301&#x2009;&#xb1;&#x2009;152 nL). Conversely, isolated RPD demonstrated most severe dysfunction (LMLS: 1.7&#x2009;&#xb1;&#x2009;0.3; AUDAC: 23.7&#x2009;&#xb1;&#x2009;5.39). Soft drusen showed intermediate impairment (LMLS: 2.2&#x2009;&#xb1;&#x2009;0.2; AUDAC: 18.4&#x2009;&#xb1;&#x2009;2.4). Drusen phenotype was the most significant predictor of DA outcomes in both regression models (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Dark adaptometry reveals distinct patterns of DA impairment across drusen phenotypes, necessitating precise drusen classification when dark adaptometry serves as a functional endpoint in iAMD clinical trials. Future studies should employ extended test protocols (40-minute ceiling) to confirm these findings.<br><br>CLINICAL TRIAL NUMBER: Not applicable.}, }
@article {pmid41655020, year = {2026}, author = {Gardner, A and Wang, S and Daniels, A and Li, D and Wu, C and Lin, L and Hong, C and Zhao, SR and Born, RT and Kruczek, K and Weist, G and Barrio Real, L and Wicks, J and Nayal, M and Carter, A and Ott, C and Haurigot, V and Cepko, CL}, title = {AAV NRF2 gene therapy preserves retinal structure and function in rodent models of oxidative damage.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2026.02.005}, pmid = {41655020}, issn = {1525-0024}, abstract = {Dry age-related macular degeneration is the most frequent cause of visual impairment in individuals over age 50 in developed countries. It is characterized by deposits of oxidized proteins and lipids and results in progressive loss of high-acuity vision. One major risk factor is smoking, which causes oxidative stress in many tissues, including the eye. We previously showed that an adeno-associated viral vector expressing human NRF2 (AAV8/Best1-NRF2), a transcription factor that regulates responses to oxidative damage, slowed degeneration in mouse models of another blinding disorder, retinitis pigmentosa, which also includes oxidative stress. Here, our AAV8/Best1-NRF2 vector was tested in a model of oxidative stress wherein sodium iodate was injected systemically, as this is often used to model dry age-related macular degeneration. Sodium iodate causes acute oxidative damage to the retinal pigment epithelial cells, which provide support to the photoreceptor cells. In addition, this toxin ultimately leads to photoreceptor death. Subretinal injection of AAV8/Best1-NRF2 led to protection of the retinal pigment epithelium and photoreceptors, as well as preservation of visual function, in rat and mouse sodium iodate models. AAV8/Best1-NRF2 may serve as an effective gene-agnostic therapy for diseases with oxidative stress, including dry age-related macular degeneration.}, }
@article {pmid41655333, year = {2026}, author = {Guo, R and Huang, Y and Zhang, X and Qin, M and Sun, H and Jin, X and Xu, J and Kang, Y and Li, K and Zhou, Y and Nan, K and Zheng, Y and Liu, S}, title = {Long-term suppression of retinal degeneration with anti-VEGF agents-loaded hollow mesoporous silica nanoparticles.}, journal = {Colloids and surfaces. B, Biointerfaces}, volume = {262}, number = {}, pages = {115527}, doi = {10.1016/j.colsurfb.2026.115527}, pmid = {41655333}, issn = {1873-4367}, mesh = {*Silicon Dioxide/chemistry ; *Nanoparticles/chemistry/ultrastructure ; Animals ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Porosity ; Receptors, Vascular Endothelial Growth Factor ; Humans ; *Ranibizumab/pharmacology/chemistry/administration &amp; dosage ; *Recombinant Fusion Proteins/pharmacology/chemistry/administration &amp; dosage ; Cell Proliferation/drug effects ; Choroidal Neovascularization/drug therapy/pathology ; Cell Movement/drug effects ; Particle Size ; *Retinal Degeneration/drug therapy/pathology ; *Angiogenesis Inhibitors/pharmacology/chemistry ; Mice ; Intravitreal Injections ; Mice, Inbred C57BL ; }, abstract = {Age-related macular degeneration (AMD) that leads to degeneration of the overlying photoreceptor in the macula and consequent loss of central vision is the leading cause of irreversible blindness in elderly population. Since vascular endothelial growth factor (VEGF) is pivotal for stimulating neovascularization, monthly intravitreal (IVT) injections of anti-VEGF agents have been used for eliminating neovascularization. However, repeated monthly IVT injections could cause side effects and serious complications. Herein, we report the development of two kinds of anti-VEGF agents (Ranibizumab (Ran) and Aflibercept (Afl))-loaded hollow mesoporous silica nanoparticles for effective treatment of AMD. The designed nanoparticles show no toxicity for both in vitro and in vivo, and could significantly inhibit VEGF-induced proliferation and cell migration. Long-term in vivo experiments in the laser photocoagulation induced choroidal neovascularization (CNV) model for wet AMD show that these nanoparticles effectively inhibit VEGF-induced neovascularization leakage and formation at least 8 weeks upon one IVT injection and therefore are a promising treatment strategy for AMD.}, }
@article {pmid41655655, year = {2026}, author = {Liu, H and Sun, X and Liu, J and Chang, Z}, title = {Exploring the causal relationship between osteoporosis and age-related macular degeneration: Evidence from observational studies and mendelian randomization.}, journal = {Experimental gerontology}, volume = {215}, number = {}, pages = {113060}, doi = {10.1016/j.exger.2026.113060}, pmid = {41655655}, issn = {1873-6815}, mesh = {Humans ; Mendelian Randomization Analysis ; *Macular Degeneration/genetics/epidemiology/etiology ; *Osteoporosis/complications/genetics/epidemiology ; Observational Studies as Topic ; Female ; Genome-Wide Association Study ; Risk Factors ; Male ; Aged ; Genetic Predisposition to Disease ; }, abstract = {OBJECTIVE: This study aimed to systematically investigate the association between osteoporosis (OP) and age-related macular degeneration (AMD), including its subtypes, by integrating observational evidence with causal inference approaches.<br><br>METHODS: We first conducted a systematic literature search and meta-analysis of relevant observational studies up to August 2025 to evaluate the observational association between OP and AMD. Subsequently, using summary data from genome-wide association studies, we performed a bidirectional two-sample Mendelian randomization (MR) analysis to examine the causal relationship between OP and four AMD subtypes. The primary causal estimates were derived using the inverse variance weighted method, and multiple sensitivity analyses were conducted to verify the robustness of the results.<br><br>RESULTS: The meta-analysis, which included three studies, indicated that osteoporosis increases the risk of AMD in women (OR: 1.46; 95% CI: 1.12-1.91, P&#xa0;=&#xa0;0.0049). Under Bonferroni correction, the MR analysis showed that genetically predicted osteoporosis significantly increased the risk of dry AMD (IVW OR: 1.26; 95% CI: 1.10-1.44, P&#xa0;=&#xa0;0.00087. Bayesian weighted MR OR: 1.25; 95% CI: 1.05-1.49, P&#xa0;=&#xa0;0.01162.), while no significant causal effects were observed for wet, early, or late AMD. Reverse MR analysis did not indicate any causal effect of AMD on OP. No significant horizontal pleiotropy or heterogeneity was detected in any of the analyses.<br><br>CONCLUSION: Osteoporosis may increase the risk of AMD in women. The MR analysis provides some genetic evidence supporting a potential causal link between osteoporosis and dry AMD. In clinical practice, patients with osteoporosis-particularly elderly women-should be considered at potential high risk for dry AMD, and early fundus screening may facilitate the early detection and intervention of dry AMD.}, }
@article {pmid41655724, year = {2026}, author = {Song, SY and Le, DD and Lee, M and Cho, SS and Park, DH}, title = {Camellia japonica hyperoside exhibits anti-age-related macular degeneration effects in an ARPE-19 cell model by inhibiting apoptosis via JNK-Nrf2/HO-1 activation.}, journal = {Journal of ethnopharmacology}, volume = {362}, number = {}, pages = {121305}, doi = {10.1016/j.jep.2026.121305}, pmid = {41655724}, issn = {1872-7573}, mesh = {Apoptosis/drug effects ; Humans ; Heme Oxygenase-1/metabolism ; NF-E2-Related Factor 2/metabolism ; *Camellia/chemistry ; Cell Line ; *Quercetin/pharmacology/analogs &amp; derivatives/isolation &amp; purification ; Plant Extracts/pharmacology ; Antioxidants/pharmacology/isolation &amp; purification ; Plant Leaves ; Retinal Pigment Epithelium/drug effects ; }, abstract = {Camellia japonica is recognized for its edible and therapeutic value in East Asia, and has anti-inflammatory, antioxidative, and antiasthmatic properties. However, the active compound and the modes of action are unclear.<br><br>AIM OF THE STUDY: To evaluate the anti-AMD effect of hyperoside isolated from the leaves and twigs of Camellia japonica and to explore the underlying mechanisms using an ARPE-19 AMD cell model.<br><br>MATERIAL AND METHODS: The hyperoside content in the extracts was evaluated using feature-based molecular network and UHPLC-MS/MS system. Network pharmacology was used to predict the interactions of hyperoside with AMD-related signaling pathways and the underlying mechanisms. For in vitro evaluation of the anti-AMD effects, ARPE-19&#xa0;cells were divided into six treatment groups: CON, no treatment; A2E, AMD induction using 30&#xa0;&#x3bc;M A2E and 20&#xa0;mW/cm[2] blue light treatment; Lutein, treatment with 25&#xa0;&#x3bc;M lutein as a positive control; and three Hyperoside groups, treated with 37.5, 75, or 150&#xa0;&#x3bc;M hyperoside. The antiapoptotic effect of hyperoside was evaluated using flow cytometry and TUNEL assays, and the intrinsic apoptotic pathway proteins (Bcl-xL, Bad, and Bim) were analyzed via western blotting. The interactions of hyperoside with JNK and p38 MAPKs were determined using western blotting, and molecular docking. The antioxidative effect of hyperoside was measured via DPPH and ABTS radical scavenging assays; Nrf2/HO-1 activation and SOD-1 stimulation were analyzed using western blotting and immunofluorescence assay. The anticarbonyl effect (4-HNE and MDA) was measured using western blotting.<br><br>RESULTS: Hyperoside was nontoxic to ARPE-19&#xa0;cells up to 150&#xa0;&#x3bc;M. It dose-dependently decreased A2E and blue light-induced AMD in ARPE-19&#xa0;cells by upregulating the antiapoptotic Bcl-2 protein (Bcl-xL) and downregulating the proapoptotic Bcl-2 proteins (Bad and Bim). Hyperoside dephosphorylated JNK and p38 MAPKs in a dose-dependent manner, eradicated DPPH and ABTS radicals, and activated Nrf2/HO-1 and SOD-1. It also decreased the levels of 4-HNE and MDA.<br><br>CONCLUSION: We conclude that C. japonica hyperoside could be a promising anti-AMD drug.}, }
@article {pmid41655766, year = {2026}, author = {Ambresin, A and Chaudhary, V and Gale, R and Koh, AHC and London, NJS and Patel, PJ and Tan, ACS and Hill, L and Kotecha, A and Margaron, P and Singer, M and , }, title = {Potential 20-Week Faricimab Dosing in Wet Age-Related Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.02.001}, pmid = {41655766}, issn = {2468-6530}, }
@article {pmid41655974, year = {2026}, author = {Gillies, M and Hashimoto, Y and Nazari, R and Arnold, J and Wang, B and Barry, R and Ferrier, R and Game, J and Barthelmes, D}, title = {Twelve-Month Real-World Outcomes of Faricimab for Treatment-Naive Neovascular AMD in Australia.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ceo.70072}, pmid = {41655974}, issn = {1442-9071}, support = {1195021//National Health and Medical Research Council/ ; //Bayer/ ; //Roche/ ; //Macular Disease Foundation Australia/ ; }, abstract = {BACKGROUND: To provide insights into the effectiveness and safety of faricimab for treatment-naïve eyes with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: A retrospective cohort study using a prospectively-designed registry. Treatment-na&#xef;ve eyes with nAMD in Australia starting treatment with faricimab between Jan 2023-Sep 2024 were included. Controls were treatment-na&#xef;ve eyes starting with aflibercept 2&#x2009;mg before 2022. Visual acuity (VA), macular neovascularisation activity, time to first inactivity, number of injections, injection intervals and number of visits at 12&#x2009;months were investigated. Eyes treated with faricimab versus aflibercept 2&#x2009;mg were compared using overlap weighting. The main outcome measure was the 12-month VA change.<br><br>RESULTS: Twenty-three practitioners treated 160 eyes with a 4-letter gain in VA (mean, 61.5-65.5 letters) and 48% attaining a dosing interval of &#x2265;&#x2009;12&#x2009;weeks, although 22% were still treated at <&#x2009;8 weekly intervals. The small proportion (6.9%) of eyes switching to another agent had improved vision but were mostly active when switching off faricimab. Eyes received 7.2 injections (mean) at 7.4 visits (mean), receiving treatment at 98% of visits indicating a strongly proactive treatment regimen. Most (71%) lesions became inactive by 12&#x2009;months with a mean time to inactivation of 10.3&#x2009;weeks. Eyes starting faricimab had a significantly higher inactivation rate with more eyes reaching the last injection interval of &#x2265;&#x2009;12&#x2009;weeks than those starting aflibercept 2&#x2009;mg.<br><br>CONCLUSIONS: These findings indicate that faricimab is safe and effective for treatment-naive eyes with nAMD. Faricimab had a stronger effect on nAMD lesion activity than aflibercept 2&#x2009;mg.}, }
@article {pmid41658256, year = {2025}, author = {Candan, O and Uney, G and Hazirolan, D and Unlu, N and Acar, MA}, title = {A 5-Year Analysis of Optical Coherence Tomography Biomarkers in The Visual Outcomes of an As-Needed Treatment Algorithm for Neovascular Age-Related Macular Degeneration.}, journal = {Beyoglu eye journal}, volume = {10}, number = {4}, pages = {226-234}, pmid = {41658256}, issn = {2587-0394}, abstract = {OBJECTIVES: This study aimed to predict the visual course of patients with neovascular age-related macular degeneration by analyzing data from a 5-year observational study and to identify biomarkers that have an impact on visual prognosis.<br><br>METHODS: The present study comprised a total of 104 patients who received the PRN treatment regimen between March 2015 and March 2021. Best-corrected visual acuity (BCVA) and optical coherence tomography findings were evaluated. Multinomial logistic regression models were used to determine predictors of BCVA at 12, 24, and 60 months.<br><br>RESULTS: Better BCVA and thicker macula at baseline, decreased BCVA at month 3, and persistence of IRF at month 3 were correlated with decreased BCVA at month 12 (all p<0.05). At 24 month, a decline in BCVA was associated with specific baseline characteristics, including better BCVA, absence of pigment epithelial detachment (PED), and presence of intraretinal cystoid fluid (IRF) (all p<0.01). Similarly, decreased BCVA and thicker macula in the 3rd month were associated with worse BCVA. At the 60-month visit, better baseline BCVA, absence of PED, presence of IRF at baseline, and persistence of IRF at month 3 were associated with a reduction in BCVA (all p<0.05). The visual prognosis had no correlation with the number of injections.<br><br>CONCLUSION: This 5-year real-life study identified prognostic markers that cause a decline in visual acuity. The use of these markers has the potential to be valuable in preserving visual gain, irrespective of the number of injections.}, }
@article {pmid41658600, year = {2026}, author = {Zhang, X and Wang, Z and Li, Z and Zhan, Z}, title = {The mechanisms, epidemiology, and clinical implications of thyroid hormones and age-related macular degeneration: a narrative review.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1765758}, pmid = {41658600}, issn = {2296-858X}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among older adults. Thyroid hormones (THs) are essential endocrine regulators of development and metabolic homeostasis, and increasing evidence suggests that TH signaling is involved in retinal physiology and AMD pathogenesis. Experimental studies have demonstrated that excessive TH signaling exacerbates oxidative stress, mitochondrial dysfunction, and apoptosis in retinal pigment epithelium (RPE) cells and photoreceptors, whereas inhibition of TH signaling confers retinal protection in animal models of dry AMD. Genetic evidence from Mendelian randomization analyses further indicates that genetically predicted higher free thyroxine (FT4), per one standard deviation increase, is associated with an increased risk of AMD (OR 1.19, 95% CI 1.06-1.33), while no causal association has been established for thyroid-stimulating hormone (TSH). Consistently, large population-based cohort studies, including the Rotterdam Study, have reported a positive association between circulating FT4 levels and the incidence of AMD. In this narrative review, we summarize and critically evaluate recent advances from basic experimental, genetic, and clinical studies on the relationship between thyroid hormones and AMD, discuss potential biological mechanisms underlying this association, and highlight current limitations and future research directions.}, }
@article {pmid41658807, year = {2026}, author = {Jayadev, C and Talwar, D and Bhende, M and Narayanan, R and Gupta, V and Chakraborty, D and Deka, S and Manayath, G and Banker, A}, title = {Expert Opinion on the First-Line Management of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema in India: The Role of Faricimab.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e100779}, pmid = {41658807}, issn = {2168-8184}, abstract = {This expert opinion article summarizes deliberations from a focused panel discussion involving nine retina specialists on the clinical utility of faricimab in managing neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). The discussion explored evolving understanding of the multifactorial disease mechanisms, including pathways beyond vascular endothelial growth factor-A, and the rationale for dual inhibition strategies. Experts shared their clinical perspectives on faricimab use in diverse patient profiles, treatment sequencing, and individualized dosing approaches to achieve durable disease control. Practical considerations around early initiation, optimization of treatment intervals, and real-world applicability were also discussed. The insights highlight expert-derived strategies for integrating faricimab as a first-line treatment into clinical practice, emphasizing its role in achieving vascular stability and the improved durability of treatment response. Overall, the panel concluded that faricimab represents a clinically valuable first-line therapeutic option for nAMD and DME, enabling individualized, durable disease control in routine practice.}, }
@article {pmid41660488, year = {2026}, author = {Blair, JPM and Guymer, RH and Krzemińska-Ściga, A and De Zanet, S and Ciller, C and Apostolopoulos, S and Wu, Z}, title = {Geographic Atrophy Structure-Function Relationships Based on Loss of OCT Outer Retinal Bands and Fundus Autofluorescence.}, journal = {Ophthalmology science}, volume = {6}, number = {3}, pages = {101035}, pmid = {41660488}, issn = {2666-9145}, abstract = {PURPOSE: To examine the association between the loss of the OCT outer retinal bands and deep visual sensitivity losses quantified by defect-mapping microperimetry (DMP).<br><br>DESIGN: Cross-sectional study.<br><br>PARTICIPANTS: Fifty individuals with geographic atrophy (GA) secondary to age-related macular degeneration.<br><br>METHODS: All participants underwent DMP testing-a strategy optimized to quantify the spatial extent of deep visual sensitivity losses through single presentations of 10 decibel stimuli-with 208 locations sampled within the central 8&#xb0; radius region. Participants also underwent OCT and fundus autofluorescence (FAF) imaging. OCT scans were automatically segmented to detect regions of retinal pigment epithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) loss, and FAF images were manually annotated for GA. The extent of these parameters in the central 8&#xb0; radius region where DMP testing was performed, and at each individual test location, was derived through image coregistration for evaluating structure-function associations.<br><br>MAIN OUTCOME MEASURES: Global structure-function correlation between the proportion of locations missed on DMP testing and the extent of loss of the structural parameters based on Spearman rank correlation coefficient (&#x3c1;), and spatial agreement between the presence of structural changes and missed stimuli on DMP testing at individual test locations based on the Dice similarity coefficient (DSC).<br><br>RESULTS: There were strong global structure-function correlations based on loss of the OCT outer retinal bands (&#x3c1; = 0.85-0.86), similar to what was seen with FAF-defined GA (&#x3c1; = 0.89; P &#x2265; 0.326). However, the spatial agreement between OCT-defined EZ and ELM loss with missed stimuli on DMP testing (DSC = 0.64 for both) was higher than that seen with RPE loss (DSC = 0.60) and FAF-defined GA (DSC = 0.62; P = 0.008 for both), but the structure-function spatial agreement was similar between RPE loss and FAF-defined GA (P = 0.152).<br><br>CONCLUSIONS: Spatial agreement with pointwise deep visual sensitivity losses was comparable based on OCT-defined RPE loss and FAF-defined GA, but higher based on EZ and ELM loss. These findings confirm the expected functional relevance of these automatically derived OCT-defined parameters and support their utility as tools for monitoring GA progression.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41661268, year = {2026}, author = {Schwämmle, ME and Blatz, KM and Bucher, F}, title = {[Extracellular vesicles and their potential in ophthalmology].}, journal = {Die Ophthalmologie}, volume = {123}, number = {3}, pages = {192-200}, pmid = {41661268}, issn = {2731-7218}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Eye Diseases/diagnosis/metabolism ; Biomarkers/analysis/metabolism ; *Ophthalmology/trends/methods ; }, abstract = {BACKGROUND: Extracellular vesicles (EV), especially small EV and microvesicles, are considered promising biomarkers as they transport molecular information from their tissue of origin and can thus reflect pathological processes. They are increasingly being investigated as biomarkers in ocular diseases.<br><br>OBJECTIVE: The aim of this study was to present the current state of knowledge on the role of EV as biomarkers for ocular diseases, to compare sample sources and to discuss the associated methodological challenges as well as clinical perspectives.<br><br>MATERIAL AND METHODS: This work is based on a&#xa0;literature search of current original articles and reviews, complemented by tabular overviews of identified EV-associated markers for ocular diseases.<br><br>RESULTS: The potential of EV as biomarkers for ocular diseases is currently being studied in tears, aqueous humor, vitreous humor, blood and urine. Alterations in EV concentration and size as well as disease-specific signatures have been reported. Numerous EV-associated molecules, particularly microRNA (miRNA) and proteins, have been proposed for diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, myopia and ocular tumors.<br><br>CONCLUSION: Although EV hold great promise as diagnostic and prognostic tools in ophthalmology, validated markers and standardized isolation and detection methods are still lacking. Key challenges include lipoprotein contamination, limited sample volumes and interindividual variability (e.g. age, sex, fasting status). In the future, after overcoming these technical challenges, small EV and microvesicles could serve as liquid biopsy tools for screening, disease monitoring and personalized management of ocular diseases.}, }
@article {pmid41663366, year = {2026}, author = {Wang, Q and Wang, Y and Chen, L and Huang, J and Cai, T and Lin, Y and Liu, J and Liu, J and Zhu, J and Li, R and Luo, D and Ding, X}, title = {Extraocular delivery of bioswitchable tri-miR-22-loaded tetrahedral DNA nanostructures for intraocular neovascular and neurodegenerative repair.}, journal = {Signal transduction and targeted therapy}, volume = {11}, number = {1}, pages = {50}, pmid = {41663366}, issn = {2059-3635}, support = {82271092//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2024A03J0171//Guangzhou Municipal Science and Technology Project/ ; }, mesh = {Animals ; Humans ; *MicroRNAs/genetics/pharmacology/chemistry/administration &amp; dosage ; Mice ; Human Umbilical Vein Endothelial Cells ; *Nanostructures/chemistry/administration &amp; dosage ; *DNA/chemistry/genetics/pharmacology ; *Choroidal Neovascularization/genetics/pathology/drug therapy/therapy ; *Diabetic Retinopathy/genetics/pathology/drug therapy/therapy ; *Macular Degeneration/genetics/pathology/drug therapy/therapy ; *Retinal Neovascularization/genetics/pathology ; }, abstract = {Ocular neovascular and neurodegenerative diseases, such as diabetic retinopathy and age-related macular degeneration, are characterized by abnormal angiogenesis, vascular leakage, and progressive retinal neurodegeneration, ultimately leading to irreversible vision loss. Here, we present a tetrahedral framework DNA-based bioswitchable Tri-miR-22 mimic delivery system (BiRDS), which is specifically engineered for extraocular administration. In vitro, BiRDS can penetrate the cell membrane within 24 h and accumulate extensively in the cytoplasm. Through transscleral-choroidal-retinal penetration, BiRDS achieves robust delivery to the choroid and retina within 18 h without the need for intravitreal injection in mice. The BiRDS can effectively inhibit the proliferation, tube formation and migration abilities of human umbilical vein endothelial cells. In murine models of choroidal neovascularization and oxygen-induced retinopathy, BiRDS not only suppresses retinal pathological neovascularization with efficacy comparable to that of current anti-VEGF agents, but also possesses unique effects that current agents lack, such as improved retinal perfusion and preserved neuronal integrity, thereby contributing to the protection of visual function. Furthermore, transcriptomic profiling and molecular validation revealed that BiRDS exerts its therapeutic efficacy by inhibiting the Wnt/β-catenin pathway, a key driver of mediating the aforementioned pathological processes. This study highlights BiRDS as a next-generation RNA nanotherapy with broad clinical potential, offering site specific, multitargeted modulation via a minimally invasive and patient-friendly route.}, }
@article {pmid41663777, year = {2026}, author = {El-Darzi, N and Dorweiler, TF and Mast, N and Busik, J and Pikuleva, IA}, title = {Retinal phenotype of APOB100 transgenic mice on a Western diet with human-like hyperlipidemia and cholesterol crystals in the retina and choroid.}, journal = {Lab animal}, volume = {55}, number = {3}, pages = {83-94}, pmid = {41663777}, issn = {1548-4475}, support = {EY018383//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; P30 EY011373/EY/NEI NIH HHS/United States ; EY011373//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01 EY018383/EY/NEI NIH HHS/United States ; EY025383//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; }, mesh = {Animals ; *Apolipoprotein B-100/genetics/metabolism ; *Cholesterol/metabolism ; Mice, Transgenic ; *Diet, Western/adverse effects ; *Hyperlipidemias/metabolism ; *Choroid/metabolism/pathology ; *Retina/metabolism/pathology ; Mice ; *Macular Degeneration/metabolism/etiology ; Humans ; Phenotype ; Mice, Inbred C57BL ; Male ; }, abstract = {Drusen and subretinal drusenoid deposits, the pathognomonic lesions for age-related macular degeneration (AMD), are rich in cholesterol. Yet, AMD is not consistently linked to plasma lipids. Here wild-type and human apolipoprotein B100-expressing (APOB100) mice were put on a Western type of diet for 13 months and then assessed for plasma lipid profile, high-density lipoprotein (HDL) heterogeneity, status of intraretinal and choroidal vasculatures, retinal structure, function, levels of cholesterol and other sterols, lipid and cholesterol distribution and expression of cholesterol-related genes. The dietary effects were more pronounced in APOB100 mice, which had human-like hyperlipidemia and different subpopulations of HDL3, than in wild-type mice. In addition, the APOB100 retina showed increased cholesterol input from the systemic circulation, higher cholesterol content, more cholesterol crystals, elevated expression of HDL-related genes, lipid accumulation in the retinal pigment epithelium and Bruch's membrane, and impaired function compared with the wild-type retina. Remarkably, in both genotypes, cholesterol crystals were detected in the choroid, piercing toward Bruch's membrane and leading to macrophage infiltration. Our data indicate how plasma lipid profile could be linked to AMD and that cholesterol crystals in the choroid should be further investigated as contributors to AMD development and progression.}, }
@article {pmid41664225, year = {2026}, author = {Saito, M and Imaizumi, K}, title = {One-year results of the intravitreal administration of faricimab in patients with naïve type 3 macular neovascularization.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {38}, pmid = {41664225}, issn = {2056-9920}, abstract = {BACKGROUND: To clarify the efficacy of the intravitreal injections of faricimab and the change in vascular morphology of retinal-retinal anastomosis (RRA) after treatment in patients with type 3 macular neovascularization (MNV).<br><br>METHODS: We retrospectively reviewed 20 consecutive eyes with treatment-naive type 3 MNV in 14 Japanese patients (mean age, 81.8 years) at different stages. All patients were treated with 3 or 4 consecutive monthly intravitreal injections of faricimab and then they were followed by a &#x201c;treat and extend, then fix&#x201d; regimen in the maintenance phase over a 12-month follow-up.<br><br>RESULTS: The mean logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA) levels improved significantly (P&#x2009;<&#x2009;0.01) from 0.87 at baseline to 0.64 at 12 months. Optical coherence tomography angiography (OCTA) findings confirmed RRA in 16 (84.2%) of the 19 eyes, except for the eye with stage 1 at baseline, and 15 (93.8%) of the 16 eyes demonstrated the presence of vascular continuity at 12 months. No progression of retinal pigment epithelium (RPE) atrophy was observed in any of the 3 eyes with RPE atrophy at baseline, and newly developed RPE atrophy was seen in 4 (23.5%) of the 17 eyes without RPE atrophy at baseline. All 20 eyes had dry macula and showed no other complications at 12 months.<br><br>CONCLUSIONS: Intravitreal faricimab injections significantly improved VA, achieved dry macula, and nearly normalized the vessels on the RRA in most patients with type 3 MNV during the 12-month study period.}, }
@article {pmid41664540, year = {2026}, author = {da Silva, CN and Inoue, TT and França Dias, M and Fialho, SL and Silva-Cunha, A}, title = {Intravitreal implants for drug delivery: clinical efficacy, safety, and translational perspectives.}, journal = {Expert opinion on drug delivery}, volume = {}, number = {}, pages = {1-19}, doi = {10.1080/17425247.2026.2629545}, pmid = {41664540}, issn = {1744-7593}, abstract = {INTRODUCTION: Chronic retinal disorders such as age-related macular degeneration, diabetic macular edema, retinal vein occlusion, and noninfectious uveitis are among the leading causes of irreversible visual loss worldwide. Their management depends on repeated intravitreal injections of anti-VEGF agents or corticosteroids, which, despite proven efficacy, are associated with high treatment burden and cumulative risks. Sustained-release intravitreal drug delivery systems (DDSs) are effective strategies to prolong therapeutic activity, enhance bioavailability, minimize adverse events, and improve patient adherence.<br><br>AREAS COVERED: This review provides an overview of the evolution, clinical efficacy, and translational potential of intravitreal DDSs, from nonbiodegradable implants to biodegradable systems. Advances in polymeric design, hydrogels, in situ forming systems, and 3D-printed architecture, are discussed alongside emerging clinical candidates. Key formulation, preclinical, and regulatory barriers to clinical translation are also examined. Comprehensive search on PubMed, Scopus, Web of Science, ClinicalTrials.gov, and regulatory repositories was performed (data published up to December 2025).<br><br>EXPERT OPINION: Intravitreal DDSs are redefining ocular pharmacotherapy by offering prolonged, localized drug release. However, further innovation in polymer design, bioerodible materials, and sterilization methods is essential to balance safety, efficacy, and manufacturability. Integration of precision medicine and next-generation biomaterials will be key to achieving fully optimized, minimally invasive retinal therapies.}, }
@article {pmid41665064, year = {2026}, author = {Tunon-Robinson, I and Zhang, R and Nguyen, AK}, title = {Visual Acuity Outcomes Following Intravitreal Biological Drug-Induced Retinal Vasculitis: An Intelligent Research in Sight Registry Retrospective Exploratory Analysis.}, journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics}, volume = {}, number = {}, pages = {10807683251412321}, doi = {10.1177/10807683251412321}, pmid = {41665064}, issn = {1557-7732}, abstract = {PURPOSE: This retrospective exploratory study examines the visual acuity outcomes following a retinal vasculitis (RV) event possibly associated with intravitreal (IVT) biological drugs using a large ophthalmic registry, to gain a better understanding of RV's impact on vision in real-world clinical settings.<br><br>METHODS: An ophthalmic registry was used in a retrospective exploratory analysis and focused on subjects who received IVT anti-VEGF and anticomplement therapies. We excluded eyes with RV in the visual acuity analysis that had received more than one IVT biological drug within 2 months before the diagnosis of RV to increase confidence that a single biological drug was possibly associated with the RV event.<br><br>RESULTS: A total of 1,998,399 subjects received IVT injections of biological drugs, and 2,115 subjects were diagnosed with RV in at least 1 eye. A total of 436 subjects (531 eyes total) were coded as having RV. There was a 78% increase in eyes that became legally blind (&#x2264;20/200 Snellen equivalent) and 46% increase in eyes reading 0 letters (&#x2264;count fingers vision) following the RV event.<br><br>CONCLUSIONS: In the real world, the number of legally blind eyes substantially increased following the RV diagnosis. Given the retrospective and exploratory nature of this study, all interpretations should be made cautiously, including any suggested association between biological therapy and the occurrence of RV, and prospective studies are necessary to confirm these associations. Further research is indicated to improve the safety of biological therapies for retinal diseases and minimize the risk of serious complications such as RV.}, }
@article {pmid41665215, year = {2026}, author = {Argun, M and Nazıroğlu, M}, title = {Selenium Nanoparticles Protect Retinal Pigment Epithelial Cells Against Experimental Age-Related Macular Degeneration-Induced Mitochondrial Oxidative Toxicity and Apoptosis Through the Modulation of the TRPM2 Channel.}, journal = {Journal of biochemical and molecular toxicology}, volume = {40}, number = {2}, pages = {e70738}, doi = {10.1002/jbt.70738}, pmid = {41665215}, issn = {1099-0461}, support = {//BSN Health, Analyses, Innovation, Consultancy, Organization, Agriculture, Industry LTD, Isparta, T&#xfc;rkiye/ ; }, mesh = {*TRPM Cation Channels/metabolism ; Humans ; *Macular Degeneration/metabolism/pathology/prevention &amp; control/drug therapy ; *Apoptosis/drug effects ; *Selenium/pharmacology/chemistry ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; *Mitochondria/metabolism/pathology/drug effects ; *Oxidative Stress/drug effects ; Cell Line ; *Nanoparticles/chemistry ; }, abstract = {Excessive Ca[2+] influx leads to mitochondrial oxidative injury and cell death, contributing to the development of age-related macular degeneration (AMD). The protective role of selenium nanoparticle (SeNPs), through inhibition of ADP-ribose- and hydrogen peroxide (H2O2)-induced TRPM2 cation channel stimulation, was recently reported in human retinal pigment epithelial 19 (ARPE-19) cells for hypoxia-induced oxidative cytotoxicity and cell death, but not for AMD. We aimed to investigate the protective effects of SeNPs through inhibition of TRPM2 on AMD (sodium iodate [NaI])-induced oxidative injury, cell death, and apoptosis in ARPE-19 cells. The ARPE-19 cells were divided into four main groups: control (CNT), SeNPs (2.5 μg/mL for 24 h), AMD (10 mM NaI for 24 h) and AMD + SeNPs. The AMD treatment increased TRPM2 current density and cytosolic Ca[2+] and Zn[2+] fluorescence intensities, as well as the percentage of cell death. It also elevated apoptotic markers (caspases 3, 8, and 9) and oxidative stress markers (mitochondrial membrane dysfunction, oxygen free radicals, and lipid peroxidation), while decreasing antioxidants (glutathione and glutathione peroxidase), cell viability and the number of live cells. TRPM2 stimulation further increased these markers. When SeNPs and TRPM2 antagonists were used to treat the AMD-induced increase in TRPM2 activation, they increased antioxidants and cell viability while decreasing oxidative stress and cell death markers. In conclusion, SeNP treatment reduced AMD-induced mitochondrial oxidative cytotoxicity and cell death by inhibiting TRPM2-mediated Ca[2+] signaling. SeNP represents a potential therapeutic option for AMD-induced retinal disorders linked to abnormal oxygen free radical production and Ca[2+] influx.}, }
@article {pmid41666372, year = {2026}, author = {Kim, E and Song, SJ}, title = {FOCAL CHOROIDAL EXCAVATIONS IN A SCREENING COHORT: FUNDUS VISIBILITY AND STRUCTURAL REMODELING IN YOUNGER ADULTS.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004796}, pmid = {41666372}, issn = {1539-2864}, abstract = {PURPOSE: To determine how fundus visibility relates to optical coherence tomography (OCT)-derived morphologic and topographic features of focal choroidal excavation (FCE) and to evaluate systemic and ocular associations in a health-screening cohort.<br><br>METHODS: We analyzed 19,048 individuals undergoing health examinations with spectral-domain OCT and fundus photography. FCEs were classified as fundus-visible or fundus-invisible. A 1:2 propensity score matching (age/sex) was performed to compare participants with FCE against non-FCE controls. Generalized estimating equations were used to analyze lesion characteristics, systemic comorbidities, and ocular parameters including intraocular pressure (IOP), choroidal thickness, and macular degeneration.<br><br>RESULTS: We identified 252 FCE lesions in 192 participants (1.0%). Compared to matched controls, the FCE group showed no significant differences in systemic comorbidities but had significantly lower IOP (P = 0.026), greater choroidal thickness (P < 0.001), and a higher prevalence of macular degeneration (P = 0.002). Among FCEs, fundus-visible lesions had greater median horizontal diameter (681.0 vs 518.0 &#xb5;m; P < 0.001) and depth (69.5 vs 45.0 &#xb5;m; P < 0.001), were located closer to the fovea (611.5 vs 1385.0 &#xb5;m; P < 0.001), and exhibited higher rates of steep slopes (62.5% vs 42.7%; P = 0.002) and outer nuclear layer thickening (61.7% vs 31.5%; P < 0.001) compared to fundus-invisible lesions.<br><br>CONCLUSION: FCE is associated with distinct ocular profiles, including lower IOP and increased choroidal thickness, independent of systemic risk factors. Fundus visibility indicates larger, deeper, and paramacular lesions with specific structural alterations, underscoring the need to recognize subtle fundoscopic irregularities for early OCT detection.}, }
@article {pmid41667492, year = {2026}, author = {Huang, W and Qin, L and Xu, M and Zheng, H and Gan, Y and Pei, S and Wu, R and Liu, Y and Zhong, J and Ni, G}, title = {Comprehensive 3D Optical Coherence Tomography Dataset for AMD and DME: Facilitating Deep-Learning-Based 3D Segmentation.}, journal = {Scientific data}, volume = {13}, number = {1}, pages = {224}, pmid = {41667492}, issn = {2052-4463}, support = {61905036//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2021T140090, 2019M663465//China Postdoctoral Science Foundation/ ; }, mesh = {*Tomography, Optical Coherence ; *Deep Learning ; *Macular Degeneration/diagnostic imaging ; Humans ; *Imaging, Three-Dimensional ; *Macular Edema/diagnostic imaging ; *Diabetic Retinopathy/diagnostic imaging ; }, abstract = {Age-related macular degeneration (AMD) and diabetic macular edema (DME) are vision-threatening pathologies for which optical coherence tomography (OCT) provides high-resolution three-dimensional imaging, facilitating comprehensive diagnostic evaluation. Three-dimensional (3D) visualization and precise 3D segmentation of lesions enable accurate assessment of morphology, dimensions, and spatial relationships, thereby enhancing clinical analysis and disease management. However, the lack of a 3D dataset for AMD and DME significantly limits the reliability, robustness, and applicability of deep learning-based 3D segmentation techniques in this field. Here, we present an OCT dataset comprising 224 volumetric images, including 122 for AMD and 102 for DME, annotated with pigment epithelial detachment and intraretinal fluid. We propose a novel 3D segmentation network based on the BiFormer Block, which employs Bi-Level Routing Attention to capture local context and long-range dependencies. Experiments demonstrated that the proposed dataset and network will facilitate the exploration and validation of novel 3D segmentation methods for AMD and DME.}, }
@article {pmid41667658, year = {2026}, author = {Shah, J and Gerendás, L and Serhan, H and Ahmed, H and Festok, M and Mahrous, MA and Kovacs, KD and Kiss, S}, title = {Association between PCSK9 inhibitor use and risk of age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {40}, number = {5}, pages = {739-740}, pmid = {41667658}, issn = {1476-5454}, }
@article {pmid41667660, year = {2026}, author = {Sadeghi, E and Gandhi, P and Davis, E and Singh, SR and Ibrahim, MN and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Eller, AW and Chhablani, J}, title = {Three-dimensional choroidal vessels assessment in age-related macular degeneration: a follow-up study.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41667660}, issn = {1476-5454}, abstract = {PURPOSE: This study evaluated longitudinal choroidal vascular changes in dry age-related macular degeneration (dAMD) eyes using a three-dimensional (3D) algorithm.<br><br>METHODS: Patients underwent swept-source optical coherence tomography during two follow-up visits. Choroidal boundaries and vessels were segmented using the ResUNet model and Phansalkar thresholding. 3D choroidal maps were created and divided into five sectors. Mean choroidal vessel diameter (MChVD), inter-vessel distance (IVD), volumetric choroidal thickness (ChT), and choroidal vascularity index (CVI) were measured in both visits.<br><br>RESULTS: This retrospective cohort study included 30 eyes with AMD. The mean age was 72.8&#x2009;&#xb1;&#x2009;9.55 years. The mean follow-up duration was 11.6&#x2009;&#xb1;&#x2009;5.02 months. The mean MChVD increased 16.4&#x2009;&#xb5;m (6.8%) over time (239.2&#x2009;&#xb1;&#x2009;19.8 to 255.6&#x2009;&#xb1;&#x2009;28.2&#x2009;&#xb5;m, P&#x2009;=&#x2009;0.003), particularly in the nasal and temporal sectors (P&#x2009;<&#x2009;0.05). The mean IVD increased 21.8&#x2009;&#xb5;m (10.8%) over time (201.8&#x2009;&#xb1;&#x2009;29.0 to 223.7&#x2009;&#xb1;&#x2009;38.2&#x2009;&#xb5;m, P&#x2009;=&#x2009;0.009), which was significant in the nasal, temporal, and superior sectors (P&#x2009;<&#x2009;0.05). The ChT showed a decreasing trend, though not statistically significant (190.7&#x2009;&#xb1;&#x2009;58.0 to 183.4&#x2009;&#xb1;&#x2009;56.8&#x2009;&#xb5;m, P&#x2009;=&#x2009;0.051). The CVI remained stable during follow-up (0.358&#x2009;&#xb1;&#x2009;0.034 vs. 0.357&#x2009;&#xb1;&#x2009;0.040, P&#x2009;=&#x2009;0.933). MChVD positively correlated with the IVD (r&#x2009;=&#x2009;+0.501, P&#x2009;=&#x2009;0.005). ChT exhibited a negative correlation with IVD (r&#x2009;=&#x2009;-0.426, P&#x2009;=&#x2009;0.019).<br><br>CONCLUSION: Eyes with dry AMD showed increased MChVD and IVD along with decreased ChT, and we hypothesise that these changes may reflect progressive small-vessel atrophy accompanied by compensatory dilation of larger choroidal vessels during follow-up.}, }
@article {pmid41669763, year = {2026}, author = {Venkatesh, R and Biradar, P and Malwe, G and Prabhu, V and Hande, P and Kathare, R and Raj, P and Roy, R and Yadav, NK and Jayadev, C}, title = {Anti-VEGF safety in evolution: A comprehensive review of ocular and systemic considerations.}, journal = {Indian journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.4103/IJO.IJO_3284_25}, pmid = {41669763}, issn = {1998-3689}, abstract = {Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has transformed the management of retinal and choroidal vascular diseases, delivering substantial and sustained visual benefits across neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. As treatment paradigms have evolved toward chronic, often lifelong therapy with repeated injections, attention has increasingly shifted from short-term procedural safety to a broader evaluation of ocular and systemic adverse events. Among these, intraocular inflammation (IOI) has emerged as the most debated ocular safety signal, ranging from mild, self-limited sterile inflammation to rare but vision-threatening occlusive retinal vasculitis. At the same time, systemic adverse events remain biologically plausible yet uncommon in the general population. This review provides a contemporary, clinically oriented synthesis of anti-VEGF safety, emphasizing that IOI and systemic events are not uniform drug effects but reflect complex interactions among drug-specific properties, delivery factors, disease substrate, patient susceptibility, and immunogenicity. We outline a mechanistic framework distinguishing acute sterile inflammation driven by innate immune activation from delayed vasculitic phenotypes associated with adaptive immune responses and anti-drug antibodies. A structured five-pillar susceptibility model is proposed to contextualize risk modifiers, alongside phenotype-driven management and prevention strategies. Systemic safety considerations are reviewed with attention to agent-specific pharmacokinetics, high-risk patient phenotypes, and cumulative exposure. By integrating mechanistic insights with clinical phenotyping, risk stratification, and preventive strategies, this review aims to support informed, individualized decision-making. A balanced, prevention-focused approach enables clinicians to preserve the transformative benefits of anti-VEGF therapy while maintaining a high standard of long-term ocular and systemic safety.}, }
@article {pmid41669765, year = {2026}, author = {Liu, W and Li, W and Wang, D and Wu, P and Jiang, J and Liu, Z and Chen, X}, title = {Ferroptosis in retinal pigment epithelial cells: Current status and future developments.}, journal = {Indian journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.4103/IJO.IJO_2875_25}, pmid = {41669765}, issn = {1998-3689}, abstract = {Retinal pigment epithelial (RPE) cells play a crucial role in maintaining the normal function of the retina. In recent years, research on ferroptosis-a novel iron-dependent form of cell death-in RPE cells has gradually attracted attention. This article reviews the mechanisms of ferroptosis in RPE cells, including iron metabolism imbalance, lipid peroxidation, and functional impairment of the glutathione-glutathione peroxidase 4 (GSH-GPX4) system. It explores the association between ferroptosis in RPE cells and retinal diseases such as age-related macular degeneration and Stargardt disease. Additionally, it analyzes the future challenges in current research on ferroptosis in RPE cells, such as gaining in-depth understanding of complex regulatory networks and developing precise intervention strategies, so as to provide new insights and directions for the prevention and treatment of retinal diseases.}, }
@article {pmid41670698, year = {2026}, author = {Hashiya, N and Maruko, I and Maruko, R and Kakehashi, M and Kawahara, K and Nishihara, S and Iida, T}, title = {Increased intraocular pressure immediately after aflibercept 8 mg intravitreal injection for neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41670698}, issn = {1435-702X}, }
@article {pmid41671246, year = {2026}, author = {Zeng, J and Shang, W and Ren, P and Ke, X and Zhao, Y and Liu, G and Liu, J and Lu, F and Jiang, X}, title = {Expression of aqueous cytokines and their correlation with retinal morphological biomarkers in nAMD patients.}, journal = {PloS one}, volume = {21}, number = {2}, pages = {e0342259}, pmid = {41671246}, issn = {1932-6203}, mesh = {Humans ; Female ; Male ; *Aqueous Humor/metabolism ; *Cytokines/metabolism ; Biomarkers/metabolism ; Aged ; Middle Aged ; *Retina/pathology/metabolism ; Tomography, Optical Coherence ; *Macular Degeneration/metabolism/pathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Cataract/metabolism ; }, abstract = {OBJECTIVE: Neovascular age-related macular degeneration (nAMD) is characterized by pathological neovascularization in the macula, leading to irreversible central vision loss. This study aimed to evaluate cytokine profiles in the aqueous humor of nAMD patients and explore correlation between specific cytokines, clinical characteristics, and retinal morphological features.<br><br>METHODS: Our protocol was registered on Chinese Clinical Trial Registry (ChiCTR) under registration number ChiCTR2500106190 and approved by the Biomedical Research Ethics Committee of West China Hospital, Sichuan University (ID: 20231375). A total of 94 patients with nAMD and 34 cataract patients as the control group were enrolled. Aqueous humor samples were collected before anti-VEGF treatment or cataract surgery, and analyzed using cytometric bead array (CBA) for cytokines (MCP-1, ICAM-1, VCAM-1, CA-1, &#x3b2;-FGF, PPK/PK, and VEGF). Retinal structural biomarkers were assessed using optical coherence tomography (OCT), with statistical analysis performed to evaluate correlations between cytokine levels and retinal morphology.<br><br>RESULTS: Compared to cataract patients, nAMD patients exhibited elevated levels of CA-1, PPK/PK, ICAM-1, VCAM-1, and MCP-1 (P&#x2009;<&#x2009;0.05). Baseline best-corrected visual acuity (BCVA) was reduced in nAMD patients with intraretinal fluid (IRF) or pigmentation compared to those without (P&#x2009;<&#x2009;0.05). Visit BCVA also deteriorated in patients with fibrosis (P&#x2009;<&#x2009;0.05). Additionally, central foveal thickness (CTR) was significantly thinner in patients with PED or SRF (P&#x2009;<&#x2009;0.05). Visit BCVA demonstrated positive correlations with baseline BCVA (r&#x2009;=&#x2009;0.689, P&#x2009;<&#x2009;0.001). In contrast, the presence of fibrosis and elevated MCP-1 concentration was associated with a poorer visual outcome. In correlation analysis, &#x3b2;-FGF exhibited a negative correlation with CA-1, PPK, ICAM-1. VCAM-1 and MCP-1.<br><br>CONCLUSION: In this cross-sectional study, the presence of IRF was significantly associated with reduced BCVA in nAMD patients. Baseline BCVA emerged as a critical predictor of visual prognosis in nAMD. Notably, retinal fibrosis development and elevated MCP-1 level linked to worse clinical outcomes, underscoring their potential as therapeutic targets. While recent anti-VEGF injections decreased VEGF levels in aqueous humor of nAMD patients, the impact of these agents on other cytokines remain unclear, suggesting a need for adjunct therapies to address multifaceted pathogenic pathways.}, }
@article {pmid41672305, year = {2026}, author = {Li, HL and Xu, Y and Mo, JS and Zhao, XY and Zhong, CL and Jia, ZW and Wang, XL and Zhao, BC and Chen, YM and Zheng, KW and Zhang, XL and Wang, QP}, title = {Single intravitreal injection of lipid nanoparticles delivering circular mRNA of nicotinamide phosphoribosyltransferase protects against dry AMD.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {392}, number = {}, pages = {114691}, doi = {10.1016/j.jconrel.2026.114691}, pmid = {41672305}, issn = {1873-4995}, mesh = {*Nicotinamide Phosphoribosyltransferase/genetics/administration &amp; dosage ; Animals ; *RNA, Circular/administration &amp; dosage ; *Nanoparticles/administration &amp; dosage/chemistry ; Intravitreal Injections ; Humans ; *Macular Degeneration/prevention &amp; control ; Mice, Inbred C57BL ; NAD/metabolism ; Male ; Mice ; *RNA, Messenger/administration &amp; dosage ; Lipids/chemistry ; Liposomes ; }, abstract = {Age-related nicotinamide adenine dinucleotide (NAD[+]) deficiency is implicated in numerous pathologies, including dry age-related macular degeneration (AMD). Current NAD[+]-boosting strategies, reliant on precursors like nicotinamide mononucleotide (NMN), necessitate repeated dosing and offer transient effects, limiting therapeutic utility. Here, we address this critical limitation by developing a single-dose therapy using circular mRNA (circ-mRNA) to deliver functional nicotinamide phosphoribosyl transferase (NAMPT), the essential rate-limiting enzyme in NAD[+] salvage. Engineered via permuted intron-exon (PIE) splicing, our circNAMPT exploits the exceptional stability and persistent translation capacity inherent to circular RNA scaffolds. Encapsulation in β-sitosterol-optimized lipid nanoparticles (LNPs) ensures robust intracellular delivery. In vitro, circNAMPT-LNP drives sustained NAMPT expression and prolonged NAD[+] elevation, circumventing precursor limitations. In a stringent sodium iodate-induced dry AMD model, a single intravitreal circNAMPT-LNP injection matched the neuroprotective efficacy of 14 consecutive daily intraperitoneal NMN doses confirmed by histological integrity and functional preservation. This work establishes engineered circ-mRNAs as a transformative platform for durable, single-dose therapeutic protein delivery and demonstrates potential as a disease-modifying therapy for dry AMD. Its applicability extends broadly to systemic disorders driven by NAD[+] deficiency in aging.}, }
@article {pmid41673898, year = {2026}, author = {Licht, A and Mavris, Y and Latz, C and Schuster, AK and Ponto, KA and Mirshahi, A}, title = {Lost to follow-up while undergoing intravitreal injection therapy: barriers to adherence in a real-world setting.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {}, pmid = {41673898}, issn = {2056-9920}, abstract = {BACKGROUND: Intravitreal anti‑VEGF therapy is effective, yet real‑world outcomes are limited by non persistence. We investigated patient‑reported reasons for discontinuation under pro-re-nata therapy protocol.<br><br>METHODS: This ambispective real-world study at a German eye hospital evaluated patients receiving intravitreal therapy for diabetic macular edema (DME), retinal vein occlusion (RVO), or neovascular age related macular degeneration (nAMD) using the pro re nata (PRN) protocol. Patient records were reviewed, and those meeting lost to follow up (LTFU) criteria (no injections or visits within 3&#x2009;months) were contacted via written letter and phone. When patients were reached surveys to assess reasons for LTFU, perceived treatment burden, mobility, and comorbidities were completed.<br><br>RESULTS: Of 657 cases, 347 (52.8%) met the LTFU- criteria, 25 of which were medically indicated. Despite multiple attempts, contact and data collection was successful for only 39 patients (response rate: 12%), major part was unwilling or unable to participate. The most common reasons for discontinuation were subjective lack of treatment need (56%), perception of being &#x201c;fully treated&#x201d; (33%), fear of injections (26%), travel difficulties (28%), and time burden (15%). Despite these barriers, 52% of patients reported that the treatment was &#x201c;not burdensome at all,&#x201d; while 3 patients (8%) continued therapy elsewhere.<br><br>CONCLUSIONS: In this exploratory, single-centre cohort, a significant portion of patients had effectively disengaged from IVI care and were unreceptive to delayed outreach. Outcome-related perceptions and organizational hurdles were key, actionable barriers. Future strategies to improve adherence should focus on proactive follow-ups shortly after therapy discontinuation.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40942-026-00808-3.}, }
@article {pmid41674610, year = {2026}, author = {Hoshi, S and Wang, X and Kadomoto, S and Liu, R and Ip, M and Sadda, SR and Sarraf, D and Zhang, Y}, title = {Early Photoreceptor Disruption in Emerging Subretinal Drusenoid Deposits Detected by Adaptive Optics Imaging.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.28.26344907}, pmid = {41674610}, abstract = {PURPOSE: Subretinal drusenoid deposits (SDDs) are a distinct entity in age-related macular degeneration (AMD) and associated with photoreceptor impairment during progression. Their early impact on photoreceptors remains incompletely understood. This study examined photoreceptor reflectivity during the phase when SDDs were not clinically detectable on optical coherence tomography (OCT) using adaptive optics scanning laser ophthalmoscopy (AOSLO).<br><br>DESIGN: Longitudinal observational study.<br><br>PARTICIPANTS: Patients with intermediate AMD.<br><br>METHODS: Six eyes of four patients with intermediate AMD and predominantly SDDs underwent multimodal imaging 3-4 times over 3.5 years. Individual SDDs were graded using an OCT-based 3-stage system at each time point. Cross-sectional retinal structure and photoreceptor reflectivity at the location where the new SDDs developed during follow-up were evaluated using OCT and AOSLO.<br><br>MAIN OUTCOME MEASURES: Photoreceptor reflectivity change prior to and during SDD development.<br><br>RESULTS: Forty-eight retinal locations where new dot-type SDDs developed during follow-up were identified. AOSLO revealed reduced photoreceptor reflectivity in these regions before OCT demonstrated clinically evident deposits (stage &#x2265; 1) between the ellipsoid zone and the retinal pigment epithelium at the corresponding sites. The mean time to development of stage 1, stage 2, and stage 3 SDDs was 11.78 &#xb1; 5.01, 17.40 &#xb1; 6.08, and 18.72 &#xb1; 4.08 months, respectively.<br><br>CONCLUSIONS: High-resolution adaptive optics confocal imaging enables detection of photoreceptor optical property alterations at a stage when SDDs are not yet evident on OCT. This finding underscores the exceptional sensitivity of photoreceptors to minimal structural or functional perturbations during SDD formation and defines an early window for potential intervention.}, }
@article {pmid41674807, year = {2026}, author = {Wu, E and Du, K and Thomas, T and Shin, C and Jiang, J and Navidzadeh, J and Hasan, N and Yao, J and Zhang, M and Sahel, J and Chhablani, J}, title = {Neoplasms Associated with the Onset of Age-Related Macular Degeneration: A Case-Control Study Using the All of Us Cohort.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {41674807}, issn = {2693-5015}, support = {OT2 OD026556/OD/NIH HHS/United States ; U2C OD023196/OD/NIH HHS/United States ; OT2 OD025315/OD/NIH HHS/United States ; OT2 OD026551/OD/NIH HHS/United States ; U24 OD023121/OD/NIH HHS/United States ; OT2 OD026552/OD/NIH HHS/United States ; OT2 OD026549/OD/NIH HHS/United States ; OT2 OD025337/OD/NIH HHS/United States ; OT2 OD025277/OD/NIH HHS/United States ; OT2 OD026555/OD/NIH HHS/United States ; OT2 OD026550/OD/NIH HHS/United States ; OT2 OD026553/OD/NIH HHS/United States ; OT2 OD025276/OD/NIH HHS/United States ; OT2 OD026557/OD/NIH HHS/United States ; OT2 OD026554/OD/NIH HHS/United States ; U24 OD023163/OD/NIH HHS/United States ; OT2 OD023206/OD/NIH HHS/United States ; U24 OD023176/OD/NIH HHS/United States ; OT2 OD026548/OD/NIH HHS/United States ; OT2 OD023205/OD/NIH HHS/United States ; T32 GM144300/GM/NIGMS NIH HHS/United States ; }, abstract = {PURPOSE: This study investigated the association between prior diagnoses of neoplasms and the onset of age-related macular degeneration (AMD).<br><br>METHODS: A retrospective case-control study was conducted using health records from 2 724 individuals in the All of Us Program, a longitudinal cohort of U.S. adults. Odds ratios (OR) and Fisher's exact tests were used to evaluate associations between neoplasms and AMD in a matched cohort. Kaplan-Meier survival analysis assessed how neoplasms affected time to AMD onset.<br><br>RESULTS: Benign neoplasms of the colon (OR: 1.90, 95% CI: 1.55-2.33), skin (OR: 1.46, 95% CI: 1.16-1.84), and rectum (OR: 2.90, 95% CI: 1.53-5.48) showing the strongest and statistically significant associations with AMD. Patients with these benign neoplasms also developed AMD earlier. Although malignant neoplasms of skin of face (OR: 1.97, 95% CI: 1.11-3.49), prostate (OR: 1.47, 95% CI: 0.98-2.22), and breast (OR: 1.39, 95% CI: 0.95-2.02) were also more frequent in AMD patients, these associations were not as significant.<br><br>CONCLUSION: Insights into the associations between neoplasms and earlier AMD onset may help ophthalmologists identify at-risk patients and enable earlier intervention. These findings suggest shared pathophysiological mechanisms, such as chronic inflammation and vascular dysfunction, may contribute to both tumour formation and AMD development.}, }
@article {pmid41675446, year = {2026}, author = {Yavari, N and Gupta, AS and Mitsios, A and Hung, JH and El-Feky, D and Nguyen, CD and Yasar, C and Anover, FA and Saengsirinavin, AO and Mobasserian, A and Akhavanrezayat, A and Elaraby, O and Zhang, X and Than, NTT and Toth, AB and Agarwal, D and Lin, J and Or, C and Nguyen, QD}, title = {Bilateral hemorrhagic occlusive retinal vasculitis and panuveitis following intravitreal faricimab injection: A clinicopathologic case study.}, journal = {American journal of ophthalmology case reports}, volume = {41}, number = {}, pages = {102532}, pmid = {41675446}, issn = {2451-9936}, abstract = {PURPOSE: To describe the clinicopathological study of severe bilateral intraocular inflammation following intravitreal (IVT) injection of faricimab in a patient with neovascular age-related macular degeneration (nAMD).<br><br>OBSERVATION: An 80-year-old Caucasian female with bilateral nAMD presented with blurry vision and ocular pain after receiving bilateral IVT injections of faricimab on separate days from different lots. The patient experienced significant reduction in her visual acuity, from 20/40 to counting-fingers in the right eye and from 20/50 to hand-motion in the left eye; intraocular pressure (IOP) was elevated in both eyes at 48&#xa0;mmHg and 49&#xa0;mmHg. Anterior segment examination revealed bilateral diffuse mutton-fat keratic precipitates and fundus examination revealed bilateral vitreous opacities. Fluorescein angiography demonstrated optic disc leakage and bilateral hemorrhagic occlusive vasculitis. Following initial management with systemic corticosteroid, a subsequent unilateral subconjunctival dexamethasone implant, and pars plana vitrectomy, ocular inflammation subsided significantly along with the normalization of IOP. Cytology examination of vitreous samples showed the presence of chronic inflammatory cells in the vitreous.<br><br>CONCLUSION: The case highlights the clinical presentation, detailed findings, and successful treatment strategy for hemorrhagic occlusive retinal vasculitis and panuveitis induced by IVT injection of faricimab. Cytopathology analysis of vitreous samples provides novel insights regarding inflammatory mechanisms underlying this rare but potentially sight-threatening complication.}, }
@article {pmid41675764, year = {2026}, author = {Habib, E and Hajj, F}, title = {ROFI: a deep learning-based ophthalmic sign-preserving and reversible patient face anonymizer.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {2}, pages = {2116-2117}, pmid = {41675764}, issn = {2049-0801}, abstract = {Ophthalmic diseases such as diabetic retinopathy, glaucoma, age-related macular degeneration, and inherited retinal dystrophies remain leading causes of visual impairment worldwide, necessitating accurate diagnosis and longitudinal monitoring. Modern ophthalmology increasingly relies on facial and ocular imaging, yet the integration of artificial intelligence (AI) into these workflows raises significant privacy concerns. ROFI (Reversible Ophthalmic Face Image anonymizer) is a novel deep learning-based framework designed to anonymize patient facial features while preserving ophthalmic signs essential for diagnosis. By employing weakly supervised learning and neural identity translation, ROFI achieves high accuracy in retaining ocular disease markers while ensuring reversibility for authorized clinical review. Comparative studies demonstrate that anonymized images maintain diagnostic fidelity for retinal disease classification, while AI-based intraoperative guidance systems further enhance surgical precision and patient safety. Despite these advances, challenges remain regarding dataset diversity, external validation, bias, and cost-effectiveness, particularly in resource-limited settings. Future strategies should emphasize multicenter validation, integration into electronic health records, and awareness campaigns to promote adoption. ROFI represents a significant step toward balancing patient privacy with diagnostic accuracy, offering a scalable solution for secure, AI-driven ophthalmic care.}, }
@article {pmid41675859, year = {2026}, author = {Habib, E and Hajj, F}, title = {Nanocarrier-based CircRNA therapeutics in inherited retinal dystrophies.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {2}, pages = {2104-2105}, pmid = {41675859}, issn = {2049-0801}, abstract = {Inherited retinal dystrophies (IRDs) are a genetically diverse group of progressive blinding disorders with limited curative options. Despite advances in gene therapy, most IRD subtypes remain untreatable due to genetic heterogeneity and delivery challenges. Circular RNAs (circRNAs), a class of stable non-coding RNAs, have emerged as novel modulators of retinal gene expression. Recent developments in nanocarrier technology enable targeted delivery of circRNA mimics and inhibitors to retinal tissues, offering a promising therapeutic alternative. These platforms utilize lipid nanoparticles, polymeric micelles, and exosomes to bypass the blood-retinal barrier and enhance cellular uptake. Preclinical studies demonstrate restoration of photoreceptor survival pathways and delayed retinal degeneration in murine IRD models. Additionally, circRNA nanotherapy has shown efficacy in related retinal conditions such as age-related macular degeneration and diabetic retinopathy. However, translational hurdles, including invasive delivery routes, off-target effects, and regulatory gaps, limit clinical adoption. Nanocarrier-mediated circRNA modulation represents a next-generation strategy for precision therapy in IRDs, with potential to reshape the future of retinal disease management.}, }
@article {pmid41676410, year = {2025}, author = {Deng, Z and Bu, Y and Hou, T}, title = {Visual impairment and frailty: insights from genetic correlation and Mendelian randomization.}, journal = {Archives of medical science : AMS}, volume = {21}, number = {6}, pages = {2513-2521}, pmid = {41676410}, issn = {1734-1922}, abstract = {INTRODUCTION: Visual impairment (VI) is associated with frailty in observational studies, but whether this relationship is causal remains uncertain. This study aimed to investigate the genetic correlation and causal associations between genetically predicted VI and frailty using Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC).<br><br>MATERIAL AND METHODS: Genome-wide association studies provided summary data for VI subtypes (glaucoma, cataracts, diabetic retinopathy, age-related macular degeneration, hypermetropia, myopia) and frailty measures (frailty index (FI) and fried frailty score (FFS)). LDSC was used to estimate genetic correlations, and MR was conducted using inverse-variance weighted (IVW) as the primary method, supplemented by MR-Egger and weighted median. Sensitivity analyses, including radial MR, Cochran's Q test, MR-Egger intercept, and MR-PRESSO, were used to assess pleiotropy and heterogeneity.<br><br>RESULTS: Significant genetic correlations were found between VI, cataracts, age-related macular degeneration, and frailty. Suggestive correlations were identified between myopia and FI. MR analysis showed increased FI and FFS risks with other cataracts (FI: p = 0.0324; FFS: p = 0.027) and diabetic retinopathy (FI: p < 0.001; FFS: p = 0.0119). Visual disturbances were associated with increased FI risk (p = 0.0101), while age-related macular degeneration elevated FFS risk (p = 0.0251). Reverse analysis revealed that frailty also increased susceptibility to VI. No causal relationships were found for other eye diseases, and analyses showed no evidence of pleiotropy or heterogeneity.<br><br>CONCLUSIONS: This study highlights significant genetic associations and bidirectional causal relationships between VI and frailty. Future research should include multiethnic populations and larger datasets to further explore these mechanisms.}, }
@article {pmid41677389, year = {2026}, author = {Youssif, AA and Liu, P and Gaczkowski, D and Quaggin, SE and Jin, J and Thomson, BR}, title = {A Highly Active Angiopoietin 1 Mimetic Potentiates Angiogenesis in Mouse Models of Choroidal Neovascularization.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {2}, pages = {16}, pmid = {41677389}, issn = {2164-2591}, support = {P30 CA060553/CA/NCI NIH HHS/United States ; P30 DK114857/DK/NIDDK NIH HHS/United States ; R01 EY025799/EY/NEI NIH HHS/United States ; R01 EY032609/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Choroidal Neovascularization/metabolism/drug therapy/pathology ; *Angiopoietin-1/pharmacology ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; Receptor, TIE-2/metabolism ; Recombinant Fusion Proteins/pharmacology ; Angiogenesis ; }, abstract = {PURPOSE: The angiopoietin (ANGPT) pathway, comprised of the ANGPT ligands and their receptor Tie2, mediates angiogenesis and is a compelling target for neovascular age-related macular degeneration (nvAMD). Tie2 phosphorylation by ANGPT1 is associated with vascular stability and may be protective in nvAMD. In contrast, ANGPT2 potentiates angiogenesis and the bispecific ANGPT2/VEGF blocking antibody Faricimab has recently been approved for nvAMD. However, despite clear links between the ANGPT pathway and nvAMD and the success of Faricimab, poor characteristics of existing ANGPT1-based therapies have hindered their adoption as an alternate targeting strategy.<br><br>METHODS: Hepta-ANGPT1 is an ANGPT1-mimetic fusion protein with improved activity, solubility, and half-life, addressing limitations of earlier mimetics. Here we used laser-induced and RNV3 (JR5558) models of mouse choroidal neovascularization (CNV) to investigate Hepta-ANGPT1 in CNV and explore its potential as a therapy for nvAMD.<br><br>RESULTS: Hepta-ANGPT1 induced robust Tie2 phosphorylation in the choroid and did not lead to angiogenesis in healthy eyes. However, after laser CNV, we observed increased neovascularization in Hepta-ANGPT1-treated eyes, as well as increased number and size of neovascular lesions in treated RNV3 mice, indicating that Hepta-ANGPT1 potentiated angiogenesis. In contrast, CNV lesion size was smaller in Tie2 knockout mice, and no Hepta-ANGPT1-mediated increase was observed in knockout animals, confirming specificity.<br><br>CONCLUSIONS: Although previous studies have found ANGPT1 to be protective in mouse CNV, Tie2 activation is pro-angiogenic in other tissues, including the cornea and iridocorneal angle. Hepta-ANGPT1 induced a similar effect in CNV, suggesting that under certain conditions, Tie2 activation can be detrimental in this disease.<br><br>TRANSLATIONAL RELEVANCE: Understanding the contexts under which Tie2 activation is beneficial and where it is harmful will be critical to successful development of new Tie2-activating drugs for nvAMD.}, }
@article {pmid41677821, year = {2026}, author = {Christou, EE and Ivanova, T and Patton, N and Moussa, G and Kiraly, P and Huelin, FJ and MacLaren, RE and Jalil, A}, title = {A literature review of macular holes in age-related macular degeneration: insights into the pathogenesis, prognosis and surgical outcomes.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41677821}, issn = {1435-702X}, }
@article {pmid41679584, year = {2026}, author = {Saeidifard, S and Saltykova, IV and Gerner-Mauro, KN and Schill, AW and Larin, KV and Poché, RA}, title = {Brillouin microscopic assessment of retinal stiffness during reactive Müller gliosis.}, journal = {Experimental eye research}, volume = {266}, number = {}, pages = {110926}, doi = {10.1016/j.exer.2026.110926}, pmid = {41679584}, issn = {1096-0007}, mesh = {Animals ; Female ; Male ; Mice ; Elasticity ; *Ependymoglial Cells/metabolism/pathology ; *Gliosis/metabolism/pathology/physiopathology ; Mice, Inbred C57BL ; Microscopy/methods ; N-Methylaspartate ; *Retina/metabolism/pathology/physiopathology ; Cytoskeletal Proteins/metabolism ; Extracellular Matrix Proteins/metabolism ; }, abstract = {Increased retinal stiffness is associated with reactive gliosis, fibrosis, and extracellular matrix remodeling-hallmarks of early retinal damage in conditions such as age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy. In this study, we demonstrate that Brillouin microscopy can detect stiffness changes in the damaged mouse retina that coincide with reactive Müller gliosis. Using acute retinal slice cultures, we generated two-dimensional Brillouin maps of both NMDA-damaged and untreated control retinas. Raw spectral images were processed to calculate the Brillouin frequency shift (BFS), which serves as a readout of tissue stiffness. Within 24 h of NMDA treatment, damaged retinas exhibited a significant increase in BFS relative to controls, indicating a rapid rise in retinal stiffness following neuronal cell death. While this biomechanical change likely reflects multiple cellular and molecular contributions, we show that the Brillouin signal localizes within the radial domain of Müller glia. These findings, along with single-cell mRNA sequencing analysis of damaged retinas, suggest that reactive Müller glia are key contributors to the observed increase in retinal stiffness. Collectively, our results establish Brillouin microscopy as a powerful tool to spatially resolve stiffness changes in the retina during neurodegeneration, provide a rationale for probing the specific mechanisms underlying these biomechanical alterations, and support the further development of Brillouin imaging as an in vivo platform for detecting early retinal pathology.}, }
@article {pmid41679663, year = {2026}, author = {Shu, Q and Lin, Y and Su, W and Peng, H and Wang, X}, title = {Exendin-4 alleviates Aβ1-40-induced apoptosis and calcium dysregulation in RPE cells through the CHP1/NHE1 complex.}, journal = {Biochemical pharmacology}, volume = {247}, number = {}, pages = {117789}, doi = {10.1016/j.bcp.2026.117789}, pmid = {41679663}, issn = {1873-2968}, mesh = {Animals ; *Apoptosis/drug effects/physiology ; *Exenatide/pharmacology ; *Calcium/metabolism ; Mice ; Mice, Inbred C57BL ; *Amyloid beta-Peptides/toxicity/antagonists &amp; inhibitors ; Humans ; *Retinal Pigment Epithelium/drug effects/metabolism ; *Peptide Fragments/toxicity/antagonists &amp; inhibitors ; Male ; Dose-Response Relationship, Drug ; Cell Line ; *Cation Transport Proteins/metabolism ; Macular Degeneration/metabolism/drug therapy ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment in elderly individuals and is influenced by various factors, such as age, genetics, and environmental conditions. While research into therapies for dry AMD is rapidly advancing, effective interventions are still lacking, underscoring the urgent need for new drug development. Recent studies have highlighted the multifaceted pharmacological activities of Exendin-4 (EX-4), including its anti-inflammatory, antioxidant, and antiapoptotic properties, along with its role in maintaining calcium homeostasis. The precise effects of EX-4 on AMD and its immediate target remain unclear. In this study, we investigated whether EX-4 could protect against Aβ1-40-induced AMD and explored the underlying mechanism. Our findings indicated that pretreatment with EX-4 alleviated apoptosis and restored calcium homeostasis both in vivo and in vitro. To identify the target of EX-4, we employed proteome microarrays and pulldown LC‒MS/MS analyses. Our results revealed that EX-4 bound to Calcineurin-like EF-hand protein 1(CHP1), reducing CHP1 protein expression in a concentration-dependent manner. This interaction led to a subsequent reduction in apoptosis and the normalization of intracellular Ca[2+] levels through the CHP1/NHE1 complex. Furthermore, we demonstrated that the inhibitory effects of EX-4 on apoptosis and calcium signaling were reversed by knocking down or overexpressing CHP1 in vitro. Finally, in AMD mice with CHP1-deficient retinas, the beneficial effects of EX-4 on apoptosis and calcium signaling were partially attenuated. In summary, our results suggest that the interaction of EX-4 with CHP1 has therapeutic potential for AMD, likely through alleviating apoptosis and restoring calcium homeostasis.}, }
@article {pmid41680690, year = {2026}, author = {Mesen, S and Yılmaz, MN}, title = {Investigation of pan-immune inflammatory value in patients with age-related macular degeneration.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {}, pmid = {41680690}, issn = {1471-2415}, mesh = {Humans ; Female ; Male ; Retrospective Studies ; Aged ; Tomography, Optical Coherence ; *Wet Macular Degeneration/immunology/blood/diagnosis ; Aged, 80 and over ; Monocytes/pathology ; Neutrophils/pathology ; C-Reactive Protein/metabolism ; *Geographic Atrophy/immunology/blood/diagnosis ; Middle Aged ; Lymphocytes/pathology ; Leukocyte Count ; *Inflammation/immunology/blood ; *Macular Degeneration/immunology ; Triglycerides/blood ; }, abstract = {PURPOSE: The purpose of this study was to evaluate the systemic pan-immune inflammatory value (PIV) in wet and dry cases of age-related macular degeneration.<br><br>METHODS: Patients diagnosed with AMD between 2020 and 2025 were retrospectively identified. The participants were divided into the wet AMD, dry AMD, and control groups. Their complete blood count (CBC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, and C-reactive protein data were obtained. Neutrophil-to-lymphocyte, monocyte-to-lymphocyte, platelet-to-lymphocyte, and neutrophil-to-HDL ratios were calculated. The PIV was calculated as follows: (neutrophil &#xd7; platelet &#xd7; monocyte/lymphocyte count). The central macular and subfoveal choroidal thicknesses were measured manually from the spectral domain optical coherence tomography (OCT) images.<br><br>RESULTS: Of the 72 cases included in the study, 25 were wet AMD, 26 were dry AMD, and 21 were controls. According to the statistical analysis, the white blood cell count (7.89&#x2009;&#xb1;&#x2009;1.82 vs. 6.66&#x2009;&#xb1;&#x2009;1.75), neutrophil count (5.02&#x2009;&#xb1;&#x2009;1.42 10[9]/L vs. 4.11&#x2009;&#xb1;&#x2009;1.35 10[9]/L), monocyte count (0.64&#x2009;&#xb1;&#x2009;0.16 10[9]/L vs. 0.49&#x2009;&#xb1;&#x2009;0.18 10[9]/L), and PIV (414.31&#x2009;&#xb1;&#x2009;268.02 vs. 270.33&#x2009;&#xb1;&#x2009;161.84) were higher in the wet AMD group than in the dry AMD group. The monocyte count (0.64&#x2009;&#xb1;&#x2009;0.16 10[9]/L vs. 0.49&#x2009;&#xb1;&#x2009;0.17 10[9]/L) and PIV (414.31&#x2009;&#xb1;&#x2009;268.02 vs. 270.13&#x2009;&#xb1;&#x2009;127.84) were higher in the wet AMD cases than in the control group. No statistically significant difference was found between the dry AMD and control groups.<br><br>CONCLUSION: In our study, the PIV was statistically significantly higher in the wet AMD group than in the dry AMD and control groups. Obtaining CBC data is a highly cost-effective and practical method for calculating PIV. PIV calculation can be helpful in the follow-up of patients with AMD, especially those at high risk of converting from dry AMD to wet AMD.}, }
@article {pmid41680791, year = {2026}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {Can MicroRNAs serve as reliable biomarkers and novel therapeutic targets in age-related macular degeneration? A systematic review and meta-analysis.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41680791}, issn = {1479-5876}, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, affecting 196 million people globally with projections reaching 288 million by 2040. Its pathogenesis involves oxidative stress, chronic inflammation, angiogenesis, and retinal pigment epithelium (RPE) dysfunction. MicroRNAs (miRNAs)—highly stable, non-coding post-transcriptional regulators—have emerged as key modulators of AMD-related pathways, including nuclear factor kappa B mediated inflammation (miR-146a, miR-155), angiogenesis (miR-23a, miR-27a), and RPE homeostasis (miR-204, miR-211). Dysregulation of miRNAs across the retina, serum, plasma, and vitreous may offer diagnostic and therapeutic potential. This systematic review and meta-analysis evaluated the diagnostic accuracy, differential expression, and functional relevance of miRNAs in AMD.<br><br>METHODS: A comprehensive literature search was performed across all major databases, including PubMed, Embase, Web of Science, Google Scholar, Scopus, and the Cochrane Library, as well as additional sources identified through websites and citation searching, covering all records from database inception to 15th June 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), with protocol registration in the International Prospective Register of Systematic Reviews (PROSPERO: CRD420251101982). Eligible studies included human case-control studies, in vitro/in vivo AMD models, and miRNA-based therapeutic investigations. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS), the Office of Health Assessment and Translation tool (OHAT), the SYstematic Review Centre for Laboratory animal Experimentation tool (SYRCLE), and a modified Toxicological data Reliability Assessment Tool (ToxRTool). Meta-analyses were performed using fixed or random-effects models based on heterogeneity. Outcomes included pooled AUC values, standardized mean differences (SMD), pooled mean miRNA expression, and distribution of up- vs. down-regulated miRNAs.<br><br>RESULTS: Twenty-two studies were included. Differentially expressed miRNAs were consistently reported, with miR-34a (up to 6.3-fold), miR-146a (2.1&#x2013;6.3-fold), miR-155, miR-19a, miR-410, and miR-126 among the most recurrent. Diagnostic accuracy meta-analysis demonstrated a pooled area under the receiver operating characteristic curve of 0.749 (95% CI: 0.713&#x2013;0.781). Individual AUCs included: vitreous ratio AUC 0.977, plasma AUC 0.914, miR-27a-3p 0.925, miR-29b-3p 0.757, and miR-195-5p 0.766. Pooled SMD comparing AMD vs. controls was 0.296 (p&#x2009;<&#x2009;0.001). Mean pooled miRNA expression in AMD was 0.296 (SE 0.0313), with highest levels in miR-486-5p (0.8016), miR-423-3p (0.7329), and miR-885-5p (0.6759). Up-vs-down-regulation analysis showed balanced distribution (pooled effect 0.520, p&#x2009;=&#x2009;0.505). Functional studies demonstrated restoration of TREM2 after miR-34a inhibition and rescue of RPE phagocytosis via miR-184 modulation. Publication bias was significant in two outcomes but corrected estimates remained directionally consistent.<br><br>CONCLUSION: Multiple miRNAs show consistent dysregulation in AMD and display moderate diagnostic accuracy, particularly miR-27a-3p, miR-146a, miR-34a, and vitreous-derived miRNA panels. Several miRNAs regulate key pathogenic pathways&#x2014;including inflammation, angiogenesis, and impaired RPE function&#x2014;supporting their potential as biomarkers and therapeutic targets. Large, standardized, multi-center studies are required to validate these findings and advance miRNA-based diagnostics and therapeutics toward clinical translation.<br><br>TRANSLATIONAL RELEVANCE: This study bridges the gap between molecular biomarker discovery and clinical application in AMD. It highlights the feasibility of incorporating miRNA profiling into AMD diagnostics and supports the future development of miRNA-targeted therapies for personalized treatment strategies.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-025-07593-x.}, }
@article {pmid41681737, year = {2026}, author = {Bepery, C and Rahaman, GMA and Debnath, R and Saha, S and Islam, MS and Abir, MEI and Sarker, SK}, title = {BanglaOCT2025: A Population-Specific Fovea-Centric OCT Dataset with Self-Supervised Volumetric Restoration Using Flip-Flop Swin Transformers.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {3}, pages = {}, pmid = {41681737}, issn = {2075-4418}, abstract = {Background: Age-related macular degeneration (AMD) is a major cause of vision loss, yet publicly available Optical Coherence Tomography (OCT) datasets lack demographic diversity, particularly from South Asian populations. Existing datasets largely represent Western cohorts, limiting AI generalizability. Moreover, raw OCT volumes contain redundant spatial information and speckle noise, hindering efficient analysis. Methods: We introduce BanglaOCT2025, a retrospective dataset collected from the National Institute of Ophthalmology and Hospital (NIOH), Bangladesh, using Nidek RS-330 Duo 2 and RS-3000 Advance systems. We propose a novel preprocessing pipeline comprising two stages: (1) A constraint-based centroid minimization algorithm automatically localizes the foveal center and extracts a fixed 33-slice macular sub-volume, robust to retinal tilt and acquisition variability; and (2) A self-supervised volumetric denoising module based on a Flip-Flop Swin Transformer (FFSwin) backbone suppresses speckle noise without requiring paired clean reference data. Results: The dataset comprises 1585 OCT volumes (202,880 B-scans), including 857 expert-annotated cases (54 DryAMD, 61 WetAMD, and 742 NonAMD). Denoising quality was evaluated using reference-free volumetric metrics, paired statistical analysis, and blinded clinical review by a retinal specialist, confirming preservation of pathological biomarkers and absence of hallucination. Under a controlled paired evaluation using the same classifier with frozen weights, downstream AMD classification accuracy improved from 69.08% to 99.88%, interpreted as an upper-bound estimate of diagnostic signal recoverability rather than independent generalization. Conclusions: BanglaOCT2025 is the first clinically validated OCT dataset representing the Bengali population and establishes a reproducible fovea-centric volumetric preprocessing and restoration framework for AMD analysis, with future validation across independent and multi-centre test cohorts.}, }
@article {pmid41681740, year = {2026}, author = {Ozturk, M and Ağın, A}, title = {Choriocapillaris Flow and Retinal Vascular Fractal Dimension in Dry Age-Related Macular Degeneration.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {3}, pages = {}, pmid = {41681740}, issn = {2075-4418}, abstract = {Background/Objective: To evaluate the association between optical coherence tomography angiography (OCTA)-derived choriocapillaris flow (CCflow), retinal vascular fractal dimension (FD), and drusen burden in eyes with dry age-related macular degeneration (AMD). Methods: This retrospective study included 113 eyes from 73 patients with dry AMD. Eyes were classified into large and small drusen groups based on median drusen area. OCTA-derived CCflow and FD indices of the superficial and deep capillary plexuses were analyzed. Patient-level clustered analyses were performed using linear mixed-effects and generalized estimating equation models to account for inter-eye correlation. Results: Eyes with large drusen showed significantly lower CCflow compared with those with small drusen (p < 0.001), whereas FDsup did not differ between groups, and FDdeep demonstrated only a near-significant trend toward higher values. CCflow was moderately and negatively correlated with drusen area (ρ = -0.452, p < 0.001), whereas FDdeep showed no significant correlation in unadjusted analyses (ρ = 0.137, p = 0.148). In patient-level age-adjusted multivariable models accounting for inter-eye dependency, CCflow remained independently associated with drusen burden, while FDdeep demonstrated an independent association only after adjustment for age. Conclusions: Reduced CCflow is independently associated with increased drusen burden in dry AMD. FD metrics provide complementary descriptive information regarding microvascular remodeling but do not function as independent biomarkers. CCflow may serve as a robust quantitative indicator of early choroidal compromise in dry AMD.}, }
@article {pmid41681815, year = {2026}, author = {Gołębiewska, J and Jędrzejewska, IK and Mędrzycka, J and Przybyś, M and Różycki, R}, title = {Non-Exudative Macular Neovascularization in Various Acquired Macular Degenerations with Double- and Triple-Layer Sign on OCT.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {3}, pages = {}, pmid = {41681815}, issn = {2075-4418}, abstract = {Background/Objectives: To investigate the rate of exudative progression over time in patients with non-exudative macular neovascularization (NE-MNV) associated with various acquired macular degenerations presenting with a double-layer sign (DLS) or triple-layer sign (TLS) on optical coherence tomography (OCT), and to identify potential predictors of this progression. Methods: Fifty-one eyes of fourty-nine patients with a DLS or TLS on OCT images were identified. OCT angiography (OCTA) was performed to detect NE-MNV, and only eyes with confirmed NE-MNV were included in the final analysis. Central macular thickness (CMT), choroidal thickness (CT), morphology of the abnormal vessels, the duration of follow-up, progression to active exudative MNV, and the status of the contralateral eye were assessed. Results: The final analysis included 32 eyes of 30 participants with NE-MNV. The median observation period was 46 months. The causes of NE-MNV were age- related macular degeneration (AMD) in 59.38% of eyes, pachychoroid epitheliopathy (PPE) in 37.50%, and other causes in 3.12%. Exudation developed in 15.62% of eyes (median time to onset: 24 months), predominantly in the AMD subgroup. Abnormalities in the fellow eye were present in 59.38% of cases. Neither age nor other factors, including sex, cause of MNV, CMT, CT, MNV morphology, or fellow eye status, were statistically significant predictors of progression to active MNV (p = 0.67, p > 0.99, p = 0.62, p = 0.09, p = 0.09, p = 0.2, p = 0.62, resp.). Conclusions: NE-MNV is an asymptomatic condition that may occur in the course of various retinal diseases. While DLS and TLS demonstrate high sensitivity and specificity for the diagnosis of NE-MNV, their presence does not always indicate concurrent MNV. Multimodal imaging is essential for accurate monitoring of these patients and detection of potential disease progression.}, }
@article {pmid41683651, year = {2026}, author = {Chao, WW and Chao, HW and Chao, HM}, title = {Combined Therapy Versus Fortified Anti-VEGF Monotherapy in Type C Polypoidal Choroidal Vasculopathy: Long-Term Outcomes and Exploratory Biomarker Insights.}, journal = {International journal of molecular sciences}, volume = {27}, number = {3}, pages = {}, pmid = {41683651}, issn = {1422-0067}, mesh = {Humans ; Male ; Female ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Biomarkers/metabolism ; Middle Aged ; Retrospective Studies ; Aged ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Photochemotherapy/methods ; Treatment Outcome ; *Choroidal Neovascularization/drug therapy/metabolism ; Visual Acuity ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Choroid/blood supply/pathology ; Ranibizumab/therapeutic use ; Polypoidal Choroidal Vasculopathy ; }, abstract = {While standard anti- vascular endothelial growth factor (VEGF) therapy, with or without photodynamic therapy (PDT), is effective for patients with polypoidal choroidal vasculopathy (PCV), not all achieve optimal visual outcomes. This study aimed to compare fortified (double the dose and the volume of the standard one) anti-VEGF combined with PDT versus fortified anti-VEGF monotherapy and to investigate biomolecular profiles and disease relationships among PCV, neovascular age-related macular degeneration (nvAMD), and central serous chorioretinopathy (CSCR). The goal was to identify novel pathways to inform future therapeutic strategies, including hypoxia-inducible factors (HIF)-1α inhibitors. This retrospective cohort study included 23 eyes with indocyanine green-confirmed type C PCV. One eye treated with transpupillary thermotherapy was not included in the following two groups. Patients received either combined therapy (PDT + fortified-dose anti-VEGF; n = 12) or fortified-dose anti-VEGF monotherapy (n = 10). Primary outcomes were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Secondary outcomes included injection burden and recurrence. Exploratory analyses examined aqueous biomarkers, including VEGF, placental growth factor (PlGF), β-catenin, HIF-1α, and Wnt1 across PCV, CSCR, and nvAMD to identify novel therapeutic targets. Significant (p = 0.003/p = 0.005) median CRT reduction was similar (p = 0.468) between groups (combined/monotherapy: 137.5 µm/106.5 µm). BCVA (median [Q1, Q3]) change in logarithm of the minimum angle of resolution (LogMAR) was not statistically significant (p = 0.279), with 0.25 [0.00, 0.98] in the combined group versus 0.00 [-0.03, 0.28] in the monotherapy group. Treatment burden of anti-VEGFs per person per year was lower with combined therapy (1.16 ± 0.47# PDT + 2.81 ± 0.92# anti-VEGF injections) compared with monotherapy (4.61 ± 1.49# injections). Six eyes demonstrated recurrence at a mean of 15.5 months. Incomplete regression of polyps and branching vascular networks was observed in all eyes. Exploratory biomarker analysis revealed significantly (p < 0.05) higher VEGF and PlGF levels in nvAMD compared with PCV. nvAMD also demonstrated significantly (p < 0.05) higher β-catenin and lower HIF-1α levels relative to PCV and CSCR, while no significant biomarker differences were observed between PCV and CSCR. Combined therapy or monotherapy with fortified anti-VEGFs reduced treatment burden and achieved significant anatomical improvement but did not yield superior functional outcomes, highlighting the therapeutic difficulty of type C PCV. Biomarker profiling revealed shared hypoxia-related mechanisms between PCV and CSCR, with elevated HIF-1α compared to nvAMD indicating a "preliminary" possible role for HIF-1α inhibitors. Differential expression of these biomarkers highlights additional molecular pathways that may inform future targeted interventions.}, }
@article {pmid41683853, year = {2026}, author = {Gong, X and Örge, FH}, title = {Glucagon-like Peptide-1 Receptor Agonists and Ocular Disease: Mechanisms, Evidence and Therapeutic Perspectives.}, journal = {International journal of molecular sciences}, volume = {27}, number = {3}, pages = {}, pmid = {41683853}, issn = {1422-0067}, mesh = {Humans ; *Glucagon-Like Peptide-1 Receptor Agonists ; Animals ; *Eye Diseases/drug therapy/metabolism ; Diabetic Retinopathy/drug therapy/metabolism ; Macular Degeneration/drug therapy/metabolism ; Glucagon-Like Peptide-1 Receptor/metabolism ; Diabetes Mellitus, Type 2/drug therapy ; Glaucoma/drug therapy/metabolism ; Hypoglycemic Agents/therapeutic use ; }, abstract = {Ocular diseases, including glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), remain major global causes of irreversible vision loss. Despite advances in clinical management, current therapies insufficiently address the shared metabolic, inflammatory, vascular, and neurodegenerative mechanisms underlying these conditions. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for type 2 diabetes and obesity, have emerged as multi-target candidates for ocular therapeutics due to their pleiotropic anti-inflammatory, antioxidant, vasculoprotective, and neuroprotective properties. Preclinical studies consistently demonstrate that GLP-1RAs preserve blood-retina barrier integrity, suppress pathological angiogenesis, mitigate oxidative and inflammatory stress, and protect retinal neurons from degeneration. Complementary clinical and real-world evidence shows a robust and reproducible reduction in glaucoma risk among GLP-1RA users across diabetic and non-diabetic populations. By contrast, findings for DR and AMD are more heterogeneous and appear context-dependent, with potential benefits most evident in early or non-exudative disease stages. Emerging safety considerations-including reports of nonarteritic anterior ischemic optic neuropathy and early DR worsening in the setting of rapid glycemic improvement-highlight the need for careful interpretation, individualized risk assessment, and appropriate ophthalmic monitoring. This review synthesizes molecular mechanisms, experimental data, clinical and pharmacoepidemiologic evidence, and safety signals to critically evaluate the therapeutic potential of GLP-1RAs in ocular disease. We also outline key translational challenges, including the need for ocular-targeted delivery strategies, prospective ophthalmology-specific trials, and precision-medicine approaches to determine when and how GLP-1RAs can be safely advanced as disease-modifying treatments in ophthalmology.}, }
@article {pmid41683912, year = {2026}, author = {Rusciano, D and Gagliano, C and Avitabile, A and Maya-Vetencourt, JF}, title = {Targeted RNA Degradation by RIBOTACs: A Novel Therapeutic Avenue for Ophthalmic Diseases.}, journal = {International journal of molecular sciences}, volume = {27}, number = {3}, pages = {}, pmid = {41683912}, issn = {1422-0067}, mesh = {Humans ; Animals ; *Eye Diseases/genetics/drug therapy/therapy/metabolism ; *RNA Stability/drug effects ; *Ribonucleases/metabolism ; }, abstract = {Ophthalmic diseases, including inherited retinal dystrophies, age-related macular degeneration (AMD), and glaucomatous neuropathies, are often driven by the expression of pathogenic proteins or dysfunctional non-coding RNAs that are currently considered 'undruggable' with conventional small-molecule therapeutics. The emerging strategy of Ribonuclease-Targeting Chimeras (RIBOTACs) offers a revolutionary approach to address this therapeutic gap. RIBOTACs are heterobifunctional small molecules designed to bind a specific target RNA with one moiety and recruit a latent endogenous ribonuclease, such as RNase L, with the other, thereby catalyzing the RNA's degradation. This targeted degradation can potentially halt the production of mutant proteins, eliminate toxic gain-of-function RNAs, or modulate key regulatory pathways involved in angiogenesis, inflammation, and apoptosis-core processes in many blinding diseases. This review explores the immense potential of applying RIBOTAC technology to ophthalmology, discussing prospective targets such as mutant alleles in retinitis pigmentosa, VEGF transcripts in neovascular AMD, and inflammatory mediators in uveitis. We will also address the unique challenges and opportunities for RIBOTAC development in the eye, including delivery strategies to overcome ocular barriers, the need for high specificity to avoid off-target RNA degradation, and the optimization of pharmacokinetic properties for intraocular administration. With continued innovation, RIBOTACs are poised to evolve into a robust therapeutic platform, expanding the druggable genome and enabling precise, durable treatments for a range of currently intractable ophthalmic conditions.}, }
@article {pmid41684578, year = {2025}, author = {Tong, L and Zhan, Q and Zhang, L}, title = {Age-related macular degeneration in the context of an update from the Global Burden of Disease Study 2019.}, journal = {Archives of medical science : AMS}, volume = {21}, number = {6}, pages = {2441-2449}, pmid = {41684578}, issn = {1734-1922}, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of central vision loss, with an increasing prevalence related to a growing economic burden. Understanding the epidemiological changes of AMD is essential for targeting the resource allocation of medicine, interventions, and the economy.<br><br>MATERIAL AND METHODS: The global prevalence and years lived with disability of AMD by sociodemographic index (SDI), sex, and age groups from 1990 to 2019 based on the Global Burden of Disease Study 2019 were retrieved and utilized to estimate epidemiological changes.<br><br>RESULTS: The global AMD population increased significantly from 3581.33 thousand in 1990 to 7792.53 thousand in 2019, and the years lived with disability significantly increased from 296.77 thousand years to 564.06 thousand years. The AMD burden was higher among females (57.77% to 59.20%), the elderly (65-74 years old), and individuals in high-middle and middle SDI regions from 1990 to 2019. The most significant increase in global burden occurred between 2014 and 2019. The age-standardized rate was predicted to remain stable, but the AMD case number was predicted to increase over the next 20 years. Tobacco use was the major diminishing risk factor.<br><br>CONCLUSIONS: The present study demonstrated the increasing AMD burden in the past 30 years and predicted the increasing change of AMD prevalence in the next 20 years in the context of the aging global population. Disease burdens, including case number and age-standardized rate, were higher among females, the elderly, and individuals in high-middle and middle SDI regions. The present findings will contribute to healthcare investment and policymaking.}, }
@article {pmid41686445, year = {2026}, author = {Hussey, KA and Eldred, KC and Guy, B and Santiago, CP and Zhang, JS and Glass, I and Reh, TA and Blackshaw, S and Goff, LA and Johnston, RJ}, title = {A cell fate specification and transition mechanism for human foveolar cone subtype patterning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {7}, pages = {e2510799123}, pmid = {41686445}, issn = {1091-6490}, support = {G2019300//BrightFocus Foundation (BFF)/ ; R01 EY030872/EY/NEI NIH HHS/United States ; DRG 32-20//Damon Runyon Cancer Research Foundation (DRCRF)/ ; F31EY033656//HHS | NIH | National Eye Institute (NEI)/ ; TA-RM-0620-0788-463 UWA//Foundation Fighting Blindness (FFB)/ ; DGE-1746891//NSF | NSF Graduate Research Fellowship Program (GRFP)/ ; GT15994//HHMI (HHMI)/ ; 2022-MSCRFD-5895//Maryland Stem Cell Research Fund (MSCRF)/ ; R01EY031685//HHS | NIH | National Eye Institute (NEI)/ ; R01EY030872//HHS | NIH | National Eye Institute (NEI)/ ; R24HD000836//HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/ ; R01EY036173//HHS | NIH | National Eye Institute (NEI)/ ; }, mesh = {Humans ; *Retinal Cone Photoreceptor Cells/metabolism/cytology ; Organoids/metabolism/cytology ; Cell Differentiation ; Signal Transduction ; Retinoic Acid 4-Hydroxylase/metabolism/genetics ; Tretinoin/metabolism ; Retina/metabolism ; Iodide Peroxidase/metabolism/genetics ; }, abstract = {In the central region of the human retina, the high-acuity foveola is notable for its dense packing of green (M) and red (L) cones and absence of blue (S) cones. To identify mechanisms that pattern cones in the foveola, we examined human fetal retinas and differentiated retinal organoids. During development, sparse S-opsin-expressing cones are initially observed in the foveola. Later in fetal development, the foveola contains a mix of cones that either coexpress S- and M/L-opsins or exclusively express M/L-opsin. In adults, only M/L cones are present. Two signaling pathway regulators are highly and continuously expressed in the central retina: Cytochrome P450 26 subfamily A member 1 (CYP26A1), which degrades retinoic acid (RA) and Deiodinase 2 (DIO2), which promotes thyroid hormone (TH) signaling. Both CYP26A1 mutant organoids and high RA conditions increased the number of S cones and reduced the number of M/L cones in retinal organoids. In contrast, sustained TH signaling promoted the generation of M/L-opsin-expressing cones and induced M/L-opsin expression in S-opsin-expressing cones, showing that cone fate is plastic. Our data suggest that CYP26A1 degrades RA to specify M/L cones and limit S cones and that continuous DIO2 expression sustains high levels of TH to transition S-opsin-expressing cones into M/L cone fate, resulting in the foveola containing only M/L cones. Given the vulnerability of the foveola in macular degeneration and other retinal disorders, these findings provide a mechanistic framework for engineering organoids for therapeutic applications.}, }
@article {pmid41687120, year = {2026}, author = {Nascimento, LM and Louzada, RN and Amaral, DC and Jacometti, R and Viegas Mendonça, VP and Chamis, B and Pereira Gonzalez, JV and Lessa, CT and Ribeiro Monteiro, ML and Ferrara, D}, title = {Associations Between Sleep Disorders and Age-related Macular Degeneration: A Systematic Review and Meta-analysis.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004800}, pmid = {41687120}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate the relationship between sleep disorders, including insomnia and obstructive sleep apnea (OSA), personal chronotype, and age-related macular degeneration (AMD).<br><br>METHODS: We systematically reviewed articles in PubMed, EMBASE, and Web of Science that provided information on AMD and sleep disorders, whether qualitative or quantitative. We systematically screened the abstracts of potentially eligible studies and subsequently assessed the full-text reports of those deemed relevant in detail. The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.<br><br>RESULTS: Twenty-two studies were included in our final review. OSA was associated with a higher risk of AMD, based on seven studies (HR 1.43; 95% CI 1.14-1.79 p < 0.001; I2 = 96%). The analysis showed a statistically significant association between the morning person chronotype and an increased odds of AMD (OR 1.19; 95% CI 1.10-1.30; p < 0.001; I2 = 0%). We found little to no association between sleep duration and insomnia.<br><br>CONCLUSION: Our meta-analyses, although based on a limited number of studies, indicate that sleep disorders, particularly OSA, are associated with increased odds of developing AMD. However, further research is needed to understand how sleep duration affects disease progression and to determine the benefits of treating sleep disorders for AMD.}, }
@article {pmid41687798, year = {2026}, author = {Kikushima, W and Gilead, N and Sherif, MZA and Zhang, C and Jiang, Z and Sun, C and Ong, C and Hong, CH and Teo, KYC and Chakravarthy, U and Cheung, CMG}, title = {Prevalence and Associated Features of Reticular Pseudodrusen in Neovascular Age-Related Macular Degeneration in an Asian Population.}, journal = {American journal of ophthalmology}, volume = {285}, number = {}, pages = {95-105}, doi = {10.1016/j.ajo.2026.02.011}, pmid = {41687798}, issn = {1879-1891}, abstract = {PURPOSE: To investigate the prevalence and associated features of reticular pseudodrusen (RPD) in an Asian cohort with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Retrospective, observational, cross-sectional study.<br><br>SUBJECTS: A total of 353 patients presenting with treatment-na&#xef;ve unilateral nAMD.<br><br>METHODS: Patients presenting with treatment-na&#xef;ve unilateral nAMD who enrolled in the Asian AMD Phenotyping study between 2015 and 2025 were reviewed. All patients underwent protocolized imaging, which included color fundus photography, spectral-domain optical coherence tomography (SD-OCT), and fluorescein and indocyanine green angiography. Images were evaluated for drusen, and RPD were considered present based on SD-OCT. Patients with ungradable eyes due to extensive neovascular changes or poor image qualities were excluded. Baseline characteristics of patients with RPD were compared with those with soft/cuticular or no drusen.<br><br>MAIN OUTCOME MEASURES: The prevalence and associated features of RPD. The systemic and ocular parameters were compared among the patients with RPD, soft/cuticular drusen, and no drusen.<br><br>RESULTS: Among 353 eligible patients (706 eyes), RPD were found in 68 eyes in 51 patients (9.6% per eye, 14.4% per patient). Patients with RPD were older compared with those with soft/cuticular or no drusen (P = .0005 and P < .0001, respectively). Eyes with RPD showed thinner choroidal thickness and higher prevalence of type 3 macular neovascularization (MNV) (odds ratio, 6.94, P = .01) compared with those with soft/cuticular or no drusen.<br><br>CONCLUSIONS: This is one of the largest series evaluating the prevalence of RPD in nAMD in the Asian population. Our findings suggest that ethnicity mainly impacts the prevalence of RPD. However, among patients with RPD, regardless of their ethnicity, there is a strong association with thin choroid and type 3 MNV.}, }
@article {pmid41687799, year = {2026}, author = {Browning, DJ}, title = {The Trouble With Photodynamic Therapy.}, journal = {American journal of ophthalmology}, volume = {285}, number = {}, pages = {261-265}, doi = {10.1016/j.ajo.2026.02.002}, pmid = {41687799}, issn = {1879-1891}, abstract = {PURPOSE: To examine the role of photodynamic therapy (PDT) in the treatment of retinal disease and the obstacles to use in the United States for evidence-based indications.<br><br>DESIGN: Perspective essay.<br><br>METHODS: This article includes a historical summary, example case report, and relevant literature review.<br><br>RESULTS: PDT has been approved by the US Food and Drug Administration for use in neovascular age-related macular degeneration (AMD), but has been superseded by anti-vascular endothelial growth factor drugs and is rarely used for this indication. It is regularly used in polypoidal choroidal vasculopathy (PCV) without reimbursement difficulty because PCV is acknowledged to be a form of AMD. It is effective for serous retinal detachment associated with choroidal hemangioma. Because this is a rare indication, insurers generally authorize its use. It is the most effective treatment for chronic central serous retinopathy (CSR), a relatively common indication; however, authorization from insurers is difficult to obtain, leading to avoidable loss of vision because patients often will not or cannot pay chargemaster prices. Many retina specialists eschew PDT because the expense in time and the laser does not balance the difficulties with reimbursement and the comparative advantage of allocating their time in other ways.<br><br>CONCLUSIONS: In the United States, finding a retina specialist who performs PDT is challenging for patients with diseases for which it is indicated. Obtaining coverage for CSR is difficult for retina specialists treating patients with CSR in the United States, but not internationally. As a result, delayed or no treatment for cases indicated leads to avoidable loss of vision. A suggested solution is that insurers agree to cover PDT for chronic CSR at a rate equal to 1.3 times Medicare reimbursement for neovascular AMD.}, }
@article {pmid41688763, year = {2026}, author = {Kim, TH and Kwon, CY and Song, JY and Yoo, HC}, title = {AAV-based gene therapies for neovascular AMD.}, journal = {Gene therapy}, volume = {}, number = {}, pages = {}, pmid = {41688763}, issn = {1476-5462}, support = {RS-2024-00412879//National Research Foundation of Korea (NRF)/ ; 2021R1C1C2006283//National Research Foundation of Korea (NRF)/ ; RS-2024-00403169//Korea Basic Science Institute (KBSI)/ ; 2024//Chung-Ang University (CAU)/ ; }, abstract = {Neovascular age-related macular degeneration (nAMD) is a major cause of irreversible vision loss in the elderly, driven by choroidal neovascularization and dysregulated vascular endothelial growth factor (VEGF) signaling. While anti-VEGF injections have transformed management, their frequent administration imposes a substantial burden on patients and limits adherence. Adeno-associated virus (AAV)-based gene therapy offers sustained intraocular delivery of anti-angiogenic agents with a single treatment, potentially overcoming these limitations. This review summarizes the rationale for AAV use in ocular gene therapy, compares major delivery routes, and highlights leading clinical candidates, including RGX-314, ADVM-022, 4D-150, and NG101. Advances in vector engineering, promoter optimization, and immune modulation are discussed alongside key challenges such as preexisting immunity and inflammation. Future directions include next-generation capsids, combination regimens, and precision patient selection. Collectively, these developments position AAV-based gene therapy as a promising strategy to redefine the therapeutic landscape of nAMD.}, }
@article {pmid41690011, year = {2026}, author = {Zhao, P and Ansaripour, R and Singh, D and Rong, G and Young, MJ and Carrier, RL}, title = {Novel explant model for human retinal progenitor cell transplantation.}, journal = {Biochemical and biophysical research communications}, volume = {807}, number = {}, pages = {153432}, doi = {10.1016/j.bbrc.2026.153432}, pmid = {41690011}, issn = {1090-2104}, mesh = {Humans ; *Retina/cytology ; Animals ; *Stem Cell Transplantation/methods ; Swine ; Hydrogels/chemistry ; Cell Survival ; *Stem Cells/cytology ; Cell Movement ; Alginates/chemistry ; }, abstract = {Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, have led to vision loss for millions worldwide. While stem/progenitor cell transplantation shows promise, its clinical application is limited by poor survival, efflux, and low integration of transplanted cells. Biopolymer scaffolds have been explored to improve viability and differentiation, but most in vitro assessments rely on simplified or endpoint analyses that fail to capture dynamic behaviors. Retinal explant models, which preserve tissue architecture and neuronal connections, provide a more physiologically relevant platform. However, conventional explant models are often limited to endpoint analyses and lack real-time monitoring capabilities. Here, we developed a novel explant model for human retinal progenitor cell (hRPC) transplantation using porcine retinal tissue slice, agarose hydrogel, and confocal microscope with an incubation cage. Retinal tissue slices exhibited comparable viability before and after imaging. Alginate-based hydrogels containing hRPCs were injected adjacent to photoreceptor or ganglion cell layer of cross-sectional retinal tissue slices, enabling visualization of the cells' position relative to retinal tissue slice over time. Real-time confocal imaging tracked key cellular behaviors, including migration, attachment, invasion, viability, and apoptosis. Injected hRPCs displayed random movement within the bulk alginate hydrogel and localized attachment or invasion at the hydrogel-tissue interface. Notably, laminin-incorporated alginate hydrogels promoted cell clustering and facilitated deeper invasion into retinal tissue compared with single cells.}, }
@article {pmid41692178, year = {2026}, author = {Yaldo, L and Ngo, A and Yaldo, M and Abdelaal, A and Ong, J and Kiryakoza, L and Sengillo, J}, title = {Obstructive sleep apnea and risk of age-related macular degeneration: A systematic review and meta-analysis.}, journal = {American journal of ophthalmology}, volume = {285}, number = {}, pages = {276-287}, doi = {10.1016/j.ajo.2026.02.016}, pmid = {41692178}, issn = {1879-1891}, abstract = {TOPIC: We evaluated whether obstructive sleep apnea (OSA) is associated with an increased risk of age-related macular degeneration (AMD). The population included adults with and without OSA. Outcomes included overall AMD risk and AMD stage-specific outcomes, including neovascular AMD (nAMD), non-neovascular AMD, late AMD with geographic atrophy (GA), and anti-VEGF therapy requirement.<br><br>CLINICAL RELEVANCE: AMD is a leading cause of irreversible vision loss worldwide. OSA, characterized by intermittent hypoxia, oxidative stress, and vascular dysregulation, shares key pathogenic mechanisms with AMD. Understanding whether OSA increases AMD risk could help identify high-risk populations for earlier detection, monitoring, and intervention.<br><br>METHODS: We conducted a systematic review and meta-analysis of observational studies. PubMed, Web of Science, and Scopus were searched to June 27, 2025, supplemented by Google Scholar and citation tracking. Eligible studies reported AMD outcomes in both OSA and non-OSA groups. Methodological quality was assessed using the National Institutes of Health Quality Assessment Tool. Random-effects models were used to pool odds ratios (ORs) and adjusted hazard ratios (aHRs). Certainty of evidence was evaluated with the GRADE framework. The protocol was registered in PROSPERO (CRD420251119881).<br><br>RESULTS: Eight studies (3,536,314 participants; 207,130 with OSA) were analyzed. In crude analyses, OSA was associated with higher odds of AMD (OR = 1.45; 95%CI: 1.13-1.84; low certainty) with similar increases for nAMD (OR = 1.76; 95%CI: 1.06-2.93; low certainty) and non-neovascular AMD (OR = 1.95; 95%CI: 1.04-3.66; low certainty). No significant associations were observed in subgroups without confounder adjustment (low certainty) or with regression adjustment (low certainty), whereas propensity-score matched studies indicated higher odds (OR = 1.92; 95%CI: 1.05-3.52; low certainty). Adjusted analyses confirmed the association (aOR = 1.44; 95%CI: 1.11-1.77; moderate certainty) with no heterogeneity. Time-to-event analyses showed an increased hazard of AMD (aHR = 1.66; 95%CI: 1.13-2.19; low certainty), though stage-specific analyses for neovascular and non-neovascular AMD were not significant (very low certainty).<br><br>CONCLUSION: OSA may be associated with an increased risk of AMD, though the certainty of evidence ranges from moderate to very low. Variability in diagnostic criteria for OSA and AMD, high heterogeneity in several analyses, and reliance on observational data limit the strength of inference.}, }
@article {pmid41692264, year = {2026}, author = {Zhang, Z and Wang, H and Pan, S and Han, W and Liu, M and Chen, Y and Li, X and Zhan, Y and Wu, H and Yao, J and Yang, J and Wu, F}, title = {Enhancing mouse fundus imaging with OCT embedding medium: Prolonging imaging duration and improving image quality.}, journal = {Experimental eye research}, volume = {266}, number = {}, pages = {110914}, doi = {10.1016/j.exer.2026.110914}, pmid = {41692264}, issn = {1096-0007}, mesh = {Animals ; *Tomography, Optical Coherence/methods ; Mice ; *Fundus Oculi ; Disease Models, Animal ; Mice, Inbred C57BL ; *Macular Degeneration/diagnostic imaging/diagnosis ; *Retinal Vessels/diagnostic imaging ; Fluorescein Angiography/methods ; *Image Enhancement/methods ; }, abstract = {Fundus diseases are common and serious ophthalmic conditions, including macular degeneration, diabetic retinopathy, glaucoma, and others, which can lead to severe vision loss. Mice, widely used as experimental animal models, play a crucial role in ophthalmic disease research. However, existing mouse fundus imaging techniques encounter several challenges during prolonged, high-precision imaging, such as corneal whitening, poor optical quality, and motion artifacts. In this study, we propose an innovative method based on an OCT embedding medium that, when applied to the mouse corneal surface, improves the alignment between the eye and the OCT lens. This method effectively reduces stray light (flare)and motion artifacts while slowing corneal dehydration. It significantly enhances the quality of mouse fundus imaging and extends imaging duration, particularly in the age-related macular degeneration (AMD) mouse model, where it improves retinal blood vessel visualization. This approach provides a novel technical solution for ophthalmic research and holds potential for clinical applications.}, }
@article {pmid41692319, year = {2026}, author = {Karami, S and Charpentier, P and Landreville, S and Proulx, S}, title = {Pigment epithelium-derived factor and osteopontin protect human retinal pigment epithelial cells from oxidative stress in 2D and 3D models.}, journal = {Free radical biology &amp; medicine}, volume = {247}, number = {}, pages = {435-447}, doi = {10.1016/j.freeradbiomed.2026.02.034}, pmid = {41692319}, issn = {1873-4596}, mesh = {Humans ; *Nerve Growth Factors/metabolism/pharmacology/genetics ; *Serpins/metabolism/pharmacology/genetics ; *Oxidative Stress/drug effects ; *Eye Proteins/metabolism/pharmacology/genetics ; *Osteopontin/metabolism/pharmacology/genetics ; *Retinal Pigment Epithelium/metabolism/cytology/drug effects ; NF-E2-Related Factor 2/metabolism/genetics ; Reactive Oxygen Species/metabolism ; Cells, Cultured ; Lipid Peroxidation/drug effects ; Epithelial Cells/metabolism/drug effects ; Melanocytes/metabolism ; Iodates/toxicity ; }, abstract = {Retinal pigment epithelial (RPE) cells are particularly vulnerable to oxidative stress. Neighboring choroidal melanocytes (CMs) secrete trophic factors, such as pigment epithelium-derived factor (PEDF) and osteopontin (OPN), which may mitigate oxidative damage in RPE cells. Herein, we investigated the ability of PEDF and OPN to protect RPE cells from extended NaIO3-induced oxidative stress damage. Primary human RPE cells were seeded on plastic (2D culture) or on a 3D tissue-engineered choroidal stroma (TECS) containing (or not) CMs. PEDF or OPN was added before, during, and after 5 days of NaIO3 exposure. Analyses included assessment of PEDF and OPN expression, intracellular reactive oxygen species (ROS), lipid peroxidation, mitochondrial superoxide, cell death, antioxidant capacity (TAC) and p-Nrf2 nuclear translocation. Adding exogenous PEDF to the growth media stimulated de novo PEDF secretion by RPE cells, whereas OPN concentration detected in the growth media corresponded to the amount added. PEDF and OPN levels were consistently lower in the growth media of 3D TECS compared to the 2D cultures. Oxidative stress significantly increased intracellular ROS, lipid peroxidation, and RPE cell death in both 2D and 3D cultures, which were reduced by PEDF or OPN supplementation. Oxidative stress and PEDF or OPN supplementation did not alter the TAC of RPE cells. PEDF or OPN supplementation promoted p-Nrf2 nuclear translocation in RPE cells on plastic, even without oxidative stress, whereas this response was not observed in 3D TECS cultures. Adding CMs to the 3D TECS did not influence p-Nrf2 nuclear translocation in RPE cells. Overall, PEDF and OPN supplementation significantly protected human RPE cells against NaIO3-induced oxidative stress damage. In 3D TECS, CMs secreted insufficient levels of PEDF and OPN for RPE cells to manage oxidative stress-induced damage. These findings demonstrate that exogenous supplementation with PEDF and OPN proteins may be beneficial for oxidative-stress related eye diseases.}, }
@article {pmid41692377, year = {2026}, author = {Vidal-Oliver, L and Garzone, D and Schloesser, L and Thiele, S and Pfau, M and Harmening, WM and Ameln, J and Dolz-Marco, R and Cuenca, N and Ortuño-Lizaran, I and Wu, Z and Guymer, RH and Finger, RP}, title = {Structural photoreceptor evaluation in age-related macular degeneration. A comprehensive review of methods and clinical significance.}, journal = {Progress in retinal and eye research}, volume = {111}, number = {}, pages = {101447}, doi = {10.1016/j.preteyeres.2026.101447}, pmid = {41692377}, issn = {1873-1635}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnosis/pathology ; *Photoreceptor Cells, Vertebrate/pathology ; Retinal Pigment Epithelium/pathology ; Clinical Relevance ; }, abstract = {Age-related macular degeneration (AMD) is a disease that primarily affects the outer retina, with progressive photoreceptor degeneration and atrophy of the retinal pigment epithelium (RPE). Advances in imaging now enable photoreceptor changes to be detected and quantified with unprecedented sensitivity, whereas comparable biomarkers of RPE dysfunction remain less developed. As such, photoreceptor-based biomarkers are increasingly considered potential surrogates for current clinical trial endpoints. This review examines the current imaging modalities-particularly optical coherence tomography (OCT) and modalities enhanced by adaptive optics (AO) -used to evaluate photoreceptor structure in AMD. We explore the intrinsic value of parameters such as outer nuclear layer thickness, external limiting membrane integrity, photoreceptor inner and outer segment thickness, ellipsoid zone (EZ) integrity, and EZ reflectivity on OCT, and cone density and regularity on AO imaging, highlighting their potential and limitations. While OCT-based metrics are the most accessible in clinical settings, their clinical utility is hampered by inconsistent segmentation protocols and methodological heterogeneity. AO imaging offers unmatched resolution but faces practical barriers to widespread adoption. The field is moving in a promising direction with emerging computational tools and artificial intelligence improving accuracy and scalability. However, progress is contingent on establishing consensus definitions, standardized acquisition and analysis protocols, and normative datasets. Future efforts should focus on translating high-resolution imaging into robust, reproducible biomarkers that can be widely adopted in both clinical practice and therapeutic development.}, }
@article {pmid41693903, year = {2026}, author = {Patel, Y and Baumann, B and Merkle, C}, title = {Blood flow analysis of retinal neovascularisations in a VLDLR mouse model using contrast-enhanced optical coherence tomography.}, journal = {Biomedical optics express}, volume = {17}, number = {2}, pages = {991-1010}, pmid = {41693903}, issn = {2156-7085}, abstract = {Age-related macular degeneration (AMD) is a major cause of global blindness that affects millions worldwide. Certain forms of AMD cause neovascularisations (NVs), which form retinal-choroidal anastomoses. This disrupts healthy haemodynamic patterns, and early detection and treatment are crucial for preserving vision. Here, we employ a custom-built optical coherence tomography (OCT) imaging system to investigate these NVs in a very low-density lipoprotein receptor (VLDLR) knockout mouse model. Mice were imaged before, during, and after contrast agent injection, aiming to enhance our understanding of the NV haemodynamics. Doppler signal analysis techniques were employed to calculate flow velocities within individual NVs. Flow rates pre- and post-injection were determined based on these velocity measurements. Particle tracking was performed on two NVs for a comparative analysis with the Doppler velocity measurements. Both methods of measuring flow velocities showed good agreement post-contrast injection. The analysis of post-injection flow rates from the NVs revealed diverse behaviours. Some NVs exhibited stable flow rates over time, while others showed signs of instability, with flow rates changing substantially or even changing flow direction at different time points. Additionally, it was observed at multiple time points that flow from certain NVs moved from the choroid to the retina at the same time that other NVs displayed flow in the opposite direction. These observations suggest complex interactions between choroidal and retinal vascular networks in diseases like AMD. Further characterisation using contrast-enhanced Doppler OCT may improve our understanding of neovascular haemodynamics.}, }
@article {pmid41694220, year = {2026}, author = {Li, J and Ma, Y and Hu, M and Zhang, Q and Wang, A and Tang, Q and Guo, Q and Huang, B}, title = {PANoptosis-Related Diagnostic Biomarkers in Non-Neovascular Age-Related Macular Degeneration: An Integrative Transcriptomic and Experimental Study.}, journal = {Genetics research}, volume = {2026}, number = {}, pages = {8903808}, pmid = {41694220}, issn = {1469-5073}, mesh = {Humans ; Animals ; *Macular Degeneration/genetics/diagnosis/pathology ; *Transcriptome/genetics ; Mice ; Biomarkers/metabolism ; Retinal Pigment Epithelium/metabolism/pathology ; Gene Expression Profiling ; Female ; Male ; Retina/metabolism/pathology ; }, abstract = {Age-related macular degeneration (AMD), particularly its non-neovascular (dry) form, is a progressive retinal disorder that causes central vision loss and substantial impairment in daily life. Inflammation and immune dysregulation are recognized as core drivers of AMD, yet the contribution of PANoptosis, a form of programmed cell death that integrates pyroptosis, apoptosis, and necroptosis, remains unclear. In this study, we integrated human single-cell transcriptomic and bulk microarray datasets from the retina and retinal pigment epithelium-choroid to characterize PANoptosis-related transcriptional changes in dry AMD. Dimensionality reduction, cell-type annotation, and PANoptosis gene-set scoring revealed a distinct PANoptosis signature enriched in AMD, with particularly strong activation in myeloid populations. By combining differential expression analysis with machine learning-based feature selection, we identified four PANoptosis-related genes (PON2, BNIP3, EPHB6, and TPD52) that robustly distinguished AMD from control samples and were associated with an altered immune microenvironment. Genetic instrument analysis further suggested a positive association between TPD52 expression and AMD risk. At the cellular level, our data highlighted macrophages, especially pro-inflammatory M1-like macrophages, as key coordinators of PANoptosis-related pathways in dry AMD. To validate these findings in vivo, we used a sodium iodate-induced mouse model of dry AMD and observed significant dysregulation of PON2, BNIP3, EPHB6, and TPD52 in the retina by RT-qPCR, consistent with the human transcriptomic results and supporting their involvement in retinal degeneration and inflammation. Together, these findings implicate PANoptosis as an important and previously underappreciated component of dry AMD pathophysiology, define a four-gene PANoptosis-related signature with diagnostic potential, and suggest new molecular targets for therapeutic intervention.}, }
@article {pmid41694267, year = {2026}, author = {Pan, L and Deng, J and Yang, J and Wang, M and Chen, Z and Wang, T and Li, Y}, title = {Causal effects of antibody-mediated immunity to pathogens on five ophthalmic diseases: a Mendelian randomization study.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {251}, number = {}, pages = {10906}, pmid = {41694267}, issn = {1535-3699}, mesh = {Humans ; Mendelian Randomization Analysis ; *Eye Diseases/immunology/genetics ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; }, abstract = {While immune responses related to infections have been linked to ocular diseases, their causal role remains to be established. This study aimed to assess the causal relationship between antibody-mediated immune responses to infectious agents and five ocular conditions: chronic iridocyclitis (CIR), scleritis, wet age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma. We performed a two-sample Mendelian randomization (MR) analysis using GWAS data to assess causality between antibody responses to 46 pathogens and five ophthalmic diseases. The instrumental variables were Single nucleotide polymorphisms (SNPs). Causal estimates were primarily generated via the inverse-variance weighted method, supplemented by MR-Egger and weighted median methods. A Bonferroni-corrected threshold of P < 2.17 × 10[-4] was applied. Sensitivity analyses included Cochran's Q, MR-Egger, and MR-PRESSO for heterogeneity and pleiotropy. Reverse MR was performed to assess bidirectionality. Forward MR identified causal effects of infection-induced immune responses on ocular diseases. Epstein-Barr virus (EBV) ZEBRA antibodies were positively correlated with CIR, whereas Varicella zoster virus glycoproteins E and I antibodies were associated with scleritis and DR as risk factors. Genetically predicted anti-polyomavirus 2 IgG seropositivity (JCV IgG+) was identified as a risk factor for DR, wet AMD and glaucoma. In contrast, The EBV EBNA-1 antibody is associated with DR, wet AMD, and glaucoma as a protective factor, whereas the EBV VCA18 antibody is negatively associated with wet AMD. Reverse MR analysis indicated that DR may elevate JCV VP1 antibody levels. This study provides the first genetic evidence of a causal link between pathogen-specific immune responses and ocular diseases, offering a foundation for targeted immunomodulatory and personalized therapies.}, }
@article {pmid41694669, year = {2026}, author = {Reinisalo, M and Helisalmi, S and Koskela, A and Küblbeck, J and Liukkonen, M and Mutikainen, M and Cree, AJ and Griffiths, H and Papp, A and Seitsonen, S and Immonen, I and Soininen, H and Urtti, A and Hiltunen, M and Winiarczyk, M and Resch, M and Ratnayaka, JA and Lotery, AJ and Kaarniranta, K and Honkakoski, P}, title = {Functional polymorphisms in pigmentation-related genes MC1R and DCT display population-specific association with wet age-related macular degeneration.}, journal = {Biochemistry and biophysics reports}, volume = {45}, number = {}, pages = {102477}, pmid = {41694669}, issn = {2405-5808}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Age-related macular degeneration (AMD) is among the leading causes of vision loss. Factors increasing the risk of AMD include aging, smoking, cardiovascular diseases and heritability. Although melanin pigment is known to protect retinal homeostasis, the link between pigmentation-related genes and AMD is unclear. We investigated associations between 26 variations in six pigmentation-related genes and wet AMD risk in a Finnish population, followed by replication in the United Kingdom (UK), Hungarian and Polish cohorts, totaling 775 patients and 959 controls. Associations of genetic components with smoking and body mass index (BMI) were tested in the Finnish and UK cohorts. The functionality of candidate variants in human retinal pigment epithelial (RPE) cells was evaluated using gene promoter analysis and gene silencing. Non-coding variants, rs1407995 in the dopachrome tautomerase (DCT) intron and rs3212351 in the melanocortin-1 receptor (MC1R) promoter, were associated with wet AMD in the Finnish cohort. The variant rs3212351 disrupts a binding site for transcription factor MITF and reduces MC1R expression in RPE cells. Unlike in the Finnish cohort, the data regarding the MC1R variant suggested a protective association in the Polish cohort. The incidence of AMD increased with age in all cohorts. Smoking increased AMD risk in the cohorts studied. Sex and BMI showed no associations. These findings suggest that variations in DCT and MC1R genes known to affect skin and eye pigmentation may also play a role in development of wet AMD. The observed population differences may be related to variable pigmentation traits.}, }
@article {pmid41697345, year = {2026}, author = {Fukuda, Y and Notomi, S and Shiose, S and Maehara, Y and Yuge, K and Kiyohara, K and Yasaka, Y and Mori, K and Ishikawa, K and Murakami, Y and Sonoda, KH}, title = {Wide-field choroidal thickness changes after loading-phase anti-VEGF therapy in treatment-naïve neovascular AMD.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41697345}, issn = {1435-702X}, support = {JP24KJ1780//Japan Society for the Promotion of Science/ ; JP25K12836//Japan Society for the Promotion of Science/ ; }, abstract = {PURPOSE: While it is known that anti-vascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD) leads to a reduction in choroidal thickness in the macula, changes in peripheral choroidal thickness remain unclear. This study aimed to evaluate choroidal thickness changes following three monthly intravitreal injections of aflibercept and faricimab in treatment-naïve nAMD.<br><br>METHODS: Treatment-na&#xef;ve nAMD patients receiving three consecutive monthly injections as the loading phase were enrolled in this study. Wide-field swept-source OCT was used to quantify regional choroidal thickness. In the 1:1 propensity score matching, sex, age, baseline best-corrected visual acuity, axial length, and nAMD subtypes were selected as covariates.<br><br>RESULTS: A total of 142 eyes from 142 patients were included, with 71 eyes receiving aflibercept and 71 eyes receiving faricimab. Significant reductions in choroidal thickness were observed in both central and peripheral areas, with the most pronounced changes occurring in the central 3&#xa0;mm-subfield. After propensity score matching, choroidal thickness change rates were compared between the two drug groups. In the central 3&#xa0;mm-subfield, aflibercept was associated with a significantly greater reduction in choroidal thickness compared with faricimab. No significant differences were observed in other subfields.<br><br>CONCLUSION: This study highlights the importance of considering both central and peripheral choroidal changes when evaluating the impact of different anti-VEGF therapies in nAMD.}, }
@article {pmid41699676, year = {2026}, author = {Yang, H and Liu, B and Zhang, Y and Zhang, Z and Tan, H and Li, X}, title = {Caffeine intake and late dry age-related macular degeneration: tea's protective role-insights from NHANES and Mendelian randomization.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {}, pmid = {41699676}, issn = {2056-9920}, support = {TJYXZDXK-037A//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; }, abstract = {BACKGROUND: Although caffeine is widely consumed and has demonstrated neuroprotective effects, its role in age-related macular degeneration (AMD) remains unclear, particularly across disease subtypes and dietary sources such as tea and coffee.<br><br>METHODS: We analyzed 2005-2008 NHANES data using weighted logistic regression and restricted cubic splines to assess the dose-response relationship between caffeine intake and the prevalence of early and late AMD. Two-sample Mendelian randomization (MR) using GWAS summary statistics was employed to evaluate causal effects of tea and coffee consumption on AMD subtypes. Furthermore, a two-step MR approach was utilized to identify potential immune-mediated pathways.<br><br>RESULTS: NHANES data showed that caffeine intake was inversely associated with late AMD (fully adjusted OR&#x2009;=&#x2009;0.65, 95% CI: 0.44-0.96). Dose-response modeling revealed an L-shaped nonlinear relationship (P for nonlinear&#x2009;=&#x2009;0.046), indicating that the protective effect of caffeine plateaued once daily intake exceeded approximately 110-150&#xa0;mg. MR analysis further supported a causal protective association between tea consumption and dry AMD, including geographic atrophy (OR&#x2009;=&#x2009;0.44, 95% CI: 0.20-0.97), which may be partially attributable to immunological mechanisms, specifically the downregulation of secretory regulatory T cells (% of CD4&#x2009;+&#x2009;Tregs) and CD45RA- CD4&#x2009;+&#x2009;T cell (% of CD4&#x2009;+&#x2009;T cell). In contrast, coffee consumption showed no significant effect.<br><br>CONCLUSIONS: Tea, a specific source of caffeine typically corresponding to moderate intake levels, may confer protection against dry AMD, including geographic atrophy, potentially through modulation of immune cell profiles. These findings suggest a potential preventive strategy and warrant further clinical investigation.}, }
@article {pmid41699888, year = {2026}, author = {Samoila, L and Farcasanu, A and Simon, S and Bodoki, E and Samoila, O and Vostinaru, O and Dinte, E and Bodoki, AE and Iudean, D and Muresan, C and Clichici, S}, title = {Noninvasive 11.7-T Magnetic Resonance Spectroscopy and Imaging Reveals Retinal Metabolic Alterations Induced by Blue Light Exposure.}, journal = {NMR in biomedicine}, volume = {39}, number = {3}, pages = {e70240}, pmid = {41699888}, issn = {1099-1492}, support = {352/390028/23.09.2021//Romanian Ministry of European Investment and Projects (MIPE)/ ; G-2024-71962/23.10.2024//Romanian Ministry of European Investment and Projects (MIPE)/ ; 390005/23.10.2024//Ministry of Research, Innovation and Digitalization (MCID)/ ; }, mesh = {Animals ; *Retina/metabolism/radiation effects/diagnostic imaging ; *Light ; Male ; Rats ; Magnetic Resonance Spectroscopy/methods ; Oxidative Stress/radiation effects ; *Proton Magnetic Resonance Spectroscopy ; Blue Light ; }, abstract = {The eye is a complex structure, with multiple systems involved in focusing and detecting light. Among them, the retina, an integral component of the central nervous system, is considered the most vital and exhibits the highest metabolic activity among all tissues in the human body. It interacts with light, and excessive exposure, especially to blue light, is prone to produce degeneration, mainly through oxidative reactions. This mechanism is involved in age-related macular degeneration or diabetic retinopathy. Animal research is important, considering the high prevalence of these diseases; yet noninvasive procedures involving this research are lacking so far. Our objective was to apply an animal model of oxidative stress and monitor the metabolic changes using 11.7-T [1]H-magnetic resonance spectroscopy ([1]H-MRS). We exposed adult rats to high intensity blue light, at 440 nm (6000 lx) and investigated retinal metabolic changes up to 48 h post exposure. The acquired spectrum highlighted the presence of several essential retinal metabolites, including lipids (alkyl chain CH2), lactate, N-acetylaspartate (NAA), glutamate (Glu), choline (Cho), taurine (Tau), creatine (Cre), and glucose (Glc). Blue light induced specific changes, relatable to oxidative stress, and [1]H-MRS allowed us to follow the dynamic metabolic changes post exposure. This is the first in vivo spectroscopic study of the retinal tissue in which no animals were sacrificed. To validate the in vivo metabolite assignments, localized ex vivo [1]H-MRS was performed on eyes from separate animals that had not been exposed to blue light.}, }
@article {pmid41699987, year = {2026}, author = {Li, ZY and Yang, D and Huang, Y and Li, Y and Zhao, T and Xu, Y}, title = {Dynamin-Related Protein 1-Dependent Disruption of Mitochondrial Homeostasis Drives Blue Light-Induced Epithelial-Mesenchymal Transition in Retinal Aging.}, journal = {Aging cell}, volume = {25}, number = {2}, pages = {e70416}, pmid = {41699987}, issn = {1474-9726}, support = {#2023A1515012397//Natural Science Foundation of Guangdong Province/ ; #2023A03J0899//Guangzhou Science and Technology Projects/ ; }, mesh = {*Epithelial-Mesenchymal Transition/radiation effects ; Animals ; Humans ; *Dynamins/metabolism ; *Mitochondria/metabolism/radiation effects ; Mice ; *Homeostasis/radiation effects ; *Light/adverse effects ; *Retinal Pigment Epithelium/metabolism/pathology ; Mitochondrial Dynamics/radiation effects ; *Retina/pathology/metabolism/radiation effects ; *Aging ; Macular Degeneration/pathology/metabolism ; Oxidative Stress ; Blue Light ; }, abstract = {Age-related macular degeneration (AMD) stands as a leading cause of blindness in the elderly, yet the fundamental aging processes that underpin its pathogenesis remain incompletely defined. The dysfunction of retinal pigment epithelial (RPE) cells is a central event in AMD, a process that shares key hallmarks with broader cellular aging, particularly the progressive decline in mitochondrial function. In this study, we investigated how a common environmental stressor-blue light-triggers a key pathological transformation, epithelial-mesenchymal transition (EMT), in RPE cells by specifically disrupting mitochondrial dynamics, a core pillar of cellular aging. Using an in vitro model of human RPE cells, we demonstrated that blue light exposure induces a marked shift in mitochondrial dynamics towards excessive fission. This imbalance directly resulted in mitochondrial dysfunction, elevated oxidative stress, and served as the critical driver for the initiation of EMT. Importantly, pharmacological inhibition of the mitochondrial fission GTPase Dynamin-related protein 1 (Drp1) with Mdivi-1 effectively restored mitochondrial network homeostasis, rescued mitochondrial function, and fully reversed the EMT phenotype. These findings were corroborated in a mouse model of blue light-induced retinal damage, where Drp1 inhibition successfully preserved retinal light responses, mitigated structural degeneration, and slowed disease progression. Our study demonstrates that Drp1-mediated excessive mitochondrial fission drives EMT in RPE cells under blue light, linking this mechanism to AMD progression. Consequently, targeting mitochondrial dynamics to maintain cellular homeostasis emerges as a promising and broadly applicable geroscience-based strategy for mitigating age-related tissue dysfunction.}, }
@article {pmid41700798, year = {2026}, author = {Trinh, M and Borrelli, E and Reibaldi, M and Foti, C and Nivison-Smith, L}, title = {Inner Retinal Reflectivity Loss and Concurrent Thickening Predict Short-Term Conversion to Neovascular AMD.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {2}, pages = {34}, pmid = {41700798}, issn = {1552-5783}, mesh = {Humans ; Retrospective Studies ; Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; *Retinal Ganglion Cells/pathology ; Case-Control Studies ; *Wet Macular Degeneration/diagnosis ; Nerve Fibers/pathology ; Aged, 80 and over ; Disease Progression ; Visual Acuity ; Middle Aged ; Follow-Up Studies ; *Retina/pathology ; }, abstract = {PURPOSE: To examine inner retinal changes preceding conversion from intermediate age-related macular degeneration (iAMD) to exudative neovascular AMD (nAMD), using topographic optical coherence tomography (OCT) reflectivity and thickness analysis.<br><br>METHODS: This retrospective case-control study included 60 individual eyes with iAMD (30 converters and 30 non-converters to nAMD within 1 year). Baseline macular OCT scans were segmented for the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL). Raw linear reflectivity (normalized against vitreous intensity) and thickness were extracted from 48 &#xd7; 48 grids. Primary outcomes were differences in reflectivity (%) and thickness (&#xb5;m) between converters and non-converters, adjusted for person-level factors. Secondary outcomes examined retinal macrovascular metrics and odds of conversion (odds ratios [ORs]), further adjusted for traditional AMD factors.<br><br>RESULTS: Converters showed global reductions in reflectivity across the RNFL (-6.24%), GCL (-2.01%), and IPL (-1.58%), with modest RNFL thickening (4.48&#xa0;&#xb5;m). Topographic analyses revealed nasal reflectivity loss in all layers and localized thickening in the nasal RNFL and paracentral GCL/IPL (P < 0.0001). Macrovascular metrics did not differ between groups. Global and topographic reflectivity loss strongly predicted conversion (univariable ORs up to 1.85 per 1% decrease; 95% confidence interval [CI], 1.38-2.72). RNFL thickening was also predictive (univariable ORs up to 1.64 per 1-&#xb5;m increase; 95% CI, 1.25-2.32). Both metrics remained significant in multivariable models, whereas drusen volume, pigmentary abnormalities, and fellow-eye status did not.<br><br>CONCLUSIONS: Inner retinal reflectivity loss with mild thickening is a strong predictor of short-term progression to nAMD. These OCT-derived biomarkers showed stronger associations with conversion than traditional risk factors and may improve short-term risk stratification and monitoring.}, }
@article {pmid41701337, year = {2026}, author = {Gilead, N and Chong, YJ and Lim, J and Teo, KYC and Ohno-Matsui, K and Cheung, CMG}, title = {ROLE OF INFLAMMATION IN ATROPHY DEVELOPMENT AND PROGRESSION IN PATHOLOGIC MYOPIA.}, journal = {Retina (Philadelphia, Pa.)}, volume = {46}, number = {3}, pages = {465-476}, doi = {10.1097/IAE.0000000000004697}, pmid = {41701337}, issn = {1539-2864}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; Disease Progression ; *Myopia, Degenerative/diagnosis/physiopathology/complications ; Atrophy/etiology ; *Tomography, Optical Coherence/methods ; Middle Aged ; Aged ; Fluorescein Angiography/methods ; Follow-Up Studies ; Inflammation ; Visual Acuity ; Fundus Oculi ; Adult ; }, abstract = {PURPOSE: To describe the progression of atrophy in pathologic myopia eyes with prior retinal inflammatory lesions consistent with punctate inner choroidopathy.<br><br>METHODS: Retrospective case series of 21 eyes with pathologic myopia and resolved retinal inflammatory lesions compared with 26 noninflamed controls (14 fellow eyes; 12 external myopic eyes with pre-existing patchy atrophy). The primary outcome was annual atrophy-area change (mm2/year) on multimodal imaging. Secondary outcomes included incident/enlarging atrophy, multifocal versus unifocal appearance, and META-PM category progression. Group comparisons used Welch t tests and Fisher exact tests; an age-adjusted linear regression examined independent associations.<br><br>RESULTS: Over 5.2 &#xb1; 3.2 years in inflamed eyes and 5.3 &#xb1; 2.4 years in controls, patchy atrophy progressed faster with inflammation (0.76 &#xb1; 0.67 vs. 0.38 &#xb1; 0.47 mm2/year; P = 0.03). Among eyes starting in myopic macular degeneration Category 1 to 2, incident atrophy occurred in 14 of 14 (100%) inflamed versus 4 of 11 (36.4%) controls (P < 0.01). Overall atrophy activity (new or enlarging) was 21 of 21 (100%) in inflamed eyes versus 19 of 26 (73.1%) controls (P < 0.01). Multifocal atrophy was more frequent with inflammation (15/21, 71.4%) than in controls (6/26, 23.1%; P < 0.01). In age-adjusted regression, inflammation remained independently associated with faster atrophy expansion (&#x3b2; = 0.41 mm2/year; 95% CI, 0.04-0.78; P = 0.033).<br><br>CONCLUSION: In pathologic myopia, prior retinal inflammation is independently associated with more frequent multifocal involvement, higher risk of incident atrophy, and a substantially faster atrophy-expansion. Beyond mechanical factors, inflammation seems to be a key driver of atrophic progression in this population.}, }
@article {pmid41701438, year = {2026}, author = {Zhang, X and Liu, ZL and Lin, X and Sun, SN and Shi, D and Tian, L and Li, Y and Jin, ZB}, title = {Wnt signaling dysregulation drives Stargardt disease pathogenesis.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {41701438}, issn = {1869-1889}, abstract = {Stargardt disease, the most common inherited juvenile macular degeneration, is primarily caused by ABCA4 mutations, yet the cellular origin of pathology remains debated. Here, we identify a critical role for Wnt signaling dysregulation, specifically non-canonical Wnt pathway suppression, in driving retinal pigment epithelium (RPE) dysfunction as a central mechanism of disease. Using patient-derived iPSC-RPE harboring distinct ABCA4 mutations, we demonstrate that ABCA4 loss disrupts RPE hexagonal morphology, reduces pigmentation, and aberrantly activates neural retinal differentiation. Mechanistically, transcriptomic and functional analyses revealed pronounced downregulation of non-canonical Wnt signaling (e.g., Wnt5a), which correlated with epithelial disorganization and ectopic neurogenesis. Notably, while canonical Wnt activation failed to rescue these pathological defects, pharmacological stimulation of non-canonical Wnt signaling restored RPE integrity and suppressed neural transdifferentiation in a mutation-dependent manner. These findings not only redefine ABCA4 as a regulator of epithelial Wnt crosstalk but also unveil a divergence in Wnt pathway vulnerability among patients. Our work positions non-canonical Wnt agonism as a therapeutic strategy for Stargardt and underscores the broader imperative for mutation-tailored interventions in inherited retinal diseases. By revealing phenotypic convergence on Wnt signaling dysregulation in ABCA4-deficient RPE, this study provides a framework for understanding epithelial-pathway-driven degeneration, with implications for AMD, fibrosis, and developmental disorders characterized by polarity loss.}, }
@article {pmid41703113, year = {2026}, author = {Frank-Publig, S and Buehl, W and Mares, V and Fuchs, P and Coulibaly, LM and Eidenberger, A and Scheschy, U and Faustmann, G and Gumpinger, M and Sükei, E and Bogunovic, H and Reiter, GS and Sacu, S and Schmidt-Erfurth, U}, title = {Artificial Intelligence-based characterization of therapeutic response in fluid types and volumes influencing retinal function in neovascular age-related macular degeneration.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {41703113}, issn = {2045-2322}, abstract = {UNLABELLED: In the real world, there are variable treatment strategies and therapeutic effects of anti-VEGF therapy in neovascular age-related macular degeneration (nAMD). To investigate mechanisms of fluid resolution in pretreated and treatment-naïve eyes, we aimed to compare treatment response through assessment of fluid types, distribution and volumes. 289 eyes of 289 real-world patients with active nAMD were included in a randomized phase III clinical trial (EudraCT-Number: 2019-003133-42). For this subanalysis, data from baseline and month 1 was collected in 285 eyes. All eyes received treatment at baseline, OCT imaging (Spectralis, Heidelberg Engineering, Germany) and standardized functional testing at both visits. Subretinal fluid (SRF), intraretinal fluid (IRF), pigment epithelial detachment (PED) were automatically quantified. Absolute and relative fluid resolution and BCVA changes were compared. Treatment-naïve eyes had higher IRF volumes before treatment and a higher reduction of IRF (p < 0.01), with no differences for SRF and PED. Accordingly, treatment-naïve patients had a significantly higher gain of BCVA with + 4.6 letters compared to + 1.2 letters (p < 0.01). Precise quantification and compartment distinctions of retinal fluid revealed treatment-naïve eyes showed greater resolution rates for IRF with consecutive significant visual improvement, suggesting that IRF dynamics are particularly relevant and volume-related, especially in the acute phase.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-40138-w.}, }
@article {pmid41703247, year = {2026}, author = {Lolli, I and Pignataro, MG and Termite, AC and Ribezzi, G and Boscia, G and Borrelli, E and Reibaldi, M and Alessio, G and Boscia, F and Viggiano, P}, title = {The progressive journey of poor-responder neovascular AMD: tracking structural evolution and visual decline over time.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41703247}, issn = {1476-5454}, abstract = {PURPOSE: To characterise the natural history of poor-responder neovascular age-related macular degeneration (AMD) by tracking structural evolution and visual decline over time.<br><br>METHODS: This retrospective longitudinal study analysed 70 eyes of 70 treatment-naive neovascular AMD patients who completed loading dose therapy, received &#x2265;7 injections in the first year, and experienced &#x2265;10 ETDRS letter visual acuity (BCVA) loss from post-loading baseline. Spectral-domain OCT imaging and BCVA were evaluated at three timepoints: baseline (post-loading), 10-letter loss, and worst visual outcome. Multivariate regression analysis identified independent predictors of visual acuity at each timepoint. Primary structural parameters assessed included macular atrophy, subretinal fibrosis, external limiting membrane (ELM) and ellipsoid zone (EZ) integrity, central retinal thickness (CRT), and fluid parameters.<br><br>RESULTS: Mean follow-up was 38.5&#x2009;&#xb1;&#x2009;22.8 months. Macular atrophy progression was dramatic (7.1%&#x2009;&#x2192;&#x2009;41.4%&#x2009;&#x2192;&#x2009;81.4%, p&#x2009;<&#x2009;0.001) and subretinal fibrosis increased substantially (11.4%&#x2009;&#x2192;&#x2009;25.7%&#x2009;&#x2192;&#x2009;57.1%, p&#x2009;<&#x2009;0.001). CRT showed paradoxical biphasic evolution (262.6&#x2009;&#x2192;&#x2009;278.6&#x2009;&#x2192;&#x2009;252.0&#x2009;&#x3bc;m). Multivariate analysis revealed three distinct phases: no independent predictors at baseline, comprehensive multi-pathway model at 10-letter loss with subretinal fibrosis (&#x3b2;&#x2009;=&#x2009;-0.536), hyperreflective material (&#x3b2;&#x2009;=&#x2009;-0.350), and intraretinal fluid (&#x3b2;&#x2009;=&#x2009;-0.223) as independent predictors (R&#xb2;&#x2009;=&#x2009;0.428), and fibrotic dominance at worst outcome where subretinal fibrosis emerged as the sole predictor (&#x3b2;&#x2009;=&#x2009;-0.469, R&#xb2;&#x2009;=&#x2009;0.220). CRT showed no predictive value across all timepoints.<br><br>CONCLUSIONS: Poor-responder neovascular AMD follows a three-phase evolutionary journey with subretinal fibrosis as the dominant independent predictor of visual decline. These findings demand a paradigmatic shift toward qualitative structural assessment focusing on fibrotic changes rather than thickness-based monitoring.}, }
@article {pmid41703248, year = {2026}, author = {Viggiano, P and Borrelli, E and Giannaccare, G and Reibaldi, M and Boscia, F}, title = {Response to: 'Comment on: 'Photobiomodulation-induced choriocapillaris perfusion enhancement and outer retinal remodelling in intermediate age-related macular degeneration: a promising therapeutic approach with short-term results".}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41703248}, issn = {1476-5454}, }
@article {pmid41703599, year = {2026}, author = {Yu, J and Zhang, Y and Gao, YL and Xu, JM and Chen, H and Ho, M and Kam, KW and Young, AL and Pang, CP and Tham, CC and Yam, JC and Chen, LJ}, title = {Metabolic vulnerability index and MetaboHealth score as risk factors for age-related macular degeneration in a large-scale prospective cohort.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-026-07863-2}, pmid = {41703599}, issn = {1479-5876}, }
@article {pmid41704651, year = {2026}, author = {Wong, MW and Li, H and Dan, YS and Lor, SC and Soh, R and Hoang, QV and Chong, RS}, title = {Associations between Intraocular Pressure or Glaucoma Medication with Axial Length and Pathologic Myopia Incidence and Progression.}, journal = {Ophthalmology science}, volume = {6}, number = {3}, pages = {101061}, pmid = {41704651}, issn = {2666-9145}, abstract = {OBJECTIVE: To investigate the relationship between intraocular pressure (IOP) and antiglaucoma medications on both the incidence and progression of myopic macular degeneration (MMD), posterior staphyloma and axial length (AXL) elongation in highly myopic (HM) eyes.<br><br>DESIGN: A retrospective multiethnic cohort study with cross-sectional and longitudinal analyses.<br><br>Nine hundred eighty-eight HM eyes from 518 multi-ethnic subjects assessed at the Singapore National Eye Centre (2017-2022). Eyes with glaucoma or on existing IOP-lowering therapy were excluded from the primary analyses. Secondary cross-sectional and longitudinal analyses included eyes with glaucoma to explore medication effects.<br><br>METHODS: Intraocular pressure was measured with noncontact tonometry. Logistic and linear regression models assessed associations between IOP and MMD/staphyloma presence and progression and AXL elongation. Multivariate analysis was performed to identify independent predictors of progression, including effects of antiglaucoma medication use.<br><br>MAIN OUTCOME MEASURES: Presence and progression of MMD and staphyloma, current AXL, and AXL elongation as determined by imaging and clinical examination. Progression was defined by changes in MMD grade, atrophic lesions, or structural staphyloma features over time.<br><br>RESULTS: In nonglaucomatous eyes, IOP was not significantly associated with the presence or progression of MMD, staphyloma, or AXL (all P > 0.05). Across all eyes, longer AXL was correlated with earlier spectacle onset, worse visual acuity, longer anterior chamber depth, presence of tilted disc, superior peripapillary atrophy, vitreomacular traction, staphyloma, epiretinal membrane, dome- or saddle-shaped macula, and lacquer crack (P < 0.05). In longitudinal analyses, baseline glaucoma medication use was significantly associated with reduced AXL elongation over time (&#x3b2; = -0.077, P = 0.036), independent of IOP, whereas tilted disc and staphyloma presence predicted greater elongation (P < 0.05). Myopic macular degeneration and staphyloma progression were primarily associated with structural factors, including presence of sloped fovea, macular retinoschisis, epiretinal membrane, and dome- or saddle-shaped macula at baseline (P < 0.05).<br><br>CONCLUSIONS: Intraocular pressure was not associated with pathologic myopia-related structural changes or AXL in HM eyes. In contrast, use of antiglaucoma medications was associated with reduced AXL elongation. These findings suggest the potential for IOP-independent pharmacologic modulation of AXL in HM eyes.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41705769, year = {2026}, author = {Huang, L and Cong, L and Grzybowski, A}, title = {Tobacco-Attributable Age-Related Macular Degeneration Vision Impairment in Japan: A National and Prefecture-Level Analysis From 1990 to 2040.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {2}, pages = {23}, pmid = {41705769}, issn = {2164-2591}, mesh = {Humans ; Japan/epidemiology ; *Macular Degeneration/epidemiology/etiology ; Male ; Female ; Aged ; Prevalence ; Disability-Adjusted Life Years ; *Vision Disorders/epidemiology/etiology ; Aged, 80 and over ; Middle Aged ; Cost of Illness ; Global Burden of Disease ; }, abstract = {PURPOSE: This study aimed to analyze the spatiotemporal burden of vision impairment due to age-related macular degeneration (AMD) in Japan from 1990 to 2021, projecting to 2040.<br><br>METHODS: Using data from the Global Burden of Disease (GBD) study, we systematically analyzed the prevalence, disability-adjusted life years (DALYs), and temporal trends of vision impairment due to AMD in Japan from 1990 to 2021 and projected disease burden to 2040. We also quantified the burden of vision impairment due to AMD attributable to tobacco.<br><br>RESULTS: From 1990 to 2021, the number of AMD-related vision impairment cases increased by 159% to 93,310 (95% uncertainty interval [UI], 78,103-112,033); DALYs increased by 134% to 8907 (95% UI, 5984-12,298). However, the age-standardized prevalence rates declined from 22.3 to 19.73 per 100,000, and DALY rates decreased from 2.34 to 1.94. Prevalence was slightly higher in females, although the DALY rate difference was minimal. Burden disparities across all 47 prefectures were small. The contribution of tobacco to age-standardized DALYs decreased by 36.3%. Projections to 2040 estimate a 42.51% increase in total cases, with a rise in the age-standardized prevalence rate among males but a decline continuing among females.<br><br>CONCLUSIONS: Despite an increase in absolute cases, age-standardized rates of AMD-related vision impairment in Japan declined from 1990 to 2021, likely due to universal health insurance coverage and effective tobacco control policies. This supports ongoing investment to alleviate the burden in an aging society.<br><br>TRANSLATIONAL RELEVANCE: Translating 30-year population data, this study shows that tobacco control and healthcare equity reduce AMD-related vision impairment burden, informing vision loss prevention in aging societies.}, }
@article {pmid41707077, year = {2026}, author = {Pandya, BU and Mihalache, A and Huang, RS and Jhaveri, A and Cao, X and Ballios, B and Felfeli, T}, title = {Effectiveness and Safety of Biosimilar Anti-Vascular Endothelial Growth Factor for Retinal Diseases: A Systematic Review and Meta-Analysis.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004807}, pmid = {41707077}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate the comparative effectiveness and safety of biosimilar anti-vascular endothelial growth factor (VEGF) versus reference anti-VEGF intravitreal injections for the treatment of retinal diseases.<br><br>METHODS: A systematic review and meta-analysis was performed on studies identified through searches of OVID MEDLINE, Embase, and the Cochrane Library between January 2015 and September 2024. Studies evaluating effectiveness and/or safety outcomes of biosimilar anti-VEGF were included. Meta-analysis was performed with a random effects model. Risk of bias (ROB) assessment was performed with the Joanna Briggs Institute (JBI) tools, and certainty of evidence was evaluated with the GRADE criteria.<br><br>RESULTS: A total of 25 studies were included in the meta-analysis. Diagnoses studied were neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and polypoidal choroidal vasculopathy. There were no significant differences in final visual acuity (VA), change in VA, final retinal thickness (RT), change in RT, and incidence of adverse events over a follow-up duration of 12-63.6 weeks. Subgroup analyses of randomized controlled trials, observational studies, AMD, DME, and agent-specific analysis (aflibercept and ranibizumab) were not significant. Findings are supported by evidence of moderate to high certainty as per the GRADE tool. There was a low to moderate ROB in the included study as per the JBI tool.<br><br>CONCLUSION: Biosimilar anti-VEGF is comparable to reference anti-VEGF with respect to safety profile and visual outcomes. Future research should prioritize including diverse patient populations and adopting standardized, extended follow-up periods to enhance the assessment of long-term safety and effectiveness of biosimilars.}, }
@article {pmid41707600, year = {2026}, author = {Posnic, A and Vaast, M and Poinas, A and Le Pabic, E and Bellamy, JP and Delhay, C and Faure, S and Le Rouic, JF and Henry, A and Lebreton, O and Masse, H and Guillaumie, T and Fournier, I and Mainguy, A and Le Lez, ML and Khanna, RK and George, A and Pipelart, V and Bernard, Y and Grimbert, P and Mazhar, D and Benzerroug, M and Briend, B and Clement, M and Jammes-Veaux, HP and Posnic, MP and Bonissent, A and Guyot, C and Rousseau, N and Trinh Van Dam, B and Bellot, L and Ferron, R and Le Meur, G and Mouriaux, F and Weber, M and Maucourant, Y and Ducloyer, JB}, title = {Extension of the intravitreal injection interval after switching to faricimab in patients with exudative AMD: The multicenter FAR WEST study.}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {3}, pages = {104795}, doi = {10.1016/j.jfo.2026.104795}, pmid = {41707600}, issn = {1773-0597}, abstract = {PURPOSE: To assess whether switching to faricimab allowed extending injection intervals without exudation in patients with neovascular age-related macular degeneration (nAMD) and to identify predictive factors for interval extension.<br><br>METHODS: FAR WEST was a multicenter, observational retrospective cohort study, including patients with nAMD treated with intravitreal anti-VEGF injections (IVI) for at least one year prior to switching to faricimab. Data were collected from the medical records at the time of the decision to switch to faricimab (M0) and at the M6 follow-up visit. The switch strategy (whether an induction phase was performed or not) was left to the practitioner's discretion.<br><br>RESULTS: A total of 814&#xa0;eyes of 705&#xa0;patients were included in 23&#xa0;centers. The recurrence-free IVI interval increased significantly from 5.6&#xa0;weeks at M0 to 7.2&#xa0;weeks at M6 (+1.6&#xa0;weeks, P<0.0001). The proportion of exudative patients decreased by 37% (P<0.0001). Among 228&#xa0;refractory cases at M0, 88 (39%) achieved a dry macula at M6. A greater interval extension was found in patients who underwent immediate extension. No significant differences were observed in terms of age, time since first injection, type of neovascularisation, or pre-switch IVI interval. The intraocular inflammation rate was 0.6% (n=5).<br><br>CONCLUSION: Switching to faricimab allowed for significantly extending the recurrence-free IVI interval and decreasing the proportion of exudative patients in this cohort. Significant extension was found in a wide range of patients, including those without a loading phase. Further controlled prospective studies are needed to assess the value of a loading phase when switching to faricimab. Safety outcomes were consistent with prior studies.}, }
@article {pmid41708012, year = {2026}, author = {Stuard Sambhariya, W and Bowes Rickman, C and D'Amore, PA and Corradetti, G and Hageman, GS and Howell, GR and Marola, OJ and Phatnani, H and Philp, NJ and Sinha, D and Toomey, CB and Stone, F and Eberhart, C and Handa, JT}, title = {Age-related macular degeneration and cerebral amyloid angiopathy have similar pathologies from cholesterol-APOE-amyloid-β-complement mediated inflammation.}, journal = {Progress in retinal and eye research}, volume = {111}, number = {}, pages = {101449}, pmid = {41708012}, issn = {1873-1635}, support = {R01 EY031594/EY/NEI NIH HHS/United States ; R01 EY033765/EY/NEI NIH HHS/United States ; R01 EY035805/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Cerebral Amyloid Angiopathy/metabolism/pathology ; *Amyloid beta-Peptides/metabolism ; *Macular Degeneration/metabolism/pathology ; *Cholesterol/metabolism ; *Inflammation/metabolism/pathology ; *Apolipoproteins E/metabolism ; *Complement System Proteins/metabolism ; Alzheimer Disease/metabolism/pathology ; }, abstract = {Age-related macular degeneration (AMD) and Alzheimer's disease (AD) are neurodegenerative conditions that afflict millions of elderly people around the world. AMD is a progressive retinal disorder that leads to central vision loss whereas AD primarily causes cognitive decline and behavioral changes. While each disease has distinct clinical manifestations, the accumulation of extracellular amyloid-β is a common histopathologic finding. Similarly, cerebral amyloid angiopathy (CAA), a vascular condition that can exist independent or with AD, is characterized by the accumulation of amyloid-β in cerebral blood vessels. While significant investigation of the pathophysiologic links between AMD and AD has been conducted, the underlying similarities and differences in the pathobiology of AMD and CAA has not been considered. In this review, we discuss the common pathological features of these two conditions. We then discuss the similar pathobiology that involves cholesterol metabolism, apolipoprotein E, amyloid-β, and complement mediated inflammation. At the same time, we discuss key differences in their pathobiology. This discussion sheds new perspective and insights of their pathobiology.}, }
@article {pmid41709128, year = {2026}, author = {Öncül, H and Dertsiz Kozan, B and Dağ, U and Çağlayan, M and Alakuş, MF and Temel, C and Utlu, ES}, title = {Evaluation of primary care physicians' knowledge, attitudes, and awareness levels regarding age-related macular degeneration.}, journal = {BMC primary care}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12875-026-03228-2}, pmid = {41709128}, issn = {2731-4553}, }
@article {pmid41709226, year = {2026}, author = {Villarruel Hinnerskov, JM and Nielsen, MK and Thomsen, AK and Steffensen, MA and Honoré, B and Vorum, H and Nissen, MH and Sørensen, TL}, title = {Complement regulatory proteins are associated with progression rate of geographic atrophy secondary to age-related macular degeneration.}, journal = {Immunity &amp; ageing : I &amp; A}, volume = {23}, number = {1}, pages = {}, pmid = {41709226}, issn = {1742-4933}, abstract = {BACKGROUND: Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is a progressive degenerative disease leading to irreversible vision loss in elderly individuals. The complement system, including the alternative pathway (AP) forms an essential part of the innate immune system. Since dysregulation of the complement system has been strongly associated with the development and progression of GA, we sought to investigate the expression of specific regulators of the complement system, known as complement regulatory proteins (Cregs), in relation to progression rate (PR) of disease in patients with GA.<br><br>RESULTS: Using flow cytometry, we determined the proportion of Cregs on peripheral blood leukocytes drawn from patients with GA. Patients were genotyped for risk-associated SNP (CFH rs1061170, ARMS2 rs10490924) and serial fundus autofluorescence images were used to determine the PR of atrophic lesions. Patients with fast GA progression had a lower proportion of CD59 on CD8&#x2009;+&#x2009;T cells compared to patients with slow progression of disease (p&#x2009;=&#x2009;0.025), suggesting that dysregulated CD59 could be involved in progression of GA. Patients with high-risk CFH genotypes had a higher proportion of CD59 on classical monocytes compared to patients carrying the low-risk genotype (p&#x2009;=&#x2009;0.044).<br><br>CONCLUSION: Our findings indicate that GA progression is associated with dysregulation of complement regulators, and Cregs could serve as a novel target for treatment of GA. However, further studies are needed to elucidate their role in GA pathogenesis and to evaluate their potential as future complement-targeting drugs.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-026-00562-y.}, }
@article {pmid41710168, year = {2026}, author = {Estreicher, A and Biedka, K and Błaszczyk, K and Wesołowski, M and Bulski, J and Sobaś, AE and Ziobro, O and Maj, FJ and Sornat, KB and Klasa, AM and Żełabowski, K and Karwacki, J and Sebzda, T}, title = {The Amsler Grid in Everyday Practice: A Review of Its Role and Limitations in Primary Care.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {542357}, pmid = {41710168}, issn = {1177-5467}, abstract = {This narrative review provides a comprehensive overview of current evidence on the use of the Amsler grid as a simple and cost-effective tool for detecting central visual field defects, particularly in macular disorders such as age-related macular degeneration (AMD). Despite the availability of advanced imaging techniques like optical coherence tomography (OCT), the grid remains valuable in primary care and home monitoring due to its accessibility and ease of use. This review includes studies evaluating its diagnostic performance, clinical applications, and recent digital adaptations, with a focus on early detection and patient self-monitoring. It facilitates early detection of visual disturbances, enabling timely diagnosis and intervention. The test is applicable in various retinal conditions, including AMD, diabetic macular edema, central serous chorioretinopathy, and epiretinal membrane. Although its diagnostic accuracy varies depending on the condition and stage, clinical studies support its reliability as an adjunctive tool in everyday practice. Recent developments include mobile and web-based platforms, as well as integration with artificial intelligence, which may enhance diagnostic accuracy, enable longitudinal monitoring, and improve patient adherence. Early detection is crucial for preserving vision and reducing the global burden of visual impairment.}, }
@article {pmid41711523, year = {2026}, author = {He, R and Ding, W and Cao, J and Guo, C and Li, X and Xiao, G}, title = {Ergothioneine: Evaluation of a Novel Antioxidant for Targeting Ocular Oxidative Stress.}, journal = {Current eye research}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/02713683.2026.2618755}, pmid = {41711523}, issn = {1460-2202}, abstract = {PURPOSE: To evaluate ergothioneine (EGT), a naturally occurring amino acid and endogenous antioxidant, as a novel therapeutic agent for oxidative stress-related ocular diseases. This evaluation specifically aimed to address the challenge of targeted ocular delivery by assessing EGT's antioxidant potency, stability, ocular tolerance, and crucially, its ability to reach the posterior segment (fundus) via topical administration.<br><br>METHODS: This study evaluated EGT as a novel ocular antioxidant by examining its radical scavenging capacity (DPPH assay compared to glutathione, astaxanthin, and coenzyme Q10), stability (at 40&#x2009;&#xb0;C/75% relative humidity for six months using HPLC), ocular tolerance (using a New Zealand rabbit model), and fundus delivery efficiency (topical D9-EGT eye drops quantified by LC-MS/MS).<br><br>RESULTS: EGT demonstrated significantly superior radical scavenging activity, exhibiting 6.4-fold and 46-fold higher rates than glutathione and coenzyme Q10, respectively, at 50&#x2009;ppm. It also showed excellent stability, retaining over 97% of its initial concentration after six months, and caused no ocular irritation at any tested concentration (score 0). Importantly, topical administration of EGT resulted in effective fundus delivery, with peak concentrations reached at 0.5&#x2009;h post-application (1181&#x2009;&#xb1;&#x2009;56&#x2009;ng/g), confirming successful penetration through corneal and scleral barriers. These findings establish EGT as a potent, multi-mechanistic antioxidant characterized by high stability, ocular safety, and exceptional posterior segment penetrance via noninvasive eye drops.<br><br>CONCLUSION: These findings establish EGT as a potent, multi-mechanistic antioxidant characterized by high stability, ocular safety, and exceptional posterior segment penetrance via noninvasive eye drops. By overcoming key delivery limitations, EGT presents a promising therapeutic strategy for oxidative stress-related ocular diseases such as age-related macular degeneration and diabetic retinopathy. Further studies are warranted to evaluate its long-term efficacy and clinical translation potential.}, }
@article {pmid41712059, year = {2026}, author = {Barbosa, M and Bartolomeo, N and Schuetz, YP and Nascimbeni, AC and Castro, DG and Barry, MP and Ambresin, A}, title = {Loading dose and 12-month outcomes in treatment-naïve patients with neovascular age-related macular degeneration treated with faricimab, with AI-based analysis of fluid dynamics.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {124}, pmid = {41712059}, issn = {1573-2630}, mesh = {Humans ; Male ; Female ; Intravitreal Injections ; *Visual Acuity ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; Treatment Outcome ; Aged, 80 and over ; Follow-Up Studies ; Fluorescein Angiography/methods ; *Artificial Intelligence ; Hydrodynamics ; Dose-Response Relationship, Drug ; Time Factors ; Fundus Oculi ; Middle Aged ; Subretinal Fluid ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To evaluate the effects of loading dose and 12 months of faricimab treatment on visual function, retinal anatomy, and fluid dynamics in a real-world cohort of treatment-naïve patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Patients received intravitreal faricimab 6&#xa0;mg monthly (to Month 4) followed by personalized treat-and-extend regimens allowing 4-week interval adjustments. Best-corrected visual acuity (BCVA), retinal anatomy, and fluid dynamics (evaluated using an artificial intelligence-based automated fluid quantification system) were assessed monthly to Month 4, then at Months 6, 9, and 12.<br><br>RESULTS: Fifty-one patients (57 study eyes; mean [SD] BCVA: 66.5 [13.4] letters; mean [SD] central retinal thickness [CRT]: 340.7 [84.7] &#x3bc;m at baseline) were enrolled. Significant improvements in mean BCVA (+&#x2009;3.3 letters; P&#x2009;<&#x2009;0.001) and CRT (-&#x2009;70.5&#xa0;&#x3bc;m; P&#x2009;<&#x2009;0.001) were observed by Month 4. Maximal pigment epithelium detachment (PED) height reduced significantly from baseline to Month 4. Improvements were maintained to Month 12. Intra- and subretinal fluid and PED volumes were significantly reduced versus baseline at all time points. At Month 12, 73.3% of patients were on treatment intervals of 12&#xa0;weeks or longer. Three adverse events were observed, including one mild intraocular inflammation.<br><br>CONCLUSION: Treatment with faricimab resulted in rapid and sustained functional and anatomical improvements in treatment-na&#xef;ve nAMD.}, }
@article {pmid41712218, year = {2026}, author = {Pitcher, JD and Koh, AHC and Tan, CS and Vakharia, P and Dagincourt, N and Patel, S and Yang, M and Margaron, P and Gallego-Pinazo, R}, title = {Rapid Fluid Resolution and Durability With Faricimab in Neovascular Age-Related Macular Degeneration.}, journal = {JAMA ophthalmology}, volume = {144}, number = {3}, pages = {269-272}, pmid = {41712218}, issn = {2168-6173}, mesh = {Humans ; *Subretinal Fluid/drug effects/metabolism ; Double-Blind Method ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Male ; Female ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Aged ; Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence ; Receptors, Vascular Endothelial Growth Factor ; Recombinant Fusion Proteins ; Treatment Outcome ; Fluorescein Angiography ; Dose-Response Relationship, Drug ; Follow-Up Studies ; Middle Aged ; Antibodies, Bispecific ; }, abstract = {IMPORTANCE: In the TENAYA and LUCERNE randomized clinical trials (RCTs), approximately 80% of study participants with treatment-naive neovascular age-related macular degeneration (nAMD) achieved at least every-12-week faricimab dosing at week 112. Subsequent post hoc analyses showed more rapid drying with faricimab compared with aflibercept, 2 mg, during the initial head-to-head dosing phase (weeks 0-12).<br><br>OBJECTIVE: To investigate whether rapid drying with faricimab, specifically intraretinal fluid (IRF) and subretinal fluid (SRF) resolution through week 12, is associated with later treatment durability.<br><br>This is a post hoc analysis of faricimab-treated study participants from the TENAYA and LUCERNE RCTs, which were randomized, double-masked, multicenter, noninferiority studies of the efficacy and safety of faricimab, 6 mg, up to every 16 weeks vs aflibercept, 2 mg, every 8 weeks. Study participants in this post hoc analysis were those who had treatment-naive nAMD and were in the faricimab arm of TENAYA and LUCERNE. Data analysis was performed from July 2024 to December 2025.<br><br>INTERVENTION: Faricimab, 6 mg, up to every 16 weeks after 4 loading doses (received once every 4 weeks). Following disease activity assessments at week 20 or 24, participants received fixed dosing up to every 16 weeks until week 60 and then a treat-and-extend-based dosing regimen.<br><br>MAIN OUTCOMES AND MEASURES: Multinomial logistic regression modeling was used to test the association between resolution of IRF and SRF through week 12 and the faricimab treatment interval at week 20 or 24 (the first opportunity to extend treatment intervals) and at week 112 (study completion).<br><br>RESULTS: This analysis included 552 participants with their dosing interval at week 20 or 24 available (265 participants with IRF and SRF resolution and 287 without resolution); among them, 478 patients had their dosing interval at 112 weeks available (223 participants with IRF and SRF resolution and 255 without resolution). Study participants with IRF and SRF resolution through week 12, compared with those without resolution through week 12, were more likely to receive every-16-week dosing than every-8-week dosing (odds ratio [OR], 1.99; 95% CI, 1.23-3.21; P&#x2009;=&#x2009;.005) and to receive every-12-week dosing than every-8-week dosing (OR, 1.77; 95% CI, 1.09-2.87; P&#x2009;=&#x2009;.02) at week 20 or 24, and they were more likely to receive every-16-week dosing than every-8-week dosing at week 112 (OR, 1.76; 95% CI, 1.10-2.83; P&#x2009;=&#x2009;.02).<br><br>CONCLUSIONS AND RELEVANCE: These findings suggest that rapid fluid resolution through week 12 with faricimab may be a predictor of extended durability (dosing intervals of every 12 weeks or longer) in participants with nAMD.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03823287 and NCT03823300.}, }
@article {pmid41712907, year = {2026}, author = {Sather, RN and Chiang, T and Moon, JY and Dev, S and Belin, PJ}, title = {Real-World Durability of Aflibercept 8 mg and Faricimab in Initiators Versus Switchers: A Multicenter Retrospective Analysis.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004813}, pmid = {41712907}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate real-world differences in treatment durability, functional, and anatomical outcomes in patients who initiated or switched to aflibercept 8 mg or faricimab.<br><br>METHODS: Patients were categorized into four cohorts: (1) initiators of aflibercept 8 mg, (2) initiators of faricimab, (3) switchers to aflibercept 8 mg, and (4) switchers to faricimab. Switchers were further stratified as early (&#x2264;5 prior injections) or late (>5 injections). Treatment durability was assessed using the mean treatment interval, defined as the average of the three most recent injection intervals before or after the switch. Multivariate linear regression models were used to assess the independent effect of treatment strategy on durability, best-corrected visual acuity (BCVA), and central subfield thickness (CST).<br><br>RESULTS: A total of 10,247 patients (12,501 eyes) with either nAMD, DME, or RVO initiated aflibercept 8 mg or faricimab. Initiators achieved greater mean treatment intervals (10 weeks) than switchers (9 weeks post-switch; p < 0.01). Early switchers showed greater durability and CST reduction (-66 &#xb5;m) than late switchers (-19 &#xb5;m; p < 0.01). Faricimab initiators had greater durability (p < 0.01) and CST reductions (p = 0.01) compared to other cohorts. Medicare coverage was associated with longer durability than Medicare Advantage recipients (p < 0.01).<br><br>CONCLUSION: In this real-world cohort, initiation of faricimab or aflibercept 8 mg was associated with greater treatment intervals and improved anatomical outcomes compared to eyes that were switched from older anti-VEGF agents. These findings support early initiation of these anti-VEGF therapies and that step-therapy delays may compromise clinical outcomes.}, }
@article {pmid41713160, year = {2026}, author = {Ashrafi, S and Sajedi, H}, title = {Task-specific neural networks for medical imaging using pretrained fragments.}, journal = {Computers in biology and medicine}, volume = {204}, number = {}, pages = {111545}, doi = {10.1016/j.compbiomed.2026.111545}, pmid = {41713160}, issn = {1879-0534}, mesh = {Humans ; *Neural Networks, Computer ; Algorithms ; *Image Processing, Computer-Assisted/methods ; *Retina/diagnostic imaging ; }, abstract = {The StitchNet framework introduced a paradigm shift in Neural Architecture Search (NAS) by proposing the construction of neural networks from pre-trained fragments. This approach reduces computational costs and enables task-specific model creation without retraining entire networks. Building on this foundation, our study evaluates the practical application of StitchNet in constructing neural networks tailored to medical image classification tasks. Specifically, we assess its performance on a dataset of retinal images classified into three categories: healthy, dry, and wet AMD (Age-Related Macular Degeneration), namely drusen and choroidal neovascularization (CNV). By employing fragments from five pre-trained networks and integrating techniques such as recurrent neural networks (RNNs) and autoencoders, we aim to validate and enhance StitchNet's capabilities. Our findings demonstrate that while StitchNet achieves competitive accuracy with reduced computational overhead, incorporating domain-specific optimizations further improves its adaptability and efficiency. So, the developed network outperforms a scientist-designed network by 6%. In the next phase, we will explore ways to improve the algorithm's efficiency and minimize the data required for processing. Fully reproducible code here: https://github.com/ShafighAshrafi/stitchnet.}, }
@article {pmid41713794, year = {2026}, author = {Liao, X and Lou, J and Liu, C and Wang, Y and Zhu, G and Ke, Y and Bai, M and Yang, P and Yang, W and Chi, W}, title = {Advancements in OCT and OCTA Imaging for AMD: An In-depth Analysis of Research Hotspots, Emerging Trends, and Technological Innovations.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {}, number = {}, pages = {105402}, doi = {10.1016/j.pdpdt.2026.105402}, pmid = {41713794}, issn = {1873-1597}, abstract = {PURPOSE: To map research hotspots and emerging trends of Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) in Age-related Macular Degeneration (AMD) from 2015-2024 using bibliometric analysis.<br><br>METHODS: We searched the Web of Science Core Collection (2015-2024) on January 2025, identified 2,471 English-language articles on OCT/OCTA in AMD, and extracted data on countries, institutions, journals, keywords, and citations. CiteSpace 6.4 and Excel were used for co-occurrence/co-citation analyses and visualization; H-indexes were compiled for countries and institutions.<br><br>RESULTS: Seventy-eight countries/regions contributed to the field; the United States led in publications and H-index, followed by China. Among 200 institutions, the University of California System produced the most studies and showed the highest influence. Publication output increased steadily (R[2]&#x2248;0.69). Core topics clustered around geographic atrophy (GA), choroidal neovascularization (CNV), ranibizumab, OCT, and AMD. Recent keyword bursts highlighted macular neovascularization (MNV), hyperreflective foci (HRF), deep learning, impact, and growth. High-impact literature underscored OCT/OCTA's noninvasive vascular imaging utility, anti-VEGF treatment outcomes, GA progression metrics, and rapid advances in AI-driven detection/segmentation and prognostication. Meta-analyses reported high diagnostic accuracy of OCTA for CNV, while technical challenges (e.g., signal-to-noise) persist. Emerging themes include multimodal integration, biomarkers such as hyperreflective foci for prognosis, and time-series/AI models for predicting GA/CNV trajectories and personalizing treatment intervals.<br><br>CONCLUSION: OCT and OCTA research in AMD has expanded substantially, with the U.S. and leading academic centers driving influence. Integrating AI with OCT/OCTA enables earlier detection, refined phenotyping, and data-informed, personalized management. Advancing precision and standardization will further improve diagnostic accuracy and therapeutic decision-making in AMD.}, }
@article {pmid41714388, year = {2026}, author = {Sadeghi, E and DeCicco, J and Gandhi, P and Hasan, N and DiCenzo, B and Jiang, JY and Rahmanipour, E and Sahel, JA and Eller, AW and Chhablani, J}, title = {Differentiation of macular atrophy secondary to neovascular age-related macular degeneration vs. de novo geographic atrophy: a multimodal analysis.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41714388}, issn = {1476-5454}, abstract = {PURPOSE: To compare macular atrophy following neovascular age-related macular degeneration (nAMD) vs. geographic atrophy (GA) following dry AMD.<br><br>METHODS: We analysed 60 eyes from 44 patients: 30 eyes with de novo GA and 30 with macular atrophy secondary to nAMD. All patients had monthly follow-ups before GA onset and continued for at least two years after. GA was defined as complete retinal pigment epithelium atrophy &#x2265;250&#x2009;&#x3bc;m using OCT scans. OCT biomarkers at GA onset, including central macular thickness (CMT), subfoveal choroidal thickness (SFCT), epiretinal membrane (ERM), double-layer sign (DLS), subretinal hyperreflective material (SRHM), hyperreflective foci (HRF), outer retinal tubulation (ORT), and intraretinal fluid (IRF), were assessed. Chi-square test, Spearman correlation, and linear mixed models were used.<br><br>RESULTS: The mean age was 80.06&#x2009;&#xb1;&#x2009;8.60 years, with 50.0% male. Eyes with nAMD progressed to macular atrophy after 31.38&#x2009;&#xb1;&#x2009;30.72 months and 8.86&#x2009;&#xb1;&#x2009;10.84 anti-vascular endothelial growth factor (VEGF) injections. Compared to de novo GA, eyes with macular atrophy following nAMD had larger baseline atrophic area (3.791&#x2009;&#xb1;&#x2009;2.661&#x2009;mm&#xb2; vs. 1.115&#x2009;&#xb1;&#x2009;0.951&#x2009;mm&#xb2;; P&#x2009;<&#x2009;0.001) and greater atrophy growth (2.646&#x2009;&#xb1;&#x2009;2.014&#x2009;mm&#xb2; vs. 0.652&#x2009;&#xb1;&#x2009;0.722&#x2009;mm&#xb2;; P&#x2009;<&#x2009;0.001), with more frequent ERM, DLS, HRF, SRHM, ORT, and IRF. Atrophy growth correlated with baseline SFCT (r&#x2009;=&#x2009;-0.545, P&#x2009;=&#x2009;0.002) and GA area (r&#x2009;=&#x2009;0.501, P&#x2009;=&#x2009;0.005) but not with the number of anti-VEGF injections (p&#x2009;>&#x2009;0.05).<br><br>CONCLUSION: Eyes with macular atrophy secondary to nAMD exhibit larger initial atrophic areas and faster progression compared to de novo GA. OCT biomarkers may detect previous exudation, helping identify cases where recently FDA-approved GA therapies may be relatively contraindicated due to prior disease.}, }
@article {pmid41714517, year = {2026}, author = {Shen, Y and Chen, Q and He, X and Agrawal, R and Grzybowski, A and Jin, K and Ye, X}, title = {Automated Report Generation in Ophthalmology: Integrating Artificial Intelligence, Multimodal Imaging, and Clinical Data.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {3}, pages = {1001-1020}, pmid = {41714517}, issn = {2193-8245}, support = {QZYY-2025-225//Project on Scientific and Technological Research of Traditional Chinese Medicine and Ethnic Medicine in Guizhou Province/ ; gzwkj2025-099//Science and Technology Fund Project of Guizhou Provincial Health Commission/ ; }, abstract = {Artificial intelligence (AI) has emerged as a transformative force in ophthalmology, enabling automated, accurate, and efficient clinical reporting. This review summarizes recent advances in AI-driven report generation, emphasizing the integration of multimodal imaging and clinical data. Deep learning and natural language processing (NLP) models can synthesize information from diverse sources-including fundus photography, optical coherence tomography, fluorescein angiography, and patient records-to generate structured, interpretable, and personalized diagnostic reports. Such systems enhance diagnostic precision, streamline workflow, and reduce interobserver variability. We outline the technological foundations underlying these systems, including convolutional and transformer-based architectures, self-supervised and multimodal learning, and large language models. Representative applications in diabetic retinopathy, glaucoma, cataract, and age-related macular degeneration are discussed, highlighting their clinical value and emerging real-world deployment. Persistent challenges-including data heterogeneity, model interpretability, ethical governance, and clinical integration-are critically reviewed. Finally, we explore future directions such as real-time AI-assisted reporting, predictive and personalized analytics, and global scalability across healthcare ecosystems. Multimodal, explainable, and clinically integrated AI systems hold promise to redefine ophthalmic diagnostics and improve both clinician efficiency and patient outcomes.}, }
@article {pmid41716475, year = {2026}, author = {Al-Latayfeh, M and Aleshawi, A and El-Mulki, OS and Baker, M and Qaddoumi, Z and Attar, D and Alma'aitah, L and Jarrah, EZ and Abu Khalil, Z and Awad, W and Dayeh, MR and Al Beiruti, S and Al-Dwairi, R}, title = {Accuracy and Reproducibility of Different Artificial Intelligence Chatbots' Responses to Patient-Based Vitreoretinal Questions: A Comparative Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {580133}, pmid = {41716475}, issn = {1177-5467}, abstract = {BACKGROUND: Generative artificial intelligence (AI) chatbots are increasingly used by patients and their reliability in complex ophthalmic conditions remains uncertain. This study aimed to compare the accuracy, comprehensiveness, and reproducibility of five AI chatbots-ChatGPT-5.o, DeepSeek R1, Meta AI, Grok 3.0, and Google Gemini 2.5 Pro-in responding to patient-centered vitreoretinal questions.<br><br>METHODS: A total of 135 questions covering diabetic retinopathy, floaters/flashes, age-related macular degeneration, retinal tear/detachment, and vitrectomy were sourced from the American Academy of Ophthalmology "Ask an Ophthalmologist" database. Each question was submitted twice to each chatbot under standardized instructions. Two board-certified vitreoretinal ophthalmologists independently graded responses for accuracy and reproducibility. Accuracy was calculated as the proportion of responses graded "Correct and Comprehensive" or "Accurate but incomplete"; reproducibility was defined as agreement between the two responses.<br><br>RESULTS: ChatGPT-5.o achieved the highest overall accuracy (94%, n=127/135, 95% CI: 89.9%-98.1%) with a reproducibility rate of 96.3% (n=130/135, 95% CI: 93.1%-99.5%). DeepSeek R1 demonstrated the greatest reproducibility (98.5%, n=133/135, 95% CI: 96.5%-100.0%) and high accuracy (92.6%, n=125/135, 95% CI: 88.1%-97.1%). Meta AI showed 91% (95% CI: 86.1%-95.9%) accuracy and 94% (95% CI: 89.9%-98.1%) reproducibility, whereas Grok 3.0 yielded the lowest accuracy (49.6%, n=67/135, 95% CI: 41.2%-58.0%) despite moderate reproducibility (88.1%, n=119/135, 95% CI: 82.7%-93.5%). Google Gemini 2.5 Pro recorded 72.6% (95% CI: 65.1%-80.1%) accuracy and the lowest reproducibility (77%, 95% CI: 69.9%-84.1%). By category, "Vitrectomy" scored the highest across all chatbots (94%, 95% CI: 87.2%-100.0%), followed by "Macular degeneration" (90%, 95% CI: 85.0%-95.0%). However, the category "Diabetic retinopathy" scored the lowest accuracy rate (64.7%, 95% CI: 52.1%-77.3%).<br><br>CONCLUSION: ChatGPT-5.o and DeepSeek R1 approached high accuracy and reproducibility comparable to clinical standards, indicating potential as patient-education tools in vitreoretinal care. However, variability across models and disease categories highlights the need for cautious clinical adoption and continued optimization to ensure safe, reliable information delivery.}, }
@article {pmid41716622, year = {2026}, author = {Rohowetz, LJ and Flynn, HW and Townsend, JH}, title = {A second occurrence of intravitreal injection-associated endophthalmitis 2 years apart.}, journal = {American journal of ophthalmology case reports}, volume = {42}, number = {}, pages = {102525}, pmid = {41716622}, issn = {2451-9936}, abstract = {PURPOSE: This case report describes a patient who developed a second episode of endophthalmitis in the same eye following intravitreal injections administered 2 years apart.<br><br>OBSERVATIONS: An 83-year-old pseudophakic male with a history of neovascular age-related macular degeneration and diabetes mellitus complained of decreased visual acuity and pain in the left eye 1 day after receiving intravitreal aflibercept 2 mg. Best-corrected visual acuity (BCVA) was light perception. The clinical examination revealed signs of endophthalmitis including fibrin and hypopyon while B-scan ultrasonography demonstrated vitreous opacities and membranes. The patient underwent vitreous tap and injection with intravitreal vancomycin, ceftazidime, and dexamethasone. Pars plana vitrectomy with posterior hyaloid detachment was performed the following day due to a relative lack of clinical improvement. Vitreous cultures ultimately demonstrated no growth and BCVA improved to baseline. Anti-VEGF therapy was resumed 3 months after the initial diagnosis of endophthalmitis. Two years later the patient presented with evidence of a second episode of endophthalmitis 4 days after receiving aflibercept 8 mg. Vitreous tap and injection was again performed and cultures revealed growth of Staphyloccoccus epidermidis. The patient demonstrated marked improvement with no evidence of residual inflammation at 2 weeks. Best-corrected visual acuity was 20/50 at 7-month follow-up examination.<br><br>CONCLUSION AND IMPORTANCE: Endophthalmitis is a rare complication of intravitreal injection. The current report describes a patient who developed a second occurrence of endophthalmitis associated with an intravitreal injection 2 years later.}, }
@article {pmid41716779, year = {2026}, author = {Hahn, W and Erffmeier, K and Schulze, M and Zahnert, F and Knake, S and Tsalouchidou, PE}, title = {Intermittent ketogenic fasting with medium-chain triglycerides improves ataxia in COQ8A-related coenzyme Q10 deficiency: A case report.}, journal = {Molecular genetics and metabolism reports}, volume = {46}, number = {}, pages = {101296}, pmid = {41716779}, issn = {2214-4269}, abstract = {BACKGROUND: Mutations in COQ8A cause primary coenzyme Q10 deficiency, which can present clinically heterogeneously: Symptoms range from cerebellar ataxia, epilepsy, encephalomyopathy, macular degeneration to nephropathy. High-dose coenzyme Q10 supplementation is widely used, yet there is little evidence on complementary strategies, particularly for non-epileptic features such as cerebellar ataxia.<br><br>CASE PRESENTATION: We report a 46-year-old female with genetically confirmed COQ8A-related coenzyme Q10 (CoQ10) deficiency, presenting with ataxia and epilepsy characterized by myoclonic and bilateral tonic-clonic seizures, who participated in a clinical protocol of ketogenic intermittent fasting, a method of intermittent fasting combined with medium-chain triglycerides (MCT) primarily designed for seizure management. The patient followed a 16:8 intermittent fasting regime combined with MCT intake for three months, followed by three months of all-alone intermittent fasting. Routine blood markers and brain MRI, including diffusion imaging were obtained before and after ketogenic fasting.<br><br>RESULTS: During the study protocol, while no seizure reduction in myoclonic seizures could be observed, ataxia - quantified by the Scale for the Assessment and Rating of Ataxia (SARA) - improved significantly from 8.5 to 6.0 during the interventions. MRI showed a trend suggesting improved cerebellar microstructural integrity.<br><br>CONCLUSIONS: This case highlights the potential of ketogenic intermittent fasting as an adjunct therapy for mitochondrial ataxia. Ketogenic intermittent fasting was associated with clinically meaningful improvement of ataxia in a patient with COQ8A-related CoQ10 deficiency, suggesting that ketogenic dietary strategies may represent a promising adjunct therapeutic approach for mitochondrial ataxia. Future research should assess this intervention in larger patient cohorts to confirm its potential benefits.}, }
@article {pmid41717027, year = {2026}, author = {Cen, S and Li, J and Reilly, J and Chen, J and Jiang, HR and Shu, X}, title = {The therapeutic potential of gypenosides for age-related macular degeneration.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1773391}, pmid = {41717027}, issn = {2296-861X}, }
@article {pmid41717163, year = {2026}, author = {Sourla, E and Zaheer, N and Chavan, R}, title = {Switching From Intravitreal Ranibizumab (Lucentis) to Biosimilar Ranibizumab (Ongavia) Injections: Insights From a Tertiary Care Eye Centre.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e101850}, pmid = {41717163}, issn = {2168-8184}, abstract = {BACKGROUND: Ranibizumab has been widely used to treat retinal conditions such as wet age-related macular degeneration, diabetic macular oedema, and macular oedema secondary to retinal vein occlusions. In 2022, the Medicines and Healthcare products Regulatory Agency (MHRA) approved Ongavia, the first biosimilar of ranibizumab. Ongavia offers comparable efficacy and safety, with a similar side effect profile to the original medication, while being more cost-effective.<br><br>METHOD: The study was conducted in the medical retina department of a tertiary care eye hospital. Data were collected from patients undergoing treatment with intravitreal ranibizumab (Lucentis) who were switched to the ranibizumab biosimilar, Ongavia, between November 2023 and February 2024.&#xa0;This study included two components. The first was a cross-sectional observational survey, in which patients being switched to Ongavia completed a satisfaction questionnaire regarding the information leaflet received and the discussions held about the switch. The second component was a retrospective review to assess the effectiveness and safety of ranibizumab biosimilar Ongavia in patients with wet AMD. After two Ongavia injections, the treatment interval for the next injection was reviewed and compared with the treatment interval with ranibizumab. Similarly, OCT scans before and after the switch were reviewed and compared. Any adverse effects documented in the clinical notes were recorded.<br><br>RESULTS: Out of 121 eyes, 92 eyes (76%) were switched to biosimilar ranibizumab (Ongavia) injections, while 18 eyes (15%) continued receiving ranibizumab injections. Patient satisfaction with the information process was 100%. Eighty-seven eyes of patients with wet AMD received more than two Ongavia injections as per the treat-and-extend protocol. Out of these 87 eyes, in 64 eyes (73.5%), injection intervals were either maintained or extended. The treatment interval was reduced in seven eyes (8%), and nine eyes (10.3%) were switched to a different anti-VEGF medication. No safety concerns were identified with biosimilar ranibizumab.<br><br>CONCLUSIONS: Patient satisfaction with the information process was high, likely due to active involvement in treatment decision-making. The results indicate that the clinical effectiveness of ranibizumab biosimilar Ongavia is comparable to ranibizumab and that it has a similar safety profile. Ongavia could serve as a cost-effective alternative, reducing healthcare system costs while maintaining high standards of patient care.}, }
@article {pmid41717238, year = {2026}, author = {Hwang, Y and Jamil, MU and Woo, KM and Kaiser, SM and Babiker, F and Rosenfeld, PJ and Waheed, NK and Fujimoto, JG}, title = {Large Hypertransmission Defects Exhibit Choriocapillaris Flow Speed Impairment in Nonexudative Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {3}, pages = {101060}, pmid = {41717238}, issn = {2666-9145}, abstract = {PURPOSE: To investigate choriocapillaris (CC) blood flow speed in regions associated with hypertransmission defects (hyperTDs) in nonexudative age-related macular degeneration (AMD) using variable interscan time analysis (VISTA) OCT angiography (OCTA).<br><br>DESIGN: Retrospective cross-sectional analysis of a prospectively collected cohort.<br><br>SUBJECTS: Thirty-one eyes from 29 subjects with nonexudative AMD.<br><br>METHODS: Patients with age-related macular degeneration were imaged using a 600 kHz A-scan rate prototype swept-source OCT with a 5 &#xd7; 5 mm field of view and 5 B-scan repeats (1.25 ms interscan time). Hypertransmission defects were traced on choroidal en face projections and categorized by their greatest linear dimension (GLD): large (&#x2265;250 &#x3bc;m), medium (63-250 &#x3bc;m), and small (<63 &#x3bc;m). Choriocapillaris blood flow speed was quantified using VISTA, which measures OCTA signal saturation dynamics across multiple interscan times. Variable interscan time analysis flow speed (VFS) was evaluated at the macula and within hyperTDs. Choriocapillaris flow speed impairment (&#x394;VFS) for each hyperTD was calculated as the difference between its VFS and the macular average. To assess spatial extent, &#x394;VFS was assessed beyond lesion boundaries. Traditional metrics of OCTA signal and flow deficits (FDs) were also evaluated.<br><br>MAIN OUTCOME MEASURES: Choriocapillaris blood flow speed impairment (&#x394;VFS) within and around hyperTDs.<br><br>RESULTS: The macular average CC VFS was 1.47 &#xb1; 0.34 ms[-1], with no significant difference between eyes with (n = 14) and without (n = 17) hyperTDs. A total of 88 hyperTDs were analyzed: 19 large, 28 medium, and 41 small. Large hyperTDs showed significant CC flow impairment (&#x394;VFS = -0.37 &#xb1; 0.18 ms[-1], Padjusted < 0.0001), with impairment extending 100 &#x3bc;m beyond lesion boundaries (Padjusted = 0.0061). Medium-sized hyperTDs demonstrated moderate impairment (&#x394;VFS = -0.30 &#xb1; 0.47 ms[-1], Padjusted = 0.031), while small hyperTDs did not. In linear mixed-effects modeling, large and medium hyperTDs were associated with significant reductions in flow speed (-0.40 ms[-1], P = 0.014; -0.31 ms[-1], P = 0.030, respectively), corresponding to approximately 25% decreases from macular average. OCT angiography signal and FD metrics also detected size-dependent flow impairment.<br><br>CONCLUSIONS: Large hyperTDs in nonexudative AMD exhibit reduced CC flow speed extending beyond the lesion boundary. Longitudinal studies will investigate whether CC flow predicts onset and progression of hyperTDs.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41719023, year = {2026}, author = {Anderer, S}, title = {Cataract Surgery Not Linked With Macular Degeneration Progression.}, journal = {JAMA}, volume = {335}, number = {11}, pages = {930}, doi = {10.1001/jama.2025.26398}, pmid = {41719023}, issn = {1538-3598}, }
@article {pmid41719329, year = {2026}, author = {Li, Y and Jing, M and Wang, W and Lin, W and Zhang, Y and Nie, T and Liu, P and Lu, WN and Chen, Y and Fielding Hejtmancik, J and Zheng, Q and Hou, L and Ma, X}, title = {DAPL1 restrains RPE PANoptosis in experimental AMD by inhibiting GRP75-mediated mitochondria-associated endoplasmic reticulum membranes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {8}, pages = {e2511926123}, pmid = {41719329}, issn = {1091-6490}, support = {2023YFC2506100//MOST | National Key Research and Development Program of China (NKPs)/ ; 82171065//MOST | National Natural Science Foundation of China (NSFC)/ ; 82571231//MOST | National Natural Science Foundation of China (NSFC)/ ; 82371081//MOST | National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Animals ; Mice ; *Mitochondria/metabolism/pathology ; *Macular Degeneration/metabolism/pathology/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; *Endoplasmic Reticulum/metabolism ; Disease Models, Animal ; *HSP70 Heat-Shock Proteins/metabolism/genetics ; Mice, Knockout ; Humans ; *Membrane Proteins/metabolism/genetics ; Calcium/metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism/genetics ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; Mice, Inbred C57BL ; *Necroptosis ; Inflammasomes/metabolism ; }, abstract = {Retinal pigment epithelium (RPE) cell damage is a critical factor of age-related macular degeneration (AMD), the leading cause of blindness among the aged population. This study focuses on the AMD susceptible gene, Death associated protein like 1 (DAPL1), and provides insights with significant therapeutic implications. DAPL1-deficient mice exhibit dry AMD-like pathological features, a phenomenon whose mechanisms have remained largely unknown. Here, we reveal that DAPL1 deficiency promotes the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs) to cause mitochondrial Ca[2+] overload and dysfunction, which triggers the activation of inflammasomes, leading RPE cells to RIPK1-mediated PANoptosis, an inflammatory programmed cell death, in an experimental dry AMD (dAMD) mouse model. Knockdown of Ripk1 in the Dapl1-/- mice RPE inhibits RPE cell PANoptosis and ameliorates the severity of dAMD pathological features. Conversely, overexpression of DAPL1 inhibits MAM formation and protects RPE cells from PANoptosis in the model. Mechanistically, DAPL1 suppresses MAM formation by downregulating GRP75 expression. This disrupts the formation of the VDAC-GRP75-IP3R axis, which comprises critical tethering proteins responsible for endoplasmic reticulum to mitochondria coupling and Ca[2+] trafficking. Knockdown of Grp75 inhibits the formation of MAM and prevents mitochondrial Ca[2+] overload, improving mitochondrial quality and inhibiting PANoptosis in RPE cells, thereby interrupting the progression of experimental dAMD in Dapl1-deficient mice. These results unveil the role of MAMs regulated by DAPL1 in RPE cell PANoptosis and AMD progression, highlighting targeting MAM formation as a potential therapeutic strategy for treating dAMD.}, }
@article {pmid41720012, year = {2026}, author = {Li, H and Xiong, Y and Zheng, Y}, title = {Hyperoside as a promising multi-target candidate for neovascular age-related macular degeneration. mechanisms involving Wnt/β-catenin signaling, oxidative stress, and inflammation suppression.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {153}, number = {}, pages = {157952}, doi = {10.1016/j.phymed.2026.157952}, pmid = {41720012}, issn = {1618-095X}, mesh = {*Oxidative Stress/drug effects ; Animals ; *Choroidal Neovascularization/drug therapy ; Inflammation/drug therapy ; *Macular Degeneration/drug therapy ; *Wnt Signaling Pathway/drug effects ; Humans ; Mice ; Mice, Inbred C57BL ; Male ; Anti-Inflammatory Agents/pharmacology ; Antioxidants/pharmacology ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology ; Vascular Endothelial Growth Factor A/metabolism ; Quercetin/analogs &amp; derivatives ; }, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD), which is primarily characterized by choroidal neovascularization (CNV), encounters limitations with current therapeutic approaches, including treatment resistance and the burden of frequent injections, highlighting the need for exploring novel effective therapeutic agents and their mechanisms for nAMD management. Oxidative stress and inflammation are core pathogenic drivers of CNV in nAMD, and hyperoside (HYP)-a major flavonoid from Cuscuta chinensis, exhibits potent antioxidant and anti-inflammatory activities. These properties position HYP as a promising candidate for addressing the unmet treatment needs of nAMD and warrant further investigation into its mechanism of action in CNV modulation.<br><br>PURPOSE: This study aimed to explore the therapeutic potential of HYP-the main active component of the traditional Chinese herb Cuscuta chinensis Lam., and to elucidate its underlying molecular mechanisms in treating nAMD.<br><br>STUDY DESIGN: A combined in vivo and in vitro experimental strategy was adopted to systematically evaluate the therapeutic efficacy of HYP against nAMD and dissect the mechanistic basis of its action on CNV progression.<br><br>METHODS: This study adopted a multi-dimensional research approach: network pharmacology was first used to predict HYP's multi-target potential in regulating inflammation, oxidative stress, and vascular endothelial growth factor (VEGF) signaling; a murine model of laser-induced CNV was established to evaluate HYP's effects on CNV lesion area, retinal/choroidal damage, and inflammatory infiltration; reactive oxygen species (ROS) levels were detected, the expression of endogenous antioxidant enzymes (Cat, Nqo1, Sod2), Vegf, pro-inflammatory cytokines (Il-1&#x3b2;, Ccl2, Il-6, Tnf-&#x3b1;), and Wnt pathway-related genes (Myc, Plcb2, Rspo1, Wnt7a/7b, Ctnnb1) and protein (&#x3b2;-catenin); lipopolysaccharide (LPS)-stimulated ARPE-19 cells were used to corroborate HYP's antioxidant, anti-inflammatory effects, and Wnt pathway inhibition; molecular docking was employed to analyze the interaction between HYP and &#x3b2;-catenin; pharmacokinetic analysis was conducted to assess HYP's distribution in ocular tissues; and integrated transcriptomic analysis (RNA-seq) and Gene Expression Omnibus (GEO) database data analyses were performed to confirm the role of the Wnt pathway in human AMD and its correlation with intraocular inflammation.<br><br>RESULTS: Network pharmacology predicted that HYP has multi-target potential against inflammation, oxidative stress, and VEGF signaling; in the murine laser-induced CNV model, HYP treatment significantly reduced CNV lesion area, alleviated retinal/chorioretinal damage, and attenuated inflammatory infiltration; mechanistically, HYP effectively scavenged ROS, significantly upregulated the expression of endogenous antioxidant enzymes (Cat, Nqo1, Sod2), and downregulated the expression of Vegf, pro-inflammatory cytokines (Il-1&#x3b2;, Ccl2, Il-6, Tnf-&#x3b1;), key Wnt pathway genes (Myc, Plcb2, Rspo1, Wnt7a/7b, Ctnnb1), and the Wnt pathway's signature protein &#x3b2;-catenin; HYP's antioxidant, anti-inflammatory effects, and Wnt pathway inhibition were corroborated in LPS-stimulated ARPE-19 cells; molecular docking suggested a direct interaction between HYP and &#x3b2;-catenin; pharmacokinetic analysis showed favorable ocular distribution of HYP, supporting its biological relevance; and integrated transcriptomic and GEO data analyses confirmed the involvement of the Wnt pathway in human AMD and its correlation with intraocular inflammation.<br><br>CONCLUSION: Collectively, the findings demonstrate that HYP ameliorates CNV in nAMD through a concerted inhibition of oxidative stress, inflammation, and angiogenesis, primarily by suppressing Wnt/&#x3b2;-catenin signaling, which positions HYP as a promising multi-target candidate for the development of novel nAMD therapies.}, }
@article {pmid41720386, year = {2026}, author = {Yang, X and Xu, W and Xie, H and Guo, X and Zhu, F and Xing, Y and Chen, C}, title = {SREBP1-driven SCD1 protects retinal pigment epithelium from oxidative damage by activating the NRF2/GPX4 axis.}, journal = {Experimental eye research}, volume = {266}, number = {}, pages = {110932}, doi = {10.1016/j.exer.2026.110932}, pmid = {41720386}, issn = {1096-0007}, mesh = {*Retinal Pigment Epithelium/metabolism/pathology ; *Oxidative Stress/physiology ; *Sterol Regulatory Element Binding Protein 1/metabolism/genetics ; *Stearoyl-CoA Desaturase/metabolism/biosynthesis/genetics ; Animals ; *NF-E2-Related Factor 2/metabolism ; Humans ; *Macular Degeneration/metabolism/pathology ; Mice ; *Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Mice, Inbred C57BL ; Disease Models, Animal ; Cell Survival ; Cells, Cultured ; Lipid Peroxidation ; Blotting, Western ; Iodates ; }, abstract = {This study reveals the pivotal role of the Sterol Regulatory Element-Binding Protein 1 (SREBP1)/Stearoyl-CoA Desaturase 1 (SCD1) lipid metabolic axis in protecting retinal pigment epithelium (RPE) against oxidative damage. We demonstrate SCD1 downregulation in age-related macular degeneration (AMD) patient tissues and sodium iodate (SI)-induced models, while its overexpression enhances cell viability and ameliorates oxidative injury. Mechanistically, we uncover a novel pathway where SCD1-derived oleic acid activates the nuclear factor erythroid 2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) signaling cascade, scavenging reactive oxygen species (ROS) and suppressing lipid peroxidation. Notably, oleic acid also mitigated oxidative stress via this pathway without directly promoting cell survival. These results not only elucidate SCD1's crucial protective mechanism in AMD pathogenesis but also establish the SREBP1/SCD1 axis as a promising therapeutic target for developing innovative interventions against retinal degeneration.}, }
@article {pmid41720710, year = {2026}, author = {Cupertino, L and Colon, CG and Kang, A and Kolosky, T and Zhou, J and Levin, MR and Alexander, JL}, title = {Accessibility and readability of Spanish and Portuguese-translated online information about common eye conditions: A cross-sectional content analysis study.}, journal = {Journal of the National Medical Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jnma.2026.01.005}, pmid = {41720710}, issn = {1943-4693}, abstract = {PURPOSE: To evaluate the readability and accountability (reliability, quality, and credibility) of online patient education materials for common eye conditions in English, Portuguese, and Spanish.<br><br>DESIGN: Cross-sectional content analysis SUBJECTS: A total of 192 websites across seven eye diseases were analyzed in three languages: English (n&#x202f;=&#x202f;63), Portuguese (n&#x202f;=&#x202f;67), and Spanish (n&#x202f;=&#x202f;62).<br><br>METHODS: First-page Google search websites for macular degeneration, cataract, diabetic retinopathy, glaucoma, conjunctivitis, uveitis, and dry eye were assessed for readability using Flesch-Kincaid Grade Level (FKGL), Gunning Fog Index (GFI), and Flesch Reading Ease (FRE). Accountability was evaluated using JAMA and DISCERN benchmarks. Websites were also categorized by source type into: academic, national, private, or crowdsourced. Statistical analyses were done using MANOVA, ANOVA, and Tukey's HSD post-hoc tests.<br><br>MAIN OUTCOME MEASURES: Readability (FKGL, GFI, FRE) and accountability (JAMA, DISCERN) indices RESULTS: English-language websites had significantly more accessible readability scores (mean FKGL 8.1) than Spanish (16.6) and Portuguese (16.0) counterparts (p&#x202f;<&#x202f;0.001). Portuguese websites had the lowest JAMA scores (1.2) and were predominantly authored by private entities. Spanish-language sites showed mixed results, outperforming English in some accountability metrics. Crowdsourced pages like Wikipedia had the highest accountability but poorest readability. Language was a significant predictor for readability and accountability in a multivariate analysis (p&#x202f;<&#x202f;0.001).<br><br>CONCLUSION: Online ophthalmology patient education materials in Portuguese and Spanish demonstrate significantly poorer readability, and in some cases, lower accountability compared to English-language resources, posing a significant barrier for patients with limited English proficiency. Future efforts should focus on developing standardized, multilingual patient education materials that balance readability with content reliability, potentially incorporating tools such as large language models (LLM's), which have shown potential in improving accessibility of non-English health information.}, }
@article {pmid41721855, year = {2026}, author = {Borchert, GA and Charbel Issa, P and Xue, K and MacLaren, RE and Cehajic-Kapetanovic, J and Downes, SM and De Silva, SR}, title = {Geographic atrophy in age-related macular degeneration: phenotypic characterisation for clinical trial consideration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41721855}, issn = {1435-702X}, abstract = {Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) and a leading cause of central vision loss. Advances in multimodal imaging for GA have improved its phenotypic characterisation, enabling more precise assessment of disease. This is increasingly important for identifying features predictive of progression to inform prognosis and guide patient counselling, enable selection for clinical trials and for disease monitoring both in routine clinical practice and in a research setting. In addition, accurately determining foveal involvement is crucial for selection of patients suitable for emerging therapies. High-resolution imaging is also important to recognise and distinguish GA subtypes such as pachychoroid GA from conventional GA, given their genetic and phenotypic differences and possible variation in response to therapy.Imaging modalities include colour fundus photography, which is widely available and allows an initial assessment of GA lesions. Fundus autofluorescence imaging permits clear visualisation of GA borders and provides an accurate topographical map of GA pattern and extent, whereas near-infrared reflectance imaging may be superior for evaluation of foveal involvement. Optical coherence tomography (OCT) allows for measurement of the ellipsoid zone which may correlate to visual function and permits differentiation between biomarkers such as nascent GA, incomplete and complete retinal pigment epithelium and outer retinal atrophy (iRORA and cRORA respectively), and identification of pachychoroid GA. Each of these have important prognostic implications and enable accurate selection for clinical trials, monitoring progression and treatment response. Emerging approaches such as red excitation light and high-resolution OCT, may provide more accurate and reliable assessment of atrophic changes. Alongside these advances, artificial intelligence-based tools show great potential in automating GA detection, characterising of structural biomarkers, measuring progression rates and screening patients for clinical trials, increasingly reliability and reproducibility. A better understanding of the important role of multimodal imaging in the classification and assessment of GA, and detection of factors that affect progression will enable clinicians to advise, monitor and, where possible, appropriately treat this major cause of sight loss.}, }
@article {pmid41722793, year = {2026}, author = {Zhuang, Z and Jia, X and Lin, H and Hu, P and Hu, J}, title = {Bidirectional causal associations between immune cell phenotypes and age-related macular degeneration subtypes: A mendelian randomization study.}, journal = {Experimental gerontology}, volume = {216}, number = {}, pages = {113074}, doi = {10.1016/j.exger.2026.113074}, pmid = {41722793}, issn = {1873-6815}, mesh = {Humans ; Mendelian Randomization Analysis ; Phenotype ; *Macular Degeneration/immunology/genetics ; Genome-Wide Association Study ; Aged ; *Wet Macular Degeneration/immunology/genetics ; Male ; Female ; Finland ; *Geographic Atrophy/immunology/genetics ; Monocytes/immunology ; HLA-DR Antigens ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly population, characterized by two primary subtypes: dry AMD (dAMD) and wet AMD (wAMD). While immune mechanisms are implicated in AMD pathogenesis, the causal relationships between specific immune cell phenotypes and AMD subtypes remain incompletely characterized.<br><br>METHODS: Bidirectional two-sample Mendelian randomization (MR) analysis was conducted to evaluate causal associations between 731 immune cell phenotypes and AMD subtypes. Immune cell phenotype data were sourced from publicly available GWAS datasets, encompassing 3757 individuals of European descent. AMD data were obtained from the Finnish Finngen R10 database, including 5239 wAMD cases and 6651 dAMD cases. The inverse-variance weighted (IVW) method was used as the primary analytical approach, complemented by reverse MR analysis to assess bidirectional relationships.<br><br>RESULTS: The MR analysis identified significant causal associations between specific immune cell phenotypes and AMD subtypes. For wAMD, the expression of HLA-DR on CD14[-]CD16[+] monocytes exhibited a positive association (OR&#xa0;=&#xa0;1.11, P&#xa0;=&#xa0;1.65&#xa0;&#xd7;&#xa0;10[-5]), whereas CD25 on CD28[+]CD4[+] T cells showed a negative association (OR&#xa0;=&#xa0;0.87, P&#xa0;=&#xa0;0.70&#xa0;&#xd7;&#xa0;10[-4]). In the case of dAMD, the expression of HLA-DR on CD14[+]CD16[+] monocytes was positively associated with disease risk (OR&#xa0;=&#xa0;1.13, P&#xa0;=&#xa0;0.84&#xa0;&#xd7;&#xa0;10[-6]). Reverse MR analysis revealed that dAMD negatively influenced the expression levels of Effector Memory CD4[-]CD8[-] T cells (OR&#xa0;=&#xa0;0.91, P&#xa0;=&#xa0;0.36&#xa0;&#xd7;&#xa0;10[-4]) and CD28[+]CD4[-]CD8[-] T cells (OR&#xa0;=&#xa0;0.92, P&#xa0;=&#xa0;0.90&#xa0;&#xd7;&#xa0;10[-4]). Notably, no evidence supported a causal effect of wAMD on immune cell phenotypes.<br><br>CONCLUSIONS: Using updated GWAS data, this study confirms subtype-specific immune associations in AMD and reports the first evidence of reverse causality: dAMD may directly modulates adaptive immune cell phenotypes. These findings refine our understanding of AMD immunopathogenesis and highlight potential targets for subtype-specific therapies.}, }
@article {pmid41723148, year = {2026}, author = {Cui, X and Hui, J and Han, Z and Han, Q}, title = {Antioxidant vitamin index and risk of age-related macular degeneration: multicenter validation and clinical translation.}, journal = {npj aging}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41514-026-00348-y}, pmid = {41723148}, issn = {2731-6068}, support = {NKSGZ202305//Nankai University Eye Institute Key Science and Technology Fund/ ; TJYXZDXK-3-004A-3//Tianjin Key Medical Discipline Construction/ ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in older adults, with oxidative stress as a central driver. We proposed the Antioxidant Vitamin Index (AVI), a composite indicator integrating vitamins A, C, and E to quantify systemic antioxidant nutritional status, and evaluated its association with AMD across three large cohorts: the UK Biobank, NHANES 2005-2008, and a Tianjin clinical cohort. Using Cox proportional hazards models for incident AMD in the UK Biobank and multivariable logistic regression for AMD prevalence in NHANES and Tianjin, complemented by restricted cubic splines, quartile analyses, and machine learning, we consistently observed that higher AVI was independently associated with a lower risk of AMD. Dose-response analyses showed a progressive decline in AMD risk with increasing AVI, and model performance improved when AVI was added to conventional risk factors. Machine learning and SHAP interpretation further identified age and AVI as dominant predictors of AMD. These findings support AVI as a biologically grounded, quantifiable metric with potential for early screening, risk stratification, and nutrition-based prevention of AMD.}, }
@article {pmid41723406, year = {2026}, author = {Moukhadder, HM and Wahoud, N and Hassan, SA and Saade, JS}, title = {A case report of spontaneously resolving Descemet's detachment after cataract surgery.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {}, pmid = {41723406}, issn = {1471-2415}, mesh = {Humans ; Male ; Aged ; *Descemet Membrane/pathology ; Visual Acuity/physiology ; Remission, Spontaneous ; *Cataract Extraction/adverse effects ; *Corneal Diseases/etiology/physiopathology ; *Postoperative Complications ; Tomography, Optical Coherence ; }, abstract = {PURPOSE: To report a case of large central Descemet's membrane detachment (DMD) following cataract surgery and discuss the potential for spontaneous resolution as an alternative to surgical intervention.<br><br>OBSERVATIONS: A 79-year-old male with a history of macular degeneration and ocular hypertension developed a large central DMD following cataract surgery complicated by posterior capsular rupture. The patient initially presented with severe corneal edema and an uncorrected visual acuity (UCVA) of 20/200. Despite medical treatment, the DMD persisted, and surgical intervention was considered at week 4 post-op. However, the patient was lost to follow-up, and the surgery could not be performed. At a six-week follow-up, the DMD had resolved spontaneously, with the patient's UCVA improving to 20/30 and best-corrected visual acuity (BCVA) to 20/20.<br><br>CONCLUSIONS AND IMPORTANCE: This case demonstrates that large central DMDs (Descemet's membrane detachments) can occasionally resolve spontaneously.}, }
@article {pmid41723561, year = {2026}, author = {Wu, L and Rojas, S and Rao, X and Politis, M and Roca, JA and Nehemy, M and Berrocal, MH and Fromow-Guerra, J and Barraza-Lino, K and Lopez, C and Maia, M and Cardenas-Mirón, A and Gabela, G and Baldivieso-Hurtado, O and Gabela, C and Chinchilla, L and Verdaguer, JI and Zas, M and Young, M and García-Aguirre, G and Ramirez-Estudillo, JA and Abreu, N and Flores, M and Velez, W and Baez, Y and Arriola-Lopez, A and Casella, AM}, title = {Early Latin American experience with faricimab for retinal diseases: FARI-LATAM study for the Pan-American collaborative retina study (PACORES) group.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00804-7}, pmid = {41723561}, issn = {2056-9920}, }
@article {pmid41724259, year = {2026}, author = {Han, M and Wei, M and Zhao, J and Yu, Y and Li, J and Li, X and Gou, J and He, H and Tang, X and Kong, J and Yin, T and Zhang, Y}, title = {Butylphthalide nanoemulsion for management of dry age-related macular degeneration via antioxidant and anti-inflammatory mechanisms.}, journal = {International journal of pharmaceutics}, volume = {693}, number = {}, pages = {126702}, doi = {10.1016/j.ijpharm.2026.126702}, pmid = {41724259}, issn = {1873-3476}, mesh = {Animals ; Emulsions ; *Antioxidants/administration &amp; dosage/pharmacokinetics/pharmacology ; *Anti-Inflammatory Agents/administration &amp; dosage/pharmacokinetics/pharmacology ; Mice ; Oxidative Stress/drug effects ; *Macular Degeneration/drug therapy/chemically induced/metabolism/pathology ; Humans ; *Benzofurans/administration &amp; dosage/pharmacokinetics/pharmacology/chemistry ; Mice, Inbred C57BL ; Male ; NF-E2-Related Factor 2/metabolism ; Disease Models, Animal ; Iodates ; NF-kappa B/metabolism ; *Nanoparticles/chemistry ; Reactive Oxygen Species/metabolism ; }, abstract = {Dry age-related macular degeneration (dry AMD) is a posterior ocular segment disease characterized primarily by progressive retinal pigment epithelium degeneration, which is driven largely by oxidative stress. Effective treatment remains challenging owing to limited therapeutic agents and intrinsic physiological barriers that hinder drug delivery to the posterior eye. To address this, we developed a butylphthalide-loaded nanoemulsion (NBP-NE) that exhibits potent reactive oxygen species-scavenging and anti-inflammatory properties. Ex vivo permeation studies and pharmacokinetic analysis revealed that NBP-NE significantly enhances corneal and scleral penetration of butylphthalide (NBP), suggesting improved posterior ocular delivery. Moreover, NBP-NE exhibited robust antioxidant and anti-inflammatory effects in both in vitro and in vivo models, mechanisms associated with upregulation of the Nrf2 pathway and suppression of NF-κB signaling. In a sodium iodate-induced mouse model of dry AMD, topical administration of NBP-NE provided superior retinal morphological and functional protection by effectively attenuating oxidative stress and inflammatory responses. These findings represent the first reported application of NBP for dry AMD therapy and position NBP-NE as a promising noninvasive strategy for managing other oxidative stress-related posterior ocular diseases.}, }
@article {pmid41725834, year = {2026}, author = {Jonas, JB and Jonas, RA and Bikbov, MM and Kazakbaeva, GM and Iakupova, EM and Wang, YX and Nangia, V and Panda-Jonas, S}, title = {Differentiation Between Moderate Versus High Myopia: The 2-Continent Eye Study.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100999}, pmid = {41725834}, issn = {2666-9145}, abstract = {OBJECTIVE: To determine the cutoff value in axial length between moderate myopia versus high myopia in dependence on the prevalence of myopic macular degeneration (MMD).<br><br>DESIGN: Population-based studies conducted in Russia, China, and India.<br><br>PARTICIPANTS: The project included the population-based investigations of the Beijing Eye Study (n = 3325; age: 40+ years), Russian Ural Eye and Medical Study (n = 5586 participants; age: 40+ years), Ural Very Old Study (n = 541; age: 85+ years) and Ural Children Eye Study (n = 4255; age: 6+ years), and Central India Eye and Medical Study (n = 4467; age: 30+ years).<br><br>METHODS: The participants underwent a series of general medical and ophthalmic examinations, including fundus photography and ocular biometry. Myopic macular degeneration was defined according to the Meta-analysis for Pathologic Myopia Study Group.<br><br>MAIN OUTCOME MEASURES: Prevalence of MMD in dependence on axial length.<br><br>RESULTS: The total study population included 36 123 eyes (18 471 individuals) (age: 47.4 &#xb1; 23.4 years; range: 6-100 years) (axial length: 23.2 &#xb1; 1.1 mm; range: 18.22-34.20 mm). In the total study population, higher MMD stage was associated with longer axial length (&#x3b2;: 0.55; B: 0.14; 95% confidence interval [CI]: 0.14-0.15; P < 0.001), older age (&#x3b2;: 0.09; B: 0.001; 95% CI: 0.001-0.001; P < 0.001), female sex (&#x3b2;: 0.12; B: 0.07; 95% CI: 0.06-0.07; P < 0.001), and Indian ethnicity (&#x3b2;: 0.10; B: 0.07; 95% CI: 0.06-0.07; P < 0.001). Higher prevalence of MMD stage 2+ and 3+ correlated with longer axial length (odds ratio [OR]: 9.10; 95% CI: 6.93-11.9; P < 0.001 and OR: 6.90; 95% CI: 5.14-9.26; P < 0.001, respectively), older age (OR: 1.06; 95% CI: 1.04-1.08; P < 0.001 and OR: 1.08; 95% CI: 1.05-1.11; P < 0.001, respectively), and Indian ethnicity (OR: 6.96; 95% CI: 2.70-17.9; P < 0.001 and OR: 3.69; 95% CI: 1.26-10.8; P = 0.02, respectively). The turning points of the regression curves of the associations of axial length with prevalence of MMD stage 2+ and 3+ were located at axial length values of between 26.0 and 26.5 mm, respectively.<br><br>CONCLUSIONS: The axial length-related cutoff for moderate versus high myopia was located approximately at 26.0 and 26.5 mm for the prevalence of MMD stage 2+ and 3+, respectively, with higher values for younger individuals. Myopic macular degeneration prevalence was higher in the Indian cohort.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41726370, year = {2026}, author = {Afarid, M and Baghban, R and Ghasemali, S and Zamani, J and Zareei, A}, title = {In Silico Design and Analysis of a Novel Ranibizumab-derived Peptide against the Vascular Endothelial Growth Factor.}, journal = {Journal of ophthalmic &amp; vision research}, volume = {21}, number = {}, pages = {}, pmid = {41726370}, issn = {2008-2010}, abstract = {PURPOSE: Blocking the interaction between vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR2) is recognized as an effective strategy for treating neovascular age-related macular degeneration (nAMD). The present research aimed at designing and modelling an anti-VEGF peptide based on ranibizumab for potential application in inhibiting the VEGF/VEGFR2 interaction.<br><br>METHODS: Effective amino acids in the interaction between VEGF and ranibizumab were analyzed using Swiss-PdbViewer (SPDBV), PyMOL, and Chimera software. The effective area in this interaction was determined and applied as a basis to design a peptide. Then, this sequence (containing 25 amino acids) was subjected to random mutagenesis, and the binding affinity of the resulting peptides was analyzed using the ClusPro software. Subsequently, GROMACS v5.0.6 was employed for molecular dynamics (MD) simulations to evaluate the stability of target-ligand complexes. Ultimately, the peptide exhibiting the highest affinity was grafted into the kB1 and MCoTI-II frameworks to enhance the stability.<br><br>RESULTS: This modification resulted in improved peptide-VEGF binding affinity, demonstrating the potential of in silico design for creating effective anti-angiogenic peptides in antiangiogenic therapies.<br><br>CONCLUSION: The findings from this study provide a basis for designing and validating peptide inhibitors against VEGF.}, }
@article {pmid41727089, year = {2026}, author = {Lim, RR and Zhao, E and Hass, DT and Wang, Y and Eminhizer, M and Ortolan, D and Niernberger, S and Tong, A and Nelson, BR and Nazario, M and Adipudi, V and Bharti, K and Hurley, JB and Du, J and Chao, JR}, title = {Nutrient microenvironments reprogram RPE metabolism.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.02.11.705448}, pmid = {41727089}, issn = {2692-8205}, abstract = {Induced pluripotent stem cell-derived retinal pigment epithelium (iPSC RPE) has become a widely used model for studying the mechanisms of age-related macular degeneration (AMD). However, the nutrient composition of currently used RPE culture media is highly variable, posing a major challenge to reproducibility in RPE metabolism and phenotype. We systematically investigate how six distinct nutrient microenvironments shape RPE phenotype, function and metabolism in both iPSC RPE and fetal RPE (fRPE). These included MEMα, DMEM-HG/F12 basal media, physiological human plasma-like medium (HPLM) supplemented with FBS or B27, and X-VIVO 10. Although canonical RPE markers were expressed across all conditions, B27 supplementation and X-VIVO 10 increased RPE cell size, hexagonality, and transepithelial resistance. Culture in HPLM+FBS induced accumulation of lipid droplets and sub-RPE deposits, whereas X-VIVO 10 resulted in the formation of large intracellular vacuoles. B27 supplementation enhanced basal respiration, while X-VIVO 10 increased glycolytic capacity. Amino acid consumption was broadly conserved across media types, including complete depletion of proline in all conditions by 48 hours; however, lipid and nucleotide metabolism varied substantially between conditions. Notably, B27 supplementation in specific media types reversed the net direction of several metabolites, with creatine, serine and taurine shifting from consumption to production, while riboflavin and guanine shifted from production to consumption. These findings establish the nutrient environment as a key determinant of RPE phenotype, function and metabolism. Our work provides a valuable resource for media selection and interpretation of cellular and metabolic phenotypes relevant to RPE disease modeling.}, }
@article {pmid41727524, year = {2026}, author = {Patel, RH and Mothy, D and Boinpally, N and Choudhry, HS and Bhavsar, P and Khouri, AS}, title = {Evaluation of Social Media Short-Form Video Content for Patient Education on Vision-Threatening Diseases.}, journal = {Journal of ophthalmology}, volume = {2026}, number = {}, pages = {8987000}, pmid = {41727524}, issn = {2090-004X}, abstract = {PURPOSE: The rapid spread of unreliable misinformation on vision-threatening diseases can significantly affect the eye health behaviors and outcomes of the patients consuming short-form social media content. This study evaluates short-form videos pertaining to vision-threatening diseases to quantify video quality, content, and popularity.<br><br>METHODS: This cross-sectional study analyzed short-form videos on cataracts, diabetic retinopathy, glaucoma, and age-related macular degeneration from TikTok, Instagram Reels, and YouTube Shorts. A hashtag search identified the first fifty videos on each disease from each social media platform. Two reviewers evaluated them, resolving discrepancies with a third. Outcome measures included number of views, likes, comments, uploader source, content type, modified DISCERN score (0-5 scale), and global quality scale (GQS) score (1-5 scale). Engagement outcomes were summarized descriptively using medians and interquartile ranges, while reliability and quality outcomes were analyzed using one-way ANOVA with Tukey post hoc comparisons.<br><br>RESULTS: TikTok videos demonstrated higher median engagement (views, likes, and comments) compared to Instagram Reels and YouTube Shorts. Videos on cataracts had higher engagement statistics compared to the other vision-threatening diseases across all platforms. Physicians were the most common video source (45%). The most common content categories were treatments/management (36%) and general symptoms (22%). YouTube Shorts had a significantly greater average DISCERN (2.93&#x2009;&#xb1;&#x2009;0.70) and GQS score (3.85&#x2009;&#xb1;&#x2009;1.26) than Instagram Reels and TikTok (p < 0.001). Videos from patients had the lowest mean DISCERN and GQS scores.<br><br>CONCLUSIONS: TikTok had the greatest median engagement levels, while YouTube Shorts had the greatest mean quality and reliability. Videos from patients and philanthropists had lower quality scores, while healthcare professionals and organizations had the highest. Future efforts should understand the patients' perspectives, address misinformation, and improve quality across all social media platforms.}, }
@article {pmid41728315, year = {2026}, author = {Liu, R and Wang, X and Corradetti, G and Soylu, C and Ferrington, DA and Sadda, SR and Zhang, Y}, title = {Adaptive Optics Fluorescence Lifetime Imaging Ophthalmoscopy for Single-Cell-Resolved In Vivo Metabolic and Structural Imaging of the Human Retinal Pigment Epithelium.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.02.07.26345814}, pmid = {41728315}, abstract = {Fluorescence lifetime imaging ophthalmoscopy permits in vivo assessment of retinal metabolism but has remained limited by insufficient cellular resolution in the human eye. Here we present adaptive optics-enhanced fluorescence lifetime imaging ophthalmoscopy (AOFLIO), a method for single-cell-resolved, in vivo structural and metabolic imaging of the human retinal pigment epithelium (RPE). Through real-time correction of ocular wavefront aberrations, precisely synchronized adaptive optics reflectance and lifetime image acquisition via a phase-locked loop-based timing architecture, and sub-pixel photon registration that localizes individual autofluorescence photons with high spatial precision, AOFLIO directly resolves the RPE cell mosaic and measures autofluorescence decay using the same photons, enabling direct structural-functional correlation at the single-cell level. We demonstrate single-cell RPE lifetime mapping in healthy subjects and reveal altered metabolic signatures and fine characterization of RPE metabolic in age-related macular degeneration. AOFLIO establishes a platform for cellular-scale metabolic imaging in the living human eye.}, }
@article {pmid41731033, year = {2026}, author = {Lamanna, F and Riotto, E and Faes, L and Fu, DJ}, title = {Infographic: ranibizumab for neovascular age-related macular degeneration: the MARINA study.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41433-026-04348-w}, pmid = {41731033}, issn = {1476-5454}, }
@article {pmid41731445, year = {2026}, author = {Seweryn, M and Kopel, J and Augustynska, J and Mikołajewicz, A and Toro, MD and Rejdak, R}, title = {Multidimensional evaluation of the potential impact of faricimab availability on healthcare system accessibility for retinal disease treatment in Poland.}, journal = {BMC health services research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12913-026-14231-9}, pmid = {41731445}, issn = {1472-6963}, }
@article {pmid41732606, year = {2026}, author = {Ladki, M and Gupta, PK and Malaya, L and Afrouzian, M}, title = {Dry Age-Related Macular Degeneration and Dense Deposit Disease: A Histopathological Comparison of Macular and Renal Lesions.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e102164}, pmid = {41732606}, issn = {2168-8184}, abstract = {Background Dry age-related macular degeneration (AMD) and dense deposit disease (DDD) in the kidney have molecular commonality due to the involvement of the complement system. DDD is a renal disease linked to defects of the complement alternative pathway, and in dry AMD, complement components have been found within drusen. In this study, pathologic features of dry AMD and DDD were studied by light and immunofluorescence microscopy to clarify whether morphologic similarities exist between the two diseases. Methodology Sections were obtained from (1) the macula of four patients with dry AMD; (2) renal biopsies of two DDD patients; (3) the macula from healthy eye donors; and (4) a kidney biopsy of a normal human subject. Sections were stained with hematoxylin and eosin, periodic acid-Schiff (PAS), and periodic-acid-methenamine silver for light microscopy and with C3b antisera for fluorescence microscopy. Results Changes observed in dry AMD specimens included (1) the presence of numerous drusen containing PAS- and silver-positive material; (2) thickening of the Bruch's membrane; (3) thickening of prominent PAS-positive intercapillary pillars; and (4) degeneration and dropouts in the choriocapillaris and dilatation and congestion of vessels in the Sattler's layer. In comparison, changes in the DDD specimens included (1) thickening of the glomerular basement membrane (GBM) and presence of double contours; and (2) mesangial and endocapillary proliferation. C3b was positive in both macular drusen and along the GBM. Conclusions Basement membrane changes in dry AMD share morphological similarities with the GBM changes in DDD, and, in both diseases, C3b is deposited, suggesting that the association between the two diseases possibly reflects a common pathogenesis.}, }
@article {pmid41732778, year = {2026}, author = {Nabil, AS and Gholami, S and Leng, T and Lim, JI and Alam, MN}, title = {Federated Learning for Multi-Disease Ophthalmic Diagnostics Using OCT Angiography.}, journal = {Ophthalmology science}, volume = {6}, number = {3}, pages = {101030}, pmid = {41732778}, issn = {2666-9145}, abstract = {PURPOSE: To conduct a comprehensive systematic evaluation of federated learning (FL) strategies for multi-disease retinal classification using OCT angiography (OCTA), implementing a 2-part experimental framework to establish foundational feasibility and optimize performance under realistic heterogeneous conditions while ensuring privacy preservation.<br><br>DESIGN: Retrospective multi-center FL study using a systematic 2-part experimental design: (1) foundational feasibility evaluation under controlled homogeneous conditions, and (2) comprehensive optimization under realistic heterogeneous conditions using Dirichlet distribution partitioning (&#x3b1; = 0.5).<br><br>PARTICIPANTS: A total of 456 OCTA images from patients with 7 retinal pathologies, with diabetic retinopathy (31.1%) and normal cases (25.2%) comprising the majority, sourced from the public OCTA-500 data set (n = 300) and a private collection from the University of Illinois Chicago (n = 156).<br><br>METHODS: Five FL aggregation strategies (federated averaging [FedAvg], federated proximal [FedProx], federated magnetic resonance imaging [FedMRI], federated Adagrad, and federated Yogi) were systematically evaluated across multiple optimization dimensions: 7 architecture configurations spanning vision transformers, established convolutional neural networks, and hybrid models; 5 transfer learning freezing strategies; 3 local epoch configurations (2, 5, and 10); and scalability analysis across 2, 3, and 5-client federations. Security mechanisms including differential privacy (&#x3b5; = 1.0-8.0) and secure aggregation were integrated and evaluated. Performance was assessed across 3 classification scenarios: 7-class, 4-class modified, and 4-class streamlined.<br><br>MAIN OUTCOME MEASURES: Classification accuracy, receiver-operating-characteristic area under the curve (ROC-AUC), and macro-averaged F1-score with comprehensive privacy-utility analysis and computational efficiency metrics.<br><br>RESULTS: Under controlled conditions, FL achieved superior performance in simplified classifications, with FedAvg, FedProx, and FedMRI reaching 72.09% accuracy versus 69.77% centralized training. Comprehensive optimization identified DenseNet121 as optimal architecture (79.55% accuracy, 89.68% ROC-AUC), with "most" freezing strategy (75% frozen layers) providing 60% training time reduction while maintaining superior performance. Federated proximal demonstrated exceptional resilience to heterogeneity (-11.7% degradation). Bonawitz secure aggregation achieved optimal privacy-utility balance (63.64% accuracy with cryptographic guarantees), whereas differential privacy maintained clinical utility under moderate constraints (&#x3b5; &#x2248; 4-6).<br><br>CONCLUSIONS: This systematic evaluation establishes FL as a comprehensive solution for privacy-preserving multi-institutional OCTA-based disease classification, with careful architectural selection, optimization strategies, and security mechanisms enabling performance that matches or exceeds centralized approaches while maintaining regulatory compliance and clinical utility.<br><br>FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid41733690, year = {2026}, author = {Ghasemi, M and Ghasemi, A and Behjati, J and Nikkhah, H}, title = {Association between diabetic retinopathy and age-related macular degeneration: a systematic review and meta-analysis.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41733690}, issn = {1435-702X}, abstract = {KEY MESSAGES: WHAT IS KNOWN : • Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are leading causes of visual impairment, and both share overlapping pathogenic mechanisms such as oxidative stress and vascular dysfunction. • Previous studies exploring the association between DR and AMD have reported inconsistent findings, with some suggesting DR as a risk factor and others reporting a protective association.<br><br>WHAT IS NEW: &#x2022; This is the first systematic review and meta-analysis specifically examining the association between DR and AMD. &#x2022;&#xa0;Our results demonstrate no significant relationship between DR and AMD, despite high between-study heterogeneity&#xa0;and robust sensitivity analyses. &#x2022;&#xa0;The findings highlight that existing evidence is primarily based on unadjusted data, emphasizing the need for well-designed prospective cohort studies that account for confounding variables and treatment effects.}, }
@article {pmid41734820, year = {2026}, author = {Gabrielle, PH and Eid, P and Aho, LS and Kodjikian, L and Souied, E and Uzzan, J and Conart, JB and Delyfer, MN and Creuzot-Garcher, C}, title = {Prognostic Factors in Patients With Submacular Haemorrhage Complicating Age-Related Macular Degeneration: A Post Hoc Analysis of the STAR Study.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ceo.70094}, pmid = {41734820}, issn = {1442-9071}, support = {//Centre Hospitalier R&#xe9;gional universitaire DIJON (CHU DIJON)/ ; }, abstract = {BACKGROUND: To investigate prognostic factors of recent submacular haemorrhage (SMH) complicating neovascular age-related macular degeneration (nAMD) treated with surgery or pneumatic displacement combined with intravitreal injection of anti-vascular endothelial growth factor.<br><br>METHODS: Post hoc analysis of the STAR randomised controlled trial data evaluating the influence of baseline clinical and imaging characteristics on visual outcomes over 6&#x2009;months using multivariate generalised additive mixed models.<br><br>RESULTS: Patients with worse baseline visual acuity (VA) had faster (estimated degree of freedom [EDF]&#x2009;=&#x2009;2.87, p&#x2009;<&#x2009;0.001) and greater predicted visual gain (difference&#x2009;=&#x2009;+21.03 [14.64; 27.42] letters for eyes with 10 vs. 40 letters at baseline, p&#x2009;<&#x2009;0.001) and lower predicted VA at 6&#x2009;months (difference&#x2009;=&#x2009;-8.82 [-15.14; -2.52] letters for eyes with 10 vs. 40 letters at baseline, p&#x2009;<&#x2009;0.001), whereas patients with better baseline VA showed more stable trajectories of predicted visual gain and higher predicted VA at 6&#x2009;months. Thinner SMH (&#x2264;&#x2009;1000&#x2009;&#x3bc;m) was significantly associated with faster (EDF&#x2009;=&#x2009;2.93 for &#x2264;&#x2009;1000&#x2009;&#x3bc;m vs. 2.66 for >&#x2009;1000&#x2009;&#x3bc;m) and greater predicted visual improvement (difference&#x2009;=&#x2009;+13.5 [3.66; 23.39] letters between &#x2264;&#x2009;1000 and >&#x2009;1000&#x2009;&#x3bc;m, p&#x2009;<&#x2009;0.001) and higher predicted final VA (difference&#x2009;=&#x2009;+13.00 [3.11; 22.80] letters between &#x2264;&#x2009;1000 and&#x2009;>&#x2009;1000&#x2009;&#x3bc;m, p&#x2009;<&#x2009;0.001). Interactions between the treatment group and both VA and SMH thickness were non-significant.<br><br>CONCLUSION: Better VA and lower SMH thickness at baseline were significantly associated with better visual outcomes over 6&#x2009;months, independently of treatment arm in SMH complicating nAMD.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02557451.}, }
@article {pmid41734823, year = {2026}, author = {Blanco-Fernández, G and Blanco-Fernández, B and Fraga-López, FJ and Luzardo-Álvarez, AM and Fernández-Ferreiro, A and Otero-Espinar, FJ}, title = {Design and evaluation of semi-solid lipid implants for controlled intravitreal release of bevacizumab.}, journal = {International journal of pharmaceutics}, volume = {693}, number = {}, pages = {126714}, doi = {10.1016/j.ijpharm.2026.126714}, pmid = {41734823}, issn = {1873-3476}, mesh = {*Bevacizumab/administration &amp; dosage/chemistry ; Delayed-Action Preparations/chemistry/administration &amp; dosage ; Humans ; *Lipids/chemistry ; *Angiogenesis Inhibitors/administration &amp; dosage/chemistry ; *Drug Implants/chemistry ; Intravitreal Injections ; Drug Liberation ; Cell Line ; Cell Survival/drug effects ; }, abstract = {Bevacizumab is a monoclonal antibody used intravitreally as an anti-VEGF therapy for some ocular diseases. However, this type of treatment presents some limitations, such as the invasiveness of its administration and the need for frequent injections due to the clearance of the antibody from the vitreous chamber. Semi-solid lipid implants emerge as an attractive possibility for the sustained release of biological drugs like bevacizumab, so they could have great potential for the subsequent treatment of VEGF-dependent degenerative retinal pathologies, such as proliferative diabetic retinopathy or neovascular age-related macular degeneration. In this work, injectable lipid implants were designed based on the lipids Precirol® ATO 5, Tefose® 63, Geleol[TM], and Tefose® 1500. The implants were easy to manufacture by melting and mixing. The surface of the implants was characterized by scanning electron microscopy, while the distribution of bevacizumab inside was characterized by confocal Raman mapping microscopy. Subsequently, the state of the antibody after release was evaluated by Raman Spectroscopy and Attenuated Total Reflection Infrared spectroscopy, showing an unaltered quaternary structure. Furthermore, the implants were able to sustain the antibody release for almost 40 days. Biocompatibility was assessed by assay with ARPE-19 cells. Finally, the calorimetry assay allowed us to refine the best possible formulation for further studies. This type of implant showed suitable properties as a potential therapeutic platform for the treatment of neovascular age-related macular degeneration and proliferative diabetic retinopathy, being injectable, easy to make, homogeneous, having sustained release and being biocompatible.}, }
@article {pmid41735681, year = {2026}, author = {Bodmer, NS and Faes, L and Gross, N and Bachmann, LM and Huber, C and Näpflin, M and Schmid, MK}, title = {Prevalence and patterns of anti-angiogenic treatment discontinuation in neovascular age-related macular degeneration-insights from health claims data.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41735681}, issn = {1476-5454}, abstract = {PURPOSE: To assess patterns and institutional variability of anti-angiogenic treatment discontinuation in neovascular age-related macular degeneration (nAMD) within Switzerland, and to examine the association of digital home monitoring with treatment persistence.<br><br>METHODS: Retrospective observational analysis combined nationwide health insurance claims data (Helsana, n&#x2009;=&#x2009;4840) and clinical data from a major tertiary centre (LUKS, n&#x2009;=&#x2009;1932; nAMD subset n&#x2009;=&#x2009;1387). Discontinuation was defined as no further injections for 31-365 days after the last intravitreal injection (IVI) and classified as supervised (&#x2009;&#x2265;&#x2009;1 follow-up visit in this period) or unsupervised (no follow-up visits in this period). Variability was evaluated among the 20 largest providers and across seven regions. Digital home monitoring's impact on non-persistence was assessed in the clinical cohort.<br><br>RESULTS: Substantial heterogeneity was observed. Supervised discontinuation ranged from 20.7 to 45.7% (pooled proportion 32.0%, 95% confidence interval [CI] 30.2-33.9%) and unsupervised from 10.9 to 25.7% (pooled proportion 18.2%, 95%CI 16.8-19.8%) across centres. In the LUKS cohort, 1-year persistence was 93.7%, dropping to 72.7% by year 4, with unsupervised discontinuation rising from 3.0 to 12.5%. In 100 patients using voluntary digital home monitoring non-persistence was less likely (adjusted OR 0.59, 95%CI 0.35-0.98); among those who discontinued, home-monitoring users were more likely to remain under supervision (74% vs 54%).<br><br>CONCLUSIONS: Treatment discontinuation in nAMD is frequent and demonstrates striking institutional and regional variability. The heterogeneity in discontinuation patterns suggests that treatment persistence may be modifiable through targeted, systematic, and patient-centred interventions. Digital home monitoring may be a promising strategy to support engagement and reduce non-persistence.}, }
@article {pmid41737035, year = {2026}, author = {Jiang, B and Zhang, L and Hong, N and Wen, Y and Li, A and Shi, Y and Dong, F}, title = {Recent Progress in Selenium Nanomedicines for Ocular Diseases.}, journal = {International journal of nanomedicine}, volume = {21}, number = {}, pages = {583175}, pmid = {41737035}, issn = {1178-2013}, mesh = {Humans ; *Selenium/chemistry/therapeutic use/administration &amp; dosage/pharmacokinetics ; *Eye Diseases/drug therapy ; *Nanomedicine/methods ; Animals ; *Nanoparticles/chemistry ; Drug Delivery Systems ; Antioxidants/administration &amp; dosage/therapeutic use ; Quantum Dots/chemistry ; }, abstract = {Vision impairment represents a significant and growing global socioeconomic burden. In the elderly population, cataracts, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR) are the predominant causes of visual loss. Conventional ophthalmic drug therapies are limited by low bioavailability and dose-related toxicity, highlighting the urgent need for safer and more effective treatments. Selenium (Se), an essential trace element, is critical for antioxidant defense, redox homeostasis, and immune regulation. Although the roles of elemental Se in ocular physiology and diseases are well-documented, its clinical application is constrained by its narrow therapeutic window and poor bioavailability. To overcome these limitations, Se nanoparticles (SeNPs) have emerged as a superior alternative, offering enhanced bioavailability, reduced toxicity, and the capability for targeted drug delivery. Strong preclinical evidence supports the therapeutic potential of Se nanomedicines in models of DR, retinal neovascularization, infectious keratitis, and cataracts. Significantly, the initial stages of clinical translation are in progress, as demonstrated by a pioneering Phase I trial involving CdSe/ZnS quantum dots (QDs) in patients with retinitis pigmentosa (RP), which has shown both tolerability and improvements in visual function. This review provides a comprehensive and up-to-date analysis of Se-based nanomedicines for ocular diseases, based on a literature search of PubMed, Scopus, Web of Science, and Google Scholar. It elucidates how SeNPs uniquely synergize intrinsic multi-mechanistic bioactivities (e.g., antioxidant, anti-angiogenic) with targeted and stimuli-responsive drug delivery, establishing them as versatile nanoplatforms with significant clinical translation potential for complex ocular pathologies. Therefore, further research is essential to optimize their design, elucidate their mechanisms of action, and ultimately facilitate their safe and effective clinical translation.}, }
@article {pmid41737853, year = {2026}, author = {Gulati, S and Coak, E and Mascia, D and Li, K and Ko, S and Bonine, NG}, title = {Cross-Sectional Survey of Real-World Physician Prescribing Practices for Anti-VEGF Agents in the Treatment of Neovascular Age-Related Macular Degeneration and Associated Patient Burden in the United States.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {572019}, pmid = {41737853}, issn = {1177-5467}, abstract = {PURPOSE: This study aimed to address the lack of data on the real-world use of the anti-vascular endothelial growth factor (VEGF)/anti-angiopoietin 2 agent faricimab and purely anti-VEGF agents in neovascular age-related macular degeneration (nAMD) in the United States.<br><br>PATIENTS AND METHODS: Data were derived from the Adelphi Real World nAMD Disease Specific Programme (DSP)&#x2122;, a cross-sectional survey of patients with nAMD and their treating physicians, conducted in the US November 2023-May 2024. Ophthalmologists provided demographic and clinical data as well as reasons for agent and dosing strategy selection, for patients with nAMD, aged &#x2265;55, prescribed anti-VEGF treatment at the time of survey.<br><br>RESULTS: Sixty-four physicians (90.6% retinal specialists), reported on 497 patients (faricimab, n = 89 patients; anti-VEGF, n = 408 patients). Mean (&#xb1; standard deviation) age was 76.0 &#xb1; 8.5, 52.1% were female and 88.5% White. Most common symptoms at survey were blurred vision (faricimab: 56.2%, anti-VEGF: 67.9%), distortion of central vision (faricimab: 44.9%, anti-VEGF: 50.7%) and loss of visual acuity (faricimab: 39.3%, anti-VEGF: 41.9%). Main reasons for agent selection were clinical factors/efficacy (faricimab 89.9%, anti-VEGF: 93.4%), and treatment administration/compliance (faricimab 71.9%, anti-VEGF: 41.4%), which included improved patient compliance and extended dosing intervals. Faricimab was commonly dosed as treat-and-extend (67.4%) and anti-VEGFs as fixed interval (38.5%). Reasons for dosing strategy selection included improvement in visual acuity, patient functionality, clinical evidence and fewer consultations for the patient. Most physicians agreed/strongly agreed that some insurers restrict (84.4%) or deny (85.9%), access to the most appropriate products for patients.<br><br>CONCLUSION: Despite receiving treatment, nAMD patients have substantial remaining symptom and treatment burden. Physicians may choose faricimab over purely anti-VEGF agents for its clinical efficacy and reduced treatment burden. Physicians take both clinical factors and patient burden into account when selecting agents and dosing regimens, while reimbursement concerns hinder prescribing in some patients.}, }
@article {pmid41739393, year = {2026}, author = {Çakır, A and Akkan, F and Kapran, Z and Ünal, M and Şerif, N and Uzundede, T and Karataş, G and Öztürk, M and Dündar, H and Erakgün, T and Alp, MN and Koçak, N and Saatci, AO and Çetin, EN and Durukan, AH and Şahin, M and Muhacir, F and Yeşiltaş, S and Uyar, OM and Emre, S and Şekeroğlu, MA and Önen, M and Bulut, M and Karalezli, A and Kadayıfçılar, S and Özdek, &#x15e; and Doğanay, S and Kaya, M and Öz, &#xd6; and Kaderli, ST and Avcı, R and Şermet, F and Demirel, S and Küçükerdönmez, C and Yıldırım, C and İpek, &#x15e;C and Ayhan, Z and Altan, T and Gürelik, &#x130;G and Görgün, E and Yenerel, NM and Seymenoğlu, G and Vural, E and Sül, S and Çıtırık, M and Özdemir, HB and Cömerter, D and Karabaş, VL and Özdemir, H}, title = {Real-World 6-Month Treatment Outcomes of Faricimab in Turkey: The FARTURK Study.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {3}, pages = {1165-1177}, pmid = {41739393}, issn = {2193-8245}, abstract = {INTRODUCTION: This work aims to evaluate the real-world efficacy and safety of intravitreal faricimab over a 6-month follow-up period.<br><br>METHODS: Data from 38 centers across Turkey were retrospectively analyzed between November 22, 2024, and May 4, 2025. Patients who received at least one intravitreal faricimab injection and had complete ophthalmic and optical coherence tomography (OCT) data with a minimum 1-month follow-up were included. Demographics, diagnosis, macular neovascularization (MNV) subtype, prior treatments, best-corrected visual acuity (BCVA-decimal/ETDRS), central macular thickness (CMT), intra/subretinal fluid, MNV size, injection number, follow-up duration, and ocular/systemic adverse events were recorded at baseline, at week 2, and at month 1 after the first injection, after three injections, and at the final visit.<br><br>RESULTS: A total of 351 eyes from 316 patients were analyzed, including neovascular age-related macular degeneration (nAMD) (72.1%), diabetic macular edema (DME) (18.2%), retinal vein occlusion (RVO) (6.0%), and other MNV subtypes (3.7%). When comparing pre-treatment and final visits, na&#xef;ve eyes showed a CMT reduction of 105.63&#x2009;&#xb1;&#x2009;114.89&#xa0;&#xb5;m (p&#x2009;<&#x2009;0.001), while switch eyes had a CMT reduction of 86.58&#x2009;&#xb1;&#x2009;108.36&#xa0;&#xb5;m (p&#x2009;<&#x2009;0.001). The total ETDRS letter gain from baseline to final visit was 16.3&#x2009;&#xb1;&#x2009;12.08 (p&#x2009;<&#x2009;0.001) in na&#xef;ve eyes and 8.3&#x2009;&#xb1;&#x2009;12.23 (p&#x2009;<&#x2009;0.001) in switch eyes. Intraretinal and subretinal fluid rates significantly decreased (p&#x2009;<&#x2009;0.001), and MNV area contracted on OCTA (p&#x2009;<&#x2009;0.001). Only one mild, self-limited intraocular inflammation case (0.16%) occurred.<br><br>CONCLUSIONS: Faricimab demonstrated rapid and significant anatomical and functional improvements in 6-month real-world data, evident as early as 15&#xa0;days after the initial injection, with a safety profile comparable to phase III trials. These findings support faricimab as a potent and reliable therapeutic option in the real-world management of nAMD and DME, though extended follow-up is needed to assess long-term outcomes.}, }
@article {pmid41740341, year = {2026}, author = {Ling, J and Wang, D and Li, J and Liang, J and Hu, Q and Zhang, Q and Zheng, Y and Lin, B and Lin, X}, title = {Targeting macrophage-mediated clearance of apoptotic cells overcomes anti-VEGF resistance in choroidal neovascularization.}, journal = {International immunopharmacology}, volume = {175}, number = {}, pages = {116410}, doi = {10.1016/j.intimp.2026.116410}, pmid = {41740341}, issn = {1878-1705}, mesh = {Animals ; *Choroidal Neovascularization/drug therapy/immunology/pathology ; *Macrophages/immunology/drug effects ; Apoptosis/drug effects ; Mice ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/therapeutic use/pharmacology ; Humans ; Endothelial Cells/drug effects ; Mice, Inbred C57BL ; Disease Models, Animal ; Drug Resistance ; }, abstract = {Neovascular age-related macular degeneration (nAMD) is a leading cause of severe vision loss in the elderly worldwide. While anti-vascular endothelial growth factor (anti-VEGF) agents are the first-line standard of care, incomplete response to therapy (IRT) occurs in approximately 50% of patients. The microenvironmental factors driving IRT remain poorly understood. This study utilized Stereo-seq technology to construct a single-cell resolution spatial transcriptomic map (ST-map) of the retina-choroid-sclera (RCS) complex in healthy control mice, and in mice with laser-induced choroidal neovascularization (CNV) receiving either no treatment or anti-VEGF therapy. The study aimed to characterize spatial gene expression patterns and cell-cell interactions within the CNV microenvironment that may contribute to therapeutic resistance. The ST-map of the RCS complex identified distinct cellular compositions and gene expression profiles across conditions. In CNV lesions, anti-VEGF treatment induced significant shifts in the gene expression signatures of macrophages (MACs), endothelial cells (ECs), and fibroblasts (Fibros). Spatial analysis defined the proximity relationships within the neovascular niche, identifying specific macrophage-endothelial cell (MAC-EC) interactions implicated in lesion persistence. Specifically, macrophage depletion led to an accumulation of apoptotic ECs in anti-VEGF-treated lesions. In contrast, targeted blockade of CD47 in combination with anti-VEGF therapy enhanced the clearance of apoptotic ECs and achieved superior anti-angiogenic efficacy compared to anti-VEGF monotherapy. Spatial transcriptomics effectively identifies aberrant gene expression and intercellular communication networks within CNV microenvironment. These findings suggest that macrophage-mediated clearance of apoptotic cells plays a critical role in the response to treatment. Combining anti-CD47 agents with anti-VEGF therapy represents a promising strategy to overcome incomplete response and improve visual outcomes in nAMD.}, }
@article {pmid41740720, year = {2026}, author = {Ghannai, S and Ribeiro, E and Pereira, B and Brito, M and Camacho, P}, title = {The potential of DNA methylation as a biomarker for age-related macular degeneration: a systematic review.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502521}, doi = {10.1016/j.oftale.2026.502521}, pmid = {41740720}, issn = {2173-5794}, abstract = {Age-related macular degeneration (AMD) is a multifactorial disease influenced by genetic and environmental factors, yet its pathogenesis remains incompletely understood. DNA methylation, increasingly recognized as a disease indicator, has been linked to AMD and may represent a promising biomarker or therapeutic target. This systematic review, conducted according to PRISMA 2020 guidelines, analyzed 13 studies addressing DNA methylation in AMD populations (2012-2025). Results revealed that 25% reported hypermethylation, 8% hypomethylation, and 41% both patterns, while 15% found no significant differences. Notably, one study described downregulation of DNA methyltransferases in advanced stages compared with early or intermediate AMD. Despite the limited evidence, findings support the relevance of methylation in AMD prognosis and therapy. Further research with robust methodologies is essential to clarify the role of epigenetic mechanisms in disease progression and to explore their potential for guiding targeted therapeutic strategies.}, }
@article {pmid41741701, year = {2026}, author = {Veritti, D and Sarao, V and Martin, AA and Bonini, F and Lanzetta, P}, title = {AI-assisted analysis of early fluid dynamics following aflibercept 8 mg in treatment-naïve neovascular AMD.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41741701}, issn = {1476-5454}, abstract = {PURPOSE: To evaluate early morphological changes following intravitreal aflibercept 8 mg in treatment-naïve neovascular age-related macular degeneration (nAMD) using artificial intelligence (AI)-assisted optical coherence tomography (OCT) segmentation.<br><br>METHODS: Thirty eyes with treatment-na&#xef;ve subfoveal nAMD received three monthly aflibercept 8&#x2009;mg injections. OCT scans were obtained at baseline and days 1, 7, 14, 30, 60, and 90. AI-based segmentation software (Fluid Monitor, RetInSight GmbH) quantified intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) volumes in the central 6-mm area. Morphologic changes were correlated with best-corrected visual acuity (BCVA).<br><br>RESULTS: IRF, SRF, and PED showed distinct reduction patterns. In eyes with IRF (n&#x2009;=&#x2009;22), mean volume decreased by 65% at day 1, 94% at day 14, and 96% at day 90 (p&#x2009;<&#x2009;0.05). Among eyes with SRF (n&#x2009;=&#x2009;28), SRF volume decreased by 18%, 84%, and 99% at days 1, 14, and 90, respectively (p&#x2009;&#x2264;&#x2009;0.002). PED volume declined more gradually among affected eyes (n&#x2009;=&#x2009;23), with mean reductions of 7% at day 1, 34% by day 14, and 53% by day 90 (p&#x2009;&#x2264;&#x2009;0.023). BCVA improved from 51.8&#x2009;&#xb1;&#x2009;14.4 to 62.6&#x2009;&#xb1;&#x2009;14.4 ETDRS letters by day 90 (mean gain +&#x2009;10.8; p&#x2009;<&#x2009;0.001). Multivariate regression identified a significant association between IRF reduction at day 14 and BCVA gain at day 90 (&#x3b2;&#x2009;=&#x2009;-0.018, p&#x2009;=&#x2009;0.036).<br><br>CONCLUSIONS: Aflibercept 8&#x2009;mg induced rapid, compartment-specific morphologic responses in treatment-na&#xef;ve nAMD, with early IRF resolution and significant BCVA improvement. AI-assisted analysis provided detailed pharmacodynamic insights and may support individualised treatment strategies during the loading phase.}, }
@article {pmid41743022, year = {2025}, author = {Trinquet, L and David, T and Chavane, F and Lorenceau, J and Matonti, F}, title = {Frequency tagged multifocal pupillary response fields identify age-related macular degeneration and diabetic retinopathy.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1653938}, pmid = {41743022}, issn = {1662-4548}, abstract = {OBJECTIVES: To quickly characterize multifocal Pupillary Response Fields (mPRF) using frequency tagging and to identify pupillary biomarkers of age-related macular degeneration (AMD) and diabetic retinopathy (DR).<br><br>METHODS: Participants with AMD (N&#x202f;=&#x202f;74), DR (N&#x202f;=&#x202f;56), and healthy controls (HP, N&#x202f;=&#x202f;62) underwent standard ophthalmologic assessments together with a multifocal Pupillary Frequency Tagging test (mPFT). The mPFT test comprised 9 retinal regions whose luminance were sinusoidally modulated at incommensurate temporal frequencies so as to elicit sustained pupillary oscillations over 45&#x202f;s of fixation.<br><br>ANALYSES: The recorded pupillary traces were corrected for blinks and transient artifacts. Features of pupillary dynamics and eye-movements, - eye instability during fixation, pupil light reflex, and spectral components of pupil oscillations - were compared across groups. Statistical analyses were performed for each feature separately using Student t-tests and Cohen's d. The Area under the Curve (AUC) of the Receiver Operating Characteristics (ROC) was computed for different combinations of the extracted features. Pearson's correlation was used to compare spectral power with other functional measures.<br><br>RESULTS: Multifocal Pupillary Response Fields (mPRF) derived from regional spectral power and phase distributions differed significantly between patients and controls, in accordance with the characteristics of each pathology: decreased power for central and paracentral sectors in AMD, diffuse defects in DR. AUCs of ROC performed with relevant features achieved excellent sensitivity (>0.9) and specificity (>0.9) in classifying patients from healthy subjects.<br><br>CONCLUSION: Fast, objective, and easily recorded, mPRF assessments evaluate the functional integrity of retino-pupillary circuits, providing spatiotemporal bio-signatures selective for maculopathies and retinopathies.}, }
@article {pmid41743586, year = {2026}, author = {Veritti, D and Misciagna, M and Teatino, C and Pontoni, C and Blasutig, M and Kuftic, M and Pece, S and Morsanutto, A and Pece, A and Lanzetta, P}, title = {Reducing the Carbon Footprint of Neovascular Age-Related Macular Degeneration Therapy: Environmental Impact of Transitioning to Aflibercept 8 mg.}, journal = {Journal of ophthalmology}, volume = {2026}, number = {}, pages = {9131955}, pmid = {41743586}, issn = {2090-004X}, abstract = {PURPOSE: To quantify and compare the carbon footprint associated with neovascular age-related macular degeneration (nAMD) treatment using real-world intravitreal aflibercept 2-mg injections versus a simulated aflibercept 8-mg regimen with extended dosing intervals.<br><br>METHODS: A life cycle assessment (LCA) combining process-based and input-output methodologies was conducted using real patient data from a tertiary ophthalmic center. The analysis included 101 patients treated with aflibercept 2&#x2009;mg and modeled the environmental impact of transitioning to aflibercept 8&#x2009;mg. The simulated aflibercept 8-mg cohort was generated by replicating the demographic and logistical characteristics of the real-world aflibercept 2-mg population while applying extended dosing intervals. Emissions were estimated in CO2 equivalents (CO2e) and included drug manufacturing, clinical materials, patient transportation, energy use, and waste disposal. Emission factors were derived from Defra and ecoinvent databases.<br><br>RESULTS: Patients treated with aflibercept 2&#x2009;mg generated an average carbon footprint of 1150&#x2009;kg CO2e per treatment cycle (2&#x2009;years), compared to 746&#x2009;kg CO2e for those modeled to receive aflibercept 8&#x2009;mg. This corresponds to an absolute reduction of 404&#x2009;kg CO2e and a relative reduction of 35%. The main driver of emissions was pharmaceutical procurement, followed by patient transportation. The lower injection frequency enabled by aflibercept 8&#x2009;mg significantly reduced both sources of emission.<br><br>CONCLUSIONS: A transition from conventional aflibercept 2-mg therapy to an aflibercept 8-mg regimen with extended dosing intervals reduces the treatment's carbon footprint by over one-third. These findings support the integration of environmental considerations into therapeutic decisions in ophthalmology, particularly for high-frequency procedures, such as intravitreal injections.}, }
@article {pmid41744421, year = {2026}, author = {Jacob, M and Stattin, M and Graf, A and Ebner, A and Ahmed-Balestra, D and Krepler, K and Ansari-Shahrezaei, S}, title = {The impact of fluid on visual acuity in exudative macular neovascularization type 1: A long-term real-life AMD study.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261424054}, doi = {10.1177/11206721261424054}, pmid = {41744421}, issn = {1724-6016}, abstract = {PurposeTo evaluate the dynamics of retinal fluid in eyes compromised by exudative macular neovascularization beneath the retinal pigment epithelium (MNV type 1) secondary to neovascular age-related macular degeneration (nAMD) and its impact on disease control over time.MethodsIn this retrospective single center study, 65 eyes of 65 patients with treatment-naive exudative MNV Type 1 were analyzed for the presence of subretinal fluid (SRF) and intraretinal fluid (IRF) in structural OCT B-scans for three years. All eyes started on three monthly intravitreal anti-VEGF injections followed by a personalized treatment interval. Primary outcome measure was visual acuity score (VAS) change based on fluid dynamics.Results29 (45%) eyes with SRF only started with a VAS of 74 ± 9 letters ETDRS, 20 eyes (31%) with SRF in the beginning that developed additional IRF had an initial VAS of 68 ± 11 letters, and 16 eyes (25%) with both, SRF and IRF measured 63 ± 13 letters at presentation. The VAS of all patients declined significantly (p = 0.003) over time, but no significant VAS change was measured between the groups.ConclusionIRF was regarded as a negative predictive OCT biomarker towards a lower VAS at the beginning but not necessarily during the course of the disease.}, }
@article {pmid41744818, year = {2026}, author = {Amaxilati, E and Chatzimichail, E and Tsiropoulos, GN and Motta, L and Empeslidis, T and Gatzioufas, Z and Panos, GD}, title = {Gene Therapy Advancements in Age-Related Macular Degeneration Treatment.}, journal = {Cells}, volume = {15}, number = {4}, pages = {}, pmid = {41744818}, issn = {2073-4409}, mesh = {Humans ; *Genetic Therapy/methods ; *Macular Degeneration/therapy/genetics ; Animals ; Dependovirus/genetics ; Genetic Vectors ; }, abstract = {Age-related macular degeneration (AΜD) remains a leading cause of irreversible vision loss. Ιn neovascular AΜD (nAΜD), frequent intravitreal anti-VΕGF injections create substantial treatment burden, while approved therapies for geographic atrophy (GA) provide modest slowing of progression. Ocular gene therapy aims to achieve sustained intraocular expression of therapeutic proteins after a single administration. Τhis review summarises the biological rationale, vector platforms, and delivery routes relevant to AΜD, with emphasis on adeno-associated virus (AAV) systems, capsid engineering, and compartment-specific administration (intravitreal, subretinal, and suprachoroidal). We synthesise the clinical landscape for sustained anti-VΕGF expression approaches in nAΜD and complement-modulating strategies for GA, and highlight how trials increasingly prioritise injection-burden reduction, anatomical endpoints, and biomarkers of target engagement. Κey challenges include intraocular inflammation and neutralising antibodies (particularly with intravitreal dosing), variability and durability of transgene expression, surgical risks associated with subretinal delivery, and practical constraints related to manufacturing scale, cost, and long-term safety surveillance for non-removable therapies. Overall, gene therapy offers a plausible route towards durable, mechanism-targeted AΜD management, but its clinical role will depend on robust controlled trials and multi-year follow-up.}, }
@article {pmid41744977, year = {2026}, author = {Zhu, W and Xia, M and He, Y and Huang, Q and Liao, Z and Wang, X and Zhou, X and Duan, X}, title = {Hydrogels as Promising Carriers for Ophthalmic Disease Treatment: A Comprehensive Review.}, journal = {Gels (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {41744977}, issn = {2310-2861}, support = {[2021YFA1101202 and 2021YFA1101200]//the National key research and development program of China/ ; [Grant No. 82501363]//the Young Scientists Fund of the National Natural Science Foundation of China/ ; [Grant No. 82471079]//the National Natural Science Foundation of China/ ; [Grant No. kq2502222]//the Changsha Municipal Natural Science Foundation of China/ ; [Grant No. 2024JJ9020]//the Natural Science Foundation of Hunan Province of China/ ; [2024AAC03823]//the Natural Science Foundation of Ningxia Hui Autonomous Region of China/ ; [Grant No. 2025RC21]//the Science and Technology Plan Project of Yinchuan City of China/ ; }, abstract = {Ocular disorders such as keratitis, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and dry eye disease (DED) are highly prevalent worldwide and remain major causes of visual impairment and blindness. Conventional therapeutic approaches for ocular diseases, such as eye drops, surgery, and laser therapy, are frequently hampered by limited drug bioavailability, rapid clearance, and treatment-related complications, primarily due to the eye's unique anatomical and physiological barriers. Hydrogels, characterized by their three-dimensional network structure, high water content, excellent biocompatibility, and tunable physicochemical properties, have emerged as promising platforms for ophthalmic drug delivery. This review summarizes the classification, fabrication strategies, and essential properties of hydrogels, and highlights recent advances in their application to ocular diseases, including keratitis management, corneal wound repair, intraocular pressure regulation and neuroprotection in glaucoma, sustained drug delivery for AMD and DR, vitreous substitutes for retinal detachment, and therapies for DED. In particular, we highlight recent advances in stimuli-responsive hydrogels that enable spatiotemporally controlled drug release in response to ocular cues such as temperature, pH, redox state, and enzyme activity, thereby enhancing therapeutic precision and efficacy. Furthermore, this review critically evaluates translational aspects, including long-term ocular safety, clinical feasibility, manufacturing scalability, and regulatory challenges, which are often underrepresented in existing reviews. By integrating material science, ocular pathology, and translational considerations, this review aims to provide a comprehensive framework for the rational design of next-generation hydrogel systems and to facilitate their clinical translation in ophthalmic therapy.}, }
@article {pmid41745467, year = {2026}, author = {Hacker, F and Roider, J and Klettner, A and Dörschmann, P}, title = {Fucoidan from Fucus vesiculosus Protects Retinal Pigment Epithelium from Lipid-Induced Damage Related to AMD.}, journal = {Marine drugs}, volume = {24}, number = {2}, pages = {}, pmid = {41745467}, issn = {1660-3397}, support = {not available//Retinologische Gesellschaft - Dr. Gaide-AMD-Preis/ ; }, mesh = {*Polysaccharides/pharmacology/isolation &amp; purification ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; Animals ; Humans ; *Macular Degeneration/drug therapy/metabolism/pathology ; Cell Survival/drug effects ; *Fucus/chemistry ; Oxidative Stress/drug effects ; Cell Line ; Swine ; Lipid Peroxidation/drug effects ; Vascular Endothelial Growth Factor A/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Fucoidans are natural compounds that exhibit bioactivity against age-related macular degeneration (AMD), the leading cause of central vision loss in industrialized nations. Pathological factors like oxidative stress and lipid peroxidation play vital roles in AMD pathogenesis. Lipid-induced alterations in the retinal pigment epithelium (RPE) contribute to AMD development. In this study, a commercial fucoidan from Fucus vesiculosus (FVs) was tested for its activity regarding lipid-peroxidation-related effects. The human RPE cell line ARPE-19, primary porcine RPE, and RPE/choroid explants were stimulated with erastin, acting as an inducer of lipid peroxidation, and treated with fucoidan. Effects on cell viability (tetrazolium bromide (MTT) or calcein staining), vascular endothelial growth factor (VEGF) and interleukin 8 (IL8) secretion (ELISA), reactive oxygen species (ROS), protein expression (glutathione peroxidase 4 (GPX4), CD59, and retinoid isomerohydrolase (RPE65), analyzed via Western blot), and gene expression (RT-qPCR) were investigated. FVs showed protective effects against erastin-induced reduction in viability (with a 12.7% increase in viability compared to erastin), RPE65 expression (with a 4.2-fold increase compared to erastin), and GPX4 expression (with a 2.3-fold increase compared to erastin) in primary RPE. Erastin-induced VEGF secretion was attenuated by FVs in ARPE-19 and primary RPE (with an up to 1.7-fold reduction compared to erastin). Elevated IL8 levels were reduced by FV treatment in primary RPE (with a 9.1-fold reduction compared to erastin). Induced VEGF in RPE/choroid explants was reduced by FVs (with an up to 2.9-fold reduction compared to erastin), and this reduction was correlated with slight improvements in viability. In conclusion, FVs exerted protective effects against lipid-induced stress. This study reveals further effects of fucoidans against AMD-related pathologies.}, }
@article {pmid41746123, year = {2026}, author = {Wall, K and Fritsch, S and Vaisband, M and Hasenauer, J and Schwenzer, N and von der Emde, L and Jauch, AS and Holz, FG and Curcio, CA and Ach, T}, title = {Near-Infrared Fluorescence Lifetime Imaging Microscopy Reveals Loss of RPE Cell Body Polarity in Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {2}, pages = {55}, pmid = {41746123}, issn = {1552-5783}, abstract = {PURPOSE: Retinal pigment epithelium (RPE) cells exhibit a markedly polarized distribution of organelles and membrane specializations. We aimed to determine whether fluorescence lifetime imaging microscopy (FLIM) using different excitation wavelengths reveals altered polarity in age-related macular degeneration (AMD).<br><br>METHODS: Retinal cross-sections from human donors (11 with AMD; 87.9 &#xb1; 4.5 years, and 9 healthy controls; 83.4 &#xb1; 2.7 years) were imaged at the fovea, perifovea, near-, mid-periphery, and ora serrata using FLIM (excitation = 488, 780 nm; 5 regions of interest [ROI; 50 &#xb5;m width] per location). At each location, individual RPE cells were classified as healthy, non-uniform, or pathological. Cell bodies were divided into four equal apical-to-basal compartments to determine the fluorescence lifetime (FLT) gradient. Post-processing included multiexponential decay modeling and phasor analysis. Ordinal logistic regression (LR) and linear mixed-effects models (LMMs) compared healthy and diseased cells.<br><br>RESULTS: In 477 ROIs (3-5 cells/ROI), healthy RPE at 780 nm displayed a distinct intracellular FLT gradient. In 52 pathological ROIs, this was significantly reduced (regression coefficient = -0.029, P = 0.007). Ordinal LR confirmed an association between polarity loss and dysmorphia (log cumulative odds ratio = -6.50, P = 0.033). Mean FLT was shorter in non-uniform (-0.009 nanoseconds [ns], P = 0.03) and pathological RPE (-0.036 ns, P < 0.001) than in healthy RPE. At 488 nm, pathological RPE exhibited prolonged FLT without an apical/basal gradient.<br><br>CONCLUSIONS: At 780 nm, FLIM detects a loss of RPE cell polarity that likely reflects intracellular reorganization and metabolic change. Disruption in NIR-autofluorescence lifetimes may provide an early biomarker for pathological RPE alterations in AMD.}, }
@article {pmid41746581, year = {2026}, author = {Itagaki, K and Mukai, R and Honjo, J and Sekiryu, T}, title = {One-year outcomes of pneumatic displacement for submacular hemorrhage secondary to neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {41746581}, issn = {1613-2246}, abstract = {PURPOSE: To investigate the one-year outcomes of pneumatic displacement for submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD). We compared cases of polypoidal choroidal vasculopathy (PCV) and non-PCV.<br><br>STUDY DESIGN: A retrospective observational study.<br><br>METHODS: We reviewed the medical records of 76 eyes of 74 patients with SMH secondary to nAMD who underwent pneumatic displacement as initial treatment. The primary outcomes were best-corrected visual acuity (BCVA), complications, and additional treatment.<br><br>RESULTS: We examined 54 eyes with PCV and 22 eyes with non- PCV. Approximately 0.5 mL of 100% sulfur hexafluoride (SF6) gas was injected into the vitreous cavity. After pneumatic displacement, 19 eyes (25%) underwent vitrectomy for complications such as vitreous hemorrhage or retinal detachment. Additionally, 95% of eyes that underwent vitrectomy had hemorrhage extending beyond the arcade vessels at baseline. During the 12 months, the average number of anti-vascular endothelial growth factor (VEGF) injections was 7.0&#xb1;3.6 in PCV cases and 7.0&#xb1;3.3 in non-PCV cases (P=0.74). The mean BCVA at 12 months improved from 0.77&#xb1;0.44 to 0.42&#xb1;0.45 in PCV cases (P<0.01) and from 1.13&#xb1;0.51 to 0.88&#xb1;0.59 in non-PCV cases (P=0.01). The PCV group had better BCVA than the non-PCV group at both time points (P<0.01). In the previously treated group, 100% of non-PCV cases had worsened visual acuity compared to pre-onset SMH, while 62% of PCV cases maintained pre-onset visual acuity (P<0.01).<br><br>CONCLUSION: Pneumatic displacement resulted in superior visual outcomes in the PCV group compared to the non-PCV group for submacular hemorrhage secondary to nAMD. .}, }
@article {pmid41746935, year = {2026}, author = {Nakagawa, N and Igarashi, A and Yokogawa, H and Kobayashi, A and Higashide, T and Yamagami, S and Hayashi, T}, title = {Impact of postoperative macular comorbidity on visual outcomes after Descemet's membrane endothelial keratoplasty: A multicenter analysis.}, journal = {PloS one}, volume = {21}, number = {2}, pages = {e0343883}, pmid = {41746935}, issn = {1932-6203}, abstract = {The aim of this study was to identify the clinical factors associated with postoperative visual acuity following Descemet's membrane endothelial keratoplasty (DMEK), with emphasis on the impact of macular diseases. This retrospective multicenter study included consecutive eyes that underwent DMEK between March 1, 2011, and June 30, 2022, and had available optical coherence tomography findings. Eyes with other ocular diseases causing visual loss were excluded. Overall, 77 eyes of 66 patients were included in the study. Univariable and multivariable regression analyses were performed to identify the predictors of best-corrected visual acuity (BCVA) at the final follow-up. Worse preoperative visual acuity and macular comorbidity were identified as independent predictors of poorer postoperative BCVA. Among macular pathologies, cystoid macular edema was most strongly correlated with reduced vision in the univariable analysis (β = 0.195; p = 0.016). In the subgroup analysis, worse preoperative visual acuity and macular comorbidity remained significant predictors (p < 0.001 and p = 0.023, respectively). Other comorbidities such as epiretinal membrane and wet age-related macular degeneration were not significant predictors. Worse preoperative visual acuity and macular comorbidity are independent risk factors for suboptimal visual recovery after DMEK. These findings highlight the importance of comprehensive preoperative retinal assessment and individualized postoperative management to optimize visual outcomes.}, }
@article {pmid41747809, year = {2026}, author = {Bernardi, E and Chakravarthy, U and Muldrew, KA and Hogg, RE and Wright, DM and Zinkernagel, M and Peto, T and Csincsik, L}, title = {Tomographic Biomarkers Differ by Progression Risk to Late Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.02.011}, pmid = {41747809}, issn = {2468-6530}, }
@article {pmid41747836, year = {2026}, author = {Murati, F and Ghahari, P and Zvavamwe, T and Williams, WW and Curran, K and Peto, T and Lengyel, I and McKay, BS and Kozak, I}, title = {Levodopa in retinal disease: Dopamine pathways, neuroprotective mechanisms, and clinical evidence.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.02.010}, pmid = {41747836}, issn = {1879-3304}, abstract = {We review the role of levodopa (L-DOPA), a dopamine precursor used to treat Parkinson disease, as a candidate for retinal neuroprotection, focusing on retinal dopamine biology, mechanisms of action, and evidence from preclinical and clinical studies. Selected experimental and clinical studies indicate that L-DOPA and related dopaminergic interventions influence multiple retinal pathways relevant to degeneration. L-DOPA, synthesized in the pigmented retinal pigment epithelium, activates GPR143 signaling and promotes the release of neuroprotective factors. In animal studies, L-DOPA supplementation rescued retinal development in albinism and reduced oxidative damage to photoreceptors. Epidemiologic analyses showed that patients on systemic L-DOPA had a delayed onset and a lower incidence of age-related macular degeneration (AMD). Small clinical studies in neovascular AMD demonstrated that adjunctive oral L-DOPA improved vision and reduced the burden of anti-vascular endothelial growth factor injections. Larger controlled trials are needed to define efficacy, optimal dosing, and long-term tolerability. Given its established pharmacology and ability to cross the blood-retinal barrier, L-DOPA is a promising candidate for therapeutic repurposing in ophthalmology.}, }
@article {pmid41748843, year = {2026}, author = {Wang, H and Zhang, J and Li, Y and Suo, Y and Wang, H and Gu, Z and Yan, H and Wang, C and Shao, L and Wei, W and Jin, X}, title = {Chinese Patient Preferences and Trade-Offs for Therapy-Related Attributes of Anti-Vascular Endothelial Growth Factor Agents in Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration: A Discrete Choice Experiment.}, journal = {The patient}, volume = {}, number = {}, pages = {}, pmid = {41748843}, issn = {1178-1661}, abstract = {BACKGROUND AND OBJECTIVE: Anti-vascular endothelial growth factor agents are the first-line treatment for macular edema associated with neovascularization or increased vascular permeability, yet patient adherence remains suboptimal. This study aimed to quantify how patient preferences for therapy-related attributes of anti-vascular endothelial growth factor agents influence trade-offs among effectiveness, safety, required injection regimen, and cost.<br><br>METHODS: A face-to-face survey-based discrete choice experiment was conducted across six Chinese cities from October 2023 to April 2024 among adults with diabetic macular edema or neovascular age-related macular degeneration. Two separate discrete choice experiment sets were developed based on literature review, focus groups, best-worst scaling, and reference to package inserts and clinical trial data. Each patient was asked to choose a preferred alternative from each of the ten choice sets. Mixed logit models estimated patient preference weights for each attribute level, relative attribute importance, and trade-offs between benefits, risks, injection regimens, and cost. Latent class models explored preference heterogeneity.<br><br>RESULTS: A total of 355 participants who passed quality checks, most preferred anti-vascular endothelial growth factor agents with longer or more flexible maintenance-phase injection intervals, greater macular edema reduction, improved visual acuity, lower risk of serious adverse events, and lower cost. For patients with diabetic macular edema, injection frequency was the most important attribute. They were willing to pay an additional &#xa5;5045.26 ($708.60) to extend injection intervals from monthly to treat-and-extend regimen, or accept a 12.97% increased risk, or forgo a 21.76% macular edema reduction, or a 14.76% visual acuity improvement. For patients with neovascular age-related macular degeneration, visual acuity improvement was the most important. They were willing to pay &#xa5;16,586.29 ($2329.54) to improve visual acuity from 20% to 43%, or accept a 17.30% increased risk, or forgo an 18.64% macular edema reduction, or an 11.88% visual acuity improvement. Patients with diabetic macular edema with senior high school education or above, or with cross-region treatment history, placed greater emphasis on visual acuity improvement, while those with more than three prior injections prioritized lower injection frequency.<br><br>CONCLUSIONS: Eliciting individual preferences can support ophthalmologists in making patient-centered recommendations during shared decision making. Understanding trade-offs across different patients is also valuable for pharmaceutical companies and payers. Future research should further explore the balance between cost, risk, and potential benefits that patients are willing to accept.}, }
@article {pmid41749475, year = {2026}, author = {Abdalbaqi, A and Kerur, N and Ohr, MP and Palmer, AF and Swindle-Reilly, KE}, title = {Murine Biocompatibility Evaluation of an Albumin-Derived Complex and Nanoparticle Delivery System for Ocular Applications.}, journal = {Journal of biomedical materials research. Part A}, volume = {114}, number = {3}, pages = {e70058}, doi = {10.1002/jbm.a.70058}, pmid = {41749475}, issn = {1552-4965}, support = {R21EY035038/NH/NIH HHS/United States ; P30EY032857/NH/NIH HHS/United States ; //College of Engineering, Ohio State University/ ; }, mesh = {Animals ; Humans ; *Nanoparticles/chemistry ; Mice ; *Biocompatible Materials/pharmacology/chemistry ; Polymers/chemistry/pharmacology ; Mice, Inbred C57BL ; *Serum Albumin, Human/chemistry/pharmacology ; *Materials Testing ; Heme/chemistry/pharmacology ; Indoles/chemistry/pharmacology ; Retinal Pigment Epithelium/drug effects/metabolism ; Heme Oxygenase-1/metabolism ; Macular Degeneration/drug therapy/pathology ; *Nanoparticle Drug Delivery System/chemistry ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the aging population, with no curative treatment currently available. Current therapies primarily target late-stage symptoms and are limited by their frequent and invasive intravitreal (IVT) injections. To address oxidative stress-induced inflammation mechanisms relevant to early retinal degeneration, we developed a heme-bound human serum albumin (heme-albumin) complex designed to transiently induce heme oxygenase-1 (HO-1), a cytoprotective enzyme with antioxidant and anti-inflammatory effects. Polydopamine nanoparticles (PDA NPs) were selected as a delivery system due to their ability to scavenge reactive oxygen species (ROS) and degrade under oxidative environments. A previous in vitro study demonstrated that heme-albumin-loaded PDA NPs reduce oxidative damage and inflammatory signaling in retinal pigment epithelium (RPE) cells. This study evaluates the in vivo biocompatibility of IVT-administered heme-albumin and unloaded PDA NPs as independent components in a murine model. At the tested doses, both components showed minimal cytotoxicity with preservation of retinal structure, establishing biocompatible dosing for future evaluation in retinal disease models.}, }
@article {pmid41750304, year = {2026}, author = {Delrue, C and Speeckaert, R and Speeckaert, MM}, title = {Molecular Crosstalk in Age-Related Macular Degeneration: Integrating Oxidative Stress, Inflammation, microRNAs, and Genetic Susceptibility Toward Precision Therapeutics.}, journal = {Biomolecules}, volume = {16}, number = {2}, pages = {}, pmid = {41750304}, issn = {2218-273X}, mesh = {Humans ; *Macular Degeneration/genetics/metabolism/therapy/pathology ; *Oxidative Stress ; *MicroRNAs/genetics/metabolism ; *Inflammation/genetics/metabolism/pathology ; *Genetic Predisposition to Disease ; Precision Medicine ; Animals ; }, abstract = {Age-related macular degeneration (AMD) is an increasingly prevalent source of permanent visual impairment in the aging population and is widely accepted as a multi-factorial neurodegenerative disorder of the retina. While there has been significant progress in treating neovascular AMD, there are currently no effective disease-sparing treatments for dry AMD and geographic atrophy. To date, research has begun to reveal the complex relationship between the environment and genetic predisposition in AMD pathogenesis. Various environmental factors responsible for AMD include oxidative stress, mitochondrial dysfunction, inflammation, abnormal complement activation, and epigenetic regulation, which interact dynamically to drive disease progression. This review summarizes recent data and provides a comprehensive model for understanding how these interacting factors lead to the progression of AMD from an early stage to advanced stages with complications associated with the disease. We highlight the central role of retinal pigment epithelial mitochondrial failure and impaired stress resilience as upstream drivers that amplify inflammation and complement-mediated injuries. We also discuss how dysregulated miRNAs and proteomic network remodeling contribute to disease heterogeneity. Emerging therapeutic strategies are reviewed in the context of molecular endotyping and personalized intervention. Finally, we outline future directions toward precision medicine in AMD, emphasizing early disease modification, rational combination therapies, and the need to bridge the translational gaps between molecular discovery and clinical trial design.}, }
@article {pmid41750784, year = {2026}, author = {Luo, WT and Wang, TW}, title = {Performance and Clinical Utility of Deep Learning for Detecting Referable Age-Related Macular Degeneration on Fundus Photographs: A Systematic Review and Meta-Analysis.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {4}, pages = {}, pmid = {41750784}, issn = {2075-4418}, abstract = {Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in older adults. Detection of referable AMD-typically intermediate or advanced disease requiring specialist evaluation-is critical for timely intervention. Deep learning (DL) applied to color fundus photographs has emerged as a potential tool to support large-scale AMD screening. This systematic review and meta-analysis evaluated the diagnostic accuracy of DL algorithms for detecting referable AMD and compared their performance with human graders. Methods: We systematically searched PubMed, Embase, Web of Science, and IEEE Xplore through 18 December 2025. Diagnostic accuracy studies assessing DL algorithms on color fundus photographs for referable AMD in adults were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using an AI-adapted PROBAST framework. Pooled sensitivity and specificity were estimated using a bivariate random-effects model. Clinical utility was evaluated using likelihood ratios, and paired head-to-head comparisons were synthesized using a contrast-based meta-analysis. Results: Fourteen studies were included. DL algorithms achieved a pooled sensitivity of 0.91 (95% CI: 0.86-0.94) and specificity of 0.93 (95% CI: 0.86-0.96), with substantial heterogeneity. The pooled positive and negative likelihood ratios were 12.22 and 0.10, respectively, indicating strong diagnostic utility. In direct comparisons, DL systems showed slightly lower sensitivity but higher specificity than human graders. Conclusions: Deep learning demonstrates high diagnostic accuracy for detecting referable AMD from fundus photographs and may support screening and referral workflows. Further prospective validation and standardized evaluation are needed before widespread clinical implementation.}, }
@article {pmid41752067, year = {2026}, author = {Ozawa, H and Sugano, E and Tabata, K and Kakizaki, T and Sato, A and Takai, Y and Sone, K and Shidomi, M and Ishii, Y and Saito, A and Totuka, K and Ozaki, T and Fukuda, T and Bai, L and Tomita, H}, title = {Pyrroloquinoline Quinone Protects Against Light-Induced Retinal Damage in Association with the Suppression of c-Fos Signalling.}, journal = {International journal of molecular sciences}, volume = {27}, number = {4}, pages = {}, pmid = {41752067}, issn = {1422-0067}, support = {22H00579//Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan/ ; 21K18278//Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan/ ; 22K09760//Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan/ ; 21K09713//Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan/ ; }, mesh = {Animals ; *PQQ Cofactor/pharmacology ; *Proto-Oncogene Proteins c-fos/metabolism ; Rats ; *Light/adverse effects ; *Signal Transduction/drug effects ; *Retina/drug effects/metabolism/radiation effects/pathology ; Cell Line ; Humans ; Male ; Rats, Sprague-Dawley ; Oxidative Stress/drug effects ; Macular Degeneration/metabolism/drug therapy/pathology/etiology ; }, abstract = {Age-related macular degeneration (AMD) is a progressive retinal disorder characterised by oxidative stress and inflammation. Although pyrroloquinoline quinone (PQQ) has been reported to exert neuroprotective effects, its specific efficacy in in vivo models of AMD pathophysiology has not yet been elucidated. In this study, we evaluated the protective effects of PQQ against all-trans-retinal (ATR)-induced cytotoxicity in ARPE-19 cells and light-induced photoreceptor degeneration in rats. Pretreatment of ARPE-19 cells with PQQ dose-dependently mitigated ATR-induced cytotoxicity. In the in vivo model, rats received a single intraperitoneal injection of PQQ (2 or 5 mg/kg) 1 h prior to 1000-lux light exposure. Retinal function and morphology were evaluated by electroretinography and haematoxylin-eosin staining, respectively. The 5 mg/kg PQQ group retained significantly greater retinal function than the vehicle group at 3 days postexposure and demonstrated significant preservation of the outer nuclear layer at 7 days postexposure, indicating the suppression of photoreceptor cell death. Western blot analysis detected the dose-dependent suppression of light-induced c-Fos upregulation following PQQ treatment. These findings suggest that the protective effect of PQQ against phototoxic damage is associated with the suppression of c-Fos signalling, thus lending support to the further investigation of PQQ as a potential therapeutic agent for AMD.}, }
@article {pmid41752910, year = {2026}, author = {Nowosielska, A and Rotuski, G}, title = {New Technique of Single-Point Scleral Fixation of the Smaller-Incision New-Generation Implantable Miniature Telescope with an 18-Month Follow-Up Period.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {2}, pages = {}, pmid = {41752910}, issn = {2075-1729}, abstract = {BACKGROUND: The implantable miniature telescope is used to provide functional vision for patients with advanced AMD. However, despite the considerable cost of the device, there are strict criteria to be met for this procedure, since the patients require challenging neuroadaptation afterward, which sometimes fails and leads to the necessity of device explantation. Visual outcomes also depend on the stability of the microtelescope; tilts cause unwanted optical aberrations and can lead to device luxation, with sight-threatening complications.<br><br>CASE REPORT: This case presents a novel technique for fixing the ophthalmic telescope device SING-IMT&#x2122;. A 76-year-old female with pre-operative visual acuity of 15 letters on the ETDRS scale underwent surgery on her left eye. The superior haptic was fixed at the 12 o'clock position with a Prolene 5-0 suture, achieving good postoperative stability. The implant was stable throughout the entire observation period.<br><br>CONCLUSIONS: Implant stability is crucial for maximizing visual potential in patients with advanced AMD selected for the procedure, since visual acuity in the peripheral retina, where the perceived image eventually lands, is much lower than the macula. Therefore, there is a need to standardize surgical approaches and use objective follow-up measures to assess long-term patient satisfaction.}, }
@article {pmid41752939, year = {2026}, author = {Racioppo, P and Wang, ZC and Sadda, SR and Hu, ZJ}, title = {SWAU-Net: Longitudinal Prediction of Geographic Atrophy via Sliding-Window Attention.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {2}, pages = {}, pmid = {41752939}, issn = {2075-1729}, support = {R21EY030619/EY/NEI NIH HHS/United States ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of central vision loss in aging populations. Geographic atrophy (GA) is the advanced, non-neovascular form of AMD. Predicting the longitudinal progression of GA remains a critical challenge in ophthalmic clinical practice and clinical trial design. Forecasting the trajectory of GA is complicated by highly variable growth rates and the inherent scarcity of long-term, high-quality imaging data. To address these challenges, we introduce the Sliding Window Attention U-Net (SWAU-Net), a hybrid architecture that integrates Transformer-based temporal modeling of GA growth with precise spatial modeling of GA location with a U-Net convolutional neural network (CNN). To ensure generalization in the low-data regime, SWAU-Net embeds explicit temporal and geometric consistency priors via a weight-shared Sliding Window Attention core and feature-level regularization that preserves sparse, high-frequency lesion boundaries across frames. Experimental results demonstrate that these structural constraints prevent the model from overfitting to imaging noise, achieving a Growth Mask Dice Similarity Coefficient (DSC) of 0.66 (representing the spatial overlap between the predicted and ground truth lesion expansion regions), a significant improvement over unregularized Transformer and standard recurrent baseline models. Our framework provides a robust tool for predicting GA lesion trajectories, potentially supporting more efficient clinical trial designs and personalized patient monitoring.}, }
@article {pmid41753141, year = {2026}, author = {Parolini, F and Pilotto, E and Midena, E and Midena, G}, title = {Inflammatory Hyperreflective Retinal Foci: An OCT Biomarker of Neuroinflammation in Geographic Atrophy.}, journal = {Journal of clinical medicine}, volume = {15}, number = {4}, pages = {}, pmid = {41753141}, issn = {2077-0383}, abstract = {Background: Inflammatory hyperreflective retinal foci (I-HRF) have been recognized as an optical coherence tomography (OCT) biomarker of aggregates of activated microglial cells. Microglia, the principal resident immune cells, are key players in geographic atrophy (GA) development and progression. Objective: To quantify I-HRF distribution across inner (IR) and outer (OR) retinal layers in GA compared with healthy controls. Methods: Retrospective observational study including patients aged ≥50 years with GA lesion area >1.25 mm[2] and age-matched healthy subjects. GA eyes were classified as bilateral GA (B-GA) or unilateral GA (U-GA; fellow eye with macular neovascularization). Using Spectralis OCT, I-HRF (≤30 μm; RNFL-like reflectivity; no posterior shadowing) were identified and counted across IR and OR. Results: Sixty-eight eyes from 46 patients with GA (B-GA: 49 eyes; U-GA: 19 eyes) and 19 control eyes were studied. I-HRF were higher in IR than in OR in all groups (p < 0.001). I-HRF were higher in GA eyes in both layers compared with controls (p < 0.05). U-GA exhibited higher I-HRF than B-GA in IR (44.32 ± 8.47 vs. 30.10 ± 7.62; p < 0.001), while I-HRF were not significantly different in OR (9.58 ± 3.04 vs. 8.02 ± 3.33; p = 0.081). Conclusions: I-HRF are increased in GA. They are more numerous in IR, consistent with their proposed inflammatory origin. These findings further support the role microglia may play in GA pathology. I-HRF may become an OCT biomarker to track GA-associated neuroinflammation in different GA phenotypes. Longitudinal studies are needed to clarify I-HRF significance in GA progression.}, }
@article {pmid41753180, year = {2026}, author = {Spindler, J and Pfister, IB and Weinberger, A and Garweg, JG}, title = {Prevalence of Polypoidal Choroidal Vasculopathy Beyond Recalcitrant Macular Neovasculopathies in a European AMD Cohort and Therapeutic Response to Brolucizumab.}, journal = {Journal of clinical medicine}, volume = {15}, number = {4}, pages = {}, pmid = {41753180}, issn = {2077-0383}, abstract = {Background: Polypoidal choroidal vasculopathy (PCV) may be underdiagnosed in Europe due to the limited use of indocyanine green angiography (ICGA), in particular, in patients with occult or poorly responsive neovascular age-related macular degeneration (AMD). Based on this, we aimed to assess the prevalence of PCV beyond clinically typical recalcitrant nAMD using OCT criteria, and to report on the anatomical and functional outcomes following a switch to brolucizumab (bro). Methods: This retrospective case series used recently established optical coherence tomography (OCT)-based criteria to differentiate clinically typical nAMD and PCV in eyes with recalcitrant disease requiring treatment every six weeks or less. The aim was to compare the impact of switching to bro on disease activity in patients with recalcitrant nAMD and PCV over 12 months. Descriptive statistics and subgroup comparisons were performed. Data are presented as mean ± standard deviation (SD) as well as median and interquartile ranges (IQR), since data were not normally distributed. Results: Of the 27 eyes examined, 16 (59.3%) presented with typical recalcitrant nAMD and 11 (40.7%) with PCV. Patients with typical nAMD were older (81.4 ± 5.7 vs. 74.7 ± 7.7 years; p = 0.016) and exhibited less fluid (central retinal thickness in typical nAMD: 349.3 ± 95.3 µm; in PCV: 597.1 ± 348.4 µm; p = 0.005). This difference could be attributed to variations in pigment epithelial detachment heights (typical nAMD: 176.5 ± 102.6 µm, PCV: 384.6 ± 284.6 µm; p = 0.023). Twelve months after switching to bro (159 injections), the treatment interval increased from 5.7 ± 1.8 to 12.6 ± 5.1 weeks in nAMD and from 5.5 ± 1.9 to 8.0 ± 1.5 weeks in PCV patients (at switch: p = 0.81; after 12 months: p = 0.040). Visual gains after switching were maintained in two out of three patients with intraocular inflammation (IOI). Conclusions: PCV is remarkably underdiagnosed and overrepresented in the group of eyes with recalcitrant nAMD. Despite the inherent risk of IOI in response to bro, these results support the potential of bro as a third-line option for patients with eyes requiring anti-VEGF treatment every 6 weeks or less, provided that patients are monitored closely.}, }
@article {pmid41753234, year = {2026}, author = {Vagge, A and Baldi, M and Musolino, M and Rivarone, V and Catti, C and Iester, M}, title = {Current and Emerging Strategies for Myopia Control in Children: A Comprehensive Evidence-Based Review.}, journal = {Journal of clinical medicine}, volume = {15}, number = {4}, pages = {}, pmid = {41753234}, issn = {2077-0383}, abstract = {Myopia has emerged as a global public health crisis, with prevalence exceeding 80% in East Asian urban populations and rising rapidly worldwide. High myopia substantially increases the lifetime risk of sight-threatening complications, including myopic macular degeneration, retinal detachment, and glaucoma. Multiple interventions have been investigated to slow myopia progression in children. Behavioral strategies, particularly increased outdoor exposure, demonstrate protective effects against myopia onset and may modestly slow progression, whereas several historically used approaches show no clinically meaningful benefit. Spectacle lens interventions include simultaneous defocus designs (e.g., DIMS, HALT, CARE) and contrast-modulating diffusion optics (DOT) lenses; collectively, these technologies have demonstrated consistent and clinically meaningful reductions in axial elongation across randomized clinical trials. Contact lens modalities, including dual-focus soft lenses and orthokeratology, have also demonstrated substantial efficacy in slowing progression in controlled studies. Low-dose atropine remains a cornerstone pharmacological therapy, particularly at concentrations between 0.01% and 0.05%, offering significant efficacy with minimal side effects. Repeated low-level red-light therapy has shown promising short-term reductions in axial elongation, although long-term safety and rebound effects remain uncertain. Combination therapy targeting complementary optical and pharmacological pathways shows additive benefits, particularly in children inadequately controlled with monotherapy. Contemporary clinical management emphasizes risk stratification based on axial length, age-specific growth targets, and structured longitudinal monitoring. The goal of modern myopia management is not merely to slow progression, but to prevent high myopia and reduce the lifetime burden of vision-threatening complications through a proactive, individualized approach increasingly regarded as the standard of care.}, }
@article {pmid41755782, year = {2026}, author = {Yu, E and Gu, SM and Kim, H and Kim, JG and Hwang, BY and Min, JK and Yun, J}, title = {Celafolin A-1 Ameliorates Subretinal Fibrosis via Inhibition of Crystallin Alpha B in a Laser-Induced Choroidal Neovascularization Mouse Model.}, journal = {Biomolecules &amp; therapeutics}, volume = {34}, number = {2}, pages = {434-447}, pmid = {41755782}, issn = {1976-9148}, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in people over 65 years old. Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for neovascular AMD (nAMD); however, fibrosis remains an unmet medical need due to the lack of effective medications. This study evaluated eight natural products from Celastrus orbiculatus, which has been reported to have anti-inflammatory effects, for their effects on the fibrotic pathological process as well as choroidal neovascularization (CNV). We investigated the half-maximal inhibitory concentration (IC50) values of these compounds on VEGF and alphasmooth muscle actin (α-SMA, a fibrosis marker) expression-induced by human acute monocytic cell (THP-1) conditioned media in retinal pigment epithelium cells (ARPE-19). Four compounds reduced both VEGF and α-SMA at 10 μM, with three-Celafolin A-1, COFH5645, and COFH543435-showing the highest potency. Intravitreal injections of the compound in a mouse model of CNV induced by laser photocoagulation confirmed its efficacy. Celafolin A-1 significantly reduced α-SMA and VEGF expression and decreased hyper-reflective lesions and CNV areas. Binding affinity measurements using biolayer interferometry identified an interaction between Celafolin A-1 and crystallin alpha B (Cryab), a protein involved in stress responses and fibrosis. Celafolin A-1 reduced the expression levels of Cryab as well as its phosphorylated form at Ser45, indicating that its mechanism involves the regulation of Cryab phosphorylation. Taken together, Celafolin A-1 exhibits dual inhibitory effects on VEGF and fibrosis, suggesting it as a candidate for the treatment of nAMD.}, }
@article {pmid41755917, year = {2026}, author = {Zhang, Y and Wei, C and Stewart, JM}, title = {Transient vitreous opacity following combined intravitreal injection of pegcetacoplan and faricimab-svoa in patients with neovascular age-related macular degeneration and geographic atrophy.}, journal = {American journal of ophthalmology case reports}, volume = {42}, number = {}, pages = {102545}, pmid = {41755917}, issn = {2451-9936}, }
@article {pmid41756519, year = {2026}, author = {John, R and George, MR and Williams, GS and Morgan, T}, title = {How Do Optometrists Approach Directed Questioning on Smoking Status in a Centrally Co-Ordinated, Publicly-Funded National Primary Care Eye Health Service?.}, journal = {Clinical optometry}, volume = {18}, number = {}, pages = {580909}, pmid = {41756519}, issn = {1179-2752}, abstract = {BACKGROUND: Tobacco use is a leading cause of preventable death worldwide, linked to various health issues, including cancers, cardiovascular diseases, and respiratory illnesses. It also adversely affects ocular health, increasing the risk of conditions like Age-Related Macular Degeneration and cataracts. The socioeconomic burden of smoking in the UK is significant, costing the National Health Service between £2.7 and £5.2 billion annually. Smoking cessation improves health outcomes and reduces healthcare costs. Optometrists are well positioned to identify smoking behaviours and offer cessation advice, yet evidence on current practice in Wales is limited.<br><br>METHODS: This cross-sectional study used an anonymous online questionnaire to assess smoking-related practice behaviours among optometrists providing National Health Service optometry services in Wales. The survey captured demographic characteristics, training history, current approaches to smoking status identification and cessation advice, confidence levels, and perceived barriers to discussing smoking with patients.<br><br>RESULTS: A total of 778 optometrists participated, with 96.3% reporting routine assessment of patients' smoking status. Most respondents felt confident discussing the impact of smoking on health; however, barriers like time constraints and perceived patient reluctance were common. Notably, those with longer professional tenures were more likely to view patient reluctance as a barrier (OR 1.46, 95% CI, 0.026-0.050, p < 0.001).<br><br>CONCLUSION: The findings suggest generally positive engagement with smoking cessation among optometrists in Wales, though barriers to patient engagement persist. While training appears to support more proactive practice, further work is needed to understand how optometric interventions influence smoking cessation outcomes and to explore why some practitioners perceive patients as hesitant to discuss health behaviours.}, }
@article {pmid41757049, year = {2026}, author = {Germer, CJ and Williams, S and Fernandes, V and Lima, RE and La Cunza, NR and Tan, LX and Panda, SR and Iorio, E and Elahi, FM and Lakkaraju, A}, title = {Acid sphingomyelinase inhibition restores RPE homeostasis and photoreceptor function in preclinical Stargardt macular degeneration models.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41757049}, issn = {2692-8205}, abstract = {Stargardt disease, which destroys central high-resolution vision in over 2 million people globally, lacks effective therapies. The primary site of damage in Stargardt disease is the retinal pigment epithelium (RPE), which safeguards photoreceptor health and function. Progressive loss of RPE integrity precedes visual deficits, yet insight into mechanisms driving RPE dysfunction and how this influences disease pathogenesis remains elusive. Here, we addressed this in cell-based and pigmented Abca4[-/-] Stargardt mice models using super-resolution imaging, bioinformatics, and biochemical approaches. We show that ceramide accumulation induced by bisretinoid-mediated overactivation of acid sphingomyelinase (ASM) in Abca4[-/-] RPE selectively disrupts Rab GTPases and ESCRT machinery involved in apical membrane trafficking and small extracellular vesicle (EV) biogenesis. Consequently, connexin 43 (Cx43) is misrouted from cell-cell junctions into EVs that are released apically by the RPE. This compromises RPE integrity and promotes subretinal immune cell recruitment, leading to photoreceptor dysfunction. Pharmacological ASM inhibition normalizes EV biogenesis and restores Cx43 localization. Decreasing RPE ceramide safeguards RPE structural integrity, limits subretinal microglia, and improves visual function in Abca4[-/-] mice. This study underscores the importance of the RPE as a communication hub in the retina and identifies ASM as a potential therapeutic target to prevent progressive vision loss.}, }
@article {pmid41757866, year = {2026}, author = {Liao, H}, title = {Brain-derived neurotrophic factor in age-related macular degeneration.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261427214}, doi = {10.1177/11206721261427214}, pmid = {41757866}, issn = {1724-6016}, abstract = {Age-related Macular Degeneration (AMD) is a leading cause of vision loss. There is no cure for AMD. Current treatments focus on preventing disease progression and preserving vision. In recent years, the role of brain-derived neurotrophic factor (BDNF) in AMD has attracted increasing attention. BDNF is widely involved in the physiology and pathophysiology of the retina. These include the development of photoreceptors during early development and synaptic communication between photoreceptors and retinal neurons. Under pathological conditions, BDNF affects the functions of multiple cell types in the retina including photoreceptors, ganglion cells, Müller cells, microglia cells, amacrine cells, and the retinal pigment epithelium (RPE). Importantly, BDNF does not act alone. Its function relates with other neurotrophic factors such as basic fibroblast growth factor (bFGF), ciliary neurotrophic factor (CNTF), and glial cell derived neurotrophic factor (GDNF). Meanwhile, the dynamic interaction between BDNF, its precursor protein proBDNF and the BDNF receptor TrkB not only affects the survival of retinal cells in AMD but may also guide the treatment strategy. Various approaches have been taken to deliver BDNF in animal models for managing AMD. Despite the exciting progress, challenges remain in implementing BDNF therapy as an effective treatment. In this review, we summarize the current research progress of BDNF in AMD and highlight the issues that need to be addressed before translation into clinical practice.}, }
@article {pmid41759060, year = {2026}, author = {Amoroso, F and Miere, A and Kodjikian, L and Couturier, A and Jean-François, K and Jung, C and Wang, X and Blanco-Garavito, R and Souied, EH}, title = {SD-OCT and OCTA: distinct or additional information on neovascular activity? The COCTAEYL Study.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004815}, pmid = {41759060}, issn = {1539-2864}, abstract = {PURPOSE: This study aimed to compare exudative recurrence features detected by optical coherence tomography angiography (OCTA) with those identified by spectral-domain optical coherence tomography (SD-OCT), considered the gold standard, and to characterize OCTA-derived profiles predictive of recurrence in patients with macular neovascularization (MNV) secondary to neovascular age-related macular degeneration (nAMD) treated with aflibercept.<br><br>METHODS: In this prospective observational cohort study, 49 patients were enrolled, yielding data from 686 examinations for concordance analysis between SD-OCT and OCTA. Following a loading phase of three-monthly intravitreal injections of 2 mg Aflibercept, patients were monitored monthly. Both SD-OCT and OCTA were performed at each visit, with intravitreal injections administered bimonthly (fixed regimen) for up to 12 months.<br><br>RESULTS: OCTA demonstrated a sensitivity of 72%, specificity of 27%, positive predictive value (PPV) of 59%, and negative predictive value (NPV) of 40% for detecting exudative activity. The area under the ROC curve (AUC) for OCTA-defined recurrence was 0.49, with an odds ratio (OR) of 0.95 for predicting neovascular activity in the next month (p=0.87). The net benefit (NB) was 0.13 for OCTA versus 0.19 for a general approach strategy. Relying on OCTA for recurrence detection instead of SD-OCT did not reduce unnecessary intravitreal injections.<br><br>CONCLUSION: OCTA and SD-OCT provide complementary information, with OCTA focusing on flow remodeling and SD-OCT highlighting exudative features. OCTA provides complementary vascular flow information to the structural data acquired with SD-OCT, allowing a more comprehensive assessment of neovascular activity, although no modification in management was observed in this cohort.}, }
@article {pmid41759077, year = {2026}, author = {Han, HY and Park, SM and Kim, CG and Cho, HJ and Kim, JH}, title = {Comparison of Initial Loading Injection Outcomes Between Aflibercept 8 mg and Faricimab in Neovascular Age-Related Macular Degeneration.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004819}, pmid = {41759077}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate and compare the initial functional and anatomical outcomes of aflibercept 8 mg and faricimab during the loading phase in treatment-naïve neovascular age-related macular degeneration (AMD).<br><br>METHODS: This retrospective observational study included 100 eyes of 100 patients with treatment-na&#xef;ve neovascular AMD who were administered three consecutive monthly loading injections of either aflibercept 8 mg (aflibercept 8 mg group, n=51) or faricimab (faricimab group, n=49). Changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT), as well as complete resolution of subretinal and intraretinal fluids, were compared between groups. Within each group, BCVA and CRT at baseline were compared with values at 3 months.<br><br>RESULTS: In the aflibercept 8 mg group, mean BCVA, measured in logarithm of the minimal angle of resolution (logMAR), improved from 0.59&#xb1;0.51 (Snellen equivalent, 20/77) at baseline to 0.39&#xb1;0.44(20/49) at 3 months(P<0.001). Correspondingly, mean CRT decreased from 450.6&#xb1;157.0 &#xb5;m to 287.3&#xb1;82.3 &#xb5;m(P<0.001). In the faricimab group, mean BCVA improved from 0.62&#xb1;0.47 logMAR(20/83) to 0.45&#xb1;0.38(20/56)(P<0.001), and mean CRT decreased from 442.4&#xb1;163.8 &#xb5;m to 248.5&#xb1;81.2 &#xb5;m(P<0.001). No significant differences were observed between groups in BCVA improvement(P=0.685) or CRT reduction(P=0.320). Complete retinal fluid resolution was observed in 80.4% and 87.8% of patients in the aflibercept 8 mg and faricimab groups, respectively, with no significant difference in fluid resolution between groups(P=0.234).<br><br>CONCLUSIONS: Aflibercept 8 mg and faricimab achieved significant and comparable functional and anatomical outcomes after three loading injections in treatment-na&#xef;ve neovascular AMD, suggesting that either agent may serve as an effective first-line treatment for this condition.}, }
@article {pmid41759572, year = {2026}, author = {Lapaquette, P and Loriot, B and Grégoire, S and Courcet, E and Acar, N and Bringer, MA}, title = {Gut inflammation affects retinal fatty acid composition.}, journal = {Experimental eye research}, volume = {267}, number = {}, pages = {110945}, doi = {10.1016/j.exer.2026.110945}, pmid = {41759572}, issn = {1096-0007}, abstract = {Inflammation and altered lipid metabolism - particularly bioavailability of polyunsaturated fatty acids of the omega-3 series (n-3 PUFAs) - are associated with age-related macular degeneration (AMD). Growing evidence suggests that the gut plays a significant role in regulating retinal physiology. Recent studies have reported that patients with chronic inflammatory bowel diseases (IBD) may have an increased risk of developing AMD. We investigated the influence of colitis on retinal fatty acids, by using a dextran sodium sulfate (DSS)-induced colitis model in mice. Compared to control mice, the retinas of DSS-treated mice exhibited a significantly higher amount of PUFAs, accompanied by a decrease in saturated fatty acids. Both retinal n-6 and n-3 PUFAs were affected by the DSS-induced colitis, including C20:4n-6 (arachidonic acid, the main retinal n-6 PUFA), and C22:6n-3 (docosahexaenoic acid, the main retinal n-3 PUFA), without altering their ratio. Analysis of gene expression involved in fatty acid biosynthesis revealed that, while Elovl2, Elovl4, and Elovl5 expression levels remained unchanged, Fasn expression tended to decrease and Fads2 expression was significantly reduced in the retinas of DSS-treated mice compared to those of controls. Besides, the retinal expression level of genes encoding pro-inflammatory cytokines (Il1b, Il6, Il8 and Tnfa) was not modified by the DSS-induced colitis. Altogether, these results indicate that although retinal cells do not express a pro-inflammatory phenotype, colitis influences the retinal bioavailability of fatty acids. In addition to providing new insights into the potential link between IBD and AMD, this study also supports the concept that gut health influences retinal physiology.}, }
@article {pmid41759744, year = {2026}, author = {Waghmare, PV and Kolekar, KA and Bashir, B and Kumbhar, PS and Patil, KS and Gupta, G and Prasher, P and Jha, SK and Disouza, J and Gurav, SS and Dua, K and Singh, SK}, title = {Advocating gut-retina connection and microbiota mediated pathways in management of age-related macular degeneration: Preclinical to clinical perspective.}, journal = {Ageing research reviews}, volume = {117}, number = {}, pages = {103071}, doi = {10.1016/j.arr.2026.103071}, pmid = {41759744}, issn = {1872-9649}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Macular Degeneration/microbiology/therapy ; Animals ; Probiotics/therapeutic use ; *Retina/metabolism ; Aging ; Dysbiosis ; }, abstract = {Age-related macular degeneration (ARMD) is the primary manifestation of permanent vision loss internationally. Different factors that contribute to ARMD involve ageing, genetic predisposition, oxidative stress, immunological imbalances, aberrations in the breakdown of lipids, and persistent inflammation. Gut microbiota has emerged as the significant cause of ARMD by disrupting systemic immune and inflammatory responses and metabolic homeostasis. Age-related changes in gut microbiota (dysbiosis) cause lowered microbial diversity, enhanced gut permeability, and pro-inflammatory species, leading to macular damage. The healthy gut microbiota containing Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, and Faecalibacterium prausnitzii, are responsible for maintaining gut homeostasis, protecting the retina, and preventing ARMD progression. In contrast, the elevated population of pathogenic species such as Escherichia coli, Prevotella, Desulfovibrio, Enterococcus faecalis, and Streptococcus salivarius in gut dysbiosis is involved in ARMD progression. This review explores gut microbiota and their dynamics in ageing. The age-dependent gut microbiota variations and potential biological implications for the progression of ARMD are discussed. The review also discusses observations from experimental animals and explores potential microbiome-centered treatment avenues, covering probiotics, synbiotics, dietary remedies, metabolite-based treatment, and fecal microbiota transplantation for managing ARMD. Furthermore, various challenges in the management of gut microbiota-driven ARMD are also briefed with future directions. Thus, a gut microbiota-focused paradigm can offer novel choices for ARMD prevention and treatment.}, }
@article {pmid41760600, year = {2026}, author = {Huang, C and Babu, VS and Bammidi, S and Arnold, JN and Ebeling, M and Widmer, G and Strassburger, P and Lazendic, M and Grüner, S and Koester, J and Dutta, P and Hose, S and Singh, S and Gautam, P and Lad, EM and Westenskow, PD and Kutsyr, O and Csaky, KG and Ghosh, S and Sripathi, SR and Proia, AD and Flores-Bellver, M and Sinha, D and Feenstra, D}, title = {STING activation induces polarized cytokine secretion of IFN-β and IL-17A promoting photoreceptor death and choroidal disruption in age-related macular degeneration.}, journal = {Cell death &amp; disease}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41419-026-08491-w}, pmid = {41760600}, issn = {2041-4889}, support = {1R01EY031594-01A1//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; K99EY033421//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; Launch Award//Maryland Stem Cell Research Fund (MSCRF)/ ; Free Family AMD Research Award//Foundation Fighting Blindness (FFB)/ ; Start-up funding//Johns Hopkins University (Johns Hopkins)/ ; M2024008N//BrightFocus Foundation (BrightFocus)/ ; }, abstract = {Age-related macular degeneration (AMD) represents one of the therapeutic challenges of aging eye diseases. Our investigation reveals the stimulator of interferon genes (STING) pathway as an orchestrator of immune-mediated retinal degeneration, exhibiting biphasic, stage-dependent functionality-providing cytoprotection in healthy tissue but driving pathogenic inflammation during early AMD progression. Through immunohistochemical analysis of human eyes, we demonstrate stage-dependent cytoplasmic STING upregulation with parallel IFN-β activation. Using patient-derived induced pluripotent stem cells-retinal pigment epithelium (iPSC-RPE) from AMD siblings, we discovered polarized cytokine secretion: apical IFN-β triggers photoreceptor apoptosis in human retinal organoids, while basal IL-17A compromises choroidal neovascularization. The Cryba1 conditional knockout (cKO) AMD-like mouse model confirms STING-driven IL-17A expression, while Il17a knock-in mice substantiate vascular alterations. STING activation establishes a pathogenic feed-forward loop between interferons and IL-17A. Single-cell transcriptomics following AAV2-mediated IFN-β overexpression reveals metabolic and phototransduction dysregulation. Both pharmacological STING inhibition with SN-011 and genetic approaches demonstrate therapeutic rescue. Cryba1/Sting double heterozygous (dhet) mice maintain homeostatic gene expression preserving retinal architecture and function. These findings establish STING as the master regulator simultaneously controlling multiple AMD pathologies through spatially organized inflammation, transforming from protective surveillance to pathogenic driver, and identifying a unified therapeutic target with demonstrated functional rescue across multiple experimental paradigms.}, }
@article {pmid41762378, year = {2026}, author = {Tillmann, A and Stillenmunkes, R and Garweg, JG and Cattaneo, J and Bartolomeo, N and Grimaldi, G and Spitznagel, T and De Oliveira Figueiredo, EC and Ambresin, A and Menghini, M and Somfai, GM and Zweifel, S and Fröhlich, J and Artemiev, D and Ebneter, A and Hatz, K and Weinberger, A and Pfister, IB and Schild, C and Eandi, C and Munk, MR and , }, title = {Correction: One-Year Outcomes of Faricimab in Treatment-Naïve Neovascular Age-Related Macular Degeneration: A Swiss Retina Research Network Report.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s40123-026-01319-y}, pmid = {41762378}, issn = {2193-8245}, }
@article {pmid41763458, year = {2026}, author = {Sim, SY and Lim, LT and Chaudhary, S and Musa, M and Hamilton, R and Nicholson, L and Pal, B and Saini, P and Mankongcharoen, P and Sen, S}, title = {Update on subthreshold micropulse laser treatment for retinal diseases: A narrative review.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.02.006}, pmid = {41763458}, issn = {1879-3304}, abstract = {Subthreshold micropulse laser (SML) has emerged as a valuable and effective alternative to conventional laser treatments for a variety of retinal diseases, offering therapeutic benefits while minimizing tissue damage. Unlike traditional continuous wave lasers which induce irreversible changes to photoreceptors and retinal pigment epithelial (RPE) cells due to thermal damage, SML delivers energy in short bursts with cooling intervals, maintaining subthreshold temperatures that trigger therapeutic cellular responses without causing visible retinal scarring. We have synthesized the latest evidence on SML's role in managing diabetic macular edema (DME), central serous chorioretinopathy (CSCR), macular edema secondary to retinal vein occlusion, and age-related macular degeneration. Across these conditions, SML demonstrates comparable visual and anatomical outcomes to conventional laser and anti-vascular endothelial growth factor therapies, with notable benefits, including a reduced injection burden in DME and improved choriocapillaris perfusion in CSCR. Additionally, emerging data suggests SML may hold an edge in more complex cases, such as chronic CSCR, pseudophakic macular edema, and dome-shaped maculopathy; however, inconsistencies in laser parameters including wavelength, duty cycle, fluence parameters and spot size continue to pose challenges in standardizing treatment protocols. The "reset theory" of RPE restoration, driven by heat shock protein activation or other described mechanisms, underscores SML's potential to offer sustained, long-term disease control. While current evidence is promising, larger, high-quality studies are still needed to fine-tune treatment settings, improve patient selection strategies, and clarify SML's role alongside other therapies. We provide a comprehensive overview of SML's progress, potential, and future direction in retinal disease management.}, }
@article {pmid41765332, year = {2026}, author = {Benito-Pascual, B and Fernández-Pérez, C and Medina, A and Rojo, D and Arriola-Villalobos, P}, title = {Population survey on visual health in Spain.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502467}, doi = {10.1016/j.oftale.2026.502467}, pmid = {41765332}, issn = {2173-5794}, abstract = {BACKGROUND AND OBJECTIVE: Conducting a national visual health survey and comparing results after 5 years.<br><br>MATERIALS AND METHODS: Cross-sectional study using a computer-assisted telephone interview with a representative sample of Spaniards over 18 years of age (except Ceuta and Melilla). The survey was designed by ophthalmologists, the selection of the sample and the conduct of the interviews (April 2017 and May 2023) was carried out through the company Metroscopia and the analysis of the anonymous data was carried out by researchers. Demographic data, knowledge about glaucoma, use of glasses, perceived visual quality, ophthalmological pathology and ocular treatments were collected.<br><br>RESULTS: 1209 and 600 people were interviewed in 2017 and 2023 respectively. The level of glaucoma awareness went from 80% to 87%. The perceived visual quality was reduced (8.2&#xa0;&#xb1;&#xa0;1.6 to 6.9&#xa0;&#xb1;&#xa0;1.8) and the frequency of access to the ophthalmologist. The prevalence of glasses use increased (50%-62%), dry eye (13%-28%), cataract (9.7%-12.4%), glaucoma (1.9%-4.6%), age-related macular degeneration (7%-11.3%), and diabetic retinopathy (1.2%-1.7%). The use of artificial tears and glaucoma drops also increased (16.9%-32.9% and 1.6%-6%, respectively).<br><br>CONCLUSIONS: The study shows that there has been an increase in self-reporting of eye diseases in recent years in Spain. These types of population surveys can serve to encourage the development of visual health programs aimed at the needs of our country.}, }
@article {pmid41765918, year = {2026}, author = {Padovani-Claudio, DA and Bastarache, L}, title = {Opportunities and challenges in leveraging multiomics and biobanks for vision science.}, journal = {Current opinion in ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICU.0000000000001209}, pmid = {41765918}, issn = {1531-7021}, abstract = {PURPOSE OF REVIEW: Emerging biobank resources allow large-scale integration of eye-specific phenotypes with clinical, genomic, and multiomic data. This convergence enables unprecedented opportunities to systematically dissect the genetic architecture, epidemiology, and mechanistic pathways of both rare monogenic and common polygenic diseases. The review aims to critically examine how contemporary data extraction, multiomics, and analytic methodologies are reshaping disease classification, genetic discovery, and translational research in ophthalmology, while highlighting the associated challenges in leveraging these advanced tools.<br><br>RECENT FINDINGS: Recent literature demonstrates the utility of genome-wide and phenome-wide association studies, transcriptomic analyses, and artificial intelligence in uncovering novel risk loci, endophenotypes, and biomarkers relevant to eye diseases. Furthermore, advances in multiancestry sampling show substantial population-specific genetic variation, enriching disease models for conditions such as glaucoma and age-related macular degeneration. Finally. integrative approaches, including Mendelian randomization and enrichment analyses, are helping elucidate shared genetic architecture between ocular and systemic diseases, informing therapeutic target identification, and refining risk prediction models.<br><br>SUMMARY: The convergence of biobank-derived multimodal data and sophisticated analytic techniques is catalyzing a path to personalized medicine in ophthalmology. For these approaches to fully translate into clinical practice ensuring scientifically robust and equitable outcomes, future research must address cohort diversity, mechanistic validation, and practical cost-effectiveness.}, }
@article {pmid41766064, year = {2026}, author = {Martin, J and Ortiz, T and Zafar, S and Kuriyan, AE}, title = {Review of current management of submacular hemorrhage.}, journal = {Current opinion in ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {41766064}, issn = {1531-7021}, abstract = {PURPOSE OF REVIEW: Subretinal hemorrhage (SRH) is most commonly associated with neovascular age-related macular degeneration (nAMD) and can cause profound vision loss in the macula through mechanical, toxic, and inflammatory mechanisms. Submacular hemorrhage (SMH) lacks consensus on management. This review summarizes current treatment options, key comparative studies, and ongoing challenges, with emphasis on SMH management.<br><br>RECENT FINDINGS: Antivascular endothelial growth factor (anti-VEGF) therapy remains central to SMH management, with outcomes comparable to surgery in small to moderate hemorrhages. Pneumatic displacement (PD) with or without recombinant tissue plasminogen activator (rtPA) shows the greatest comparative benefit in more extensive SMH. Adjunctive rtPA improves hemorrhage displacement rates, and meta-analyses support its efficacy with anti-VEGF therapy. Pars plana vitrectomy (PPV) remains an option for large or refractory hemorrhages but has not consistently shown superior visual outcomes compared to less invasive modalities.<br><br>SUMMARY: Early intervention is consistently associated with improved outcomes, but there is no universally accepted treatment algorithm. Ongoing randomized trials and advances in multimodal imaging have the potential to refine patient selection and treatment strategies. Future efforts should focus on balancing efficacy, safety, and cost-effectiveness to establish evidence-based guidelines for SMH management.}, }
@article {pmid41767319, year = {2026}, author = {Wei, PY and Wang, XZ and Han, JM}, title = {A bibliometric and visualized analysis of choriocapillaris from 2013 to 2023.}, journal = {International journal of ophthalmology}, volume = {19}, number = {3}, pages = {600-611}, pmid = {41767319}, issn = {2222-3959}, abstract = {AIM: To assess the current research status and emerging trends of the choriocapillaris (CC) by bibliometric analysis.<br><br>METHODS: Publications spanning from January 2013 to May 2023 were retrieved on June 27th, 2023, using the Web of Science Core Collection. Bibliometric and visualized analyses were performed employing the bibliometrix, CiteSpace and VOSviewer.<br><br>RESULTS: A total of 1563 papers met the inclusion criteria, and a publication growth trend was observed. The United States was the leading country in the CC field. Retina and Investigative Ophthalmology &amp; Visual Science stood out as highly impactful and prolific journals. Research topics in the CC field encompassed choroidal neovascularization, choroidal thickness, central serous chorioretinopathy, age-related macular degeneration, myopia, choroidal vascularity index, and diabetic retinopathy, based on the co-citation analysis. The keyword "high myopia" experienced a burst lasting until 2023.<br><br>CONCLUSION: In the past decade, research in the field of CC has flourished due to recent advancements in choroidal imaging; with focus shifting towards elucidating its role in various diseases. This will provide novel insights into managing chorioretinal diseases and vision-preserving interventions.}, }
@article {pmid41767914, year = {2025}, author = {Ni, G and Cao, K and Qin, X and Zeng, X and Wu, R and Wan, L and Zhong, J and Liu, Y}, title = {Advanced 3D retinal lesion segmentation using channel-spatial attention-guided multi-scale feature aggregation.}, journal = {Biomedical optics express}, volume = {16}, number = {5}, pages = {2093-2110}, pmid = {41767914}, issn = {2156-7085}, abstract = {Diabetic macular edema (DME) and age-related macular degeneration (AMD) have emerged as leading causes of vision impairment worldwide; optical coherence tomography (OCT) has proven to be a crucial diagnostic tool for these diseases, for its rapid, non-invasive high-resolution imaging of retinal structures. Further accurate assessment of lesions in retinal OCT images plays a pivotal role in the early diagnosis of DME and AMD. However, current diagnosing of AMD and DME is restricted to utilizations of OCT two-dimensional images, for crucial three-dimensional (3D) lesion information inherent in OCT 3D images cannot be effectively extracted and utilized without appropriate methods. Here, we proposed an innovative deep-learning network characterized by fusing multi-scale feature extraction-aggregation and channel-spatial joint attention for high-accuracy 3D lesion segmentations of DME and AMD. Extensive experiment results demonstrated that our proposed method has commendable 3D segmentation performances and robust generalization capabilities, probably helping to understand DME and AMD diseases better and providing great convenience for clinical diagnosis and treatment.}, }
@article {pmid41768996, year = {2026}, author = {Yang, X and Xu, W and Xie, H and Guo, X and Zhu, F and Xing, Y and Chen, C}, title = {The contribution of ferroptosis to the epithelial-mesenchymal transition phenotype in models of age-related macular degeneration.}, journal = {Frontiers in cell and developmental biology}, volume = {14}, number = {}, pages = {1718715}, pmid = {41768996}, issn = {2296-634X}, abstract = {PURPOSE: Age-related macular degeneration (AMD) involves dysfunction of the retinal pigment epithelium (RPE), where cellular senescence and epithelial-mesenchymal transition (EMT) are key pathological features. The upstream mechanisms linking these processes are not fully understood. This study investigates the potential role of ferroptosis in contributing to senescence-associated EMT in RPE cells.<br><br>METHODS: We utilized an aging mouse model and two cellular models in ARPE-19 cells, induced by D-galactose (D-gal) and low-dose sodium iodate (SI), respectively. Ferroptosis, EMT, and oxidative stress markers were evaluated via immunofluorescence, flow cytometry, and Western blotting. The specific ferroptosis inhibitor Ferrostatin-1 was used to assess the involvement of ferroptosis.<br><br>RESULTS: Aged mouse RPE/choroid complexes and stressed ARPE-19 cells exhibited features of EMT along with increased ferroptosis hallmarks, including lipid peroxidation and iron accumulation. A downregulation of the xCT/GPX4 anti-ferroptotic axis was observed. Pretreatment with Fer-1 alleviated ferroptosis by reducing iron levels and lipid peroxidation, and restored xCT/GPX4 expression. Furthermore, Fer-1 attenuated the EMT phenotype, as evidenced by the restoration of epithelial markers and reduction of mesenchymal markers (Vimentin, &#x3b1;-SMA) in both D-gal and SI models.<br><br>CONCLUSION: Our findings suggest that ferroptosis may contribute to linking RPE senescence with EMT, potentially via oxidative stress pathways. The combined targeting of both senescence and ferroptosis could therefore represent a potential therapeutic strategy for addressing RPE dysfunction and AMD progression.}, }
@article {pmid41771640, year = {2026}, author = {Walker, R and Ellett, L and Norton, D and Rouabhi, H and Coughlan, H and Akthar, F and DaSilva Morgan, K and Tait, R and Lisi, M and Ffytche, D}, title = {Charles Bonnet Syndrome: associations between psychosocial measures and visual hallucination characteristics in the visually impaired.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {1}, pages = {}, pmid = {41771640}, issn = {2397-3269}, mesh = {Humans ; Male ; Female ; *Charles Bonnet Syndrome/psychology ; Middle Aged ; *Quality of Life/psychology ; Aged ; Adult ; *Persons with Visual Disabilities/psychology ; Self Report ; *Hallucinations/psychology ; Anxiety/psychology ; Surveys and Questionnaires ; *Vision Disorders/psychology ; Mental Health ; Aged, 80 and over ; }, abstract = {BACKGROUND/AIMS: The emotional response to Charles Bonnet Syndrome (CBS) (visual hallucinations in individuals with sight loss) is associated with negative affect, suggesting a link between psychological measures and hallucination characteristics. This study set out to investigate whether the association extends to a broader range of hallucination attributes and psychological measures, taking into account clinical factors likely to influence such associations.<br><br>METHODS: 70 participants with self-reported CBS completed an online survey assessing hallucination attributes of frequency, duration, emotional valence, distress, level of control over hallucinations and impact on quality of life (QoL). Anxiety and depression were measured using the Hospital Anxiety and Depression Scale while loneliness was assessed using the University of California Los Angeles (UCLA) Loneliness Scale. All three measures were combined as a mental health factor. Regression models tested relationships between hallucination attributes and mental health, controlling for age, sex assigned at birth, years of sight loss, years experiencing hallucinations, presence of migraine and visual field loss.<br><br>RESULTS: All visual hallucination attributes except level of control were associated with the mental health factor; higher factor scores were associated with more frequent, longer lasting, more unpleasant and more distressing hallucinations and also with a more negative impact of hallucinations on QoL. These associations were independent of years of sight loss and CBS.<br><br>CONCLUSION: Mental health measures are linked to a wider range of CBS attributes than previously recognised, with greater clinical attention required to identify people with CBS who are experiencing psychological difficulties to help provide appropriate treatment and support.<br><br>LIMITATIONS: The study did not include a control group of visually impaired participants without hallucinations and has an uneven representation across age and gender with a small sample size for the sub-group analysis. The study relied on self-reported online data without clinical assessment; details of participants' medication use were not collected.}, }
@article {pmid41772510, year = {2026}, author = {Rao, T and Yang, J and Chen, H and Li, X}, title = {OCT-based morphological prognostic factors for structural improvement after anti-VEGF therapy in wet age-related macular degeneration.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04690-3}, pmid = {41772510}, issn = {1471-2415}, }
@article {pmid41772933, year = {2026}, author = {Rizzo, C and Vannozzi, L and Lupidi, M and Savastano, MC and Borrelli, E and Mastropasqua, R and Panini, F and Crincoli, E and Faraldi, F and Virgili, G and Giansanti, F and Bacherini, D}, title = {Prechoroidal cleft in neovascular age-related macular degeneration (AMD): A narrative review of pathophysiology, clinical implications and prognosis.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70095}, pmid = {41772933}, issn = {1755-3768}, abstract = {The prechoroidal cleft (PC) is a hyporeflective space visualized on optical coherence tomography (OCT), typically located within the pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration (nAMD). Although its pathogenesis is not yet fully understood, proposed mechanisms include fluid accumulation secondary to macular neovascularization (MNV), contractile forces from fibrovascular tissue and chronic structural remodelling of the outer retinal layers. This narrative review synthesizes the current evidence regarding the imaging features, pathophysiological mechanisms, clinical relevance and prognostic implications of the PC in nAMD. The presence of a PC has been variably associated with MNV activity, poor visual outcomes, increased treatment burden and a higher risk of complications, such as retinal pigment epithelium (RPE) tears and submacular haemorrhage (SMH). However, emerging data suggest that the cleft may regress following sustained anti-VEGF therapy, implying a potential role as a marker of therapeutic response and anatomical improvement. Thus, the PC may serve as a dynamic biomarker of disease activity in nAMD patients. Nevertheless, its precise role in disease progression remains unclear, highlighting the need for further longitudinal and histopathological studies.}, }
@article {pmid41773161, year = {2026}, author = {Nakao, G and Hara, C and Nishida, K}, title = {Bilateral Diffuse Uveal Melanocytic Proliferation Masquerading as Refractory Subretinal Fluid Due to Peripapillary Pachychoroid Syndrome.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e102512}, pmid = {41773161}, issn = {2168-8184}, abstract = {We describe a case of peripapillary pachychoroid syndrome (PPS) that appeared resistant to conventional treatment and was subsequently diagnosed as bilateral diffuse uveal melanocytic proliferation (BDUMP) based on fundus autofluorescence (FAF) images. A 79-year-old man presented with vision loss in both eyes and was initially diagnosed with PPS based on optical coherence tomography, fluorescein angiography, and indocyanine green angiography findings. The patient underwent photodynamic therapy in both eyes, photocoagulation in the left eye, and 2 mg aflibercept injections in both eyes. Although he responded to the initial treatments, the response gradually diminished with subsequent injections. Due to the progression of his cataracts, the patient underwent cataract removal surgery. He was later diagnosed with BDUMP based on subsequent FAF images, which revealed characteristic ocular fundus findings known as giraffe-like patterns. Subsequent systemic evaluation revealed prostate cancer. BDUMP can masquerade as PPS or neovascular age-related macular degeneration (n-AMD), resulting in delayed diagnosis and treatment, and should be considered in the differential diagnosis of cases where PPS or n-AMD is refractory to conventional treatment, even in the absence of a known malignancy.}, }
@article {pmid41773239, year = {2026}, author = {Shiratori, M and Maruyama-Inoue, M and Yanagi, Y and Inoue, T and Kadonosono, K}, title = {Comparison of Short-term Outcomes Between Faricimab and High-Dose Aflibercept in Patients With Neovascular Age-related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261423302}, pmid = {41773239}, issn = {2474-1272}, abstract = {Purpose: To compare functional and morphologic outcomes after loading doses of faricimab and high-dose aflibercept for treatment-naive neovascular age-related macular degeneration (nAMD). Methods: We retrospectively enrolled 62 consecutive patients (64 eyes) with nAMD whose initial visual acuity (VA) was ≤20/25. Patients received 3 consecutive monthly loading doses of intravitreal 6.0 mg/0.05 mL faricimab (IVF) or intravitreal 8.0 mg/0.07 mL high-dose aflibercept (IVHDA). Changes in best-corrected VA (BCVA) and fluid were assessed at 4, 8, and 16 weeks compared with baseline. Results: Two patients were excluded from the final analysis, yielding a total of 60 patients (62 eyes). In the IVF group (n = 31 eyes), the logMAR BCVAs at baseline, 4, 8, and 16 weeks were 0.40, 0.35, 0.33, and 0.30, respectively; significant improvement occurred at 16 weeks only (P = .004 vs baseline). In the IVHDA group (n = 31 eyes), the logMAR BCVAs at the respective timepoints were 0.44, 0.36, 0.30, and 0.32; significant improvements occurred at 8 and 16 weeks (P = .001 and P = .007, respectively, vs baseline). At 16 weeks, 90.3% of patients receiving IVF and 80.6% receiving IVHDA had dry macula (P = .473). Conclusion: Significant BCVA improvements were achieved with both treatments, although improvement was faster with IVHDA. High rates of dry macula were achieved at 16 weeks in more patients in the IVF group than in the IVHDA group.}, }
@article {pmid41774087, year = {2026}, author = {Weatherston, D and Jones, JA and Vargis, E}, title = {Changes in ApoE and TIMP-1 expression correlate with outer blood-retinal barrier disruption in an in vitro model of retinal aging.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {41774087}, issn = {2509-2723}, support = {EY028732/EY/NEI NIH HHS/United States ; M2019109//BrightFocus Foundation/ ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Unfortunately, the early stages of this disease are poorly understood, which has led to limited treatment options. Investigating normal changes in tissues eventually affected by AMD can further elucidate the mechanisms of disease progression and lead to novel therapeutic targets. The primary cell layer affected in AMD is the retinal pigment epithelium (RPE), which forms the outer blood-retinal barrier (oBRB). Beneath the RPE lies Bruch's membrane, a proteinaceous layer that naturally thickens and stiffens with age. These changes to Bruch's membrane are also implicated in RPE dysfunction and AMD progression. To investigate the relationship between normal, age-related changes in Bruch's membrane and AMD development, we engineered a tunable in vitro model of Bruch's membrane to support primary porcine RPE cells. We performed transepithelial electrical resistance (TEER) measurements, viability assays, morphological analysis, immunocytochemistry, and enzyme-linked immunosorbent assays (ELISA) to evaluate monolayer integrity and angiogenic factor expression. Cells cultured on our aged model exhibited changes similar to those seen in AMD, including reduced monolayer integrity, the formation of sub-RPE deposits, and eventual cell death. Notably, apolipoprotein E (ApoE), a known drusen component and Alzheimer's disease marker, was overexpressed prior to deposit accumulation and cell death. Regions of ApoE overexpression corresponded with disrupted expression of zonula occludens-1, a junctional protein. While most angiogenic factors remained unchanged, tissue inhibitor of metalloproteinases-1 (TIMP-1) was transiently overexpressed before cell death. These findings suggest that ApoE and TIMP-1 may play key roles in early AMD pathogenesis and represent potential targets for future therapeutic intervention.}, }
@article {pmid41776295, year = {2026}, author = {Eilon, E and Lishinsky-Fischer, N and Levy, J}, title = {Response to: 'Comment on 'Systemic prostacyclin analogues in pulmonary hypertension are associated with reduced risk of age-related macular degeneration: a cohort study".}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41776295}, issn = {1476-5454}, }
@article {pmid41777091, year = {2026}, author = {Arkhipchenko, AA and Semenov, AN and Chesalin, DD and Sidorenko, SV and Bodunova, DV and Gorokhov, ES and Yakovleva, MA and Feldman, TB and Moysenovich, AM and Senin, II and Shebardina, NG and Tiulina, VV and Ramonova, AA and Andreev, VS and Morozov, PV and Bilan, DS and Ilyinsky, NS and Zernii, EY and Maksimov, EG and Ostrovsky, MA and Kirpichnikov, MP}, title = {Photooxidation Dynamics of Lipofuscin in the Presence of Carotenoid-Binding Protein AstaP: Fluorescence Lifetime Imaging and Pigment Composition Analysis.}, journal = {The journal of physical chemistry. B}, volume = {130}, number = {11}, pages = {2974-2986}, doi = {10.1021/acs.jpcb.5c06621}, pmid = {41777091}, issn = {1520-5207}, mesh = {*Lipofuscin/chemistry/metabolism ; Humans ; Oxidation-Reduction ; Optical Imaging ; Chromatography, High Pressure Liquid ; Retinal Pigment Epithelium/cytology/metabolism ; *Carotenoids/metabolism/chemistry ; Retinoids/chemistry/metabolism ; Cell Line ; Photochemical Processes ; }, abstract = {To introduce noninvasive optical diagnostic methods based on detection of tissue autofluorescence signals into medical practice, it is necessary to correlate the optical response with the functional state of a particular chromophore. Diagnostics of the state of lipofuscin granule chromophores is an important task to assess pathologic changes in the visual system in various diseases, primarily age-related macular degeneration. A key feature of lipofuscin granules (LGs) is the diversity of the chromophores and their susceptibility to oxidation. Here, we used time-resolved emission spectroscopy, confocal fluorescence lifetime imaging microscopy, and high-performance liquid chromatography (HPLC) to follow changes of LG chromophore composition upon photooxidation. In both isolated LGs and LG-loaded retinal pigment epithelium cells (ARPE-19), the distributions of the short lifetime component and its amplitude of LG fluorescence shifted, and the mean lifetime increased upon photooxidation, indicating depletion of population of rapidly relaxing bisretinoids, including A2E, and accumulation of their oxidized species, as confirmed by HPLC data. We applied differential evolution algorithms to decompose LG autofluorescence parameters and identified distinct photooxidation patterns in the presence and absence of antioxidant protection. Delivery of zeaxanthin by water-soluble carotenoprotein ΔNC-AstaP attenuated photooxidation-induced changes in the decay kinetics of both isolated and intracellular LGs, suppressed the accumulation of oxidized bisretinoids, and prevented complete photooxidation. Taken together, our results establish that time-resolved lipofuscin autofluorescence provides a quantitative, label-free readout of chromophore composition and oxidative status that is compatible with functional imaging. We propose that such lifetime-based measurements can be employed for early assessment of retinal pathology and for monitoring antioxidant interventions targeting lipofuscin-induced oxidative stress in emerging clinical techniques such as fluorescence lifetime imaging ophthalmoscopy.}, }
@article {pmid41778671, year = {2026}, author = {Jiménez-Loygorri, JI and Cuervo, AM and Ferrington, DA and Boya, P}, title = {Chaperone-mediated autophagy: the Achilles heel of the retinal pigment epithelium during age-related macular degeneration.}, journal = {Autophagy}, volume = {}, number = {}, pages = {1-3}, doi = {10.1080/15548627.2026.2636093}, pmid = {41778671}, issn = {1554-8635}, abstract = {Chaperone-mediated autophagy (CMA) is a selective autophagy pathway that targets specific proteins containing a KFERQ-like motif for lysosomal degradation. It has been shown by us and others that CMA decreases during physiological aging in most tissues, and its impairment is associated with increased incidence of age-related pathologies, such as cardiovascular disease, neurodegenerative disorders or sarcopenia. However, its involvement in age-related macular degeneration (AMD), a prevalent progressive maculopathy that leads to bilateral central vision loss, had not been explored. In the early stages of AMD, the retinal pigment epithelium (RPE), a monolayer of cells that provides trophic support to photoreceptors, already presents major morphological and functional alterations but the cause of this cell type-specific vulnerability is unknown. In our latest work, we analyzed human donor RPE samples and found that CMA is selectively impaired in the RPE of AMD patients compared to healthy donors. These alterations lead to the accumulation of undegraded CMA substrates and untimely recycling of other proteins. Crucially, these findings are conserved in donor-derived iPSC-RPE models. We used this clinically relevant model to assess the consequences of dysfunctional CMA in AMD and found that it caused proteotoxicity, increased oxidative damage, and altered metabolism. Most importantly, using the new-generation CMA activator CA77.1, we restored proteostasis in AMD iPSC-RPE. Our findings shed light on the selective vulnerability of the RPE in AMD and provide evidence in support of CMA as a novel druggable target against AMD.}, }
@article {pmid41779364, year = {2026}, author = {Kitay, AM and Tillmann, A and Pfister, I and Schild, C and Bonanata, M and Heck, K and Spitznagel, T and Gabathuler, F and Bartolomeo, N and Magnin, S and Löliger, J and Munk, MR and Menghini, M and Hatz, K and Somfai, GM and Zweifel, S and Ambresin, A and Eandi, CM and Feltgen, N and Weinberger, A and Garweg, JG and Kurz-Levin, MM}, title = {One-Year Real-World Outcomes of Switching to Aflibercept 8 mg in Eyes with Neovascular Age-Related Macular Degeneration: A Swiss Retina Research Network Report.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41779364}, issn = {2193-8245}, abstract = {INTRODUCTION: This multicenter, longitudinal, observational real-world study evaluated the efficacy and safety of switching to intravitreal aflibercept 8 mg (Afl 8) in pretreated eyes with neovascular age-related macular degeneration (nAMD) within the Swiss Retina Research Network. A total of 283 eyes from 245 patients previously treated with other anti-vascular endothelial growth factor (anti-VEGF) agents (aflibercept 2 mg, faricimab, and ranibizumab) were included, with 1-year efficacy outcomes analyzed in 246 eyes and safety assessed in all treated eyes.<br><br>METHODS: We recorded demographics, baseline functional and anatomical parameters-including spectacle-corrected visual acuity (VA) and optical coherence tomography (OCT) data-treatment history and outcomes over 12&#xa0;months after switching to Afl 8. The main outcome measures were change in VA, central subfield thickness (CST), presence of intra- and subretinal fluid (IRF/SRF) and pigment epithelial detachment (PED), treatment intervals, and adverse events.<br><br>RESULTS: Twelve months after the switch to Afl 8, mean VA remained stable, while mean CST decreased from 329.1 to 302.8&#xa0;&#xb5;m (p&#x2009;<&#x2009;0.001). The portion of eyes without retinal fluid increased from 29.9% at baseline to 47.5% after 12&#xa0;months. In parallel, the mean treatment interval was extended by 32.3% from 7.1 to 9.4&#xa0;weeks (p&#x2009;<&#x2009;0.001). At 1 year, 35.4% of eyes reached intervals of 8-11&#xa0;weeks, while 20.2% achieved intervals of 12&#xa0;weeks or longer. Intraocular inflammation was reported in 11 cases (3.9%).<br><br>CONCLUSIONS: In pretreated nAMD eyes with high treatment demand, switching to Afl 8 resulted in a significant anatomical improvement and longer treatment intervals in a majority of patients. These real-world results highlight the therapeutic potential of Afl 8, with no new or unexpected safety issues.}, }
@article {pmid41779676, year = {2026}, author = {Maggio, E and Avogaro, F and Casillo, L and Mete, M and Vingolo, EM and Maraone, G and Sanfilippo, L and Guerriero, M and Pertile, G}, title = {Long-term Evolution and Growth Rate Assessment of Non-Exudative Macular Neovascularization: A Multicenter Analysis.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {}, number = {}, pages = {1-17}, doi = {10.1159/000551308}, pmid = {41779676}, issn = {1423-0267}, abstract = {PURPOSE: A population of patients with age-related macular degeneration (AMD) was analyzed to investigate the prevalence of non-exudative macular neovascularizations (neMNV), the conversion rate to exudation, and to discern differences between neMNVs that exhibited exudation versus those that remained non-exudative.<br><br>DESIGN: Retrospective observational case series.<br><br>METHODS: In this retrospective, multicentric, longitudinal study, consecutive patients treated with anti-VEGF between august 2008 and June 2023, presenting exudative AMD in one eye and intermediate AMD in the fellow eye, were analyzed. The presence of neMNVs in the fellow eyes and their conversion rate to exudation were assessed. Clinical and anatomical features were compared between eyes that developed exudation versus those that did not. The correlation between lesion major diameters and areas was examined to evaluate their equivalence as parameters for assessing neMNV growth rate.<br><br>RESULTS: A total of 61 eyes out of 840 (7.3%) exhibited neMNV. Of these, 21 neMNV (34.42%) converted to exudation in a mean time of 24.14 months (min. 7 - max. 113). The remaining 40 eyes did not develop exudation during a mean follow-up of 32.5 months (min. 12 - max. 101). No significant differences were found regarding visual acuity, OCT angiography features, or baseline lesion diameters. NeMNV that developed exudation exhibited a higher lesion growth rate (p-value <0.001). The growth rate evaluated using lesion major diameters was consistent with that obtained through lesion area measurements.<br><br>CONCLUSION: The results highlight lesion growth rate as a marker of conversion risk. Lesion diameter was identified as a reliable parameter for monitoring neMNV progression. Despite a long-term follow-up, many lesions did not develop exudation. These results support the idea that neMNV may represent a spectrum of neovascularizations with different characteristics and clinical courses.}, }
@article {pmid41780904, year = {2026}, author = {Bernal-Morales, C and Burgos Herrera, S and Giralt, L and Alforja, S and Romero-Núñez, B and Catalan-Coronado, S and Bilbao, V and Sala-Puigdollers, A and Pelegrin-Colas, L and Zarranz-Ventura, J and Adan, A and Casaroli-Marano, R and Figueras-Roca, M}, title = {Faricimab for recalcitrant neovascular age-related macular degeneration: a real-life study following aflibercept nonresponse.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcjo.2026.02.009}, pmid = {41780904}, issn = {1715-3360}, abstract = {OBJECTIVE: To evaluate anatomical and functional outcomes following a switch to intravitreal faricimab in patients with active, recalcitrant neovascular age-related macular degeneration (nAMD) previously treated with aflibercept in a real-life setting.<br><br>DESIGN: A retrospective, observational, single-centre study.<br><br>METHODS: Demographic data and prior intravitreal treatment (IVT) history were collected. Best-corrected visual acuity (BCVA) and disease activity were assessed using optical coherence tomography (OCT), including fluid compartments: intraretinal fluid, subretinal fluid (SRF), pigment epithelial detachment, and subretinal hyperreflective material.<br><br>RESULTS: A total of 161 eyes from 145 patients (mean age: 80.1&#x202f;&#xb1;&#x202f;7.8 years) were included. Mean prior IVT duration was 2.9&#x202f;&#xb1;&#x202f;2.5 years. All eyes were active at the time of switching, with 82.0% showing persistent SRF. Disease inactivation occurred in 42.9% of eyes after the switch, more frequently in eyes with shorter prior treatment duration. BCVA remained stable throughout the follow-up. SRF resolved in 50.8% of eyes, with 52.2% achieving resolution after a single injection. Mean treatment intervals increased significantly in inactivated eyes (+4.9&#x202f;&#xb1;&#x202f;5 weeks). Disease relapse occurred in 54.6% of the initially inactivated eyes. No adverse events were reported.<br><br>CONCLUSIONS: Switching to faricimab may offer a valuable therapeutic option for recalcitrant nAMD, particularly in eyes with persistent SRF, providing improved anatomical outcomes while maintaining visual acuity in real-life practice. Prospective studies are warranted to better define response profiles and guide personalized treatment strategies.}, }
@article {pmid41782931, year = {2026}, author = {Zhou, Y and Zhan, Z and Wang, Z and Liu, C}, title = {Efficacy and safety of aflibercept biosimilars compared to aflibercept in the treatment of neovascular age-related macular degeneration: a systematic review and meta-analysis.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1719493}, pmid = {41782931}, issn = {1663-9812}, abstract = {BACKGROUND: This study aimed to evaluate the aflibercept biosimilars compared to the reference product aflibercept (Eylea®) in terms of efficacy, safety, and immunogenicity in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: We searched PubMed, Web of Science, Cochrane Library, and Embase from inception to 13 August 2025. We included studies reporting changes in best-corrected visual acuity (BCVA), changes in central subfield thickness (CST), changes in the leakage lesion of choroidal neovascularization (CNV), and adverse events from baseline to endpoint. All statistical analyses were performed using Stata 18.0 software and assessed the certainty of evidence for each outcome using the GRADE approach.<br><br>RESULTS: A total of seven studies involving 2,829 participants were included. There were no statistically significant differences in visual and anatomical outcomes between the aflibercept biosimilars (SB15, P041, SDZ-AFL, AVT06, SCD411, ABP 938, and QL1207) and the reference aflibercept. No significant differences were detected between aflibercept biosimilars and the reference aflibercept with respect to serious ocular and non-ocular adverse events [relative risk (RR) = 1.71, 95% confidence interval (CI): 0.70, 4.19; I [2] = 0.0%, P = 0.913; RR = 1.08, 95% CI: 0.82, 1.42; I [2] = 0.0%, P = 0.936, respectively). Although a slightly higher rate of treatment-emergent adverse events (TEAEs) was noted in the biosimilar group (RR = 1.07, 95% CI: 1.00-1.15; I[2] = 26.1%), the difference was not statistically significant (P = 0.248).<br><br>CONCLUSION: Based on the seven included randomized controlled clinical trials, aflibercept biosimilars demonstrated comparable safety and efficacy to the reference aflibercept. Future research requires more rigorous studies.}, }
@article {pmid41783117, year = {2026}, author = {Zhao, CS and Do, DV and Sanislo, SR and Ludwig, C and Rahimy, E and Mruthyunjaya, P and Wai, KM}, title = {Prevalence of Systemic Comorbidities and Ocular Complications in Patients With Bilateral Retinal Telangiectasia.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261423313}, pmid = {41783117}, issn = {2474-1272}, abstract = {Purpose: To compare systemic comorbidities in bilateral retinal telangiectasia, a proxy for macular telangiectasia (MacTel) type 2, vs matched controls. Methods: We conducted a retrospective cohort study of a large electronic health research network of patients who were older than 45 years at bilateral retinal telangiectasia diagnosis vs controls receiving eye care. Patients with macular edema or exudative age-related macular degeneration were excluded. Propensity score matching was performed on demographics. The prevalence of hypertension, diabetes mellitus, obesity, hyperlipidemia, and death within 5 years of retinal telangiectasia diagnosis or eye care visit were compared. Results: 2320 patients with bilateral retinal telangiectasia and 1 671 600 patients with an eye care visit were included. After matching, no demographic differences persisted. Bilateral retinal telangiectasia (vs control) patients had higher rates of type 2 diabetes mellitus (32.8% vs 20.7%; odds ratio [OR], 1.87; 95% CI, 1.64-2.14; P < .005) and obesity (19.9% vs 16.9%; OR 1.22; 95% CI:1.05-1.42; P = .01) and a lower rate of hyperlipidemia (32.0% vs 39.5%; OR 0.71; 95% CI, 0.63-0.80; P < .005). No differences occurred in hypertension or death. Conclusions: Retinal telangiectasia and MacTel type 2 are uncommon and poorly understood, with high coexisting rates of diabetes and obesity. Systemic disease associations should be investigated to identify disease interactions, the impact of systemic interventions, and leads for potential new treatments.}, }
@article {pmid41783478, year = {2026}, author = {Tsutsumi, N and Sakata, S and Ikari, R and Ebihara, N}, title = {Long-term follow-up of a Tay-Sachs disease patient with cherry-red spot.}, journal = {American journal of ophthalmology case reports}, volume = {42}, number = {}, pages = {102548}, pmid = {41783478}, issn = {2451-9936}, abstract = {PURPOSE: To describe the clinical progression and ophthalmic findings in a Japanese boy with Tay-Sachs disease at ages 5 and 8 months.<br><br>RESULTS: The patient was born at 38 weeks of gestation and developed normally until motor skill delays were identified at age 1 year and 1 month. At that time, brain magnetic resonance imaging revealed diffuse T2 hyperintensity in the bilateral basal ganglia. At age 1 year and 6 months, he was able to fix and follow objects, and the optic discs appeared normal, but bilateral cherry-red spots were observed in the maculae. Based on these findings, together with hypersensitivity to sound and markedly reduced &#x3b2;-hexosaminidase A activity, Tay-Sachs disease was biochemically diagnosed. By age 2 years and 1 month, the patient had lost the ability to fixate on and follow objects. Fundoscopy at age 4 years and 4 months revealed optic atrophy and reduced cherry-red spots, electroretinography (ERG) at age 4 years and 9 months showed a complete loss of retinal responses, and optical coherence tomography at age 5 years and 3 months demonstrated retinal thinning. Long-term observation revealed progressive degeneration, consistent with previous reports. Lipid deposition in all retinal layers was considered to contribute to retinal atrophy.<br><br>CONCLUSIONS: This report highlights progressive retinal degeneration with optic atrophy, retinal thinning, and reduction in cherry-red spots. The flat ERG waveform in this patient suggests more advanced retinal involvement than in previous reports and provides insights into the ocular manifestations of Tay-Sachs disease.}, }
@article {pmid41783692, year = {2026}, author = {Xiao, K and Gao, J and Zhang, Y and Chen, R and Wang, Y and Gu, C and Liu, J and Huang, Y and Li, L}, title = {Healthy Dietary Patterns and Risk of Major Eye Diseases: Evidence From Nationally Population-Based Data and Bibliometric Analysis.}, journal = {Food science &amp; nutrition}, volume = {14}, number = {3}, pages = {e71528}, pmid = {41783692}, issn = {2048-7177}, abstract = {The associations between dietary patterns and major eye diseases remain incompletely understood. This study conducted a cross-sectional analysis of 4241 participants from the 2005-2008 National Health and Nutrition Examination Survey. Eye diseases were assessed using fundus photography and self-reported information, while dietary patterns were evaluated based on two 24-h dietary recalls. Survey-weighted logistic regression and restricted cubic spline models were applied with adjustment for complex sampling design and relevant covariates, alongside subgroup and dietary component-specific analyses. In fully adjusted models, higher HEI-2020 scores were associated with lower odds of retinopathy and composite eye disease outcomes with or without cataract surgery. Similarly, greater adherence to the DASH was inversely associated with retinopathy and composite eye disease outcomes. Mediterranean diet adherence was also associated with reduced odds of retinopathy, and a non-linear association was observed between Mediterranean diet adherence and cataract risk. Subgroup analyses indicated effect modification by age, body mass index, alcohol consumption, and hyperlipidemia status. Whole grains, total vegetables, and nuts emerged as protective dietary components, whereas refined grains were identified as a potential risk factor. In conclusion, higher adherence to HEI-2020, DASH, and Mediterranean dietary patterns was associated with a lower prevalence of selected major eye diseases. These findings reflect associations rather than causation, and prospective studies and randomized trials are needed to clarify temporal and causal relationships.}, }
@article {pmid41783718, year = {2026}, author = {Terao, R and Tsusu, C and Saeki, Y and Yashiro, K and Ota, M and Aoki, S and Kitamoto, K and Azuma, K}, title = {Evaluation of Reticular Pseudodrusen by Polarization-Sensitive Optical Coherence Tomography: Case Report.}, journal = {Case reports in ophthalmology}, volume = {17}, number = {1}, pages = {171-178}, pmid = {41783718}, issn = {1663-2699}, abstract = {INTRODUCTION: Reticular pseudodrusen (RPD) are an important clinical biomarker associated with progression to late age-related macular degeneration (AMD). We report polarization-sensitive optical coherence tomography (PS-OCT) findings in a case of RPD and evaluate the entropy characteristics of these lesions.<br><br>CASE PRESENTATION: A 73-year-old man presented for evaluation of retinal angiomatous proliferation in his right eye. The left eye demonstrated multiple round, white-yellowish macular lesions consistent with RPD. Optical coherence tomography (OCT) angiography showed no macular neovascularization in the left eye. Swept-source (SS-OCT) revealed hyperreflective, spike-like deposits between the photoreceptor outer segments (PROSs) and the retinal pigment epithelium. Corresponding PS-OCT B-scans demonstrated moderately elevated polarimetric entropy values at the same locations. En face images reconstructed from the PROS layer showed circular RPD-like lesions on SS-OCT, which precisely matched high-entropy areas on PS-OCT. Merged en face maps confirmed one-to-one correspondence between RPD and regions of increased entropy.<br><br>CONCLUSION: PS-OCT successfully visualized RPD as moderately high-entropy lesions in the PROS layer, suggesting that these deposits are composed of non-retinal pigment epithelium material, such as lipids or inflammatory cells. These findings indicate that PS-OCT may serve as a useful complementary modality for detecting RPD and may enhance current imaging strategies for assessing RPD and monitoring AMD progression.}, }
@article {pmid41784091, year = {2026}, author = {Devin, F and Kodjikian, L and Fourmaux, E and Deudon-Combe, A and Boulet, JF and Pouriel, M and Marquet, G and Balez, S and Derquenne, F and Savary de Beauregard, V and Souied, E}, title = {Results from a French brolucizumab access program for pretreated patients with neovascular age-related macular degeneration.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721251414691}, doi = {10.1177/11206721251414691}, pmid = {41784091}, issn = {1724-6016}, abstract = {PurposeFollowing European Medicines Agency (EMA) approval, France implemented a managed access program (MAP) to provide brolucizumab to patients with neovascular age-related macular degeneration (nAMD) who lacked treatment alternatives. The French MAP data analysis evaluated efficacy and safety of brolucizumab in brolucizumab-naïve patients.MethodsOf 599 patients enrolled between February 2022 and January 2024, 360 pretreated with anti-VEGF therapy but brolucizumab-naïve were assessed at baseline for clinical and anatomical benefits of brolucizumab in a close-to-real-world setting.ResultsAfter 18 months, patients received a median of eight injections, maintaining visual acuity and achieving a mean central subfield macular thickness (CSMT) reduction of -92.0 µm among those with baseline CSMT ≥300 µm. Intraretinal fluid, subretinal fluid, and pigment epithelial detachment occurred in 32.8%, 75.3%, and 61.7% patients at baseline, and 16.5%, 47.0%, and 51.3% patients at 18 months. Patients previously requiring Q4 or Q5-Q7 injections successfully extended their intervals to Q8 or longer. Intraocular inflammation rate was 8.0% (n = 29).ConclusionResults demonstrated functional and anatomical benefits of brolucizumab in patients with refractory or suboptimally controlled nAMD, with a manageable safety profile. These findings highlight the potential of brolucizumab to reduce treatment burden in chronic nAMD.}, }
@article {pmid41784336, year = {2026}, author = {Chen, C and Razavi, R and Romano, F and Niessen, H and Sabokrohiyeh, S and Konda, A and Chevrefils, C and Arbour, JD and Rhéaume, MA and Nissan, R and Rojewski, A and Sorya, P and Santucci, L and Campbell, S and Ploumi, I and Zhu, Y and Ding, X and Sylvestre, JP and Miller, JB and Nassar, K}, title = {Hyperspectral Imaging for the Classification and Analysis of Drusen in Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {10}, pmid = {41784336}, issn = {1552-5783}, mesh = {Humans ; *Retinal Drusen/classification/diagnosis/etiology ; Cross-Sectional Studies ; Female ; Male ; *Tomography, Optical Coherence/methods ; Prospective Studies ; Aged ; *Macular Degeneration/complications/diagnosis/classification ; Aged, 80 and over ; *Hyperspectral Imaging/methods ; ROC Curve ; Middle Aged ; Sensitivity and Specificity ; }, abstract = {PURPOSE: To characterize the spatial-spectral signatures of drusenoid deposits [soft, hard, and reticular pseudodrusen (RPD)] in eyes with non-exudative age-related macular degeneration (AMD).<br><br>METHODS: In this observational, cross-sectional, prospective study, hyperspectral retinal images and corresponding Optical Coherence Tomography (OCT) images were collected from 152 eyes of 100 participants with non-exudative AMD. Drusenoid deposits were manually annotated in 148 eyes (97 participants) by retinal specialists using OCT as the reference standard. Automated drusen identification was then performed using spectral angle mapper (SAM) and random forest classifiers.<br><br>RESULTS: Hyperspectral imaging revealed that RPD was most distinct at 470-500&#xa0;nm, soft drusen at 525-575&#xa0;nm, hard drusen at 620-675&#xa0;nm, and pigmentary abnormalities at 650-725&#xa0;nm. Using the SAM classifier, drusenoid deposits were identified with 97% sensitivity and 70% specificity. The random forest classifier achieved higher overall performance, with 88% sensitivity, 99% specificity, and an area under the receiver operating characteristic curve of 0.96. Pixel-wise SAM mapping delineated drusenoid deposits and healthy retina, extending beyond annotated regions.<br><br>CONCLUSIONS: Distinct spatial-spectral signatures for soft drusen, hard drusen, and RPD were identified using hyperspectral imaging. Both SAM and random forest classifiers demonstrated promising results for automated drusenoid deposit detection. These findings support the role of hyperspectral retinal imaging as a noninvasive tool for automated drusen mapping and patient risk stratification in nonexudative AMD.}, }
@article {pmid41786217, year = {2026}, author = {Chaikitmongkol, V and Somkuna, T and Patikulsila, D and Ruamviboonsuk, P and Jirarattanasopa, P and Srisomboon, T and Narongchai, C and Ratanasukon, M and Bhurayanontachai, P and Kunavisarut, P and Watanachai, N and Choovuthayakorn, J and Chotcomwongse, P and Sangkaew, A and Ingviya, T and Bressler, NM}, title = {Factors predicting fluid-free retina and complete polypoidal regression in polypoidal choroidal vasculopathy eyes receiving 2-mg aflibercept treatments.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {100298}, doi = {10.1016/j.apjo.2026.100298}, pmid = {41786217}, issn = {2162-0989}, abstract = {PURPOSE: To determine predictive factors for fluid-free retina and complete polypoidal choroidal vasculopathy (PCV) regression following 1-year aflibercept monotherapy in PCV.<br><br>METHODS: Multicenter, retrospective cohort of treatment-na&#xef;ve PCV eyes receiving 2-mg aflibercept treatments for 1 year from 2015 to 2018 collected demographic data, de-identified fundus photography, optical coherence tomography (OCT), and indocyanine green angiography (ICGA) images at baseline and 1-year of study eyes were graded to identify baseline features and outcomes.<br><br>RESULTS: Of 100 study eyes, mean age [SD] was 63.8 [8] years; 100% were Thai patients. At 1 year, eighty-five eyes (85%) had fluid-free retina; 48 eyes (48%) had complete polypoidal regression. Multivariate analyses showed baseline OCT and ICGA features associated with 1-year outcomes: sharply-peaked PED with/without double-layer sign on OCT and smaller lesion size on ICGA (<1 disc diameter) were associated with fluid-free retina (OR 6.57; 95%CI 1.27-34.10, and OR 7.86; 95%CI 1.33-46.54, respectively). Multilobulated PED on OCT was associated with poor (20/200 or worse) final VA (OR 4.53; 95%CI 1.33-15.36). Smaller number (1-5) of polypoidal lesions on ICGA was associated with complete polypoidal regression (OR 4.87; 95%CI 1.44-16.43) CONCLUSION: Results suggest baseline OCT and ICGA features could predict fluid-free retina and complete polypoidal regression following aflibercept monotherapy.}, }
@article {pmid41786219, year = {2026}, author = {Phan, LT and Chin, J and Broadhead, GK and Hong, TH and Mehta, H and Chang, JH and Fraser-Bell, S and Cheung, CMG and Sun, CZ and Luckie, AP and Wickremasinghe, SS and Liew, G and Gilhotra, JS and Simunovic, MP and Verma, N and Chang, AA}, title = {Faricimab for previously-treated eyes with neovascular age-related macular degeneration with inadequate response - 6-month interim analysis of the FURGGHORN study.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {100299}, doi = {10.1016/j.apjo.2026.100299}, pmid = {41786219}, issn = {2162-0989}, abstract = {PURPOSE: To investigate the effect of switching to faricimab therapy patients with neovascular age-related macular degeneration currently treated with anti-VEGF therapy.<br><br>DESIGN: Phase IV, prospective, single-arm, open-label, multi-center, investigator-initiated clinical trial.<br><br>METHODS: Eligible eyes received four initial doses of faricimab 6&#x202f;mg/0.05&#x202f;mL every 4-weeks. From week 12, dosing intervals were increased to eight weeks and then modified according to a treat-and-extend based regimen. This interim analysis reports changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), retinal fluid proportions, and the incidence of adverse events from baseline through to week 24.<br><br>RESULTS: One-hundred-and-two patients of mean age 76.0 years were recruited from 12 sites across Australia and Singapore. Baseline BCVA was 72 Early Treatment Diabetic Retinopathy Study letters and baseline CST was 384&#x202f;&#xb5;m. Seventy-two percent of eyes were being treated with aflibercept 2&#x202f;mg and 28% with ranibizumab. After switching to faricimab, mean BCVA change was +&#x202f;1.9 letters at week 12 (P&#x202f;<&#x202f;0.001), and +&#x202f;1.9 letters at week 24 (P&#x202f;<&#x202f;0.001). Mean CST change was -83.9&#x202f;&#xb5;m at week 12 (P&#x202f;<&#x202f;0.001), and -82.2&#x202f;&#xb5;m at week 24 (P&#x202f;<&#x202f;0.001). The proportion of eyes with fluid resolution was 54% at week 12, and 59% at week 24. The proportion of eyes assigned to 4-weekly, 8-weekly, and 12-weekly treatment intervals were 16%, 35% and 49% respectively at week 24. Anterior chamber inflammation occurred in one eye with no cases of vasculitis or occlusive retinitis.<br><br>CONCLUSIONS: In this pre-specified interim analysis of a prospective study, patients switching to faricimab experienced improved anatomic outcomes and maintained visual function, with a large proportion assigned extended dosing intervals under a flexible treatment regimen.<br><br>TRIAL REGISTRATION NUMBER: ACTRN12623000215628.}, }
@article {pmid41786848, year = {2026}, author = {Chung, DH and Jee, D and Roh, YJ and Ra, H and Lee, MY and Won, JY and Shin, JA and Jung, SH and Park, YH}, title = {Short term real-world effectiveness of faricimab in neovascular age-related macular degeneration patients in the Republic of Korea.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-41488-1}, pmid = {41786848}, issn = {2045-2322}, support = {RS-2025-25417985//Patient-Centered Clinical Research Coordinating Center (PACEN) funded by the Ministry of Health &amp; Welfare, Republic of Korea/ ; }, abstract = {To analyze visual and anatomic outcomes of faricimab injection in neovascular age-related macular degeneration (nAMD) in a real-world setting in Korea. We collected data from nAMD patients who received faricimab injection from 2024 to 2025. The past injection history, and faricimab injection history was obtained. Visual acuity (VA) and central macular thickness (CMT) outcomes for 1, 3, 6, 12 months after initial faricimab injection were compared to baseline, and also compared between sex, different age-groups, and naïve vs. non-naïve groups. A total of 286 patients, 293 eyes from 8 university hospitals were included in this study. VA improved from baseline 58.9 ± 17.1 letters to 60.7 ± 23.5, 61.0 ± 18.1, 59.9 ± 19.3, 60.5 ± 18.2 letters at 1, 3, 6, 12 months respectively (statistically significant at 3 months, p = 0.009), while CMT improved by -60.6 ± 89.0, -55.9 ± 87.3, -46.5 ± 97.5, -70.7 ± 97.8 μm compared to baseline (p < 0.001 at all timepoints). An age group analysis showed that the youngest age group (< 60 years) had superior VA results, while the naïve group showed superior outcomes compared to the non-naïve group. CMT fluctuation showed inverse correlation with visual acuity at 6 months, with lower CMT fluctuation being associated with the young and naïve. Faricimab injection for nAMD, in a real-world setting in the Republic of Korea, showed significant functional and anatomic improvements with superior results in the younger age group and naïve group, suggesting promising effectiveness of a bispecific blockage of VEGF-A and Ang-2 at the initial phases of nAMD.}, }
@article {pmid41786902, year = {2026}, author = {Judkiewicz, R and Berkowitz, E and Meisel, M and Michaeli, T and Behar, JA}, title = {Shifting the retinal foundation models paradigm from slices to volumes for optical coherence tomography.}, journal = {NPJ digital medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41746-026-02496-7}, pmid = {41786902}, issn = {2398-6352}, abstract = {Optical Coherence Tomography (OCT) is essential in ophthalmology for cross-sectional imaging of the retina. Pretrained foundation models facilitate task-specific model development by enabling fine-tuning with limited labeled data. However, current foundation models rely on a single B-scan (usually the central slice), overlooking volumetric context. This research investigates video foundation models to capture full 3D retinal structure and improve diagnostic performance. V-JEPA, a state-of-the-art video foundation model, was benchmarked against retinal foundation models (RETFound, VisionFM) and a natural image foundation model (DINOv2). All were fine-tuned to detect Age-related Macular Degeneration or Glaucomatous Optic Neuropathy using five OCT datasets. V-JEPA consistently equaled or outperformed image-based models, achieving an average AUROC of 0.94 (0.80-0.99), versus 0.90 (0.76-0.98) for the best image model, a statistically significant improvement (p < 0.001). To our knowledge, this is the first application of transformer-based video models to volumetric OCT, highlighting their promise in 3D medical imaging.}, }
@article {pmid41788302, year = {2026}, author = {Tsiropoulos, GN and Topouzis, F and Amoaku, W and Panos, GD}, title = {Anti-VEGF Agents and the Inner Retina in nAMD: A Narrative Review of RNFL and Ganglion Cell Changes.}, journal = {Drug design, development and therapy}, volume = {20}, number = {}, pages = {591127}, pmid = {41788302}, issn = {1177-8881}, mesh = {Humans ; *Retinal Ganglion Cells/drug effects/pathology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Angiogenesis Inhibitors/pharmacology/administration &amp; dosage ; Tomography, Optical Coherence ; *Macular Degeneration/drug therapy ; *Nerve Fibers/drug effects/pathology ; *Retina/drug effects ; }, abstract = {Anti-vascular endothelial growth factor (anti-VEGF) therapy is the cornerstone of care for neovascular age-related macular degeneration (nAMD), yet its effects on the inner retina are not widely studied. We conducted a narrative review, guided by the SANRA checklist, to map evidence on peripapillary retinal nerve fibre layer (pRNFL), macular RNFL, and ganglion cell-derived metrics (GCL/GCIPL/GCC) during anti-VEGF treatment. Major databases were searched from inception to 10 November 2025 for human studies reporting optical coherence tomography (OCT) measurements of inner-retinal structure during anti-VEGF treatment. Data were charted for study design, OCT device/segmentation, scan protocol, timing relative to injections, treatment regimen, fluid phenotype (intraretinal fluid [IRF], subretinal fluid [SRF], pigment epithelial detachment [PED]), follow-up interval, and magnitude of change (µm). Across cohorts and agents, global pRNFL thickness was largely stable over weeks to years, with short-term peri-injection fluctuations typically within device test-retest limits. In contrast, macular ganglion cell layers more often showed modest thinning over time, most consistently in eyes with baseline IRF; SRF-predominant disease showed less consistent inner-retinal change. Apparent between-agent differences were small and inconsistent; evidence specific to faricimab remains limited but generally reassuring for structural stability. Overall, most observed changes were often within OCT test-retest variability. In practice, clinicians should prioritise GCL/GCIPL monitoring where IRF is present, interpret small absolute changes against device repeatability, and avoid attributing trivial sectoral shifts to drug toxicity without corroboration.}, }
@article {pmid41788885, year = {2026}, author = {Wu, W and Guo, H and Wang, L and Yang, M}, title = {SRF and SHRM in nAMD: Retrospective Analysis of Visual Prognosis.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {590001}, pmid = {41788885}, issn = {1177-5467}, abstract = {OBJECTIVE: This study aimed to investigate the correlation between subretinal fluid (SRF) and subretinal hyperreflective material (SHRM) with visual prognosis in neovascular age related macular degeneration (nAMD).<br><br>METHODS: A retrospective analysis was conducted on 60 nAMD patients diagnosed at our ophthalmology department from March 2017 to December 2024. All patients received intravitreal anti-vascular endothelial growth factor (VEGF) injections monthly for the first 3 months, followed by pro re nata (PRN) treatment for the subsequent 9 months. Quantitative measurements&#xa0;of SRF and SHRM (height and width on OCT) were collected, along with patient demographics, best corrected visual acuity (BCVA), and central foveal thickness (CMT).<br><br>RESULTS: After 12 months of treatment, BCVA, CMT, and SRF parameters significantly improved (P < 0.05). The visual improvement group showed superior reductions in SRF and SHRM height compared to the nonimprovement group (P < 0.05). Greater baseline SRF thickness (>180&#xa0;&#x3bc;m) was significantly associated with better final visual acuity&#xa0;(P = 0.034), while&#xa0;baseline SHRM presence correlated with worse final BCVA and CMT&#xa0;(P < 0.05). These findings indicate that SRF serves as a favorable prognostic indicator, whereas SHRM is a key predictor of poor visual outcomes&#xa0;(P = 0.001).<br><br>DISCUSSION: SRF and SHRM morphological features are linked to nAMD treatment response. SRF thickness positively correlates with visual improvement, serving as a prognostic indicator. Persistent SHRM, however, is associated with fibrotic components that may impair retinal function, making it a key parameter for poor outcomes. These findings align with prior studies, highlighting the importance of quantitative SRF and SHRM assessment in predicting treatment response.<br><br>CONCLUSION: SRF and SHRM are clinically significant biomarkers in nAMD treatment, effectively predicting visual prognosis and guiding individualized therapeutic strategies. Their quantitative evaluation may aid in optimizing treatment tolerance strategies and improving real world clinical outcomes.}, }
@article {pmid41788972, year = {2026}, author = {Distefano, A and Calcagno, D and Grasso, G and Monasson, O and Peroni, E and Oliveri, V}, title = {Tolcapone Interferes With Key Pathological Features in Alzheimer's Disease.}, journal = {Bioinorganic chemistry and applications}, volume = {2026}, number = {}, pages = {1036276}, pmid = {41788972}, issn = {1565-3633}, abstract = {Tolcapone, a clinically approved drug for the treatment of Parkinson's disease as an adjunct therapy, has recently emerged as a potential modulator of amyloid-β aggregation and toxicity, which are hallmark features of Alzheimer's disease and are also involved in ocular neurodegenerative disorders, including glaucoma and age-related macular degeneration. Despite these noteworthy findings, the molecular basis of the interaction between amyloid-β and tolcapone remains poorly understood, and the mechanisms by which tolcapone affects metal-amyloid-β species have yet to be explored. In this work, we investigate the binding interactions of tolcapone with both copper-free amyloid-β and copper-associated amyloid-β complexes, using a combination of techniques including UV-vis spectroscopy, circular dichroism, mass spectrometry, and surface plasmon resonance. The results reveal that tolcapone binds directly to amyloid-β monomers. Furthermore, in vitro assays confirm the capacity of tolcapone to act as a radical scavenger and to compete with amyloid-β for the binding of copper ions. Altogether, our findings suggest that tolcapone exerts a multifaceted protective effect, potentially inhibiting toxic metal-free and metal aggregation pathways by preventing metal coordination to amyloid-β or disrupting preformed amyloid-β-metal complexes, thus offering new perspectives to explore and develop its analogs for the treatment of neurodegenerative disorders.}, }
@article {pmid41789719, year = {2026}, author = {Heloterä, H and Sund, R and Rikkonen, T and Kaarniranta, K}, title = {The impact of systemic long-term medications for the development of age-related macular degeneration.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70113}, pmid = {41789719}, issn = {1755-3768}, support = {//the Aarne Koskelo Foundation/ ; //the P&#xe4;ivikki and Sakari Sohlberg Foundation/ ; //the Mary and Georg C. Ehrnrooth Foundation/ ; //the Finnish Eye and Tissue Bank Foundation/ ; //the Finnish Eye Foundation/ ; //Sokeain Yst&#xe4;v&#xe4;t ry-De Blindas V&#xe4;nner sr/ ; 5503770//Kuopio University Hospital VTR grant/ ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of central vision loss in the elderly; however, the systemic factors that modulate its incidence and progression remain unclear. We sought to determine whether long-term use of systemic medications, including diabetes and antithrombotic medications, corticosteroids and immunosuppressants, is associated with the development of AMD.<br><br>METHODS: The data included a pooled cohort of two follow-up studies: the Kuopio Osteoporosis Risk Factor and Prevention Study and the Kuopio Fall Prevention Study. A total of 16&#x2009;518 women born between 1932 and 1946 living in eastern Finland were followed up between 1993 and 2021. The long-term medication use was indicated as &#x2265;5&#x2009;years of regular purchase of drugs. Incidence for AMD was analysed per long-term medication group, but also during the 5&#x2009;years period in age matched groups.<br><br>RESULTS: We observed increased odds for AMD among long-term users of systemic corticosteroids (HR 1.348, p&#x2009;<&#x2009;0.001), immunosuppressants (HR 1.623, p&#x2009;=&#x2009;0.004) and antithrombotic (HR 1.145, p&#x2009;=&#x2009;0.042) medication. However, results with antithrombotic medications were not as consistent as with corticosteroids and immunosuppressants. Interestingly, the mean age at diagnosis of AMD was later among antithrombotic medication users compared to the control group (77.9 vs. 76.1, respectively, p&#x2009;<&#x2009;0.001) and earlier among patients using other diabetes medications than metformin (75.3 vs. 77.1, p&#x2009;=&#x2009;0.026).<br><br>CONCLUSIONS: People with long-term corticosteroid and immunosuppressant use are at greater risk for developing AMD. Further research on systemic components behind corticosteroid and immunosuppressant use, modulating AMD progression, is warranted.}, }
@article {pmid41790302, year = {2026}, author = {Giannuzzi, F and Hu, L and Cusato, M and Cestrone, V and De Vico, U and Caputo, CG and Rizzo, C and Di Fede, L and Carlà, MM and Crincoli, E and Rizzo, S}, title = {Management of submacular hemorrhage: from a case report to a comprehensive review of current treatment strategies.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {41790302}, issn = {1573-2630}, mesh = {Humans ; *Retinal Hemorrhage/therapy/diagnosis/etiology ; *Vitrectomy/methods ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Visual Acuity ; Intravitreal Injections ; Tissue Plasminogen Activator/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Disease Management ; }, abstract = {PURPOSE: To evaluate current pharmacological and surgical strategies for managing submacular hemorrhage (SMH), a vision-threatening complication which primarily occurs with macular neovascularization in age-related macular degeneration (AMD).<br><br>METHODS: The research involved a literature review of recent studies about SMH treatment methods including anti-vascular endothelial growth factor (VEGF) therapy, tissue plasminogen activator (tPA), pneumatic displacement and pars plana vitrectomy techniques through meta-analyses, comparative studies and case series.<br><br>RESULTS: SMH treatment is guided by hemorrhage size: small (&#x2265;&#xa0;1 to&#xa0;<&#x2009;4 disc diameters), medium (&#x2265;&#xa0;4 disc diameters within the temporal arcade), massive (exceeding temporal arcades). Pharmacological management includes anti-VEGF monotherapy, which demonstrates efficacy comparable to surgical interventions for smaller hemorrhages, while offering a superior safety profile. Combined of tPA and anti-VEGF therapy achieves an 86% displacement success rate, with comparable efficacy between subretinal and intravitreal delivery methods. Surgical methods include pneumatic displacement, which achieves 85-100% efficacy in displacement and 45-80% rates of visual improvement, whereas pars plana vitrectomy is preferred for cases involving dense, organized hemorrhages. Retrospective studies indicate that outcomes are primarily influenced by patient-specific factors, such as hemorrhage size and baseline visual acuity, rather than the treatment modality employed. Intervention within 7 to 14&#xa0;days has been shown to enhance outcomes, particularly when using a stepwise protocol that begins with less invasive techniques and escalates only as necessary.<br><br>CONCLUSIONS: Modern SMH management emphasizes individualized, time-sensitive treatment based on hemorrhage characteristics. A stepwise approach, beginning with pharmacological therapy and moving to surgery only when necessary, tends to offer the best balance between visual recovery and safety. Timely diagnosis and intervention are essential factors for success due to the rapid damage&#xa0;of photoreceptors occurring within 24-72&#xa0;h of onset.}, }
@article {pmid41790421, year = {2026}, author = {Baljoon, A and Diaby, V and Suther, S and Dutton, M and Ali, A and Eljilany, I}, title = {Cost-Utility Analysis of Faricimab Versus Aflibercept in Treating Neovascular Age-Related Macular Degeneration (nAMD) in the United States.}, journal = {PharmacoEconomics - open}, volume = {}, number = {}, pages = {}, pmid = {41790421}, issn = {2509-4254}, abstract = {BACKGROUND/OBJECTIVE: Neovascular age-related macular degeneration (nAMD) imposes a substantial clinical and economic burden in the United States (US). Faricimab offers the potential for longer dosing intervals than aflibercept, but its economic value in the US setting has not been established. This study evaluated the cost utility of faricimab versus aflibercept for treating nAMD from the US payer perspective.<br><br>METHODS: A Markov model of five health states defined by best-corrected visual acuity (BCVA) simulated disease progression over 5 years. Clinical inputs were drawn from pooled 1-year data of the TENAYA and LUCERNE phase III trials (n&#xa0;=&#xa0;1329), which compared faricimab with aflibercept for treating nAMD patients. Direct medical costs encompassed drug acquisition, intravitreal administration, monitoring, office visits, and management of endophthalmitis. Outcomes included total costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and net monetary benefit (NMB) at a willingness-to-pay (WTP) threshold of US$100,000/QALY. Scenario, deterministic, and probabilistic sensitivity analyses (10,000 iterations) were conducted.<br><br>RESULTS: In the base case, faricimab yielded 2.80 QALYs for US$52,797, whereas aflibercept produced 2.72 QALYs at US$62,367. Faricimab was therefore dominant (-&#x2009;US$9570; +&#x2009;0.08 QALY), with an incremental NMB of US$17,981. Faricimab required markedly fewer injections over 5 years (22.6 vs 34). Scenario analyses did not materially change the directionality of the base-case results, with faricimab being dominant or cost effective. The model was most sensitive to drug acquisition prices and BCVA-state utilities, yet faricimab remained below the WTP threshold across all plausible ranges. Probabilistic analysis showed a 97% probability of faricimab being cost effective at US$100,000/QALY.<br><br>CONCLUSIONS: Faricimab is estimated to be a cost-effective treatment option compared with aflibercept for nAMD from a US payer perspective. This finding may support its inclusion in treatment guidelines and formulary decisions, pending confirmation in real-world practice.}, }
@article {pmid41790486, year = {2026}, author = {Ruuth, J and Tamminen, T and Toropainen, E and Tanila, H and Hyttinen, JMT and Malm, T and Kaarniranta, K and Koskela, A}, title = {Overproduction of 42 Amino Acids Long Amyloid Beta Leads to Activation of Secretory Autophagy and Development of Drusen-Like Structures Originating From Retinal Pigment Epithelium.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {5}, pages = {e71608}, pmid = {41790486}, issn = {1530-6860}, support = {333302//Academy of Finland/ ; //GeneCellNano/ ; //Paivikki ja Sakari Sohlberg Foundation/ ; 5503770//Kuopio University Hospital district/ ; //Sigrid Jus&#xe9;liuksen S&#xe4;&#xe4;ti&#xf6; (Sigrid Jus&#xe9;lius Stiftelse)/ ; //Silm&#xe4;s&#xe4;&#xe4;ti&#xf6; (Finnish Eye Foundation)/ ; //De Blindas V&#xe4;nner (DBV)/ ; //Finnish eye and Tissue Bank Foundation/ ; //Mary and Georg C. Ehrnrooths Foundation/ ; //Finnish Cultural Foundation-North-Savo/ ; }, mesh = {Animals ; *Autophagy/physiology ; *Retinal Pigment Epithelium/metabolism/pathology ; *Amyloid beta-Peptides/metabolism/genetics ; Mice ; *Retinal Drusen/metabolism/pathology ; *Macular Degeneration/metabolism/pathology ; Mice, Transgenic ; Humans ; Disease Models, Animal ; Sequestosome-1 Protein/metabolism ; Alzheimer Disease/metabolism/pathology ; }, abstract = {Age-related macular degeneration (AMD) is a global vision threatening disease affecting the macular region of the retina. AMD is classified into two forms: dry and wet AMD. There are no effective treatment options available for dry AMD (80% of cases). The cellular pathology includes oxidative stress and dysfunctional autophagy challenging the homeostasis of the retinal pigment epithelial (RPE) cells. Clinical findings include the formation of drusen deposits beneath the RPE cells consisting of 42 amino acids long amyloid beta (Aβ) among other components. However, the origin of drusen remains elusive. The 5xFAD (familiar Alzheimer's disease) mouse model of Alzheimer's disease produces abundant levels of Aβ making it an interesting model to study the possible relationship of Aβ to the formation of extracellular deposits and AMD-like pathology. An immunohistology analysis of the 5xFAD mouse model showed accumulation of autophagic markers SQSTM1 (sequestosome 1) and ubiquitin in the RPE. Concurrently, the markers of secretory autophagy enabling the delivery of the intracellular material to the extracellular lumen were upregulated. Aβ, SQSTM1, ubiquitin, catalase, and TRIM16 (tripartite motif containing 16) shifted age-dependently from intracellular origin to drusen-like deposits beneath the RPE cells. Additionally, classical proteins secreted via secretory autophagy, IL-1β (interleukin 1β), HMGB1 (high mobility group box-1), and ferritin showed similar accumulation which became visible in fundus age-dependently. These findings suggest a role for Aβ in the cellular pathogenesis of AMD. Furthermore, this model showed activated secretory autophagy pathway suggesting a role for Aβ in drusen-like deposition formation.}, }
@article {pmid41790719, year = {2026}, author = {Iby, J and Coulibaly, L and Hollaus, M and Yeghiazaryan, L and Schmidt-Erfurth, U and Bühl, W and Sacu, S}, title = {Efficacy of a single dose switch from aflibercept to ranibizumab in the treatment of neovascular age-related macular degeneration.}, journal = {PloS one}, volume = {21}, number = {3}, pages = {e0342927}, pmid = {41790719}, issn = {1932-6203}, mesh = {Humans ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Male ; Female ; Aged ; Retrospective Studies ; Aged, 80 and over ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Visual Acuity/drug effects ; *Macular Degeneration/drug therapy/pathology ; Treatment Outcome ; Tomography, Optical Coherence ; }, abstract = {PURPOSE: To analyze morphological and functional response after administration of a single dose of ranibizumab in eyes under treat&amp;extend aflibercept in neovascular age related macular degeneration (nAMD). Additionally, we aimed to identify predictive factors in anti-vascular endothelial growth factor (VEGF) treatment.<br><br>METHODS: A total of 115 patients (133 eyes; 34 male, 81 female, m:f&#x2009;=&#x2009;1:2.4) with a mean age of 79.9&#x2009;&#xb1;&#x2009;8.3 years at baseline (BSL) were included in this retrospective analysis. All eyes had received aflibercept treatment for nAMD before BSL and were subsequently administered a single dose of intravitreal ranibizumab. Data of two visits pre and two visits after BSL were evaluated and compared. Primary outcome measure was the mean change in central macular thickness (CMT, &#xb5;m). CMT-changes between BSL and the next follow-up visit (V4) were roughly divided into decrease (<-10&#xb5;m), equal (-10 to +10 &#xb5;m) or increase (> +10&#xb5;m). We also assessed changes in best-corrected visual acuity (BCVA) and identified influencing factors on CMT and BCVA using linear mixed models (LMM).<br><br>RESULTS: No significant differences in CMT and BCVA were observed over the visits (p&#x2009;>&#x2009;0.05). Factors influencing CMT included prior anti-VEGF injections (p&#x2009;<&#x2009;0.001), the time interval between BSL and visit 4 (p&#x2009;<&#x2009;0.001), and patient age (p&#x2009;=&#x2009;0.032). The number of prior anti-VEGF injections significantly influenced BCVA (p&#x2009;=&#x2009;0.003). After a single administration of ranibizumab, in 19.5% (n&#x2009;=&#x2009;26) of eyes CMT decreased, in 21.8% of eyes (n&#x2009;=&#x2009;29) CMT increased and in 36.8% of eyes (n&#x2009;=&#x2009;49) it remained equal.<br><br>CONCLUSION: Our study indicates that changes in CMT are affected by age, the number of previous injections, and the time interval between visits. These biomarkers may offer valuable insights for future research on switching anti-VEGF drugs to optimize treatment strategies for nAMD. A single dose treatment switch to ranibizumab yielded non-inferior outcomes.}, }
@article {pmid41791029, year = {2026}, author = {Jaffe, GJ and Boyer, D and Hu, A and Warrow, D and Xavier, S and Gonzalez, V and Lad, E and Rosen, RB and Do, DV and Schneiderman, T and Ho, AC and Munk, MR and Tedford, SE and Croissant, CL and Rückert, R and Lavin, P and Tedford, CE}, title = {Long-term Efficacy and Safety of Photobiomodulation in Dry Age-Related Macular Degeneration (LIGHTSITE III: 24-Month Analysis).}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004822}, pmid = {41791029}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate the safety and efficacy of multiwavelength photobiomodulation (PBM) in nonexudative (dry) age-related macular degeneration (AMD).<br><br>METHODS: LIGHTSITE III employed a double-masked, randomized, sham-controlled, parallel-group, prospective study design. Subjects were enrolled with a diagnosis of dry AMD and treated with multiwavelength PBM (Valeda&#xae; Light Delivery System; 590, 660 and 850 nm) or Sham treatment. A treatment series included 9 PBM or Sham treatments delivered 3x/week over 3-5 weeks every 4 months (M) for 24M.<br><br>RESULTS: A total of 148 eyes (100 subjects) with dry AMD were randomized into the study. LIGHTSITE III met the prespecified primary BCVA efficacy endpoint at M21 with a significant difference between treatment groups (p = 0.0036) and a +6.2 letter gain following PBM. At M21, 61.5% of PBM-treated eyes showed &#x2265;5, 23.1% showed &#x2265;10, and 4.4% showed &#x2265;15 letter gains. A favorable safety profile was observed with no signs of phototoxicity. Disease progression to Geographic Atrophy (GA) showed a significant decrease in incidence (Sham, 24.0% vs. PBM, 6.8%; p = 0.007) following PBM treatment at M24. Significant benefit in vision QoL was observed.<br><br>CONCLUSIONS: Multiwavelength PBM represents an interventional therapy that restores visual function and has potential disease-modifying effects in intermediate dry AMD.}, }
@article {pmid41791476, year = {2026}, author = {Hurst, J and Alber, J and Bredehorst, J and Schnichels, S}, title = {A porcine ex vivo angiogenesis model for retinal neovascular diseases.}, journal = {Experimental eye research}, volume = {267}, number = {}, pages = {110958}, doi = {10.1016/j.exer.2026.110958}, pmid = {41791476}, issn = {1096-0007}, abstract = {Retinal and choroidal vascular diseases are the leading causes of vision loss, with diabetic retinopathy and neovascular age-related macular degeneration as prominent examples. Current treatments such as laser photocoagulation and anti-VEGF injections have limitations and side effects. Therefore, there is a need for novel therapies to improve our understanding of underlying disease mechanisms. Animal welfare regulations also mandate a reduction in the use of animals. This study aimed to develop an ex vivo angiogenesis model using porcine retinal explants to study retinal neovascular diseases without using living animals. Porcine retina shares similarities with the human retina, making it a suitable model for studying retinal diseases. Porcine retinas were obtained from a local abattoir and retinal explants were cultured with pro-angiogenic factors to induce neovascularization. Vessel formation was observed using bright-field microscopy and the presence of endothelial cells was confirmed by CD31 immunostaining. qRT-PCR analysis revealed increased expression of angiogenesis-related genes in the treated explants compared to that in the controls. However, this model has limitations such as a lack of blood flow and limited cultivation time. Strategies to address these challenges include optimizing the tissue extraction time, exploring alternative coating materials, and maintaining the retinal tissue-retinal pigment epithelium interface. Nevertheless, this ex vivo porcine retinal angiogenesis model provides a valuable tool for investigating innovative treatment approaches for retinal neovascular diseases while reducing the use of living animals in research.}, }
@article {pmid41791650, year = {2026}, author = {Wu, S and Jeong, H and Reed, HA and Abbass, NJ and Kaelber, DC and Talcott, KE and Singh, RP}, title = {Associations Between Systemic Tyrosine Kinase Inhibitors and Development of Age-Related Macular Degeneration in Patients with Cancer.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.02.018}, pmid = {41791650}, issn = {2468-6530}, abstract = {PURPOSE: To evaluate the association between systemic tyrosine kinase inhibitor (TKI) therapy and the risk of age-related macular degeneration (AMD) onset, and whether this relationship varies by anti-VEGF activity of TKIs.<br><br>DESIGN: Retrospective cohort study using a large de-identified electronic health records research platform.<br><br>PARTICIPANTS: Patients &#x2265;50 years old with cancer encounter diagnoses were divided into groups with (treatment) and without (control) systemic TKI prescription codes and followed for incident AMD diagnosis.<br><br>METHODS: Landmarked time-to-event analyses were performed at 1, 3, and 5 years post-cancer diagnosis. Treatment and control groups were propensity score matched, followed from landmark date until incident ICD-10 AMD encounter diagnosis, death, or last recorded clinical encounter, and compared using hazard ratios for incident AMD. A three-arm sub-analysis was also performed by stratifying TKIs by anti-VEGF activity, comparing the TKI-with-anti-VEGF and TKI-without-anti-VEGF subgroups to the control group, and to each other.<br><br>MAIN OUTCOME MEASURES: Hazard ratios (HRs) for an incident ICD-10 AMD encounter diagnosis code after the landmark date. Significance was defined as 95% confidence interval (CI) <0.9 and >1.1.<br><br>RESULTS: Across landmark analyses, TKI prescriptions were not consistently associated with the hazard of receiving a new ICD-10 AMD encounter diagnosis code compared with matched controls: 1 year (HR=0.97; 95% CI=0.85, 1.12), 3 years (HR=0.90; 95% CI=0.78, 1.05), and 5 years (HR=0.81; 95% CI=0.69, 0.96). In the subanalysis, the TKI with-anti-VEGF subgroup showed significant reduction only at the 5-year landmark, HR=0.60; 95% CI=0.40, 0.89). The TKI-without-anti-VEGF subgroup demonstrated no significant association between systemic TKI exposure and the hazard of receiving a new ICD-10 AMD encounter diagnosis code at any time point: 1 year (HR=0.98; 95% CI=0.84, 1.15), 3 years (HR=0.97; 95% CI=0.82, 1.15), and 5 years (HR=0.87; 95% CI=0.73, 1.05). In contrast, across analyses, TKI prescriptions were consistently associated with increased hazards of mortality and fewer ophthalmology encounters.<br><br>CONCLUSIONS: This explorative study found that TKI prescriptions are not associated with incident AMD diagnosis. These findings do not support a population-level protective effect of systemic TKIs on AMD risk.}, }
@article {pmid41794975, year = {2026}, author = {Moghul, I and Pontikos, N and Sharma, A and Liu, T and Soomro, T and Wagner, SK and Silva, AS and Zhang, G and Naik, G and Bagga, P and Chan, YW and Keane, PA and Cipriani, V and Sivaprasad, S and Webster, AR and Balaskas, K}, title = {Integrating genetics, age and imaging to predict treatment outcomes in neovascular age-related macular degeneration: a proof-of-concept study.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-41931-3}, pmid = {41794975}, issn = {2045-2322}, support = {R190001//Moorfields Eye Charity/ ; }, }
@article {pmid41795704, year = {2026}, author = {Valmaggia, P and Ansari, G and Inglin, N and Schärer, N and Zuche, H and Gabrani, C and Yahya, F and Cattaneo, M and Pfau, K and Giani, A and Esmaeelpour, M and Yamaguchi, TC and Prünte, C and Scholl, HPN and Feltgen, N and Schmetterer, L and Pfau, M and Maloca, PM}, title = {The optical coherence tomography and microperimetry biomarker evaluation in patients with geographic atrophy (OMEGA) study: Geographic atrophy progression in fundus autofluorescence - OMEGA report 3.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70119}, pmid = {41795704}, issn = {1755-3768}, support = {YTCR 43/23//Schweizerische Akademie der Medizinischen Wissenschaften/ ; 323530_199395//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung/ ; //Boehringer Ingelheim Pharma GmbH &amp; Co. KG/ ; }, abstract = {PURPOSE: To measure the progression of geographic atrophy (GA) in subjects with age-related macular degeneration (AMD) in a natural history study.<br><br>METHODS: We analysed fundus autofluorescence (FAF) images using a semiautomatic method (RegionFinder) to quantify the GA area in a monocentric study. Three independent graders analysed each eye. Patient visits were scheduled at baseline, 12, 24 and 48&#x2009;weeks. The primary endpoint was the progression of GA area per eye. Potential correlations with clinical and imaging-based parameters were analysed.<br><br>RESULTS: The annual GA progression rate was 1.16&#x2009;mm[2]/year (95% CI: 0.76-1.56; p&#x2009;<&#x2009;0.001), with faster growth in eyes with larger baseline lesions (R[2]&#x2009;=&#x2009;0.74). After square root transformation, the progression rate was 0.34&#x2009;mm/year (95% CI: 0.26-0.43; p&#x2009;<&#x2009;0.001), and the size dependency was reduced (adjusted R[2]&#x2009;=&#x2009;0.16). Multivariable mixed-effects models identified a significant association between larger GA lesion sizes per eye and the number of smoking pack-years (p&#x2009;=&#x2009;0.017), the presence of perilesional hyperautofluorescence (p&#x2009;=&#x2009;0.044) and a multifocal configuration of the GA lesions (p&#x2009;=&#x2009;0.038). Intermediate AMD in the fellow eye was significantly associated with faster GA progression (p&#x2009;=&#x2009;0.041).<br><br>CONCLUSION: GA progression in AMD is significantly influenced by baseline lesion size and a larger number of smoking pack-years is associated with larger GA lesions. The marked variability between individuals underscores the multifactorial nature of GA dynamics. Quantitative FAF analysis is a reliable method for assessing lesion progression and may inform risk-based monitoring strategies.}, }
@article {pmid41796178, year = {2026}, author = {Tapia-Aguayo, A and Cisneros-Pardo, A and De Los Santos-González, BE and Hernández-Pérez, J and González-Valdez, J and Ramos-Parra, PA}, title = {Carrot extracellular nanovesicles as carotenoid carriers in an in vitro macular degeneration model.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-41792-w}, pmid = {41796178}, issn = {2045-2322}, }
@article {pmid41796922, year = {2026}, author = {Li, J and Peng, J and Liu, J and Cao, Y and Ju, Y and Li, D}, title = {Choroid blood flow analysis in the contralateral eye of neovascular age-related macular degeneration patients with subretinal fibrosis using OCTA.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {}, number = {}, pages = {105429}, doi = {10.1016/j.pdpdt.2026.105429}, pmid = {41796922}, issn = {1873-1597}, abstract = {PURPOSE: To evaluate choroidal vascular alterations in the contralateral eyes of patients with neovascular age-related macular degeneration (N-AMD) and subretinal fibrosis (SRFi) using optical coherence tomography angiography (OCTA).<br><br>METHODS: This retrospective study included 57 patients (57 eyes) with unilateral N-AMD and a normal fellow eye. Patients were classified by multimodal imaging into SRFi (24 eyes) and non-SRFi (32 eyes) groups. Best-corrected visual acuity (BCVA, logMAR), subfoveal choroidal thickness (SFCT), and OCTA-derived choriocapillaris and choroidal vessel density (VD, %) were measured. Group differences were assessed using binarized OCTA scans, and correlation and logistic regression analyses were performed.<br><br>RESULTS: SFCT was significantly reduced in the SRFi group compared with controls (P<0.05) and was positively correlated with choroidal VD (r=0.414, P=0.045). Multivariate logistic regression identified SFCT (OR=0.98, 95% CI: 0.96-0.99, P=0.006) and choroidal VD (OR=0.85, 95% CI: 0.72-1.00, P=0.047) as independent risk factors for SRFi.<br><br>CONCLUSION: Decreased SFCT and choroidal VD in the contralateral eyes of N-AMD patients with SRFi suggest a potential role in disease pathogenesis and progression. These parameters may serve as early biomarkers for the onset of SRFi in N-AMD.}, }
@article {pmid41798214, year = {2026}, author = {Hashimoto, Y and Barthelmes, D and Gillies, M}, title = {The Fight Retinal Blindness! registry: An international treatment outcomes registry for retinal diseases.}, journal = {Annals of clinical epidemiology}, volume = {8}, number = {1}, pages = {28-35}, pmid = {41798214}, issn = {2434-4338}, abstract = {The Fight Retinal Blindness! Registry is a prospectively-designed registry developed in 2009 that collects international data on treatment outcomes for eye diseases including neovascular age-related macular degeneration, diabetic macular edema and retinal vein occlusion. The validated and high-quality data have generated significant real-world evidence regarding clinically relevant issues, such as long-term visual outcomes, dosing regimens and practitioner variation. This paper outlines the Fight Retinal Blindness! Registry, highlighting its pros and cons, and introduces some findings from the registry.}, }
@article {pmid41799763, year = {2026}, author = {Zhou, Y and Wang, Z and Huang, C and Yu, X and Chen, J and Jiang, X and Dong, J and Peng, Q and Li, L and Song, X and Lu, X}, title = {Gut Microbiota Signatures and Potential Mediators in the Trajectory of Age-related Macular Degeneration: A Phased Atlas by Genetic Inference.}, journal = {International journal of medical sciences}, volume = {23}, number = {3}, pages = {950-962}, pmid = {41799763}, issn = {1449-1907}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics/immunology ; *Macular Degeneration/genetics/microbiology/immunology/pathology ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Disease Progression ; Polymorphism, Single Nucleotide ; }, abstract = {PURPOSE: To depict an atlas of stage-stratified gut microbiota (GM) signatures and intermediatory metabolites, inflammatory proteins, and immune cell traits, governing the AMD trajectory.<br><br>METHODS: We deployed bidirectional two-sample Mendelian randomization (TSMR) integrating GWAS data of 207 GM taxa from the Dutch Microbiome Project (N = 7,738), and multiple AMD stages/subtypes, including 'Macular degeneration (senile) of retina', 'Early AMD', 'Disease progression to GA/CNV', 'Dry AMD includes GA', and 'Wet AMD', encapsulating the disease trajectory (N > 410,000), complemented by multivariable MR (MVMR) mediation analysis of 1,400 circulating metabolites, 731 immune cell traits, and 91 inflammatory proteins.<br><br>RESULTS: We identified 12/8/5/2/9/8 genetically predicted causal GM taxa of various AMD stages/subtypes as a stage-stratified GM signature across the AMD trajectory, among which g.Ruminococcaceae and s.Ruminococcaceae_bacterium_D16 were the sole shared GM taxa in triple AMD stages, while s.Bacteroides eggerthii, c.Gammaproteobacteria, s.Dorea and s.Ruminococcus_obeum influence dual AMD stages. Bidirectional analysis revealed that f.Streptococcaceae, g.Erysipelotrichaceae_noname, g.Streptococcus, s.Streptococcus_thermophilus, g.Ruminococcaceae_noname, and s.Ruminococcaceae_bacterium_D16 exhibited genetically reciprocal causation with AMD. We also proposed that Firmicutes may exhibit stage-specific duality depending on their constituent members and AMD stages. Several understudied GM from p.Actinobacteria and p.Verrucomicrobia have been implicated as AMD-associated taxa for the first time. Key metabolites, immune cell traits, and inflammatory proteins were established as significant mediators of GM-AMD links.<br><br>CONCLUSIONS: This first phased atlas uncovers GM effects over the AMD course, identifying potential microbial and biochemical targets for intervening in disease development.}, }
@article {pmid41799797, year = {2026}, author = {Addo, EK and Lucci, L and Nilson, J and Pasaye, M and Pappas, C and Spoth, E and Ord, L and Jridi, A and Brintz, BJ and Hageman, GS and Hartnett, ME and Bernstein, PS}, title = {Carotenoid Status and Psychological Impact of Presymptomatic Macular Degeneration Genetic Risk Assessment: The MAGENTA Randomized Trial.}, journal = {Ophthalmology science}, volume = {6}, number = {4}, pages = {101083}, pmid = {41799797}, issn = {2666-9145}, abstract = {PURPOSE: Genetic testing for age-related macular degeneration (AMD) risk reliably offers insight into an individual's susceptibility for future visual loss; however, an American Academy of Ophthalmology expert panel in 2012 discouraged routine AMD genetic risk testing because there was no evidence that such knowledge would alter an individual's clinical course. To address this knowledge gap, we investigated whether disclosure of AMD genetic risk to presymptomatic individuals would encourage healthier lifestyle adoption that could reduce the incidence of AMD later in life.<br><br>DESIGN: The Moran AMD Genetic Testing Assessment (MAGENTA) trial is a single-site, prospective, controlled clinical study (NCT05265624) that randomized 80 presymptomatic subjects in a 3:1 ratio to immediate or 1-year deferred disclosure groups. We stratified participants into high-, intermediate-, and low-risk groups by Mendelian randomization.<br><br>SUBJECTS: We enrolled Whites aged 18 to 64 years with no clinical signs of AMD.<br><br>METHODS: As a biomarker of healthy nutritional status, participants' skin, plasma, and macular carotenoid concentrations were measured using resonance Raman and reflectance spectroscopies, high-performance liquid chromatography, and autofluorescence imaging, respectively. Nutritional and emotional status were assessed with validated surveys.<br><br>MAIN OUTCOME MEASURES: We looked for changes in skin, plasma, and macular carotenoids as biomarkers of healthier lifestyle adoption and for the impact of AMD genetic risk disclosure on participants' psychological well-being.<br><br>RESULTS: Of the 80 participants, 94% had a family history of AMD, and the AMD genetic risk distribution was 36% high, 24% intermediate, and 40% low. We found no statistically significant difference in skin, plasma, and macular carotenoids between study groups at 12 months relative to baseline (P > 0.05 for all comparisons). Participants' interest and compliance were high, as shown by the 95% subject study completion rate, and there was no evidence of worsening stress following AMD genetic risk disclosure to the participants.<br><br>CONCLUSIONS: While AMD genetic risk disclosure did not significantly impact nutritional biomarker levels over 12 months, there were no adverse psychological effects, and the subjects generally felt knowledge of their AMD risk was valuable. Our findings could guide future presymptomatic AMD genetic testing trials with extended biomarker assessments in larger and more diverse populations.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41799798, year = {2026}, author = {Gee, EE and Guymer, RH and Blodi, BA and Holz, FG and Jaffe, GJ and Liakopoulos, S and Sadda, SR and Schmitz-Valckenberg, S and Bjelopera, E and Brown, T and Choong, J and Clifton, B and Hadoux, X and He, Y and Heathcote, J and Jannaud, M and Lentzsch, AM and Mahmoudi, A and Pak, JW and Saßmannshausen, M and Skalak, C and von der Emde, L and Wu, Z}, title = {Geographic Atrophy on Fundus Autofluorescence and Color Fundus Photographs: Association with Deep Visual Sensitivity Losses.}, journal = {Ophthalmology science}, volume = {6}, number = {4}, pages = {101096}, pmid = {41799798}, issn = {2666-9145}, abstract = {PURPOSE: To determine the functional characteristics of color fundus photograph (CFP)- and fundus autofluorescence (FAF)-defined geographic atrophy (GA) lesions by evaluating the prevalence of repeatable deep visual sensitivity defects.<br><br>DESIGN: Reader study.<br><br>PARTICIPANTS: One hundred seventy-one pairs of CFP and FAF images from 60 eyes of 53 individuals.<br><br>METHODS: High-density, targeted microperimetry testing (with Goldmann Size III stimuli) was performed twice per visit in a 3.5&#xb0; (approximately 1000 &#x3bc;m) diameter region of interest with retinal pigment epithelium and outer retinal atrophy on OCT imaging. Twelve readers from 6 established reading centers assessed CFP and FAF images within these regions sampled on microperimetry for GA, and performed annotations where GA was deemed to be present. Geographic atrophy on CFP was defined as a well-demarcated, roughly round or oval region of hypopigmentation, separately with and without requiring increased visibility of the underlying choroidal vessels (referred to as CFP-defined GA1 and GA2, respectively). GA on FAF was defined as a region of definite decreased autofluorescence.<br><br>MAIN OUTCOME MEASURES: Prevalence of a repeatable &#x2264;10 dB defect for CFP- and FAF-defined GA &#x2265;175 &#x3bc;m, and the minimum lesion size showing a &#x2265;90% prevalence of a repeatable &#x2264;10 dB defect (deemed characteristic of regions with a truly nonresponding test location on microperimetry).<br><br>RESULTS: Color fundus photograph-defined GA1 and GA2 and FAF-defined GA &#x2265;175 &#x3bc;m were graded as present in 13%, 31%, and 41% of images, respectively, and 77%, 67%, and 62% lesions, respectively, had a repeatable &#x2264;10 dB defect. Only CFP-defined GA1 &#x2265;625 &#x3bc;m, CFP-defined GA2 &#x2265;650 &#x3bc;m, and FAF-defined &#x2265;675 &#x3bc;m had a &#x2265;90% prevalence of a repeatable &#x2264;10 dB defect.<br><br>CONCLUSIONS: Color fundus photograph and FAF-defined GA lesions &#x2265;175 &#x3bc;m do not show the same functional characteristics as regions with a truly nonresponding test location, and only much larger lesions (approximately &#x2265;650 &#x3bc;m) showed such similar functional characteristics. These findings provide crucial insights when considering CFP- and FAF-defined atrophic endpoints for clinical studies.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41801974, year = {2026}, author = {Pompös, IM and Polenz, D and Kociok, N and Winkler, S and Strauß, O}, title = {Evaluation of risk promoting effects for age-related macular degeneration by estradiol.}, journal = {PloS one}, volume = {21}, number = {3}, pages = {e0340477}, pmid = {41801974}, issn = {1932-6203}, mesh = {Animals ; *Macular Degeneration/etiology/pathology/blood/metabolism ; Female ; *Estradiol/deficiency/blood ; Rats ; Ovariectomy ; Estrogen Receptor beta/metabolism ; Retina/pathology/metabolism ; Disease Models, Animal ; Aging ; Risk Factors ; }, abstract = {Early menopause increases the risk for age-related macular degeneration (AMD), the most common cause of vision loss in industrialized countries. The supplementation with estradiol reduces the risk in these cases and suggesting that estradiol deficiency is a mediator of the risk association. We investigated rat models of estradiol deficiency mimicking either biological ageing (22 months of age) or early menopause by ovariectomy and age of 22 months. Serum analysis of gonadal hormones in both models showed the expected reduction in estradiol levels compared to 6 months old controls but also increases in progesterone, corticosterone and dehydroepiandrosterone sulfate (DHEA-S). Comparing the two estradiol deficiency models, we found no differences except for DHEA-S that were reduced in ovariectomized rats. The hormone status was associated with degenerative changes in the retina with higher activity of mononuclear phagocytes and p16/p21-dependent senescence. Mainly the estrogen receptor beta (ERβ) expressing cells were affected by estradiol deficiency: ganglion cells, cells of the inner nuclear layer (INL) and retinal pigment epithelial cells. An exception are photoreceptors that were ERβ negative, showed stronger degeneration in ovariectomized rats compared to sham treated animals. We conclude that either biological or ovariectomy induced estradiol deficiency might not cause but rather promote mechanisms that lead to AMD. The phenotype depends on a broader spectrum of altered hormones than on estradiol alone. Photoreceptor degeneration and cellular senescence that were ERβ independent in ovariectomized rats suggest non-estradiol effects to increase AMD risk by early menopause.}, }
@article {pmid41803521, year = {2026}, author = {Ahmed, F}, title = {HOG-CNN: Integrating Histogram of Oriented Gradients with Convolutional Neural Networks for Retinal Image Classification.}, journal = {Journal of imaging informatics in medicine}, volume = {}, number = {}, pages = {}, pmid = {41803521}, issn = {2948-2933}, abstract = {The analysis of fundus images is critical for the early detection and diagnosis of retinal diseases such as diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (AMD). Traditional diagnostic workflows, however, often depend on manual interpretation and are both time- and resource-intensive. To address these limitations, we propose an automated and interpretable clinical decision support framework based on a hybrid feature extraction model called HOG-CNN. Our key contribution lies in effectively integrating handcrafted Histogram of Oriented Gradients (HOG) features with representations learned by the pretrained deep convolutional neural network EfficientNetB3. This fusion enables our model to capture both local texture patterns and high-level semantic features from retinal fundus images. We evaluated our model on three public benchmark datasets: APTOS 2019 (for binary and multiclass DR classification), ORIGA (for Glaucoma detection), and IC-AMD (for AMD diagnosis); HOG-CNN demonstrates consistently high performance. It achieves 98.5% accuracy and 99.2 AUC for binary DR classification, and 94.2 AUC for five-class DR classification. On the IC-AMD dataset, it attains 92.8% accuracy, 94.8% precision and 94.5 AUC, outperforming several state-of-the-art models. For Glaucoma detection on ORIGA, our model achieves 83.9% accuracy and 87.2 AUC, showing competitive performance despite dataset limitations. We show, through comprehensive appendix studies, the complementary strength of combining HOG and CNN backbone (EfficientNetB3) features. The model's lightweight and interpretable design makes it particularly suitable for deployment in resource-constrained clinical environments. These results position HOG-CNN as a robust and scalable tool for automated retinal disease screening.}, }
@article {pmid41804429, year = {2026}, author = {Matsuno, T and Tomita, R and Takeuchi, J and Nishiguchi, KM and Yuki, K}, title = {Giant Retinal Pigment Epithelium Tear Secondary to Hypotony After Trabeculectomy for Open-Angle Glaucoma With Preoperative Untreated Choroidal Neovascularization: A Case Report.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e103122}, pmid = {41804429}, issn = {2168-8184}, abstract = {Retinal pigment epithelium (RPE) tears are frequently observed following anti-vascular endothelial growth factor therapy for age-related macular degeneration. While rare, giant RPE tears have also been reported secondary to choroidal detachment (CD) induced by postoperative hypotony after trabeculectomy (TLE). Although mechanical stress on the RPE is considered a common underlying factor in both scenarios, the exact mechanisms remain unclear. This report describes a case of a giant RPE tear originating from the site of a previously untreated choroidal neovascularization (CNV) following TLE. A 65-year-old male underwent TLE for intraocular pressure (IOP) control in his left eye with primary open-angle glaucoma. Preoperative IOP was 39 mmHg, and fundus examination revealed untreated CNV and sub-RPE hemorrhage. The scleral flap sutures were sequentially laser lysed on postoperative days two and four, as the postoperative IOP remained stable between 12 and 14 mmHg. On postoperative day seven, IOP decreased to 4 mmHg, and CD was observed. Following observation, the IOP increased to 7 mmHg on postoperative day 10, revealing a giant RPE tear and serous retinal detachment (SRD). An additional scleral flap suture was performed on the same day, and the IOP subsequently stabilized around 10 mmHg. During follow-up, the SRD spontaneously resolved by postoperative day 41, while the RPE tear persisted. Visual field testing revealed worsening of visual field defects compared to preoperative findings, with defects corresponding to the location of the RPE tear. The rapid IOP reduction following TLE may have induced mechanical stress on a vulnerable RPE region affected by CNV, leading to the RPE tear. A rapid IOP reduction may increase the risk of an RPE tear when vulnerable RPE areas exist due to CNV or other factors; therefore, careful preoperative evaluation for vulnerable RPE regions and cautious perioperative IOP management should be considered.}, }
@article {pmid41805144, year = {2026}, author = {Zhou, B and Mokhashi, N and Skondra, D}, title = {Emerging strategies in drug repurposing for decreasing the risk of age-related macular degeneration.}, journal = {Expert opinion on drug discovery}, volume = {21}, number = {3}, pages = {339-354}, doi = {10.1080/17460441.2026.2635492}, pmid = {41805144}, issn = {1746-045X}, mesh = {Humans ; *Macular Degeneration/prevention &amp; control/physiopathology/drug therapy ; *Drug Repositioning/methods ; Animals ; Hypoglycemic Agents/pharmacology/administration &amp; dosage/adverse effects ; Oxidative Stress/drug effects ; Metformin/pharmacology/administration &amp; dosage ; }, abstract = {INTRODUCTION: Vision loss in older adults is largely driven by age-related macular degeneration (AMD), characterized by progressive central visual field damage and functional decline. While current options for wet and dry AMD are limited and expensive, drug repurposing represents a promising strategy to accelerate the discovery of effective, accessible treatment by leveraging medications with established safety profiles. Notably, anti-diabetic agents including metformin, sulfonylureas, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and insulin have emerged as modulators of the retinal pigment epithelium (RPE) function, photoreceptors, and retinal vascular integrity.<br><br>AREAS COVERED: This review highlights the roles of oxidative stress, inflammation, and complement-mediated immune dysregulation in AMD pathogenesis, alongside preclinical data demonstrating metformin's protective effects via AMP-activated protein kinase (AMPK) activation. Population-based studies and meta-analyses further suggest a modest reduction in AMD risk associated with metformin use in both diabetic and non-diabetic cohorts. Additional pharmacological agents include statins, glyburide, L-DOPA, fluoxetine, dimethyl fumarate, and nutraceuticals such as curcumin, melatonin, and N-acetylcysteine.<br><br>EXPERT OPINION: Early AMD prevention through repurposed therapeutics, guided by AI-driven design and systems biology, may enable personalized care via multimodal risk stratification incorporating genetic, metabolomic, and microbiome data. Rigorous, stratified clinical trials integrating bioinformatics and precision medicine are essential to validate the most effective candidates.}, }
@article {pmid41805146, year = {2026}, author = {Gan, Y and Pu, J and Yang, S and Chen, X and Zhang, X and Su, Y and Li, M and Wen, F}, title = {Novel Quantitative OCTA Biomarkers of Choroidal Neovascularization and Associations With Disease Activity and Etiology.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {3}, pages = {10}, pmid = {41805146}, issn = {2164-2591}, mesh = {Humans ; *Choroidal Neovascularization/diagnostic imaging/etiology/diagnosis ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; Female ; Male ; Aged ; Middle Aged ; Biomarkers ; Fluorescein Angiography/methods ; Aged, 80 and over ; *Wet Macular Degeneration/diagnostic imaging ; }, abstract = {PURPOSE: The purpose of this study was to develop a semi-automated optical coherence tomography angiography (OCTA) framework for quantitative morphological assessment of choroidal neovascularization (CNV) to examine associations between quantitative metrics and CNV etiology, activity, and lesion patterns.<br><br>METHODS: This retrospective study analyzed treatment-na&#xef;ve eyes with neovascular age-related macular degeneration (nAMD), myopic CNV (mCNV), or inflammatory CNV (iCNV). OCTA images were processed with a standardized pipeline combining AngioTool, ImageJ, and custom Python algorithms to extract vascular-network and contour-heterogeneity metrics.<br><br>RESULTS: Sixty&#x2011;six eyes were analyzed (21 with nAMD, 23 with mCNV, and 22 with iCNV). The nAMD lesions were largest and most branched, showing the greatest median vessel area (1.24 mm2), perimeter (8.369 mm), MaxFeret (2.603 mm), MinFeret (1.598 mm), and total vessel length (14.583 mm)-all significantly greater than mCNV (all P < 0.017). The mCNV lesions were compact and regular. The iCNV lesions exhibited pronounced contour irregularity with lowest circularity (0.621) and vertex index (0.843), and highest maximum (0.243 mm) and mean (0.137 mm) depression depths. For activity assessment, a five-parameter model (vessel area, vessel density, total junctions, average depression, and circularity) discriminated active versus inactive CNV with excellent accuracy (area under the curve [AUC] = 0.901).<br><br>CONCLUSIONS: Quantitative OCTA biomarkers distinguish CNV etiologies and activity, providing a noninvasive, objective basis for clinical assessment and individualized treatment planning.<br><br>TRANSLATIONAL RELEVANCE: This study bridges the gap between image processing and clinical practice by validating a quantitative OCTA pipeline sensitive to etiology-specific morphological variations. The resulting multivariate model provides an objective, noninvasive tool for assessing CNV activity. Ultimately, these OCTA biomarkers offer a reproducible method to optimize disease monitoring and guide personalized management of CNV.}, }
@article {pmid41805150, year = {2026}, author = {McLeod, DS and Bhutto, IA and Messinger, JD and Berlin, A and Grebe, R and Bijon, J and Freund, KB and Curcio, CA and Edwards, MM}, title = {Choroidal Vascular Findings in a Case of Multifocal Geographic Atrophy: A Clinicopathologic Correlation.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {19}, pmid = {41805150}, issn = {1552-5783}, mesh = {Humans ; Female ; *Geographic Atrophy/pathology/diagnosis ; *Choroid/blood supply ; Aged, 80 and over ; *Choroidal Neovascularization/pathology/diagnosis/etiology ; Fluorescein Angiography ; Microscopy, Confocal ; Tomography, Optical Coherence ; Retinal Pigment Epithelium/pathology ; Immunohistochemistry ; }, abstract = {PURPOSE: We examined the choroid in both eyes from a donor with multifocal geographic atrophy (GA), enlarged choroidal vessels, and choroidal neovascularization (CNV) secondary to age-related macular degeneration, using histology and immunohistochemistry, and we correlated the findings with multimodal clinical imaging.<br><br>METHODS: A Caucasian woman with bilateral GA was followed clinically for 5 years, until 6 years prior to her death at age 93. To correlate clinical and histologic features, the right eyecup was photographed before dissecting the posterior pole. Choroidal blood vessels were labeled with Ulex europaeus agglutinin-1 (UEA-1) lectin following retinal pigment epithelium removal and imaged by confocal microscopy. Selected regions were embedded and sectioned for histologic staining. The left eye was used for ultrastructure analysis.<br><br>RESULTS: The posterior pole exhibited areas of atrophy surrounded by mottled retinal pigment epithelium overlying calcified drusen. Confocal imaging of the UEA-1 lectin-labeled choroidal flatmounts showed limited visualization of the submacular vasculature, consistent with masking by basal laminar and lipid-rich deposits seen in histologic sections. In well-labeled regions of the posterior pole, the choriocapillaris was attenuated and widely separated by markedly thickened, hyalinized intercapillary pillars. Venules and veins appeared dilated, and arteries exhibited arteriosclerotic changes. A choroidal neovascular complex was observed superior to the optic nerve head near the atrophic border; the adjacent choriocapillaris was attenuated.<br><br>CONCLUSIONS: In this single case of multifocal GA, choroidal thickening and large-caliber outer choroidal vessels coexisted with marked choriocapillaris degeneration and adjacent neovascularization. These observations suggest that structural choroidal enlargement does not preclude choriocapillaris failure and may be associated with ischemic and neovascular phenotypes.}, }
@article {pmid41805864, year = {2026}, author = {Hüsken, D and Webster, E and Künzel, SE and Knecht, V and Strauß, O and Joussen, AM and Zeitz, O}, title = {[Plasma proteomics in age-related macular degeneration].}, journal = {Die Ophthalmologie}, volume = {123}, number = {3}, pages = {184-191}, pmid = {41805864}, issn = {2731-7218}, mesh = {Humans ; *Proteomics/methods ; Biomarkers/blood ; *Proteome/analysis/metabolism ; *Macular Degeneration/blood ; *Blood Proteins/metabolism/analysis ; Aged ; Male ; Female ; }, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) shows a heterogeneous treatment response to anti-vascular endothelial growth factor (VEGF), but the underlying mechanisms remain poorly understood. Classical approaches focus on single biomarkers, whereas the multifactorial and systemic nature of the disease has received less attention.<br><br>METHOD: In the BIOMAC cohort blood proteomes of patients with nAMD were systematically analyzed. Mass spectrometry, dimensionality reduction and pattern-based classifiers were applied to capture systemic proteomic signatures and link them to clinical phenotypes. As a supplement metabolomic analyses were carried out including a&#xa0;focus on xenobiotics.<br><br>RESULTS: The findings demonstrate a&#xa0;distinct yet complex influence of systemic signals: a&#xa0;subset of patients was characterized by oxidative stress and respiratory patterns independent of the ocular morphology. Individual proteins such as aldolase C were associated with disease control but lacked predictive power when considered alone. Only high-dimensional patterns of many proteins enabled a significant, although not yet perfect separation between effectively controlled and chronically active courses of choroidal neovascularization (CNV). Metabolomic profiling further identified unexpected candidates, such as the sweetener saccharin, which consistently showed protective effects in both patients and experimental models.<br><br>CONCLUSION: Systemic plasma proteome and metabolome signatures reflect the clinical phenotype of nAMD. Modern statistical methods supported by artificial intelligence are the key to unravelling these complex datasets. Although no valid single biomarker has yet emerged, the pattern-based approach provides novel translational insights and can potentially broaden the therapeutic target space for nAMD.}, }
@article {pmid41806579, year = {2026}, author = {Song, Y and Xu, T and Zhang, H and Hu, S and Wei, S and Cao, M and Wang, H and Yin, D}, title = {Emerging organophosphate flame retardant CDP causes neovascular macular degeneration-like alterations of outer blood-retinal barrier via paracrine VEGFA signaling.}, journal = {Journal of hazardous materials}, volume = {507}, number = {}, pages = {141669}, doi = {10.1016/j.jhazmat.2026.141669}, pmid = {41806579}, issn = {1873-3336}, abstract = {Visual impairment is an urgent public health concern. Increasing epidemiological research has demonstrated a strong correlation between environmental contaminant exposure and retinal diseases, but the underlying mechanism remains unclear. The disruption of the outer blood-retinal barrier (oBRB) is closely implicated in the pathogenesis of multiple vision-threatening disorders. Given its critical physiological role and anatomical position, we systematically investigated the effects of cresyl diphenyl phosphate (CDP, one emerging organophosphate flame retardant) on the oBRB, applying both zebrafish larvae and an in vitro human oBRB model consisting of ARPE-19 and HUVECs. The downregulation of tight junction expression and retinal neovascularization were observed in the zebrafish larvae under CDP treatment. The establishment of the oBRB model further discovered that CDP exposure caused barrier dysfunction and increased VEGFA secretion of ARPE-19. Through the paracrine signaling, VEGFA promoted the angiogenesis of HUVECs, eliciting pathological feature similar to neovascular macular degeneration. This study was the first to reveal an association between eOPFR exposure and retinal-related diseases, highlighting the significance of paracrine signaling in the pathological process.}, }
@article {pmid41807615, year = {2026}, author = {Talks, J and de Salvo, G and Patel, PJ and de Silva, SR and Gale, RP and McKibbin, M and Varma, D and Pearce, I and Peto, T and Reynolds, R and Bailey, C and Downey, L and Kiire, CA and Sivaprasad, S and Downey, AK and James, N and Chi, GC and Dodds, M and Dayal, P}, title = {Real-world treatment patterns and visual outcomes of faricimab in patients with neovascular age-related macular degeneration in the UK at 12 months: the FARWIDE-nAMD study.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41807615}, issn = {1476-5454}, abstract = {BACKGROUND: The Faricimab Real-World Evidence (FARWIDE) studies are evaluating real-world outcomes of eyes with neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DMO) treated with faricimab in the UK. Here, we present results from FARWIDE-nAMD for eyes with 12 months of follow-up after faricimab initiation.<br><br>METHODS: nAMD patient-eyes that received &#x2265;1 faricimab injection after May 2022 at one of 35 participating UK National Health Service retinal clinics with &#x2265;12 months of follow-up after faricimab initiation as of July 2024 were included. Treatment-na&#xef;ve (TN) eyes had no prior anti-VEGF treatment. Previously treated (PT) eyes switched from an anti-VEGF to faricimab. Baseline characteristics, VA, and injection frequency were assessed. Intraocular inflammation (IOI) and presumed infectious endophthalmitis (PIE) rates were pooled for nAMD and DMO eyes with any follow-up duration on faricimab. Analyses are descriptive.<br><br>RESULTS: 5854 nAMD patients (6991 eyes; 26.5% TN, 73.5% PT) were included. 83.3% of PT eyes switched from aflibercept 2.0&#x2009;mg. TN eyes received a mean (SD) of 4.7 (0.7) faricimab injections in months 1-6 and 2.2 (1.1) injections in months 7-12. PT eyes received 4.5 (1.0) injections in months 1-6 and 3.0 (1.2) in months 7-12. In TN eyes, mean (SD) VA increased from 56.4 (16.3) Early Treatment Diabetic Retinopathy Study letters at baseline to 60.1 (19.4) at 12 months (mean [SD] change 3.6 [14.7] letters). PT eyes had stable VA. IOI and PIE rates were consistent with faricimab phase 3 trials.<br><br>CONCLUSIONS: These 1-year data support real-world faricimab effectiveness, durability, and safety in nAMD.}, }
@article {pmid41807617, year = {2026}, author = {Ibrahim, FN and Fan, KR and Chan, HH and Ong, C and Sun, C and Sim, S and Tan, AC and Tan, TE and Teo, KY and Mathur, R and Chan, CM and Cheung, CMG and Fenner, BJ}, title = {Clinical characteristics and progression rates of geographic atrophy in an Asian population from Singapore.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41807617}, issn = {1476-5454}, abstract = {PURPOSE: To characterise geographic atrophy (GA) associated with age-related macular degeneration (AMD) and its progression rates in an Asian cohort.<br><br>METHODS: Retrospective study of 170 eyes characterising GA lesions using near infrared (NIR) and spectral domain optical coherence tomography (SD-OCT).<br><br>RESULTS: The majority of patients were Chinese (88.2%), followed by Malay (4.7%), Indian (3.5%) and Others (3.5%). Mean age at baseline was 78.4 (SD 8.2) years, with 42.9% males. Mean baseline GA area was 4.25mm[2] (SD 4.25), best-corrected visual acuity 0.71logMAR units (SD 0.52) and subfoveal choroidal thickness (SFCT) 168.3&#x2009; &#x3bc;m (SD 77.4). Multifocal GA was present in 97 (57.1%) of eyes, foveal involvement in 114 (67%) and bilateral in 42 (24.7%). Macular neovascularisation was present in the fellow eye of 48 (28.2%) patients. Mean follow-up was 4.12 (SD 2.95) years, with a mean GA progression rate of 0.98 (SD 1.26)mm[2]/yr (SQRT 0.22&#x2009;mm/yr SQRT, SD 0.21). Bilateral disease (p&#x2009;=&#x2009;0.005), reticular pseudodrusen (p&#x2009;=&#x2009;0.02), larger baseline GA area (p&#x2009;<&#x2009;0.001) and multifocal disease (p&#x2009;=&#x2009;0.01) were independently associated with greater odds of rapid GA progression.<br><br>CONCLUSION: We evaluated AMD-associated GA in Asian patients, predominantly of Chinese descent, using NIR and SD-OCT. These findings are valuable to identify high-risk patients and guide future GA therapies in Asian populations.}, }
@article {pmid41807973, year = {2026}, author = {Mi, Y and Zong, J and Wang, S and Zhu, Q and Lin, S and Zheng, X and Hong, Y and Zhou, J and Ye, L}, title = {Accelerometer-derived "weekend warrior" physical activity pattern and risk of age-related eye diseases: a prospective cohort study.}, journal = {Eye and vision (London, England)}, volume = {13}, number = {1}, pages = {}, pmid = {41807973}, issn = {2326-0254}, support = {2023YFC3604104//Key Technologies Research and Development Program/ ; 2023-PT320-04//Special Funds for the Basic Research and Development Program in the Central Non-profit Research Institutesof China/ ; }, abstract = {BACKGROUND: International guidelines recommend at least 150 min of weekly moderate-to-vigorous physical activity (MVPA), but whether concentrated versus distributed activity patterns differ in their associations with age-related eye diseases remains unclear.<br><br>METHODS: This prospective cohort study included 86,271 UK Biobank participants free of age-related eye diseases at baseline. Physical activity was assessed using wrist-mounted triaxial accelerometers (Axivity AX3) over seven consecutive days. Two MVPA thresholds were examined:&#x2009;&#x2265;&#x2009;150&#xa0;min/week (primary) and&#x2009;&#x2265;&#x2009;300&#xa0;min/week (secondary). Participants were categorized as: inactive (below threshold), weekend warriors (WW; meeting threshold with&#x2009;&#x2265;&#x2009;50% MVPA concentrated within 1-2&#xa0;days), or regularly active (meeting threshold without WW criteria). Cox proportional hazards regression models were used to assess associations over a median follow-up of 7.9&#xa0;years.<br><br>RESULTS: At the&#x2009;&#x2265;&#x2009;150&#xa0;min/week threshold, both WW (hazard ratio [HR]&#x2009;=&#x2009;0.89, 95% confidence interval [CI]: 0.84-0.94, P&#x2009;<&#x2009;0.001) and regularly active patterns (HR&#x2009;=&#x2009;0.93, 95% CI: 0.87-0.99, P&#x2009;=&#x2009;0.028) were associated with a reduced risk of cataract compared to inactivity. The WW pattern was also associated with a reduced risk of diabetic retinopathy (DR, HR&#xa0;= 0.74, 95% CI: 0.55-0.99, P&#x2009;=&#x2009;0.043) and age-related macular degeneration (AMD, HR&#x2009;=&#x2009;0.85, 95% CI: 0.75-0.97, P&#x2009;=&#x2009;0.016). Direct comparisons between the WW and regularly active patterns showed no significant differences for these conditions (all P&#x2009;>&#x2009;0.05), except for a nominal difference in glaucoma (P&#x2009;=&#x2009;0.036). At the&#x2009;&#x2265;&#x2009;300&#xa0;min/week threshold, only the WW pattern remained significantly associated with reduced risk of cataract (HR&#x2009;=&#x2009;0.91, 95% CI: 0.86-0.97, P&#x2009;=&#x2009;0.002) and glaucoma (HR&#x2009;=&#x2009;0.86, 95% CI: 0.75-0.97, P&#x2009;=&#x2009;0.019).<br><br>CONCLUSION: Both the WW and regularly active patterns demonstrate protective associations with age-related eye diseases compared to inactivity, with no statistically significant differences between the two active groups for most outcomes. These findings suggest that the WW approach is a viable and flexible alternative for individuals who find it difficult to maintain daily physical activity.}, }
@article {pmid41808823, year = {2026}, author = {Uppal, M and Hosseini, A and Bilal, K and Tan, N and Ai, Z and Khan, W and Samad, I and Gill, G and Yoo, HS and Chakravarthy, H and Kuo, CH and Xi, J and Granville, DJ and Matsubara, JA}, title = {Granzyme B from mast cells contributes to choroidal neovascularization in a model of wet age-related macular degeneration.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1710965}, pmid = {41808823}, issn = {1664-3224}, mesh = {*Mast Cells/metabolism/immunology ; Animals ; *Granzymes/metabolism/genetics ; *Choroidal Neovascularization/pathology/metabolism/etiology ; Humans ; Mice ; Mice, Knockout ; Disease Models, Animal ; *Wet Macular Degeneration/pathology/metabolism/etiology ; Cell Degranulation ; Choroid/pathology/metabolism ; Mice, Inbred C57BL ; Male ; Female ; }, abstract = {PURPOSE: Wet age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV), yet current anti-VEGF therapies are ineffective in many patients. This study investigates the role of mast cell-derived granzyme B (GzmB), a serine protease responsible for the abnormal cleavage of the extracellular matrix in the outer retina.<br><br>METHODS: Human and mouse choroidal tissues were analyzed for mast cell distribution, GzmB expression, and age-related changes. An ex vivo choroidal sprouting assay (CSA) was used to evaluate the effects of mast cell degranulation and/or stabilization, and the pharmacologic inhibition of GzmB, using tissues from wild-type and GzmB knockout (KO) mice.<br><br>RESULTS: Aging increased mast cell accumulation and degranulation in both the human and mouse choroid, leading to elevated GzmB. GzmB KO mice exhibited reduced choroidal sprouting, and exogenous GzmB promoted angiogenesis. Both GzmB inhibition and mast cell stabilization suppressed angiogenic events, confirming GzmB's role in mast cell-driven angiogenesis.<br><br>CONCLUSIONS: GzmB is a key mediator of mast cell-induced CNV. Targeting GzmB, either directly or through mast cell stabilization, offers a promising strategy for reducing angiogenesis in a condition such as wet AMD.}, }
@article {pmid41809655, year = {2026}, author = {Zhou, B and Parekh, Z and Phung, C and Rodriguez, SH and Skondra, D}, title = {The gut-retina axis in age-related macular degeneration: immune crosstalk and metabolite production.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {251}, number = {}, pages = {10847}, pmid = {41809655}, issn = {1535-3699}, mesh = {Humans ; *Macular Degeneration/immunology/microbiology/metabolism ; *Gastrointestinal Microbiome/immunology/physiology ; Animals ; Dysbiosis/immunology ; *Retina/immunology/metabolism/pathology ; }, abstract = {Current therapies slow down advanced features but do not halt or reverse degeneration and neovascularization in dry and wet age-related macular degeneration (AMD). Recent research implicates the gastrointestinal microbiome as a potential critical modulator in AMD pathogenesis through the gut-retina axis. Dysbiosis, characterized by imbalanced microbial diversity, composition and function, can exacerbate systemic and retinal inflammation through microglial priming, inflammasome activation, and secretion of pro-angiogenic cytokines (IL-6, IL-1β, TNF-α, VEGF). Additionally, microbiome-derived metabolites such as short-chain fatty acids and bile acids may exert modulatory roles in host immunity and homeostasis. Their depletion in conjunction with enrichment of specific microbial taxa have been linked to progression of advanced AMD. Together, these complex systems of immune crosstalk in relation to dysbiosis highlight the gut-retina axis as a promising therapeutic target. Dietary modifications, particularly Mediterranean and high-fiber diets, enhance production of protective metabolites and are associated with decreased AMD progression risk compared to Western dietary patterns. Experimental strategies such as fecal microbiota transplantation in animal models and drug repurposing strategies show promise in modulating disease severity. This review synthesizes current mechanistic insights into microbial-immune crosstalk in AMD, emphasizing the interplay of dysbiosis, immune activation, and metabolite signaling.}, }
@article {pmid41810055, year = {2026}, author = {El Mollayess, G and Jaroudi, M and Tlaiss, Y and Itaoui, R and Abiad, B}, title = {Surgical management of acute choroidal neovascularization related submacular hemorrhage: Three case reports.}, journal = {World journal of clinical cases}, volume = {14}, number = {6}, pages = {118545}, pmid = {41810055}, issn = {2307-8960}, abstract = {BACKGROUND: Acute submacular hemorrhage (SMH) secondary to choroidal neovascularization (CNV), most commonly in neovascular age-related macular degeneration, is a vision-threatening emergency. Thick, fovea-involving SMH can cause rapid photoreceptor injury, and timely intervention aimed at clot lysis and displacement, while continuing CNV suppression with anti-vascular endothelial growth factor (anti-VEGF) therapy, may improve anatomic outcomes.<br><br>CASE SUMMARY: We report a retrospective case series of three eyes with acute, fovea-involving CNV-related SMH treated with pars plana vitrectomy (PPV), subretinal tissue plasminogen activator (tPA), and expansile gas tamponade, with intravitreal anti-VEGF administered at the end of the procedure and continued postoperatively. Two cases had early intraocular pressure-related events (transient hypotony in one patient and transient ocular hypertension in another) requiring close postoperative monitoring and medical management. Follow-up color fundus photography and optical coherence tomography documented postoperative evolution of the hemorrhage compared with baseline, with ongoing anti-VEGF therapy planned to control the underlying CNV.<br><br>CONCLUSION: PPV with subretinal tPA and gas tamponade is a practical surgical strategy for acute, thick, fovea-involving SMH secondary to CNV, particularly when rapid displacement is desired. Careful documentation of operative parameters, strict postoperative monitoring for pressure-related complications, and continued anti-VEGF therapy are essential components of care.}, }
@article {pmid41811401, year = {2026}, author = {Aslam, TM and Ziemssen, F and Loewenstein, A and Nair, R and Thurston, M and Hawkins, A and Daly, A}, title = {Post-Visual Diagnosis Distress: The Weight of Threatened Sight.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41811401}, issn = {2193-8245}, abstract = {Receiving a diagnosis of a vision-threatening eye condition is a psychologically salient event for many patients. Across ophthalmology, fear, uncertainty, and emotional distress are commonly observed at the time of diagnosis, often before substantial functional vision loss occurs. Although depression and anxiety are well documented in chronic eye disease, diagnosis-linked distress remains inconsistently recognised and is rarely addressed systematically within routine ophthalmic care. This article introduces post-visual diagnosis distress (PVDD) as a descriptive, nondiagnostic framework to characterise the predictable, loss-related emotional responses that may arise following the diagnosis of a vision-threatening or irreversible eye condition. PVDD is not proposed as a psychiatric disorder, but as a clinically meaningful construct that helps legitimise patient experience, supports empathetic communication, and facilitates timely recognition and appropriate signposting when distress is significant. Drawing on evidence from age-related macular degeneration, glaucoma, and other chronic eye diseases, and informed by multidisciplinary perspectives spanning ophthalmology, psychiatry, counselling, patient advocacy, and public health, the article argues that recognising PVDD may improve patient engagement, quality of life, and psychological outcomes.}, }
@article {pmid41814099, year = {2026}, author = {Di Criscio, A and Rosso, P and Fico, E and Iannetta, D and Marenco, M and Lambiase, A and Tirassa, P}, title = {VEGF and Neurotrophins Interaction in the Retinal Neurovascular Unit Homeostasis: A Target for Ocular Disease Treatment and Management.}, journal = {Pharmaceutical research}, volume = {}, number = {}, pages = {}, pmid = {41814099}, issn = {1573-904X}, abstract = {Emerging evidence underscores the central role of the retinal neurovascular unit (RNVU) in the pathogenesis of major retinal disorders, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Traditionally considered as primarily vascular diseases, these conditions are now increasingly recognized to involve early neurodegenerative processes that may precede vascular dysfunction. Although anti-VEGF therapies have revolutionized the treatment of neovascular retinal diseases, long-term VEGF inhibition has been associated with adverse effects, including retinal atrophy and diminished neuroprotection, underscoring the need for more targeted strategies. Recent studies have highlighted the differential roles of VEGF-A splice isoforms, particularly the pro-angiogenic VEGF-Axxxa and the anti-angiogenic VEGF-Axxxb, in maintaining RNVU homeostasis and contributing to disease progression. In parallel, neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have demonstrated the ability to exert neuroprotective, anti-inflammatory, and vasomodulatory effects, partly through modulation of VEGF-A signaling. Notably, we have recently demonstrated that NGF modulates VEGF-A isoform expression and VEGFR-2 levels in diabetic retinas, further supporting the hypothesis of a functional cross-talk between neurotrophins and angiogenic pathways. Based on this evidence, a new model is proposed, in which NGF and BDNF interact bidirectionally with VEGF-A to preserve RNVU integrity. This integrated therapeutic perspective, combining neurotrophic support with selective modulation of VEGF-A isoforms, may enhance treatment efficacy, reduce long-term side effects, and minimize the burden of care in chronic retinal neurodegenerative diseases.}, }
@article {pmid41814222, year = {2026}, author = {Aune, D and Jayedi, A and Kazemi, A and Soltani, S and Rezaei, F and Leitzmann, MF}, title = {Physical activity and the risk of cataract and age-related macular degeneration: a systematic review and meta-analysis of cohort studies.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04721-z}, pmid = {41814222}, issn = {1471-2415}, }
@article {pmid41814235, year = {2026}, author = {Han, HY and Park, SM and Lee, JH and Kim, CG and Kim, JH}, title = {Twelve-month lesion reactivation after initial loading injections of faricimab in neovascular AMD: a comparison between three and four loading injections.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04707-x}, pmid = {41814235}, issn = {1471-2415}, }
@article {pmid41814654, year = {2026}, author = {Andres-Mateos, E and Kozlowski, C and Zhang, H and Fajardo, D and Xu, E and Enamorado, IN and Calabro, KR and Rayaprolu, S and Havlik, LP and Handy, TE and Plummer, CE and Stevenson, V and Rind, H and Leahy, M and Boyd, RF and Coleman, KE and Boye, SL and Boye, SE}, title = {Laterally spreading AAV.SPR enables safe and efficient RS1 delivery to the macula after peripheral subretinal injection.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2026.03.014}, pmid = {41814654}, issn = {1525-0024}, abstract = {Mutations in RS1 are associated with X-linked retinoschisis (XLRS), a common cause of juvenile macular degeneration in males. Schisis cavities in the central retina of these patients have hampered submacular delivery with conventional adeno-associated viruses (AAVs). Clinical trials employing intravitreally injected AAVs showed a lack of efficacy and inflammation. Here, we demonstrate, in non-human primate (NHP) retina, that AAV.SPR, a laterally spreading capsid, transduced photoreceptors in the macula/fovea without the need for central retinal detachment, enabling transgene expression multiple millimeters beyond the subretinal injection (SRI) bleb margins. Peripheral SRI of AAV.SPR-hGRK1-RS1 resulted in robust and properly localized RS1 expression in NHP fovea. Despite being a secreted protein, biodistribution of RS1 remains confined to the area of AAV-RS1 transduction. Having established feasibility for the approach, we performed preclinical proof-of-concept, safety, and efficacy studies in support of "ATSN-201" (NCT05878860). In RS1KO mice, a "hybrid" efficacy/safety study demonstrated dose-dependent improvements in retinal function and structure and proper localization of RS1 following treatment with ATSN-201. A good laboratory practice (GLP) toxicology study in NHPs established safety at the highest dose evaluated. The enhanced transduction and lateral spreading ability of AAV.SPR make it an attractive option for treating inherited retinal diseases including, but not limited to, XLRS.}, }
@article {pmid41815438, year = {2026}, author = {Spooner, KL and Fraser-Bell, S and Fu, DJ and Faes, L and Romano, F and Cozzi, M and Chang, AA and Sivaprasad, S}, title = {Imaging and functional correlates of fibrosis in neovascular age-related macular degeneration: a systematic review.}, journal = {Frontiers in ophthalmology}, volume = {6}, number = {}, pages = {1786309}, pmid = {41815438}, issn = {2674-0826}, abstract = {BACKGROUND: Despite intravitreal anti-vascular endothelial growth factor (VEGF) therapy being the standard of care for neovascular age-related macular degeneration (nAMD), long-term visual decline remains common, with subretinal fibrosis representing a major cause of irreversible vision loss. Objective: To systematically evaluate how imaging-defined fibrosis in nAMD is defined and quantified, its incidence under anti-VEGF therapy, associated baseline associations, and its impact on visual outcomes.<br><br>METHODS: We systematically searched MEDLINE, Embase, CENTRAL, and Scopus through September 2025 for studies reporting imaging-defined fibrosis in anti-VEGF-treated nAMD. Eligible studies included randomized controlled trial secondary analyses, prospective and retrospective cohorts, and registries. Two reviewers independently extracted data on fibrosis definitions, imaging modalities, associations, and functional outcomes. Random-effects meta-analyses pooled the best-corrected visual acuity (BCVA) difference (ETDRS letters) and the odds ratio for incident fibrosis. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool, and the certainty of evidence was evaluated using the GRADE approach.<br><br>RESULTS: Fifty-eight studies were included (12 randomized trial secondary analyses, 18 prospective studies, and 28 retrospective studies). Across studies, subretinal fibrosis developed in approximately 10-15% of eyes within 2 years and 40-50% by 5 years of anti-VEGF therapy, with a lower incidence under fixed or treat-and-extend regimens compared with pro re nata dosing. Eyes with fibrosis had consistently worse visual outcomes (pooled BCVA difference -29 ETDRS letters; 95% CI -47 to -12). Key associations included type 2 macular neovascularisation (OR 5.7), subretinal hyperreflective material (OR 2.7), intraretinal fluid (OR 3.6), and large haemorrhage (OR 2.3), while subretinal fluid appeared protective (OR 0.6). Definitions and quantification approaches varied widely across imaging modalities.<br><br>CONCLUSIONS: Fibrosis remains a frequent and vision-limiting sequela of treated nAMD, with substantial heterogeneity in imaging definitions and grading methods limiting cross-study comparability. Standardised OCT-anchored definitions, reproducible quantitative measures, and functional endpoints beyond BCVA are needed to advance anti-fibrotic therapeutic development and improve long-term visual outcomes.<br><br>https://www.crd.york.ac.uk/prospero/, identifier CRD420231132016.}, }
@article {pmid41817413, year = {2026}, author = {Shen, Y and Yin, W and Xiao, X and Lu, Y and Feng, Y and Yang, P}, title = {Cigarette Smoking and Eye Diseases: A Comprehensive Review.}, journal = {Ocular immunology and inflammation}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/09273948.2026.2633446}, pmid = {41817413}, issn = {1744-5078}, abstract = {PURPOSE: Cigarette smoking remains a major global public health challenge, with the eye being particularly vulnerable due to its direct exposure to environmental insults. This review aims to synthesize epidemiological and mechanistic evidence linking traditional combustible cigarette smoking to a broad spectrum of ocular diseases.<br><br>METHODS: A comprehensive literature search was conducted to identify studies examining the association between smoking and various ocular conditions, with a focus on epidemiological data and underlying pathological mechanisms.<br><br>RESULTS: Smoking is established as the strongest modifiable risk factor for age-related macular degeneration and is associated with a 10.8-fold increased risk of cataract development. It strongly predicts retinopathy onset after 9 years of diabetes duration. The reviewed evidence links diverse ocular diseases-from common conditions like dry eye and cataracts to less frequently discussed associations such as strabismus and amblyopia-to a unified set of pathological mechanisms centered on cigarette smoke-induced oxidative stress, chronic inflammation, neovascularization, and immune imbalance.<br><br>CONCLUSIONS: This review provides a comprehensive disease-to-mechanism panorama of smoking-related ocular damage. The findings underscore the critical importance of smoking cessation as a primary preventive strategy to mitigate the burden of avoidable vision loss.}, }
@article {pmid41818339, year = {2026}, author = {Guo, G and Wang, R and Zhang, S and Zhang, Y and Li, L and Liu, M and Yin, L and Wei, C and Gong, Y and Jiao, L and Li, D and Zhou, J and Liu, M and Ran, J}, title = {Preserving the UFMylation-cilium axis mitigates blue light-induced retinal degeneration.}, journal = {Journal of molecular cell biology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jmcb/mjag007}, pmid = {41818339}, issn = {1759-4685}, abstract = {Blue light damage (BLD) is a complex process implicated in a variety of ocular diseases, including age-related macular degeneration and dry eye diseases. However, the molecular mechanisms underlying the BLD process remain largely unknown. In this study, using a mouse model, we identify photoreceptor cilium disruption as a key event in BLD and show that the UFMylation of kinesin family member 11 (KIF11) is decreased under BLD conditions. We further reveal that ubiquitin-fold modifier 1-specific ligase 1 (UFL1), the sole ligase for UFMylation, localizes to the basal body and is required for maintaining photoreceptor cilia. Strikingly, exposure to blue light disrupts the basal body localization of UFL1, leading to ciliary defects and subsequent photoreceptor dysfunction. Ufl1 knockout mice exhibit similar ciliary donlefects and retinal impairments. Importantly, intravitreal injection of agents that enhance UFMylation or ciliogenesis can mitigate the pathological changes induced by blue light exposure. These findings establish that UFL1-mediated ciliary integrity contributes to retinal deficits associated with BLD and demonstrate that targeting the UFMylation-cilium axis represents a promising therapeutic strategy for BLD-associated retinal diseases.}, }
@article {pmid41818422, year = {2026}, author = {Lin, CC and Cheng, CK and Peng, PH and Cheng, SF}, title = {Real world practice of Artificial intelligence Diagnostic System for Diabetic Retinopathy in Taiwan.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004826}, pmid = {41818422}, issn = {1539-2864}, abstract = {PURPOSE: We evaluated the alterations of applying artificial intelligence (AI) diagnostic system for diabetic retinopathy (DR) screening in real-world practice.<br><br>METHODS: This retrospective study included 11,713 diabetic patients from the government-led Diabetes Shared Care Network. The AI system Verisee was integrated into the clinical workflow to identify referable diabetic retinopathy (RDR). Its performance was compared with ophthalmologist grading at the patient level using sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Subgroup analysis was performed by age and gender, with additional referral diseases identified by ophthalmologists.<br><br>RESULTS: Verisee achieved a sensitivity of 0.88, specificity of 0.86, accuracy of 0.86, PPV of 0.58, NPV of 0.97, and AUC of 0.87 in detecting RDR. Performance declined with increasing age, whereas sex distribution remained consistent across age groups. The AI system identified a higher proportion of RDR than ophthalmologists (27.45% vs. 18.15%). In addition to 1,818 patients with RDR, ophthalmologists identified other referral-warranted ocular conditions in 4.5% of cases. The AI system referred age-related macular degeneration (grades 2-4), whereas referral decisions for macular hole and macular edema (grades 1-2) varied; however, glaucoma (grades 0-1) identified by clinicians was not consistently referred.<br><br>CONCLUSION: Verisee demonstrated high accuracy in detecting RDR but exhibited reduced performance in older patients. It had a higher referral rate than ophthalmologists yet missed certain conditions such as glaucoma. Despite effectiveness in DR screening, further refinement is required to support broader ophthalmic disease detection.}, }
@article {pmid41818449, year = {2026}, author = {Maltsev, DS and Kulikov, AN and Kalinicheva, YA}, title = {Possible Association Between Retinal Arterial Occlusions and Subretinal Drusenoid Deposits: A Missing Link.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {57}, number = {3}, pages = {168-173}, doi = {10.3928/23258160-20251202-01}, pmid = {41818449}, issn = {2325-8179}, mesh = {Humans ; Female ; Male ; Tomography, Optical Coherence ; *Retinal Drusen/diagnosis/physiopathology/etiology ; Aged ; Fluorescein Angiography ; *Choroid/blood supply ; *Retinal Artery Occlusion/diagnosis/physiopathology/complications ; Middle Aged ; Visual Acuity ; Aged, 80 and over ; Microcirculation/physiology ; }, abstract = {BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the association between retinal artery occlusion (RAO), subretinal drusenoid deposits (SDD), and choroidal circulation.<br><br>PATIENTS AND METHODS: Patients with RAO and healthy age-matched volunteers were included in this study. The presence of SDD, choriocapillaris perfusion area, and subfoveal choroidal thickness were analyzed using optical coherence tomography (OCT) and OCT angiography.<br><br>RESULTS: In total, 25 patients with RAO (14 women and 11 men, 71.5 &#xb1; 8.9 years) and 19 healthy individuals (10 women and 9 men, 69.0 &#xb1; 5.2 years) were included. SDD were found in seven RAO patients (28.0%), among whom four (18.2%) had no age-related macular degeneration. Patients with RAO had a statistically significantly lower choriocapillaris perfusion area and subfoveal choroidal thickness than healthy controls (P < .05).<br><br>CONCLUSION: RAO may have an association with the presence of SDD that agrees with common systemic risk factors and changes of posterior eye segment microcirculation for both conditions.}, }
@article {pmid41818453, year = {2026}, author = {Prenner, S and Fine, HF and Do, DV}, title = {Photobiomodulation for Dry Age-related Macular Degeneration.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {57}, number = {3}, pages = {146-148}, doi = {10.3928/23258160-20251125-02}, pmid = {41818453}, issn = {2325-8179}, }
@article {pmid41819515, year = {2026}, author = {Abboud, I and Fam, A and Almobayed, A and Guillaume, GI and ElSheikh, RH and Lee, RK and Elhusseiny, AM}, title = {Association Between Pseudoexfoliation Glaucoma and Central Serous Chorioretinopathy.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.03.009}, pmid = {41819515}, issn = {1879-1891}, abstract = {PURPOSE: To evaluate whether pseudoexfoliation glaucoma (PXG) is associated with an increased hazard of developing central serous chorioretinopathy (CSCR) compared with primary open-angle glaucoma (POAG).<br><br>DESIGN: Retrospective cohort study using a multicenter, real-world electronic health record database.<br><br>SUBJECTS: Adults aged &#x2265;18 years diagnosed with PXG (study group) or POAG (control group).<br><br>METHODS: We obtained deidentified patient data from the TriNetX U.S. Collaborative Network. Patients with a history of age-related macular degeneration (AMD) or prior anti-vascular endothelial growth factor (anti-VEGF) therapy were excluded. We performed multivariable Cox proportional hazards models to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), adjusting for baseline demographics; ocular and systemic comorbidities; psychiatric conditions; medication exposures (including corticosteroids); and prior ocular surgeries.<br><br>MAIN OUTCOME MEASURES: The primary outcome was the development of CSCR within 1- and 5-year follow-up periods following the glaucoma diagnoses.<br><br>RESULTS: A total of 10,347 patients with PXG and 205,065 with POAG were included. In the Cox proportional hazards model, PXG was significantly associated with a higher hazard of developing CSCR compared with POAG. The aHR for CSCR was 1.807 (95% CI, 1.041-3.136; p&#x202f;=&#x202f;0.036) at the 1-year follow-up and 1.631 (95% CI, 1.014-2.622; p&#x202f;=&#x202f;0.044) at 5 years.<br><br>CONCLUSIONS: PXG is associated with an increased hazard of developing CSCR compared with POAG. These findings suggest that PXG may be associated with an increased susceptibility to posterior segment vascular pathology. Prospective studies incorporating longitudinal imaging are warranted to further elucidate shared choroidal mechanisms underlying this association.}, }
@article {pmid41821033, year = {2026}, author = {Felfeli, T and Lane, NM and Mandelcorn, ED}, title = {Guiding syringe selection for intravitreal injections: injectability and stability analysis of compounded pegcetacoplan (SYFOVRE) and the broader implications for high-viscosity ophthalmic therapies.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00832-3}, pmid = {41821033}, issn = {2056-9920}, }
@article {pmid41822409, year = {2026}, author = {Klufas, MA and Regillo, CD and Mandava, NK and Miller, EG}, title = {Evolution of Anti-Vascular Endothelial Growth Factor Clinical Trial Design for Treating Neovascular Age-Related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261427831}, pmid = {41822409}, issn = {2474-1272}, abstract = {Anti-vascular endothelial growth factor (anti-VEGF) treatment protocols for neovascular age-related macular degeneration (nAMD) have evolved from fixed, monthly, or bimonthly dosing to individualized, extended dosing regimens. Although a PRN (as-needed) injection protocol may reduce the number of injections, it confers a similar treatment burden by requiring regimented follow-up visits, and disease activity may resurface between visits. Various personalized treatment intervals have been implemented in more recent randomized controlled clinical trials (RCTs), reflecting a shifting focus toward individualized, variable, extended treatment intervals rather than the frequent, fixed regimens used in older RCTs. Newer agents, such as faricimab and aflibercept 8.0 mg, have been evaluated in phase 3 RCTs and potentially offer extended durability of dosing in intervals of up to 12-16 weeks or longer. Recently introduced anti-VEGF agents were tested in pivotal trials using individualized, variable, extended treatment intervals, with results showing adequate nAMD control compared to older, fixed dosing regimens, but additional studies are needed to determine the real-world durability of these agents compared to older anti-VEGF agents.}, }
@article {pmid41822529, year = {2026}, author = {Fong, KCS and Wong, WJ and Samsudin, A and Ganasan, DK and Goh, WN and Tai, JY and Fong, SN and Cheong, CYJ and Rajamanickam, G and Shunmugam, M}, title = {PAIR: Evaluating the Limits of Agreement Among Non-Retinal Specialist Using PathFinder Artificial Intelligence Tool for Retinal Disease Referrals: A Prospective Observational Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {584717}, pmid = {41822529}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate the diagnostic and referral agreement between non-retina specialists (NRS) using the PathFinder artificial intelligence (AI) assistant and fellowship-trained retina specialists (RS - gold standard) in interpreting macular optical coherence tomography (OCT) scans.<br><br>METHODS: This cross-sectional study included 202 consecutive patients undergoing OCT on the CIRRUS platform with the PathFinder AI module. Three RS independently graded all scans without clinical data, while three NRS interpreted the same scans using PathFinder assistance and full clinical information. The gold standard for both diagnosis and referral was defined by agreement of at least two of the three RS. The NRS recorded diagnostic confidence and time to AI-assisted decision. Agreement was assessed with Cohen's and Fleiss' &#x3ba; and sensitivity, and specificity were computed for four major pathologies.<br><br>RESULTS: Among 202 eyes (mean age 62.7 &#xb1; 12.3 years), RS inter-agreement was moderate for diagnosis (overall &#x3ba; = 0.59) and referral (&#x3ba; = 0.47). NRS showed substantial (NRS1 &#x3ba; = 0.78) to moderate (NRS2 &#x3ba; = 0.64; NRS3 &#x3ba; = 0.54) diagnostic agreement and high specificity (> 90% for all). Sensitivity varied across raters and diagnoses (0.57-0.89), with comparatively lower sensitivity observed for certain vision-threatening conditions such as age-related macular degeneration and macular hole. Referral agreement varied (&#x3ba; = 0.68, 0.24, 0.34) amongst NRS. Visual acuity was the only significant predictor of referral discordance (OR 0.66, 95% CI 0.55-0.80, p < 0.001). Median NRS with PathFinder assistance processing time was < 20s. The most significant false-positive diagnoses made by PathFinder-assisted NRS in eyes deemed normal by RS was ERM (40.0%), followed by PED (20.0%) and AMD (13.3%), observed across a small number of eyes and does not affect the results.<br><br>CONCLUSION: PathFinder is a valuable real-time decision-support tool in resource-limited settings; however, disease-specific refinements and clinical oversight remain important, particularly for vision-threatening conditions.}, }
@article {pmid41824262, year = {2026}, author = {Avery, R and Diack, C and Holekamp, N and Lhor, M and Mar, F and Maass, K}, title = {Ocular Half-Life: What it Does and Does Not Mean for Intravitreal Anti-angiogenic Drug Durability.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41824262}, issn = {2193-8245}, abstract = {Our commentary provides a conceptual foundation for the relationship between ocular half-life and treatment durability with respect to intravitreally administered anti-angiogenic therapies typically used for the treatment of retinal diseases, such as neovascular age-related macular degeneration and diabetic macular edema. Of note, we critically examine claims suggesting that increasing the dose of aflibercept can reduce ocular clearance and, consequently, increase ocular half-life. By reviewing the available data and exploring the underlying pharmacokinetic principles, this commentary seeks to provide an evidence-based understanding of the factors influencing treatment durability in this therapeutic area.}, }
@article {pmid41825596, year = {2026}, author = {Choi, J and Choi, E and Kang, SW and Kim, SJ and Hwang, S and Lee, H}, title = {Impact of intravitreal anti-vascular endothelial growth factor injections on cataract development.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.03.009}, pmid = {41825596}, issn = {1549-4713}, abstract = {PURPOSE: To evaluate the association between intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and incident cataract surgery.<br><br>DESIGN: Retrospective, interventional case series SUBJECTS: Patients with phakic lens status in both eyes at baseline who received &#x2265;12 unilateral anti-VEGF injections.<br><br>METHODS: Electronic medical records were analyzed to compare the incidence of cataract surgery between injected eyes (receiving anti-VEGF treatment) and untreated fellow eyes. Cumulative incidence was assessed using the Kaplan-Meier survival analysis. Lens opacity grades at the time of surgery and change in best-corrected visual acuity before and after the surgery were also analyzed.<br><br>MAIN OUTCOME MEASURES: Hazard ratio (HR) and 95% confidence interval (CI) for incident cataract surgery in the injected eye, compared with the fellow eye.<br><br>RESULTS: A total of 603 patients were followed for a median of 74 months. The 10-year cumulative incidence of cataract surgery was 40.7% (95% CI, 35.9-45.1) and 7.2% (95% CI, 4.1-10.3) in the injected and fellow eyes, respectively. The injected eye (HR, 8.174; 95% CI 5.767-11.586) and older age (HR, 1.069; 95% CI 1.052-1.086) were associated with an increased risk of cataract surgery. At the time of surgery, all lens opacity grades, including nuclear, cortical, and posterior subcapsular, were significantly higher in injected eyes (all p < 0.001), with the greatest difference observed in posterior subcapsular opacity.<br><br>CONCLUSION: Long-term intravitreal anti-VEGF treatment was associated with a significantly increased risk of developing cataract for which surgical intervention was performed.}, }
@article {pmid41826177, year = {2026}, author = {Cornejo-Uixeda, S and Borrás-Blasco, J and Valcuende-Rosique, A and Perez Gil, L and Monteagudo-Martinez, N and Merino, V}, title = {Dosing interval optimization and persistence with faricimab in age-related macular degeneration: An observational study in real-world clinical practice.}, journal = {Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.farma.2026.02.009}, pmid = {41826177}, issn = {2171-8695}, abstract = {OBJECTIVE: To evaluate treatment persistence and dosing interval extension with faricimab in neovascular age-related macular degeneration (nAMD) in real-world practice.<br><br>METHODS: Retrospective observational study conducted in a tertiary hospital (March 2024-March 2025). Patients receiving faricimab (treatment-na&#xef;ve or pre-treated with anti-VEGF therapy), with &#x2265;1 post-loading dose, were included. Dosing intervals were analyzed at baseline, 6 and 12&#x202f;months, Adherence was assessed with the medication possession ratio (MPR), with >80% considered adherent. Persistence was defined as the time from treatment initiation to discontinuation or end of follow-up. Persistence was estimated using Kaplan-Meier survival analysis.<br><br>RESULTS: We included 129 patients (148 eyes), mean age 74.5&#x202f;&#xb1;&#x202f;8.85&#x202f;years; 55% were female. A total of 39 patients (30.2%) were treatment-na&#xef;ve and 90 (69.8%) were pretreated. At 12&#x202f;months, 48.8% of na&#xef;ve and 55.5% of pretreated patients achieved 8-12&#x202f;weeks intervals. Mean persistence was 12.2&#x202f;months (SD 0.2; 95% CI: 11.8-12.6). The median was not reached by the end of the study. Persistence rate was 93% at 6 and 12&#x202f;months. Only one patient discontinued due to inefficacy. No serious adverse events or endophthalmitis occurred.<br><br>CONCLUSIONS: Faricimab showed excellent persistence and extended dosing intervals in real-world practice. This is the first study specifically evaluating faricimab real-world persistence in nAMD.}, }
@article {pmid41826348, year = {2026}, author = {Li, S and Ren, J and Wang, F and Wu, J and Li, Y and Wang, X and Zhang, M and Hu, H and Song, Y and Cao, W and Zhou, X and Li, M}, title = {Routine blood tests and machine learning identify complications in high myopia.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-70891-5}, pmid = {41826348}, issn = {2041-1723}, abstract = {High myopia can lead to cataract, glaucoma, retinal detachment, choroidal neovascularisation, and macular degeneration, causing irreversible vision loss. Imaging detects these complications, but population screening is limited by equipment, and specialist availability. Here we show that a machine learning model using routine blood test results identifies people at increased risk of complications related to high myopia during standard health examinations. We develop the model in a multicentre study of 10,661 participants and validate it in two independent cohorts. The model shows high accuracy across centres (area under the receiver operating characteristic curve=0.9010-0.9649) and flags individuals who receive a clinical diagnosis in a hospital-based prospective follow-up study of 5,067 participants. In a community screening study of 311,254 adults, the model increases the yield of detected complications among those referred for ophthalmic assessment (positive predictive value = 74%). This scalable blood-based approach supports opportunistic screening and earlier referral in primary care and community settings.}, }
@article {pmid41827105, year = {2026}, author = {Nashine, S and Kenney, MC}, title = {Characterization of the Effects of a Humanin Fragment Peptide (HNF14) in Age-Related Macular Degeneration.}, journal = {Journal of clinical medicine}, volume = {15}, number = {5}, pages = {}, pmid = {41827105}, issn = {2077-0383}, support = {20/20 Society Pilot Research Grant//20/20 Society Pilot Research Grant/ ; }, abstract = {Background: Age-related macular degeneration (AMD) is a leading cause of vision loss and is strongly associated with mitochondrial dysfunction in retinal pigment epithelial cells. Mitochondrial-derived peptides, including Humanin and its analogs, have demonstrated cytoprotective effects in AMD-related cellular models. However, the effects of shorter Humanin-derived fragments in disease-specific mitochondrial models remain incompletely characterized. Methods: Transmitochondrial retinal pigment epithelial cybrid cell lines containing mitochondria from AMD patients or age-matched normal donors were treated with HNF14, a 14-amino acid Humanin fragment peptide. Cellular metabolic activity, cytotoxicity, oxidative stress, apoptotic signaling, inflammatory markers, angiogenic factor expression, and amyloid-β1-42-induced apoptosis were evaluated using biochemical assays, protein analyses, and live-cell imaging approaches. Results: HNF14 treatment was associated with improved metabolic activity and reduced cytotoxicity in AMD cybrids, with minimal effects in normal cybrids. HNF14 significantly reduced intracellular and mitochondrial oxidative stress, suppressed apoptotic and inflammatory markers, and decreased VEGF-A protein expression in AMD cybrids. In addition, HNF14 attenuated amyloid-β1-42-induced apoptotic signaling in AMD cybrids. These effects were selective for cybrids containing AMD-derived mitochondria. Conclusions: This study demonstrates that HNF14 mitigates mitochondrial and cellular stress responses in AMD transmitochondrial cybrid cells. The findings indicate that a short Humanin-derived fragment retains cytoprotective activity in a disease-specific mitochondrial context and support further investigation of mitochondrial-derived peptides as modulators of mitochondrial dysfunction relevant to AMD pathophysiology.}, }
@article {pmid41827447, year = {2026}, author = {Remolí-Sargues, L and Monferrer-Adsuara, C and Castro-Navarro, V and López-Salvador, B and Francés-Muñoz, E and Marín-Payá, E and Marín-Montiel, J and López-Sánchez, E}, title = {Real-World Outcomes and Choroidal Vascular Structural Changes After Switching to Faricimab in Neovascular Age-Related Macular Degeneration.}, journal = {Journal of clinical medicine}, volume = {15}, number = {5}, pages = {}, pmid = {41827447}, issn = {2077-0383}, support = {10Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO)//10Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO)/ ; }, abstract = {Objectives: The objective of this study was to investigate choroidal structural alterations and evaluate the outcomes of switching to faricimab in patients with neovascular age-related macular degeneration (nAMD) previously treated with other anti-vascular endothelial growth factor (anti-VEGF) therapies after 12 months of follow-up. Methods: We performed a retrospective study of 30 eyes from 30 patients with nAMD who were switched to faricimab. The choroidal vascularity index (CVI), best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (CST), and the presence of subretinal fluid, intraretinal fluid, and wet macula were assessed at baseline and after 6 and 12 months. Results: CVI remained stable during follow-up (p > 0.05). BCVA improved significantly after 6 months (p = 0.041), but not at 12 months (p = 0.075). A significant reduction in CMT was observed (p < 0.05). Additionally, wet macula improved after 12 months (p < 0.05). Moreover, treatment intervals increased from 7.53 ± 2.39 to 12.47 ± 4.51 weeks. Conclusions: Switching to faricimab in patients with nAMD previously treated with other anti-VEGF therapies was associated with anatomical improvement, extended treatment intervals, and short-term visual gains, while choroidal vascular structure was maintained. Nonetheless, additional studies are warranted to more comprehensively evaluate the effectiveness of switching to faricimab, as well as the associated changes in choroidal vascular structure.}, }
@article {pmid41827932, year = {2026}, author = {Alizadeh, A and Alenezi, A and Khakestari, N and Amizadeh, Y and Jodeiri, A}, title = {Investigating the Impact of Semi-Supervised Learning Methods to Improve the Quality of Diagnosis of Retinal Diseases from OCT Images.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {5}, pages = {}, pmid = {41827932}, issn = {2075-4418}, support = {72122//Tabriz University of Medical Sciences/ ; }, abstract = {Background: Age-related Macular Degeneration (AMD) is a leading cause of irreversible vision loss, particularly in the elderly. Optical Coherence Tomography (OCT), a noninvasive imaging modality, is widely used for retinal disease detection. However, the limited availability of labeled OCT datasets poses a significant challenge, making semi-supervised learning a promising approach. This study introduces a novel Iterative Teacher-Student (ITS) framework, which refines pseudo-labeling strategies to improve AMD detection accuracy, particularly in low-data scenarios. Methods: Initially, an optimal supervised model based on EfficientNet was developed to classify AMD using a dataset from Noor Eye Hospital, consisting of 16,822 OCT images. The dataset size was then progressively reduced to 70%, 50%, 20%, and 5% to evaluate model performance under data scarcity. Unlike conventional semi-supervised learning approaches, our ITS framework iteratively refines pseudo-labels, ensuring more reliable knowledge transfer from teacher to student models. Results: The optimized supervised model achieved 87.14% accuracy in AMD classification. As dataset size decreased to 20% and 5%, accuracy declined to 77.05% and 54.78%, respectively. Implementing the ITS framework improved accuracy to 88.56% at 20% and 64.15% at 5%, outperforming traditional semi-supervised methods. Conclusions: This study highlights the potential of semi-supervised learning, particularly our iterative teacher-student approach, to enhance AMD detection when labeled OCT data are scarce. The proposed framework introduces a novel iterative refinement strategy, which can serve as a foundation for future research in retinal disease diagnosis with limited labeled datasets.}, }
@article {pmid41828731, year = {2026}, author = {Zong, M and Qiu, Y and Li, C}, title = {Focus on Lactate and Lactylation Modification: The Potential Role in Ophthalmic Disease Treatment.}, journal = {International journal of molecular sciences}, volume = {27}, number = {5}, pages = {}, pmid = {41828731}, issn = {1422-0067}, mesh = {Humans ; *Protein Processing, Post-Translational ; *Eye Diseases/metabolism/therapy ; Animals ; *Lactic Acid/metabolism ; Lysine/metabolism ; Signal Transduction ; }, abstract = {Lysine lactylation represents a novel post-translational modification (PTM) involved in cellular functions including glycolysis and macrophage polarisation. It differs in form and mechanism from other PTMs such as acetylation, methylation, phosphorylation, ubiquitination, and SUMOylation. As a recently discovered modification, lactylation has been implicated in the progression of multiple diseases. Recent studies further indicate lactylation's association with multiple ocular pathologies. This review systematically summarises and discusses lactylation's involvement in prevalent eye diseases, including myopia, retinopathy, ocular melanoma, uveitis, and macular degeneration. We further collate emerging data suggesting lactylation signalling pathways may represent potential therapeutic targets for ocular pathologies. This review aims to provide a comprehensive overview for holistic intervention strategies and multidimensional assessment across various ocular conditions, while offering valuable insights for future research and development from a lactylation perspective.}, }
@article {pmid41830174, year = {2026}, author = {Jafar Hussain, HM and Wang, M and Yang, P and Tasharrofi, B and Li, Y and Clark, RL and Fale-Olsen, E and Waldow, G and Keramatipour, M and Asadollahi, M and Pennesi, ME and Chen, R}, title = {Bi-allelic Variants in AP5Z1 and AP5B1 lead to retinal degeneration.}, journal = {HGG advances}, volume = {}, number = {}, pages = {100584}, doi = {10.1016/j.xhgg.2026.100584}, pmid = {41830174}, issn = {2666-2477}, abstract = {Inherited retinal diseases (IRDs) comprise a diverse group of disorders that frequently lead to progressive vision impairment and blindness. Despite advances in genetic testing, a significant number of IRD cases remain genetically unsolved, often due to unidentified disease-associated genes or variants. This study aims to report additional cases for the newly discovered IRD genes of the AP5-complex. A comprehensive ophthalmological evaluation was performed for all patients, including retinal imaging (multimodal imaging), visual field testing and electroretinogram (ERG) testing. Whole genome and exome sequencing (WGS &amp; WES) were performed for clinically unsolved IRD patients, and data were analyzed to identify underlying causal variants. The identified variants were subsequently validated using Sanger sequencing. Five unrelated patients from Europe and Iran were identified with a distinctive macular degeneration associated with bi- allelic variants in AP5Z1 (HGNC: 22197) and AP5B1 (HGNC: 25104), subunits of the vesicular fifth adaptor protein (AP-5) complex. AP-5 complex is the part of the intracellular trafficking machinery thought to be involved in cellular homeostasis and lysosomal functioning in the retinal pigment epithelium (RPE). The identification of bi-allelic variants in two proteins of AP-5 complex expand the characterization of AP-5 genes in sustaining and preserving normal macular function.}, }
@article {pmid41830184, year = {2026}, author = {Germano-Morrel, CS and Tomishige, KS and Macchione, RM and Ottaiano-Poli, PA and Kasahara, N}, title = {Comparison of the illness perception between age-related macular degeneration and glaucoma patients living in a middle-income country.}, journal = {Journal of health psychology}, volume = {}, number = {}, pages = {13591053261430435}, doi = {10.1177/13591053261430435}, pmid = {41830184}, issn = {1461-7277}, abstract = {The aim of this cross-sectional study was to compare the cognitive and emotional representations of illness in patients with primary open angle glaucoma (POAG) and age-related macular degeneration (AMD) living in a developing country. All subjects answered the Brief Illness Perception Questionnaire (Brief IPQ) to assess mental defeat. The summed scores were compared among the groups with the ANOVA test. The sample comprised 60 patients with AMD, 64 with POAG and 60 controls. Both AMD and POAG patients scored higher than controls (50.4 ± 10.5, 49.5 ± 14.4, and 10.7 ± 17.6, respectively, p < 0.000). The difference between AMD and POAG did not reach statistical significance (Tukey HSD p = 0.978). Despite different diseases, POAG and AMD patients had similar illness perceptions in a cohort of patients living in a developing country. These results can help patients to take actions to regulate their emotions and improve treatment outcomes of their illness.}, }
@article {pmid41830999, year = {2026}, author = {Neri, G and Bacherini, D and Mastropasqua, R and Dolz-Marco, R and Gallego-Pinazo, R and Reiter, GS and Reibaldi, M and Borrelli, E}, title = {OCTA in age-related macular degeneration: consensus on practical guidelines for optimal imaging strategies across different clinical scenarios.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41830999}, issn = {1435-702X}, }
@article {pmid41832250, year = {2026}, author = {Demarinis, G and Yeung, I and Preston, E and Patel, PJ and Huemer, J and Hamilton, RD and Nicholson, L and Tucker, WR and Montesel, A}, title = {Clinical spectrum of intraocular inflammation following faricimab intravitreal injections: evidence from a large real-life cohort in the United Kingdom.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41832250}, issn = {1476-5454}, abstract = {OBJECTIVE: To describe the clinical findings and report the incidence of patients developing non-infectious intraocular inflammation (IOI) following intravitreal faricimab injections (IVFs).<br><br>METHODS: A retrospective review of electronic medical records was conducted for patients receiving faricimab intravitreal injections for neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO) at Moorfields Eye Hospital, London, United Kingdom, over a 24-month period.<br><br>RESULTS: 3985 eyes from 3151 patients were included and underwent a total of 28,535 IVFs (20,982 for nAMD, 7553 for DMO). 57 eyes from 46 patients presented at least one episode of IOI. The 2-year estimated incidence of IOI was 0.20% [95% CI 0.15-0.26] per injection, 1.43% [95% CI 1.08-1.85] per eye and 1.46% [95% CI 1.07-1.94] per patient. Mean visual acuity (VA) was significantly different between the day of IVF (0.48&#x2009;&#xb1;&#x2009;0.43 logMAR, range: 0-1.8) and the day of IOI diagnosis (0.67&#x2009;&#xb1;&#x2009;0.52, range: 0-2.3) (p&#x2009;<&#x2009;0.001). VA after IOI resolution showed no significant difference from baseline (p&#x2009;>&#x2009;0.99). Intravitreal injections were resumed in 42 eyes. IVFs re-challenge was attempted in 9 eyes, with 5 developing another episode of IOI.<br><br>CONCLUSIONS: This study describes one of the largest reported cohorts of IOI cases following faricimab treatment. It confirms that the incidence of IOI is rare and aligns with the rates of IVF-related adverse effects reported in clinical trials and in recent real-world studies. Overall, faricimab demonstrated a favourable safety profile with good prognosis in cases of IOI.}, }
@article {pmid41832694, year = {2026}, author = {Krishnaswami, V and Janakiraman, K and Sethuraman, V and Raja, J}, title = {Nanomicelles in Ocular Drug Delivery: Overcoming Barriers and Enhancing Therapeutic Efficacy.}, journal = {Current pharmaceutical design}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113816128416157251203061416}, pmid = {41832694}, issn = {1873-4286}, abstract = {This study provides a comprehensive overview of nanomicelle-based drug delivery methods used to treat ocular disorders. A review of current literature was conducted by scanning electronic databases up until December 2024, including PubMed, Scopus, Web of Science, and Google Scholar. Keywords such as "Nanomicelles" and specific ocular conditions including "Glaucoma," "Conjunctivitis," "Cataract," and "Retinopathy" were used to identify relevant material. Original research articles, reviews, and clinical trials were given special attention. Administering drugs to the eye remains one of the most challenging tasks among various drug delivery systems. Delivering drugs to the posterior pole or the delicate anatomical layers of the eye poses a substantial challenge for researchers and pharmacologists. Conventional formulations often exhibit inadequate corneal penetration, poor absorption, or noticeable adverse visual effects. Nanotechnology has greatly facilitated the development of novel therapeutic strategies for ocular disorders. Nanomicelle-based formulations benefit significantly from the nano-delivery platform. Nanomicelles can overcome anatomical barriers and clearance processes. Depending on the polymer used, nanomicelles can be engineered and released to meet specific requirements. They are notable for their small size, low toxicity, ability to improve drug penetration through ocular epithelia with minimal irritation, enhancement of hydrophobic drug solubility, achievement of therapeutic concentrations, and prevention or reduction of drug degradation. This study highlights the use of nanomicellar-based delivery systems in treating ocular diseases such as diabetic retinopathy, glaucoma, age-related macular degeneration, cataract, conjunctivitis, keratitis, and retinoblastoma.}, }
@article {pmid41835293, year = {2026}, author = {Chakraborty, S and Sheth, JU and Ganguly, S and Reddy, R}, title = {Vitrectomy with Subretinal Tissue Plasminogen Activator for Submacular Hemorrhage: A Multicenter Retrospective Analysis of Functional and Anatomical Outcomes Across Multiple Etiologies.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {589150}, pmid = {41835293}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate visual and anatomical outcomes of pars plana vitrectomy (PPV) with subretinal tissue plasminogen activator (tPA) and gas or air tamponade for large submacular haemorrhage (SMH>4 disc diameters) of varied etiologies and assess postoperative anti-vascular endothelial growth factor (anti-VEGF) requirements in a multicenter real-world cohort.<br><br>PATIENTS AND METHODS: This retrospective, two-center study included 32 eyes undergoing PPV with subretinal tPA (25-50 &#xb5;g/0.1-0.2 mL) and SF6 or air tamponade, followed for &#x2265;6 months. The primary outcome was change in best-corrected visual acuity (BCVA). Secondary outcomes included central macular thickness (CMT), SMH dimensions, subretinal/intraretinal fluid (SRF/IRF) status, intraocular pressure (IOP), and anti-VEGF use.<br><br>RESULTS: Mean patient age was 60.8 &#xb1; 19.1 years; etiologies included polypoidal choroidal vasculopathy (PCV; 53.1%), neovascular age-related macular degeneration (nAMD; 28.1%), trauma (12.5%), and retinal artery macroaneurysm (RAM; 6.3%). BCVA improved significantly from 1.13 &#xb1; 0.30 to 0.56 &#xb1; 0.26 logMAR (P<0.001), with 55.2% gaining &#x2265;3 lines. CMT reduced from 501 &#xb1; 219 to 276 &#xb1; 70&#xa0;&#xb5;m (P<0.001), and SMH size decreased from 5 &#xb1; 2 to 0 disc diameters by 6 months. SRF resolved in 65.65% of eyes (P<0.001), while IRF remained stable (P=0.51). IOP normalized after a transient 1-month rise. Mean anti-VEGF use was 1.2 injections/eye (bevacizumab 88.2%, brolucizumab 11.8%). No major complications occurred; one transient vitreous hemorrhage and three cataract progressions were noted.<br><br>CONCLUSION: PPV with subretinal tPA achieved rapid hemorrhage clearance, significant visual gain, and durable anatomical restoration with minimal complications and limited anti-VEGF need. It offers an effective, safe option for large SMH across etiologies, enabling timely foveal recovery and improved long-term functional outcomes.}, }
@article {pmid41835799, year = {2026}, author = {Shiromani, S and Chhablani, J}, title = {Deep learning in geographic atrophy: rethinking age-related macular degeneration progression and treatment.}, journal = {Annals of translational medicine}, volume = {14}, number = {1}, pages = {7}, pmid = {41835799}, issn = {2305-5839}, }
@article {pmid41837474, year = {2026}, author = {Cho, M and Lee, J and Kim, Y and Kim, YJ and Doguer, C and Kim, M and Ha, JH}, title = {Hot-Air-Dried Eruca sativa Mill. Extracts Prevent Retinal Inflammation and Unfolded Protein Responses in ARPE-19 Cells.}, journal = {Journal of medicinal food}, volume = {29}, number = {2}, pages = {91-101}, doi = {10.1177/1096620X251412888}, pmid = {41837474}, issn = {1557-7600}, mesh = {Humans ; *Plant Extracts/pharmacology ; Endoplasmic Reticulum Stress/drug effects ; *Unfolded Protein Response/drug effects ; Cell Line ; *Retinal Pigment Epithelium/drug effects/immunology/cytology ; NF-kappa B/genetics/immunology ; Vascular Endothelial Growth Factor A/genetics/immunology/metabolism ; Tumor Necrosis Factor-alpha/genetics/immunology ; Apoptosis/drug effects ; *Diabetic Retinopathy/drug therapy/genetics/immunology ; *Macular Degeneration/drug therapy/genetics/immunology ; Inflammation ; Lipopolysaccharides ; }, abstract = {Age-related macular degeneration (AMD) and diabetic retinopathy (DR) constitute leading causes of irreversible visual impairment; both are pathologically linked to chronic inflammation and endoplasmic reticulum (ER) stress in retinal pigment epithelial (RPE) cells. This study aimed to investigate the protective effects of hot-air-dried Eruca sativa Mill. extract (ESH) on lipopolysaccharide (LPS)- and thapsigargin (Tg)-induced inflammatory and ER stress responses, respectively, in ARPE-19 cells. ESH pretreatment significantly suppressed LPS-induced phosphorylation of nuclear factor kappa B (NF-κB), inhibitor of kappa B alpha, and c-Jun N-terminal kinase, indicating effective inhibition of inflammatory signaling cascades. At the transcriptional level, ESH markedly attenuated the expression of tumor necrosis factor-α mRNA, suggesting downstream prevention of NF-κB-mitogen-activated protein kinase-mediated inflammatory gene activation. Under ER stress conditions, ESH significantly attenuated the upregulation of CCAAT/enhancer-binding protein (C/EBP) homologous protein and X-box binding protein-1, along with reductions in the expressions of cleaved caspase-3 and -9, indicating mitigation of ER stress-associated retinal apoptosis. Additionally, ESH prevented Tg-inducible vascular endothelial growth factor (VEGF) mRNA expression, VEGF protein secretion, and intracellular calcium level. Strong positive correlations were observed between intracellular calcium and VEGF secretion (r = 0.888), and between VEGF mRNA and protein levels (r = 0.843), supporting a potential mechanistic link. Collectively, these findings demonstrate that ESH modulates inflammatory, ER stress, apoptotic, and angiogenic pathways, suggesting its potential as a functional dietary supplement to mitigate RPE dysfunction in AMD and DR.}, }
@article {pmid41837572, year = {2026}, author = {Pfau, M}, title = {Introducing Christine A. Curcio and Cynthia Owsley, the 2025 Recipients of the Proctor Medal.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {35}, pmid = {41837572}, issn = {1552-5783}, mesh = {*Awards and Prizes ; Humans ; *Ophthalmology/history ; History, 21st Century ; History, 20th Century ; *Macular Degeneration/history ; United States ; }, abstract = {Christine A. Curcio, PhD, and Cynthia Owsley, PhD, MSPH, have been jointly honored with the 2025 Proctor Medal by ARVO. This distinguished award recognizes their 40 years of pioneering contributions to vision science and ophthalmology, especially in uncovering the early stages of age-related macular degeneration (AMD). Their unique collaboration has effectively connected basic neuroscience with clinical psychophysics, greatly transforming scientific and clinical approaches to the early detection and prevention of AMD. In their Proctor Medal Lecture, titled "The Science of Rod-Mediated Dark Adaptation, an Outcome Measure for Age-Related Macular Degeneration," Drs. Curcio and Owsley combined insights from two research careers on retinal biology, visual function, aging, and AMD.}, }
@article {pmid41837573, year = {2026}, author = {Curcio, CA and Owsley, C}, title = {The Science of Rod-Mediated Dark Adaptation, an Outcome Measure for Age-Related Macular Degeneration: The 2025 Proctor Medal Lecture.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {34}, pmid = {41837573}, issn = {1552-5783}, mesh = {Humans ; *Macular Degeneration/physiopathology/diagnosis ; *Dark Adaptation/physiology ; *Retinal Rod Photoreceptor Cells/physiology ; Retinal Pigment Epithelium/pathology ; Awards and Prizes ; Tomography, Optical Coherence ; }, abstract = {Age-related macular degeneration (AMD) degrades central vision in older adults worldwide. To enable precision prevention and early intervention, the longitudinal Alabama Study of Age-related Macular Degeneration 2 (ALSTAR2) seeks functional and imaging outcomes at the aging-AMD interface. ALSTAR2 relies on accurate two-dimensional maps of photoreceptor and retinal pigment epithelium (RPE) distributions and a histology-informed, deposit-driven progression sequence involving dysregulated bi-directional transport between photoreceptors and circulation. This transport is globally assessed by rod-mediated dark adaptation (RMDA), a dynamic measure of rod sensitivity recovery after exposure to a bright light. RMDA measured at the rim of the high-risk macula lutea is affected earlier and is more predictive of AMD onset and progression than steady-state functional measures of rods, cones, and neural circuitry, in both tested and fellow eyes. Delayed RMDA incorporates the Oil Spill hypothesis of drusen formation, which posits that lipoprotein particles constitutively released by RPE are trapped by aged Bruch's membrane and choriocapillaris. Subretinal drusenoid deposit, associated with poor RMDA and risk for advanced AMD, may represent a late-appearing barrier to transport at the level of the RPE. Although RMDA slowing is already underway before routinely visible AMD pathology, some structural and metabolic imaging technologies may assist early detection.}, }
@article {pmid41837574, year = {2026}, author = {Sharma, A and Kizy, S and Singh, NK}, title = {Understanding the Molecular Basis of Pathological Retinal Angiogenesis: Roles of Lipids, Non-Coding RNAs, and Cellular Crosstalk.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {33}, pmid = {41837574}, issn = {1552-5783}, mesh = {Humans ; *Retinal Neovascularization/metabolism/genetics ; *RNA, Untranslated/physiology ; Animals ; *Lipid Metabolism/physiology ; Signal Transduction ; *Lipids/physiology ; Vascular Endothelial Growth Factor A/metabolism ; Retinal Pigment Epithelium/metabolism ; Angiogenesis ; }, abstract = {Pathological retinal neovascularization is a prevalent cause of blindness, impacting millions of individuals across all age groups, from infants to older adults. It is a key clinical feature of several retinal diseases, such as diabetic retinopathy (DR), retinopathy of prematurity (ROP), age-related macular degeneration (AMD), and Coats disease. Researchers have extensively investigated the involvement of vascular endothelial growth factor (VEGF) signaling, hypoxia inducible factor (HIF) signaling, and inflammation in the regulation of pathological retinal neovascularization. Recent breakthroughs have demonstrated the influence of several substances and cells in the retina on the regulation of pathological retinal neovascularization. This review emphasizes the rising significance of substances such as lipid mediators, non-coding ribonucleic acids, as well as the involvement of several retinal cell types, including endothelial cells (ECs), pericytes, glial cells, and the retinal pigment epithelium (RPE) in the regulation of pathological neovascularization. Here, we emphasize the interactions among these cell types in maintaining retinal homeostasis and their role in abnormal neovascularization in diseases like DR, AMD, ROP, etc. This review aims to highlight the importance of molecules and cells that go beyond the VEGF-centric therapeutic focus to treat pathological neovascularization.}, }
@article {pmid41838271, year = {2026}, author = {Das, T and Jalali, S and Jonas, J and Kawasaki, R and Saw, SM and Sivaprasad, S and Tan, ACS and Ruamviboonsuk, P}, title = {From Science and Technology to Eye-Health Policy: A Review on Global and Asia-Pacific Strategies on the Prevention of Blindness from Retinal Diseases.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41838271}, issn = {2193-8245}, abstract = {The World Health Organization (WHO) is making a concerted effort to enhance health, including eye health and overall well-being. This global effort has resulted in a reduced age-standardized prevalence of avoidable blindness and no increase in avoidable moderate and severe vision impairment. However, the absolute number of cases has increased for both avoidable blindness and moderate-to-severe vision impairment. Globally, the leading causes of visual impairment include uncorrected refractive errors and cataract, though many retinal conditions equally contribute. All causes of blindness and moderate-to-severe visual impairment are higher in low- and middle-income countries, including many in the Asia-Pacific region. This inequality could be reduced by harmonizing science and technology and translating them into regulatory policy to close the care loop.This review aimed to provide a perspective on the disease burden of common retinal conditions such as diabetic retinopathy, age-related macular degeneration, myopia, and retinopathy of prematurity; the latest science and technology for diagnosing and treating these conditions; and recommendations to translate them into national policy. We also reviewed the WHO's global policy and targets related to the United Nations Sustainable Development Goals, recommended to prevent global blindness by the year 2030. The national health and eye care systems, from primary to tertiary care, in an Asia-Pacific country, which align with "Integrated People-Centered Eye Care" proposed by WHO, are also reviewed.}, }
@article {pmid41840324, year = {2026}, author = {Sharma, A and Sheth, JU and Kuppermann, BD}, title = {Anti-Vascular Endothelial Growth Factor Biosimilars for Use in the Aging Eye.}, journal = {Drugs &amp; aging}, volume = {}, number = {}, pages = {}, pmid = {41840324}, issn = {1179-1969}, abstract = {Anti-vascular endothelial growth factor (anti-VEGF) therapies have revolutionized the treatment of neovascular age-related macular degeneration (nAMD), a leading cause of vision loss, in addition to other retinal vascular diseases such as diabetic macular edema (DME), retinal vein occlusions (RVO). Biosimilars, which are nearly identical versions of original biologic drugs, offer a promising alternative to these costly treatments. Several biosimilars for anti-VEGF drugs including bevacizumab, ranibizumab, and aflibercept are in various stages of development and approval (e.g. Afilivu, Yesafili, Enzeevu, Ahzantive, AVT-06, ABP 938, and ALT L9). These biosimilars have shown comparable results in improving visual acuity and reducing retinal fluid in patients with nAMD but their adoption in clinical practice faces challenges, including regulatory hurdles, physician and patient acceptance, and the need for extensive post-marketing surveillance to monitor long-term safety and efficacy. However, as more data becomes available and biosimilars gain approval, they are expected to become an integral component in the management of nAMD. This review explores the current landscape of anti-VEGF biosimilars, their clinical efficacy, safety profiles, and the economic implications for treating the aging eye. It also addresses the challenges and future directions in the integration of biosimilars into routine ophthalmic practice.}, }
@article {pmid41840936, year = {2026}, author = {Cho, YJ and Kook, KY and Park, DH and Ji, YS}, title = {Effectiveness Of Ultrathin 40-Gauge Needles for Intravitreal Injections.}, journal = {Korean journal of ophthalmology : KJO}, volume = {}, number = {}, pages = {}, doi = {10.3341/kjo.2025.0134}, pmid = {41840936}, issn = {2092-9382}, abstract = {PURPOSE: To compare pain perception and immediate post‑procedural complications of intravitreal injections (IVIs) performed with conventional 30‑gauge (30 G) needles versus ultrathin 40‑gauge (40 G) needles.<br><br>METHODS: &#x2003;This single center, retrospective crossover study reviewed consecutive patients who underwent serial IVIs for neovascular age related macular degeneration, diabetic macular edema, retinal vein occlusion, myopic choroidal neovascularization, or other indications between April and October 2020. Each patient received one injection with a 30&#x202f;G needle and one with a 40&#x202f;G needle-either to the fellow eye on the same day or to the same eye one month apart. Injections (0.05&#x202f;mL bevacizumab, ranibizumab, or aflibercept) were administered in an operating room by a single surgeon following Avery et&#x202f;al. guidelines. Pain was recorded immediately post injection on a visual analogue scale (VAS). Subconjunctival hemorrhage (SCH) and vitreous reflux (VR) were graded 0-4.<br><br>RESULTS: &#x2003;Mean age was 69.3&#x202f;&#xb1;&#x202f;11.5&#x202f;years; 69&#x202f;% were men. VAS pain scores were significantly lower with 40&#x202f;G needles than with 30&#x202f;G needles (2.33&#x202f;&#xb1;&#x202f;1.26 vs&#x202f;4.02&#x202f;&#xb1;&#x202f;1.73; mean paired difference -1.69&#x202f;&#xb1;&#x202f;0.33; p&#x202f;<&#x202f;0.001). Median VR grade declined from&#x202f;2 (IQR&#x202f;2-3) to&#x202f;0 (IQR&#x202f;0-1) with 40&#x202f;G needles (p&#x202f;<&#x202f;0.001). SCH grade did not differ between gauges (median&#x202f;0, IQR&#x202f;0-1; p&#x202f;=&#x202f;0.93). No injection related adverse events occurred.<br><br>CONCLUSIONS: &#x2003;Using an ultrathin 40&#x202f;G needle for IVIs significantly reduces patient&#x2011;reported pain and vitreous reflux without increasing subconjunctival hemorrhage. These findings support the integration of 40 G needles into routine IVI practice to enhance long-term patient adherence and treatment efficacy.}, }
@article {pmid41841063, year = {2026}, author = {Pagán-Melvin, C and Izquierdo, N and Alejandro, KC}, title = {Clinical Validation of a CRX Variant Leading to a Cone-Rod Dystrophy.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e103528}, pmid = {41841063}, issn = {2168-8184}, abstract = {Patients with cone-rod dystrophy (CORD) due to CRX mutations have progressive visual impairment characterized by central vision loss, photophobia, and color vision defects. On ophthalmic examination, patients with CRX-associated CORD may have macular abnormalities, changes in the retinal pigment epithelium, and progressive macular degeneration, affecting central visual function. Variants in the CRX gene located on chromosome 19q13 lead to photoreceptor dysfunction and retinal degeneration. Variant classification in CRX presents unique challenges, as approximately half of heterozygous missense variants may be benign, requiring careful phenotype-genotype correlation for accurate pathogenicity determination. Our patient had progressive vision loss, bilateral macular abnormalities, and visual symptoms compatible with CORD. The patient's clinical findings included central visual field defects, reduced multifocal electroretinography responses, and preserved full-field electroretinography consistent with macular-restricted disease. Next-generation sequencing showed a heterozygous, likely pathogenic variant c.166G>A (p.Ala56Thr) located within the homeodomain at residue 56. Comprehensive ophthalmic examination, electrophysiological testing, and genetic studies may all help reach a CORD diagnosis. This case highlights the importance of phenotype-driven variant interpretation for reclassifying CRX variants from "likely pathogenic" to "pathogenic" and raises clinical awareness for the critical role of genotype-phenotype concordance in inherited retinal dystrophies.}, }
@article {pmid41841116, year = {2026}, author = {Kaganovski, A and Bhuiyan, A and Kasi, A and Kamyab, D and Grinberg, A and Chen, S and Thomson, R and Bhuiyan, T and Govindaiah, A and Deobhakta, A and Lema, G and Tai, K and Weissman, MA and Amoruso, L and Smith, RT}, title = {Elevated prevalence of age-related macular degeneration in a low-income urban primary care setting.}, journal = {Discover public health}, volume = {23}, number = {1}, pages = {321}, pmid = {41841116}, issn = {3005-0774}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss among adults over 50. Early detection enables interventions such as Age-Related Eye Disease Study (AREDS) supplementation to slow disease progression, yet AMD remains underdiagnosed in primary care, particularly in underserved populations. This study assessed AMD sample prevalence and its association with social determinants of health in a diverse, urban primary care cohort.<br><br>METHODS: We performed a post hoc analysis of a cross-sectional study conducted from June 2020 to May 2023 at a hospital-based primary care clinic in New York City (NYC). Patients aged 50-89 underwent nonmydriatic color fundus photography graded independently by two physicians using Beckman Initiative criteria. Median household income by ZIP code served as a proxy for socioeconomic position. Multivariable logistic regression examined associations between AMD and demographic or social determinants of health variables.<br><br>RESULTS: Of 393 patients enrolled, 312 were included in the final analysis. Referable AMD was present in 48.4% of participants based on the Beckman classification, representing the sample prevalence within this clinic cohort and exceeding national population-based estimates. Only 4 of 151 AMD cases had been previously diagnosed. Referable AMD prevalence was higher in males than females (56.2% vs. 44.4%) and increased with age. Median household income was significantly lower among patients with referable AMD compared with those without ($72,000 vs. $151,000; p&#x2009;<&#x2009;0.0001). In adjusted models, male sex (OR&#x2009;=&#x2009;2.00, 95% CI 1.02-4.00) and lower income were strongly associated with referable AMD prevalence; race and age were not.<br><br>CONCLUSION: Undiagnosed referable AMD was highly prevalent within this primary care clinic sample of low-income, urban patients. Integrating affordable retinal screening, potentially aided by artificial intelligence, into primary care may help address vision health disparities driven by social determinants of health.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12982-026-01672-0.}, }
@article {pmid41841652, year = {2026}, author = {Chen, CH and Lin, CW and Wu, SH and Yang, ZW and Lin, CW and Shen, YC and Cheng, YW and Su, MW and Tang, SC}, title = {NOTCH3 Pathogenic Variant and Risk of Age-Related Macular Degeneration: Findings From the Taiwan Biobank and Small Vessel Disease Registry.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {37}, pmid = {41841652}, issn = {1552-5783}, mesh = {Humans ; *Receptor, Notch3/genetics/metabolism ; Female ; Male ; Taiwan/epidemiology ; *Macular Degeneration/genetics/epidemiology ; Middle Aged ; Aged ; Registries ; Risk Factors ; Biological Specimen Banks ; Prevalence ; *Mutation ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of central vision loss involving retinal microvascular dysfunction. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary small vessel disease caused by NOTCH3 mutations, primarily affects the cerebral vasculature but may also involve the retinal microvasculature. This study investigated the association between the NOTCH3 R544C variant and AMD using the Taiwan Biobank and validated the findings in a hospital-based cohort.<br><br>METHODS: In the Taiwan Biobank, individuals carrying the NOTCH3 R544C variant were matched with noncarriers (1:10) by demographic and cardiovascular factors. Odds ratios (ORs) for self-reported AMD and other eye diseases were calculated. Validation was performed in the Taiwan-Associated Genetic and Non-Genetic Small Vessel Disease (TAG-SVD) cohort, including 64 NOTCH3 R544C carriers and 84 age-matched controls who underwent ophthalmic evaluation.<br><br>RESULTS: In the Taiwan Biobank, NOTCH3 R544C carriers (n = 1134) had higher prevalence rates of stroke (OR = 2.23; 95% confidence interval [CI], 1.30-3.84), family history of stroke (OR = 2.05; 95% CI, 1.78-2.35), and AMD (OR = 2.26; 95% CI, 1.38-3.71) compared with matched controls (n = 11,340), but not of other eye diseases. Individuals with AMD were older and more likely to have diabetes, higher fasting glucose, HbA1c, total cholesterol, and low-density lipoprotein levels. Multivariate analysis identified age (OR = 1.06; 95% CI, 1.01-1.11) and diabetes (OR = 5.51; 95% CI, 1.84-14.79) as independent correlates. In the TAG-SVD cohort, AMD prevalence was higher in carriers (23.4%) than in controls (13.1%), although not statistically significant (P = 0.10).<br><br>CONCLUSIONS: The NOTCH3 R544C variant may be associated with an increased risk of AMD, warranting further studies to clarify the underlying mechanisms.}, }
@article {pmid41841653, year = {2026}, author = {Nodecker, KN and Romano, F and Stettler, I and Shah, S and Ploumi, I and Cort, T and Ding, X and Chen, C and Zhu, Y and Nigalye, A and Choi, H and Gumustop, S and Bannerman, A and Vingopoulos, F and Laíns, I and Miller, JW and Vavvas, DG and Husain, D and Miller, JB}, title = {Reduced Macular Pigment Optical Volume Is Linked to High-Risk OCT Biomarkers and Lower Contrast Sensitivity Function in iAMD.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {36}, pmid = {41841653}, issn = {1552-5783}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; Aged ; *Macular Pigment/metabolism ; Biomarkers/metabolism ; *Contrast Sensitivity/physiology ; Visual Acuity/physiology ; *Retinal Pigment Epithelium/pathology ; Middle Aged ; Aged, 80 and over ; *Macular Degeneration/physiopathology ; Macula Lutea ; }, abstract = {PURPOSE: To investigate relationships among macular pigment optical volume (MPOV), optical coherence tomography (OCT) biomarkers, and contrast sensitivity (CS) measured by the quantitative contrast sensitivity function (qCSF) test in intermediate age-related macular degeneration (iAMD).<br><br>METHODS: Sixty-five eyes from 34 patients with OCT-confirmed iAMD, visual acuity (VA) >20/100, and no confounding comorbidities underwent same-day qCSF testing (area under the logarithmic CS function [AULCSF], contrast acuity [CA], and CS at 1-18 cycles per degree [cpd]), MPOV imaging, and macular OCT. OCT features evaluated within the central 3-mm circle included outer nuclear layer (ONL) thickness, retinal pigment epithelium (RPE) volume, subretinal drusenoid deposits, hyporeflective drusen cores (hDCs), intraretinal hyperreflective foci, and incomplete RPE and outer retinal atrophy (iRORA). MPOV was quantified at 1&#xb0;, 2&#xb0;, and 9&#xb0; eccentricities (plateau set at 9&#xb0;). Generalized linear mixed-effects models assessed associations of MPOV with OCT biomarkers and qCSF metrics.<br><br>RESULTS: Lower MPOV values were associated with reduced ONL thickness (&#x3b2;*, 0.343-0.424; all P < 0.01), presence of hDCs (&#x3b2;*, -0.80 to -0.60; all P < 0.01), and iRORA at 1&#xb0; (&#x3b2;*, -0.43; P = 0.03). MPOV at all eccentricities was associated with lower AULCSF (&#x3b2;*, 0.32-0.45), CA (&#x3b2;*, 0.38-0.48), and CS at 3 cpd and 6 cpd (&#x3b2;*, 0.39-0.69; all P < 0.05), but not with VA (&#x3b2;*, 0.10-0.28; all P > 0.05).<br><br>CONCLUSIONS: MPOV was significantly associated with high-risk OCT biomarkers and qCSF-derived CS metrics in iAMD, highlighting its potential role as a biomarker of structural integrity and functional impairment not captured by standard VA testing.}, }
@article {pmid41841662, year = {2026}, author = {Janetos, TM and Gill, MK and French, DD}, title = {Associations Between Social Determinants of Health and Treatment of Exudative Age-Related Macular Degeneration: A Retrospective Cohort Analysis.}, journal = {Ophthalmic epidemiology}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/09286586.2026.2645106}, pmid = {41841662}, issn = {1744-5086}, support = {K12 TR005104/TR/NCATS NIH HHS/United States ; }, abstract = {PURPOSE: To evaluate associations between social determinants of health (SDOH) and treatment rates among patients with exudative age-related macular degeneration (exAMD).<br><br>METHODS: Retrospective cohort study of patients with exAMD utilizing data from the NIH All of Us Research Program. The primary outcome was annual rate of intravitreal injections abstracted from the EHR. Negative binomial regression was used to assess associations between the treatment rate and individual SDOH constructs developed from survey responses among other sociodemographic factors, adjusting for bilateral disease status and follow-up duration. An exploratory factor analysis (EFA) of all SDOH constructs was performed to identify potential latent constructs associated with the primary outcome.<br><br>RESULTS: Among sociodemographic factors, Black individuals had significantly lower injection rates (IRR: 0.32, 95% CI: 0.13-0.79) compared to White individuals. When correcting for multiple comparisons, among the SDOH constructs, there were none that were significantly associated with treatment rate. Within the exploratory factor analysis, a factor identified by poor English proficiency, transportation difficulty, rural care access issues, worse health literacy, and provider concordance issues was associated with a significantly decreased rate of treatment (IRR: 0.73, 95% CI: 0.55-0.96), as well as a factor identified by high neighborhood disorder, high loneliness, high perceived health care and everyday discrimination, and high stress (IRR: 0.74, 95% CI: 0.60-0.92).<br><br>CONCLUSIONS: This study identifies significant racial disparities and SDOH constructs associated with exAMD treatment rates. These findings underscore the complexity of sociodemographic influences on treatment and suggest potential inequities which warrant additional study.}, }
@article {pmid41842764, year = {2026}, author = {Whang, K and Garg, I and Harel, ID and Katz, R and Cui, Y and Zeng, R and Duich, M and Wescott, HE and Koch, T and Bannerman, A and Baldwin, G and Nigalye, A and Lains, I and Eliott, D and Patel, NA and Kim, LA and Vavvas, DG and Miller, JW and Hussain, D and Miller, JB}, title = {Comparative Study of Swept-source Optical Coherence Tomography Angiography Metrics Between Eyes With Adult Onset Vitelliform Dystrophy, Age-related Macular Degeneration, and Healthy Controls.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {}, number = {}, pages = {1-8}, doi = {10.3928/23258160-20260122-02}, pmid = {41842764}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: The aim of this study was to investigate swept-source OCT angiography (SS-OCTA) metrics in adult-onset foveovitelliform dystrophy (AOFVD), intermediate age-related macular degeneration (iAMD), and healthy control eyes.<br><br>PATIENTS AND METHODS: A cross-sectional study analyzing SS-OCTA foveal avascular zone (FAZ), vessel skeletonized density (VSD), and vessel density (VD) using the ARI network was conducted. A mixed-effects multiple regression model adjusting for age was used for statistical analyses.<br><br>RESULTS: The cohort included 204 eyes of 125 patients (control, n = 63; iAMD, n = 93; AOFVD, n = 48). Compared to iAMD, AOFVD eyes had significantly reduced VD, VSD, and FAZ circularity on 3 &#xd7; 3-mm and 6 &#xd7; 6-mm angiograms, and significantly increased FAZ area and FAZ perimeter on 6 &#xd7; 6-mm angiograms. There was no difference on 12 &#xd7; 12-mm angiograms. Compared to controls, AOFVD eyes had significantly reduced FAZ circularity on 3 &#xd7; 3-mm angiograms.<br><br>CONCLUSION: SS-OCTA metrics may help in distinguishing AOFVD from iAMD.}, }
@article {pmid41842765, year = {2026}, author = {Mohan, N and Schulgit, MJ and Bellanda, V and Barbosa, GCS and Szigiato, A and Talcott, KE and Mammo, DA and Babiuch, AS and Kaiser, PK and Ehlers, JP and Rachitskaya, A and Yuan, A and Srivastava, SK and Sharma, S}, title = {Long-term Outcomes of Faricimab in Previously Treated Neovascular Age-related Macular Degeneration.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {}, number = {}, pages = {1-7}, doi = {10.3928/23258160-20260127-02}, pmid = {41842765}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate long-term outcomes of intravitreal faricimab injections (IFIs) in previously treated neovascular age-related macular degeneration (nAMD).<br><br>PATIENTS AND METHODS: This retrospective cohort included 204 eyes from 178 patients with nAMD previously treated with anti-vascular endothelial growth factor (anti-VEGF) therapy. Clinical and imaging data were collected at baseline, after three injections, 1 year, 2 years, and final follow-up.<br><br>RESULTS: Patients were followed for 2.5 &#xb1; 0.3 years. Central subfield thickness decreased from 267.6 &#xb1; 61.0 &#xb5;m to 225.8 &#xb1; 42.1 &#xb5;m (P < .001), and treatment intervals extended from 6.5 &#xb1; 2.4 to 11.5 &#xb1; 8.0 weeks (P < .001). Intraretinal fluid declined from 44.5% to 29.5% (P = .048) and subretinal fluid from 67.5% to 36.8% (P < .001), while vision and pigment epithelial detachment height remained stable. Switching from faricimab to another agent provided no added benefit.<br><br>CONCLUSION: Faricimab demonstrated sustained anatomical improvement and treatment durability over 2.5 years, with a subset of patients showing lasting benefit.}, }
@article {pmid41844139, year = {2026}, author = {Kim, Y and Kim, YT and Kong, M and Kim, JH}, title = {Risk Factors and Quality of Life in Patients With Geographic Atrophy, a Late Stage of Age-Related Macular Degeneration: Findings From the Korea National Health and Nutrition Examination Survey.}, journal = {Journal of Korean medical science}, volume = {41}, number = {10}, pages = {e63}, pmid = {41844139}, issn = {1598-6357}, mesh = {Humans ; *Quality of Life ; Male ; Republic of Korea/epidemiology ; Female ; Aged ; Cross-Sectional Studies ; Risk Factors ; Nutrition Surveys ; *Geographic Atrophy/epidemiology/pathology/diagnosis/complications ; Middle Aged ; *Macular Degeneration/pathology/epidemiology ; Aged, 80 and over ; Smoking ; Diabetes Mellitus/epidemiology ; Adult ; }, abstract = {BACKGROUND: To evaluate the risk factors and quality of life (QoL) in geographic atrophy (GA) in a Korean population.<br><br>METHODS: This cross-sectional study, based on data from the Korea National Health and Nutrition Examination Survey (2017-2021), included 15,030 subjects aged &#x2265; 40 years. Participants were classified into four categories: early age-related macular degeneration (AMD) (n = 2,068), wet AMD (n = 94), GA (n = 36), and no AMD (n = 12,832). Demographics and activity limitations were compared across these groups. Additionally, the subjects' QoL was assessed using the EuroQoL-5 Dimension (EQ-5D) and Health-Related Quality of Life Instrument with 8 Items (HINT-8) methods.<br><br>RESULTS: Among the four groups, the GA group showed highest mean age (72.47 &#xb1; 7.45 years), prevalence of current smokers (61.11%), and prevalence of diabetes (41.67%). GA group reported activity limitations (16.67%) and vision problems (5.56%) at relatively higher rates compared to other groups. In the QoL assessment, the EQ-5D evaluation showed that the GA group experienced a similar decline in QoL as the wet AMD group (0.93 &#xb1; 0.02 vs. 0.93 &#xb1; 0.01; P = 0.971), while the HINT-8 evaluation indicated a relatively more severe QoL decline in GA group compared to wet AMD group (22.74 &#xb1; 3.70 vs. 20.35 &#xb1; 3.33; P = 0.007). GA group frequently reported difficulties with mobility (27.27%), usual activities (15.15%), and climbing stairs (61.54%), which were comparable to the frequencies observed in patients with wet AMD.<br><br>CONCLUSION: In South Korea, patients with GA tended to have relatively higher rates of current smoking and diabetes compared to individuals without GA. A decline in QoL in these patients was primarily associated with activity limitations. To improve patients' QoL, social support is needed to help overcome these activity limitations. Furthermore, it will be necessary to introduce therapeutic interventions to slow the progression of GA.}, }
@article {pmid41844146, year = {2026}, author = {Chotikavanich, S and Phisalprapa, P and Kositamongkol, C and Choopong, P and Eiamsamarng, A and Muneesri, P and Yingyong, R and Nujoi, W and Dongngam, S and Jai-Ai, J and Sarinak, N and Eksupapan, E and Sagan, S}, title = {Socioeconomic impact assessment of low vision and blindness on patients and households in Thailand.}, journal = {Clinical &amp; experimental optometry}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/08164622.2026.2641537}, pmid = {41844146}, issn = {1444-0938}, abstract = {CLINICAL RELEVANCE: Services for patients with low vision and blindness aim to improve their well-being. This can be achieved by understanding the effects of vision loss on all aspects of life, thereby enabling clinicians to design appropriate rehabilitation models.<br><br>BACKGROUND: This study explored the socioeconomic impact of low vision and blindness, mainly due to untreatable bilateral eye diseases, on individuals and their households.<br><br>METHODS: A cross-sectional study conducted at a low-vision clinic, in which participants were interviewed regarding socioeconomic changes following visual impairment. Multivariable logistic regression was used to identify predictors of income reduction.<br><br>RESULTS: A total of 110 patients (mean age 51.4&#x2009;&#xb1;&#x2009;14.6&#x2009;years) were enrolled. Retinitis pigmentosa was the leading cause of visual impairment (35.4%), followed by optic atrophy, glaucoma, and age-related macular degeneration. Following vision loss, 41.8% of patients became unemployed. A significant occupational shift occurred, with many transitioning from professionals to having no occupation (p&#x2009;<&#x2009;0.001). The primary monthly income of patients decreased significantly (p&#x2009;<&#x2009;0.001), and the proportion of patients with no income increased (7.3-50.9%). Multivariable analysis showed significant associations between primary income reduction and age groups of 31-40&#x2009;years (adjusted odds ratio [AOR] 10.7, 95% CI: 1.2-96.0, p&#x2009;=&#x2009;0.035), 51-60&#x2009;years (AOR 8.4, 95% CI: 1.2-59.9, p&#x2009;=&#x2009;0.034), and over 60&#x2009;years (AOR 46.5, 95% CI: 4.8-445.6, p&#x2009;<&#x2009;0.001). Although not significant, the income decline was greater in patients with poor visual acuity or large peripheral field loss than in those with central scotoma. Most patients had family caregivers who remained employed.<br><br>CONCLUSION: Low vision and blindness due to incurable bilateral eye disease were associated with substantial income loss and transition out of paid employment, underscoring the need for integrated rehabilitation and social protection policies to address functional and socioeconomic needs.}, }
@article {pmid41844666, year = {2026}, author = {Shen, J and Zhao, H and Fang, Y and Lv, X and Chen, L and Miao, Y and Wu, Z and Liu, N and Zhang, Q and Yang, Y and Chen, Q}, title = {Permeable nanoreactor eye drop for enzymatic cascade-mediated treatment for acute retinal injury model mimicking geographic atrophy.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-70761-0}, pmid = {41844666}, issn = {2041-1723}, abstract = {Geographic atrophy (GA), the most prevalent form of age-related macular degeneration (AMD), remains clinically challenging due to its complex pathogenesis. Using an acute retinal injury model that mimics GA pathology (oxidative stress-induced retinal apoptosis), we identify enzymatic cascade restoration as a promising therapeutic strategy. To overcome ocular delivery barriers, we engineer zwitterionic nanocages for co-delivering catalase (CAT) and superoxide dismutase (SOD) (Z(CAT&amp;SOD)). These optimized nanocages achieve a remarkable 9.32% ocular penetration rate, which significantly outperforms free peroxidase (0.54%), through conjunctival-sclera-retina and conjunctival-blood-retina penetration pathways, and achieve therapeutic efficacy comparable to intravitreal injection. In the chronic management of GA, the non-invasive Z(CAT&amp;SOD) eye drops show superior therapeutic effects to the current gold standard clinical antioxidants and lutein supplement. Therefore, this work reveals the possible association between retinal peroxidase deficiency and GA progression, and proposes a non-invasive, highly effective zwitterionic nanocage for AMD treatment.}, }
@article {pmid41844873, year = {2026}, author = {Cebatoriene, D and Vilkeviciute, A and Duseikaite-Vidike, M and Pileckaite, E and Bruzaite, A and Kriauciuniene, L and Zaliuniene, D and Liutkeviciene, R}, title = {Genetic variants and serum biomarkers of CXCL8, MAP3K7, LTA/TNF, EXOC3L1, PROCR, and TRAF2 in Age-Related macular degeneration: associations with disease risk and therapeutic response.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-42838-9}, pmid = {41844873}, issn = {2045-2322}, abstract = {Since age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in the aging population, it is a significant global health concern. Although anti-vascular endothelial growth factor (anti-VEGF) treatments are effective, not all patients respond to them fully. This study focuses on key single-nucleotide variants in the CXCL8 (rs2227306), MAP3K7 (rs157432), LTA/TNF (rs2229094), EXOC3L1 (rs868213), PROCR (rs867186), TRAF2 (rs10781522), and serum levels of these genes in AMD development and treatment response. It examines the genetic factors associated with susceptibility to AMD and how they influence response to therapy. The study investigates the relationships between specific genetic variations, serum protein levels, and both exudative and early AMD, as well as responses to anti-VEGF treatment. These findings may help guide risk assessment and personalized AMD therapies.}, }
@article {pmid41846907, year = {2026}, author = {Loya, A and Chen, V and Siddiqui, T and Rao, P and Chang, EY}, title = {Morphologic Changes of Macular Choroidal Neovascularization on OCT Angiography Following Faricimab Therapy in Patients With AMD.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261427833}, pmid = {41846907}, issn = {2474-1272}, abstract = {Purpose: To describe morphologic changes on optical coherence tomography angiography (OCTA) in 4 eyes with exudative neovascular age-related macular degeneration (nAMD) after a switch in treatment from aflibercept to faricimab. Methods: A total of 4 eyes from 3 patients were evaluated. Results: Three patients (4 eyes) with nAMD were included. Treatment was switched to faricimab due to inadequate control of exudation or limited treatment interval extension with other antivascular endothelial growth factor (anti-VEGF) therapies. All eyes showed morphologic changes in macular neovascularization (MNV) on OCTA after the switch from aflibercept to faricimab. The MNV trunk persisted in all eyes, with regression of the lacy vasculature after treatment. Despite residual MNV, exudation was well controlled in all eyes at 9- to 11-week treatment intervals. Notably, morphologic changes were seen on OCTA even when structural findings remained largely unchanged. Conclusions: Long-term faricimab therapy is associated with distinct morphologic changes in MNV seen on OCTA that were not observed with other anti-VEGF therapies, highlighting the added value of OCTA for assessing treatment response.}, }
@article {pmid41847520, year = {2026}, author = {Johnson, EJ and Poteet, J and Gioia, N and Maharaj, RRL and Benitez-Del-Castillo, JM and Labetoulle, M}, title = {B Vitamins and Ocular Health.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {575752}, pmid = {41847520}, issn = {1177-5467}, abstract = {The B vitamins are a varied family whose members are integral to metabolic pathways and cellular processes throughout the body. Unlike vitamins A, C, and E, the B complex has generally not been considered among the key ingredients of supplements intended to maintain eye health and prevent age-related disease and vision loss. This perspective may be shifting with the emergence of 3 elements: (1) a greater understanding of the pathogenic mechanisms involved in conditions such as age-related macular degeneration, diabetic retinopathy, glaucoma, cataracts, dry eye disease, and other ocular surface disorders; (2) observational studies linking B vitamins to risk of eye disease development or progression; and (3) preclinical and clinical evidence supporting supplementation with B vitamins to improve potential ocular outcomes. This review synthesizes the available data on the role of B vitamins in promoting healthy eye structure and function, highlighting connections between individual vitamins and disease, and discussing the clinical considerations for B vitamin supplementation.}, }
@article {pmid41848365, year = {2026}, author = {Wang, CX and Wang, J and Hormel, TT and Hwang, TS and Lujan, BJ and Bailey, ST and Huang, D and Jia, Y}, title = {Volumetric and En Face Hyper-Reflective Henle Fiber Layer in Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {41}, pmid = {41848365}, issn = {1552-5783}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; Aged ; *Macular Degeneration/diagnosis/pathology ; Aged, 80 and over ; Fluorescein Angiography ; Geographic Atrophy ; Retinal Drusen ; Retinal Pigment Epithelium/pathology ; Middle Aged ; }, abstract = {PURPOSE: To analyze Henle fiber layer (HFL) hyper-reflectivity in age-related macular degeneration (AMD) with en face optical coherence tomography (OCT).<br><br>METHODS: A total of 279 eyes affected by AMD were imaged with either an Optovue Avanti or Optovue Solix device. Imaging was conducted within a 3 &#xd7; 3-mm area centered on the foveal avascular zone. Hyper-reflective HFL (hr-HFL) regions were segmented by binarizing en face OCT images generated by projecting a slab 45 to 65 &#xb5;m below the inner nuclear layer and outer plexiform layer boundary. Pathological changes, including drusen, subretinal fluid, pigment epithelial detachments (PEDs), macular neovascularization (MNV), and geographic atrophy (GA) were semi-automatically segmented. We investigated the association of these features with the hr-HFL by measuring the overlap ratios, defined as the proportion of hr-HFL area overlapping with the pathological regions after projection onto the same plane.<br><br>RESULTS: Hyper-reflective HFL regions were distinguished by distinct patterns in AMD eyes. It consistently colocalized with drusen, subretinal fluid, PEDs, MNV, and GA. Quantitatively, hr-HFL area was significantly larger in AMD eyes compared to healthy controls (P < 0.001) but did not differ across AMD severity stages. The hr-HFL area correlated with the size of pathologic features (r = 0.64-0.93; all P < 0.001), suggesting that the hr-HFL marks outer retinal abnormalities in AMD.<br><br>CONCLUSIONS: Hyper-reflective HFL regions are a robust marker of outer retinal pathology in AMD. Structural changes such as drusen, fluid, and atrophy likely alter HFL orientation, leading to hyper-reflectivity. Although not specific to any single pathology, the hr-HFL reliably reflects the presence of AMD-related pathological changes.}, }
@article {pmid41849558, year = {2026}, author = {Li, S and Zhang, E and Pan, J and Xu, Y and Zheng, K and Xu, X and Fang, Q}, title = {Usability Evaluation of a Macular Quantitative Square Grid Self-Examination Application in Patients With Macular Disease: Mixed Methods Study.}, journal = {JMIR human factors}, volume = {13}, number = {}, pages = {e79699}, pmid = {41849558}, issn = {2292-9495}, mesh = {Humans ; Female ; Male ; Aged ; Middle Aged ; *Self-Examination/methods ; *Macular Degeneration/diagnosis ; *Vision Disorders/diagnosis ; Diabetic Retinopathy/diagnosis ; Aged, 80 and over ; *Mobile Applications ; }, abstract = {BACKGROUND: Digital self-monitoring applications could provide individuals with macular disease with a convenient, quantitative method for tracking metamorphopsia at home; yet the usability of such tools remains to be fully established.<br><br>OBJECTIVE: This study evaluated the usability of a macular quantitative square grid self-examination application, a semiquantitative, touch-based self-monitoring application for macular function.<br><br>METHODS: This study used a convergent mixed methods design. The application quantifies (1) distortion severity, (2) distortion area, and (3) temporal trends through a 3-step touch interface. A total of 24 adults with neovascular age-related macular degeneration or diabetic macular edema, accompanied by self-reported metamorphopsia, participated in a single supervised test session. A 10-item System Usability Scale (SUS) was used to assess usability, and semistructured interviews were conducted to gather further insights. Quantitative data were summarized descriptively, and qualitative feedback underwent inductive thematic analysis.<br><br>RESULTS: A total of 24 participants completed the GridMacuScan application self-assessment, the SUS questionnaire, and 11 participants completed the interview when data saturation was achieved. All eyes that showed distortion on the Amsler grid also produced positive distortion maps on the GridMacuScan application, yielding 100% diagnostic concordance. The mean SUS score was 82.1 (SD 8.7), indicating "good-excellent" usability. The inductive thematic analysis yielded four overarching themes: (1) high usability and positive overall experience, (2) perceived functional advantages, (3) shortcomings and optimization suggestions, and (4) strong willingness for continued use.<br><br>CONCLUSIONS: The GridMacuScan application demonstrated diagnostic sensitivity comparable to that of the traditional Amsler grid and received high user ratings for usability. Furthermore, it provided quantitative distortion metrics that could facilitate longitudinal disease surveillance. Future research must be conducted to validate performance in unsupervised home environments and investigate whether sustained use improves time-to-disease-progression detection and treatment outcomes.}, }
@article {pmid41850516, year = {2026}, author = {Datta, M and Bessen, BM and Patel, MJ and Hackam, AS}, title = {Cellular responses of human Muller glia exposed to test dust pollution.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {397}, number = {}, pages = {127968}, doi = {10.1016/j.envpol.2026.127968}, pmid = {41850516}, issn = {1873-6424}, support = {P30 EY014801/EY/NEI NIH HHS/United States ; R21 EY036169/EY/NEI NIH HHS/United States ; }, abstract = {Air pollution is a global environmental hazard and is associated with increased severity and progression of several retinal diseases, including glaucoma and age-related macular degeneration. Muller glia are radial glia in the retina that play essential roles in metabolic support, redox balance and neuroprotection. Despite their importance, the effects of pollution on retinal glial responses are not well characterized. The objectives of this study were to determine the effects of a test dust preparation on viability, injury responses and oxidative stress levels in human Muller glia cell line. Arizona test dust (ATD) contains silica, oxides, particulate matter smaller than 10 μm and other potentially harmful components. Subconfluent cultures of Muller glia MIO-M1 cells were exposed to ATD (0.1 - 50 μg/mL) and cell viability, reactive oxygen species (ROS) production, antioxidant gene expression and transcriptomic analyses were performed. ATD exposure led to increased ROS without reducing viability, and was accompanied by reduced expression of antioxidant genes NRF2 and SOD1. Bulk RNA-seq analysis demonstrated downregulation of numerous mitochondrial genes and alterations in genes regulating migration, inflammation and adhesion. Therefore, these findings indicate that ATD pollution disrupts antioxidant protective mechanisms and mitochondrial gene expression in Muller glia, potentially leading to oxidative imbalance and transcriptional alterations that could contribute to retinal dysfunction.}, }
@article {pmid41850601, year = {2026}, author = {Parashar, AK and Kumar, B}, title = {A framework of hybrid deep learning and nature-inspired algorithms for accurate multi-class fundus disease classification.}, journal = {Experimental eye research}, volume = {267}, number = {}, pages = {110966}, doi = {10.1016/j.exer.2026.110966}, pmid = {41850601}, issn = {1096-0007}, abstract = {Fundus imaging is an essential technique for detecting anatomical changes indicative of various ophthalmological diseases. These alterations-including changes in the macula, optic disc, fovea, and blood vessels-can signal conditions such as diabetic retinopathy, glaucoma, age-related macular degeneration, cataracts, and myopia. In this paper, we propose a novel hybrid framework for classifying multi-class fundus images by combining deep learning feature extraction with nature-inspired algorithms. Pre-trained ResNet-18 and GoogLeNet architectures are employed to extract features, which are subsequently refined using nature-inspired algorithms including Particle Swarm Optimization, Grey Wolf Optimizer, Differential Evolution, Firefly Algorithm, and Genetic Algorithm. Finally, machine learning classifiers, such as K-Nearest Neighbor, Gaussian Naive Bayes, Support Vector Machine, and Logistic Regression, are applied to the optimized feature sets. Our extensive experiments on the ODIR and RFMiD datasets demonstrate that the proposed framework-specifically the combination of the Firefly Algorithm with K-Nearest Neighbor (FAKNN)-achieves state-of-the-art performance, reaching 100% accuracy, recall, precision, Kappa, F1 score, and Area Under the Curve. This approach not only improves diagnostic accuracy but also demonstrates significant potential for clinical application, facilitating early intervention and better patient outcomes.}, }
@article {pmid41851144, year = {2026}, author = {Oh, JY and Chae, JB and Lee, HK and Park, CW and Bae, M and Kim, G and Oh, Y and Yang, G and Kim, S and Ok, HW and Kim, D and Kim, C and Lee, S and Jang, J and Chung, H and Ryu, JH}, title = {Bst2-targeted senotherapy restores visual function by eliminating senescent retinal cells.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-70797-2}, pmid = {41851144}, issn = {2041-1723}, support = {RS-2023-00281553//National Research Foundation of Korea (NRF)/ ; 2020M3A9D8038192//National Research Foundation of Korea (NRF)/ ; RS-2025-00553501//National Research Foundation of Korea (NRF)/ ; RS-2025-16063013//National Research Foundation of Korea (NRF)/ ; RS-2025-25454860//Korea Health Industry Development Institute (KHIDI)/ ; }, abstract = {Senescent cells contribute to degenerative processes in multiple tissues, including the retina. In the retinal pigment epithelium (RPE), their accumulation is closely associated with retinal aging and disease progression. Eliminating senescent RPE cells has shown therapeutic potential, but conventional senolytics often lack the specificity required to spare non-senescent cells, raising safety concerns. To overcome this, we performed integrated transcriptomic analyses of male mouse-derived RPE cells under natural aging and chemically induced senescence conditions. These analyses identified Bst2 as a membrane-localized marker selectively upregulated in senescent RPE cells, with minimal expression in young controls. Based on this discovery, we developed a modular, antibody-pluggable drug delivery platform-B-Z-PON-comprising mesoporous silica nanoparticles functionalized with a recombinant Fc-binding domain and conjugated with anti-Bst2 antibodies. This nanocarrier selectively accumulates in Bst2-expressing senescent RPE cells, enabling targeted drug delivery and sparing healthy retinal cells. In vivo administration of ABT-263-loaded B-Z-PON in aged and senescence-induced retinal degeneration models resulted in the selective ablation of senescent cells, restoration of RPE function, and improved visual outcomes. Together, our study integrates senescence-specific marker discovery with precision nanomedicine, establishing a versatile platform for targeted senotherapy. These findings offer a promising therapeutic approach for retinal aging disorders, such as age-related macular degeneration.}, }
@article {pmid41853443, year = {2026}, author = {Moniruzzaman, M and Azzam, M and Nessa, MS and Ahmed, A and Ahmed, T and Rahman, M}, title = {Intravitreal Brolucizumab Use for Retinal Vascular Diseases in Resource-Constrained Settings: A Retrospective Study From Bangladesh.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e103620}, pmid = {41853443}, issn = {2168-8184}, abstract = {Background Anti-Vascular Endothelial Growth Factor (VEGF) therapy has been proven effective and safe for retinal vascular diseases, but the use of this agent is scarce in resource-constrained countries, including Bangladesh. Considering the limited literature, we have described 17 cases and their outcome using an anti-VEGF agent (brolucizumab) for retinal vascular diseases. Methods This retrospective case review described patients undergoing intravitreal brolucizumab at a tertiary eye care center in Bangladesh from January 2022 to December 2023. Eighteen eyes of 17 patients with complete best corrected visual acuity (BCVA) data for four follow-ups were included. Outcomes of the treatment over six months were changes in BCVA and optical coherence tomography (OCT) measurements, including foveal center point thickness, central subfield retinal thickness, and macular volume. Results Ten eyes were refractory cases who switched from other anti-VEGF agents, while eight were treatment naïve. The median age of the patients was 56 years (Interquartile range or IQR: 48-68 years). Out of all, 52.9% were female patients (n=9) and 47.1% were male patients (n=8). Diabetic retinopathy (n=10, 55.6%) was the most common indication, followed by age-related macular degeneration (n=6, 33.3%). Average BCVA improved in both naïve and refractory eyes over the course of treatment. Median OCT measurements showed a decrease in both naïve and refractory cases. No adverse events occurred. Conclusion Brolucizumab demonstrated visual gain in the short term with a favorable safety profile in a series of cases in the real-world settings of Bangladesh. Larger studies with extended follow-up can further elucidate its long-term utility.}, }
@article {pmid41853568, year = {2026}, author = {Gayraud, L and Lequy, E and Hucteau, E and de Hoogh, K and Coeuret-Pellicer, M and Schweitzer, C and Korobelnik, JF and Delyfer, MN and Vienneau, D and Goldberg, M and Zins, M and Delcourt, C}, title = {Association of Air Pollution Exposure with Incident Cataract Surgery and Neovascular Age-Related Macular Degeneration in 2 French Nationwide Cohorts.}, journal = {Ophthalmology science}, volume = {6}, number = {4}, pages = {101099}, pmid = {41853568}, issn = {2666-9145}, abstract = {PURPOSE: Age-related macular degeneration (AMD) and cataracts are part of the leading causes of blindness globally, with oxidative stress being a key factor in their development. Air pollution, known to exacerbate oxidative stress, may contribute to the progression of these diseases. This study aims at investigating the association between ambient air pollution exposure and the incidence of cataract surgery and neovascular AMD (nAMD).<br><br>DESIGN: Two nationwide prospective French cohorts.<br><br>PARTICIPANTS: The study involved 36 140 participants, including 17 911 Electricit&#xe9; de France-Gaz de France employees from the Gazel cohort and 18 229 individuals from the general French population in the Constances cohort, all aged over 53 years at inclusion and followed up for 10 years.<br><br>METHODS: Cataract surgery and nAMD cases were identified using the French National Health Data System (SNDS), which provided medical procedures and prescriptions. Air pollution exposure to nitrogen dioxide (NO2), fine particulate matter, and black carbon (BC) were estimated using land-use regression models. Cox proportional hazards models adjusted for age, sex, and education were used to assess associations. Analyses were stratified by area of residence (urban vs. rural), because of significant interactions.<br><br>MAIN OUTCOME MEASURES: Neovascular AMD was identified through intravitreal anti-VEGF injections, and cataract surgery by the first surgery date, both extracted from SNDS data.<br><br>RESULTS: Among the 36 140 participants included (39% women, mean age 60.2 years), 5543 incident cataract surgery and 266 nAMD cases were identified. In the combined Constances and Gazel populations, urban individuals exposed to more than 34.8 &#x3bc;g/m[3] of NO2 had an 8% higher risk of cataract surgery (HR = 1.08, 95% confidence interval [CI]: 1.01-1.16, P = 0.017), while no significant effect was observed among rural participants. Additionally, in the Constances cohort, participants exposed to the fourth quartile (&#x2265;2.33 10[-5]/m) of BC had an 88% increased risk of nAMD compared to those exposed to the first quartile (HR = 1.88, 95% CI: 1.03-3.45, P = 0.041). No significant association with BC was observed in the combined Constances and Gazel populations.<br><br>CONCLUSIONS: This study provides new insights into the impact of air pollution on ocular aging at a national level, highlighting the distinct effects observed between urban and rural populations.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41853572, year = {2026}, author = {Kaufmann, A and Blair, J and Lasagni Vitar, R and Wykoff, CC and Cao, J and Staurenghi, G and Cozzi, M and Ciller, C and Apostolopoulos, S and De Zanet, S}, title = {Phenotyping of Patients with Age-Related Macular Degeneration Using Artificial Intelligence-Driven Biomarker Patterns in OCT.}, journal = {Ophthalmology science}, volume = {6}, number = {4}, pages = {101101}, pmid = {41853572}, issn = {2666-9145}, abstract = {PURPOSE: To leverage artificial intelligence-based OCT analysis to classify age-related macular degeneration (AMD) images into distinct subgroups based on retinal layer and fluid biomarkers.<br><br>DESIGN: Retrospective analysis of a data set of retinal OCT images.<br><br>PARTICIPANTS: Anonymized data from 157 patients with AMD and 58 healthy volunteers.<br><br>METHODS: This study analyzed OCT scans from patients with AMD and healthy volunteers to extract retinal layer thickness and fluid biomarkers by artificial intelligence-driven image segmentation. We performed dimensionality reduction using parametric Uniform Manifold Approximation and Projection, followed by k-means clustering to partition the continuous disease space into 9 subphenotypes for analysis. Statistical analyses included linear mixed-effects modeling, analysis of variance, and Fisher exact tests to assess biomarker differences, visual acuity (VA), and lesion size across clusters. We mapped International Classification of Diseases, 10th Revision (ICD-10) codes to validate disease staging.<br><br>MAIN OUTCOME MEASURES: We examined the potential of artificial intelligence-driven biomarker patterns based on the comparison to traditional clinical measures such as VA, lesion size, and ICD-10 codes for different disease stages.<br><br>RESULTS: By dividing the continuous landscape into 9 regions for interpretability, we observed that each cluster was characterized by a distinct biomarker pattern. Clusters exhibited outer retinal thinning of varying degrees and showed significant differences in inner retinal layers, choroidal thickness, subretinal pigment epithelium material, and fluid presence compared with a healthy cohort, suggesting diverse AMD subtypes beyond simple characterization by VA and atrophic lesion size alone. The distribution of ICD-10 codes further supported the interpretation of the AMD landscape as a representation of AMD progression.<br><br>CONCLUSIONS: This study reveals a continuous AMD landscape based on OCT-derived biomarkers, suggesting the existence of subphenotypes beyond traditional staging methods. The findings further highlight the limitations of fundus-based disease classification and support the role of OCT scans in personalized disease management.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41854587, year = {2026}, author = {Liu, TYA and Ko, S and Rosettie, KL and Bonine, NG and Pletcher, A and Burke-Conte, Z and Flaxman, AD and Lei, J and Oron, AP and Borkar, D and Brodie, FL}, title = {Prevalence and Health Care Disparities of Retinal Conditions: A Meta-Analysis.}, journal = {JAMA ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {41854587}, issn = {2168-6173}, abstract = {IMPORTANCE: Age-related macular degeneration (AMD), diabetic retinopathy (DR), diabetic macular edema (DME), and retinal vein occlusion (RVO) are leading causes of vision impairment and can lead to permanent, irreversible blindness.<br><br>OBJECTIVE: To update age-standardized prevalence estimates for AMD, DR, DME, and RVO by gender, race and ethnicity, and US state or county for 2022.<br><br>DATA SOURCES: The National Health and Nutrition Examination Survey (NHANES; 2005-2008 and 2017-March 2020), Medicare fee-for-service claims (2017-2019), IBM MarketScan commercial insurance claims (2016), and eligible population-based studies.<br><br>DATA EXTRACTION AND SYNTHESIS: Bayesian meta-regression analysis of data sources containing prevalence information for AMD, DR, DME, and RVO in the US. Data were analyzed from March to September 2024.<br><br>MAIN OUTCOMES AND MEASURES: AMD prevalence was estimated for ages 40 years and older and reported as total AMD (inclusive of early and late stage). DR (stratified by vision threatening and non-vision threatening) and DME prevalence were estimated across all ages as a proportion of people with diabetes (as defined in NHANES). RVO, defined by the presence of either retinal branch or central vein occlusion, was estimated for ages 18 years and older. Age-standardized estimates were calculated using the 2010 US Census age pyramid.<br><br>RESULTS: For 2022, age-standardized prevalence estimates per 100&#x202f;000 people were 5677 (95% uncertainty interval [UI], 4513-7374) for AMD, 2710 (95% UI, 2112-3647) for DR, 317 (95% UI, 243-505) for DME, and 214 (95% UI, 168-409) for RVO. For all conditions, prevalence was higher in males than females. White individuals had 1.7-fold higher AMD prevalence than Black individuals and 2-fold higher RVO prevalence than Hispanic individuals; Black individuals had more than 2-fold higher DR prevalence and 4.6-fold higher DME prevalence than White individuals, and Hispanic individuals had 1.8-fold higher DR prevalence and 3.7-fold higher DME prevalence than White individuals. State-level prevalence (per 100&#x202f;000 people) ranged from 3497 to 7214 for AMD, 1654 to 3607 for DR, 126 to 504 for DME, and 157 to 273 for RVO.<br><br>CONCLUSIONS AND RELEVANCE: In this meta-analysis, the US prevalence of retinal conditions was substantial, highlighting a considerable health care burden. The updated estimates and sex, race and ethnicity, and regional disparities identified in this study could inform resource allocation across the US and aid in the development of approaches to improve treatment accessibility and patient outcomes for underserved communities.}, }
@article {pmid41854807, year = {2026}, author = {Gil-Rojas, Y and Nicholson, L and Eymere, S and Cox, O and Bagijn, M}, title = {Beyond Cost: Faricimab as a Driver of Service Efficiency and Quality in Neovascular Age-Related Macular Degeneration Care.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41854807}, issn = {2193-8245}, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a chronic, vision-threatening condition requiring ongoing anti-vascular endothelial growth factor (anti-VEGF) injections. As the population ages and the demand for eye care rises, capacity-constrained healthcare systems struggle to deliver timely treatment. In the UK, many patients experience delays, increasing the risk of irreversible visual loss. Therapies with extended dosing intervals, such as faricimab, may reduce treatment burden and improve care quality.<br><br>METHODS: A microsimulation model was developed representing a hypothetical UK National Health Service (NHS) retinal clinic over 5 years, comparing service and cost outcomes for two nAMD therapies. The study included a pairwise comparison (base case) of faricimab versus biosimilar aflibercept 2&#xa0;mg, and a future market analysis comparing contrasting payer strategies, 'treatment choice' (75% faricimab market share) versus 'strict biosimilar mandate' (75% biosimilar market share). Outcomes included quality care delivery metrics, service utilisation, NHS provider costs, and litigation costs. Sensitivity analyses were performed to explore uncertainty.<br><br>RESULTS: Across all scenarios, faricimab reduced injection frequency, clinic visits, and treatment delays compared with biosimilar aflibercept 2&#xa0;mg. In the base case, faricimab reduced delayed visits by 97.4% (158 vs 6171) and improved the key quality care delivery metric of loading phase completion by 54.1 percentage points (95.8% vs 43.7%). Faricimab was also associated with lower acquisition costs, with additional savings arising from reduced service and litigation-related costs. In the future market analysis, a treatment choice policy resulted in improved operational and quality-of-care metrics compared with a strict biosimilar mandate, resulting in lower total costs.<br><br>CONCLUSION: In capacity-constrained settings, more durable options like faricimab can unlock operational capacity, enabling health systems to treat more patients, reduce delays, and more effectively achieve quality standards. These improvements not only help preserve vision but also generate economic value, as operational efficiencies can reduce service and litigation costs, complementing potential reductions in acquisition costs.}, }
@article {pmid41855010, year = {2026}, author = {Wang, XC and Hong, GH and Yun, YS and Choi, IW and Yuk, J and Cha, GH}, title = {Ferroptosis modulation by Toxoplasma gondii suppresses sodium iodate-driven age-related macular degeneration.}, journal = {Genes &amp; genomics}, volume = {}, number = {}, pages = {}, pmid = {41855010}, issn = {2092-9293}, support = {RS-2025-16068439//Basic Science Research Program of the National Research Foundation of Korea/ ; }, }
@article {pmid41856306, year = {2026}, author = {Yan, D and Ouyang, W and Li, K and Sun, X}, title = {Targeting the cGAS-STING pathway in ophthalmology: from innate immunity to therapeutic innovation.}, journal = {Experimental eye research}, volume = {267}, number = {}, pages = {110978}, doi = {10.1016/j.exer.2026.110978}, pmid = {41856306}, issn = {1096-0007}, abstract = {The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a key mediator of the innate immune response to cytosolic DNA, with growing implications beyond traditional host defense mechanisms. Recent research has linked the abnormal activation of this pathway to a wide range of ocular diseases, such as age-related macular degeneration, diabetic retinopathy, corneal injuries, glaucoma, and ocular tumors. This review examines the multifaceted roles of cGAS-STING signaling in ocular inflammation, tissue degeneration, fibrosis, angiogenesis, and immune surveillance. We emphasize the mechanistic basis through which the cGAS-STING pathway orchestrates various pathological processes across different ocular compartments, from the ocular surface to the retina. Additionally, we discuss its interactions with autophagy, cellular senescence, and cell death, exploring its potential as a therapeutic target in inflammatory and neoplastic eye conditions. Finally, we identify key unresolved questions and outline future research directions aimed at exploiting cGAS-STING modulation for precision therapies in vision-threatening diseases.}, }
@article {pmid41857480, year = {2026}, author = {Wu, TE and Chen, HS}, title = {Ocular complications from glucagon-like peptide-1 receptor agonists: Clinical evidence, potential mechanisms, and clinical recommendations.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {}, number = {}, pages = {}, doi = {10.1097/JCMA.0000000000001370}, pmid = {41857480}, issn = {1728-7731}, abstract = {Glucagon-like peptide-1 receptor agonists (GLP-1 RAs)-central to type 2 diabetes mellitus (T2DM) management owing to their comprehensive benefits (glycemic control, weight reduction, cardiovascular benefits, and renal protection)-exhibit a concerning ocular safety profile. Clinical trial data, notably from SUSTAIN-6, revealed a higher incidence of diabetic retinopathy (DR) complications with semaglutide, particularly in patients with pre-existing DR and rapid HbA1c reduction, reflecting early worsening. Conversely, the REWIND and LEADER trials reported no significant DR, suggesting variability among agents and the potential influence of glycemic trajectory. Observational studies and meta-analyses provide mixed findings: some suggest increased DR progression risk in vulnerable populations, while others indicate a lower risk than insulin therapy. Beyond DR, recent pharmacoepidemiologic studies and pharmacovigilance reports have implicated GLP-1 RAs-especially semaglutide-in nonarteritic anterior ischemic optic neuropathy (NAION), leading the European Medicines Agency to classify NAION as a very rare adverse effect and prompting regulatory scrutiny. Conversely, real-world data suggest possible protective associations with other retinal disorders, including reduced incidence of neovascular age-related macular degeneration and diabetic macular edema, although findings remain inconsistent. The mechanistic pathways involve rapid metabolic shifts, vascular dysregulation, and potentially direct effects on retinal or optic nerve tissue. While GLP-1 RAs confer substantial systemic benefits, their ocular risks appear concentrated in high-risk subgroups. Individualized prescribing, baseline ophthalmic assessment, and interdisciplinary monitoring are essential until ongoing prospective trials clarify their long-term ocular impact.}, }
@article {pmid41858558, year = {2026}, author = {Tran, MH and Pruitt, K and Bryarly, M and Emordi, I and Ali, A and Ma, L and Fei, B}, title = {Development and validation of a high-resolution hyperspectral imaging system for the retina.}, journal = {Journal of biomedical optics}, volume = {31}, number = {3}, pages = {036006}, pmid = {41858558}, issn = {1560-2281}, mesh = {Animals ; *Hyperspectral Imaging/methods/instrumentation ; Mice ; *Retinal Vessels/diagnostic imaging ; Algorithms ; Phantoms, Imaging ; *Retina/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Oxygen/metabolism ; Deep Learning ; Mice, Inbred C57BL ; }, abstract = {SIGNIFICANCE: Early detection of Alzheimer's diseases, diabetic retinopathy, or macular degeneration with advanced retinal imaging technologies can help improve patient care and treatment outcome.<br><br>AIM: We aim to create a high-resolution hyperspectral imaging (HSI) system for the retina. Retinal vessel diameter and oxygenation rate will be extracted simultaneously from HSI data.<br><br>APPROACH: Our hyperspectral retinal imaging system consists of a snapshot hyperspectral camera, a high-resolution RGB camera, a beamsplitter, and an imaging endoscope. Multiple pansharpening algorithms, including deep learning methods, were developed to generate high-resolution hyperspectral images that were further used for the measurement of vessel size and oxygenation rate in mice.<br><br>RESULTS: The hyperspectral retinal imaging system was tested for its spatial resolution and spectral fidelity in retina phantoms. In vivo imaging experiments were performed in mice. The deep learning-based pansharpening algorithm achieved a root mean square error (RMSE) of 2.15 &#xb1; 0.64 , a correlation coefficient (CC) of 0.96 &#xb1; 0.05 , a spectral angle score of 0.06 &#xb1; 0.03 radians, and an error relative global dimensionless synthesis (ERGAS) score of 2.37 &#xb1; 1.71 . Oxygen saturation (sO 2) and lumen diameters of blood vessels were measured in the retina. The average lumen diameter of the venules was 45.7 &#xb1; 13.6 &#x2009;&#x2009; &#x3bc; m , whereas the average lumen diameter of the arterioles was 31.5 &#xb1; 8.7 &#x2009;&#x2009; &#x3bc; m . The average arteriole sO 2 was 98%, whereas the average venule sO 2 was 58%.<br><br>CONCLUSIONS: A high-resolution hyperspectral imaging system was developed and validated for retina imaging and measurement of blood vessels and oxygen saturation.}, }
@article {pmid41858680, year = {2026}, author = {Prasad, M and Nagarkar, A and Agron, E and Weber, C and Chew, EY and De Silva, T and Mukherjee, S}, title = {A Datasheet for the Age-Related Eye Disease Study (AREDS) on the database of Genotypes and Phenotypes.}, journal = {Ophthalmology science}, volume = {6}, number = {4}, pages = {101115}, pmid = {41858680}, issn = {2666-9145}, abstract = {OBJECTIVE: Over the years, the Age-Related Eye Disease Study (AREDS) has contributed to the natural history and understanding of progression related to age-related macular degeneration (AMD) and cataracts. This paper summarizes AREDS data elements available for research.<br><br>DESIGN: Data set description for data acquired during AREDS.<br><br>PARTICIPANTS: Adults aged 55 to 80 years with no to advanced AMD in 1 eye but visual acuity >20/32 in eye without advanced AMD.<br><br>METHODS: database of Genotypes and Phenotypes archives and distributes data acquired in clinical studies such as AREDS. This article provides a detailed description of the data available under controlled access under the National Institutes of Health genomic data sharing Policy.<br><br>MAIN OUTCOME MEASURES: Age-Related Eye Disease Study evaluated progression to advanced AMD, 15-letter decrease in visual acuity, and progression of lens opacities as primary outcome measures.<br><br>RESULTS: The data set includes 4757 participants enrolled across 11 participating clinical centers representing varying AMD severity categories and lens opacities. The participants' demographics and clinical variables were collected during baseline and follow-up visits, and data elements included ophthalmic images (fundus and lens photographs) with reading center gradings; nutritional estimates captured from food frequency questionnaires; data related to quality of life, hospitalization, morbidity, and mortality; and genetic data (available in a subset of approximately 2400 participants who submitted blood samples).<br><br>CONCLUSIONS: Summary of data available under controlled access acquired as part of AREDS was provided. The AREDS data set offers a valuable resource for advancing our understanding of AMD and cataract progression and for developing novel tools and applications to transform ophthalmic diagnostics and therapeutics.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41858838, year = {2026}, author = {Cheng, SY and Giguere, D and Kim, S and Seddon, JM and Caiazzi, J and Gross, K and McHugh, N and Echeverria, D and Alterman, JF and Gray-Edwards, H and Benatti, HR and Renner, L and Woolard, H and Stoddard, J and McGill, TJ and Neuringer, M and Brush, RS and Agbaga, MP and Khvorova, A and Punzo, C}, title = {An siRNA targeting S6k1 identifies photoreceptor phospholipid metabolism as a contributor to lipid buildup in age-related macular degeneration.}, journal = {Molecular therapy. Nucleic acids}, volume = {37}, number = {2}, pages = {102878}, pmid = {41858838}, issn = {2162-2531}, abstract = {Age-related macular degeneration (AMD) remains a leading cause for visual impairment in the elderly. We recently showed that activated mammalian target of rapamycin complex 1 (mTORC1) in photoreceptor cells causes AMD-like pathologies in mouse. Employing mouse genetics, we dissect the mTORC1 pathway and identify ribosomal protein S6 kinase beta-1 (S6k1) as a key component required for disease onset in our mouse model. Using a previously identified fully chemically modified tetravalent small interefing RNA (siRNA) that enriches in photoreceptors, we target S6k1 in mouse, pigs, and non-human primates (NHP) by intravitreal injection. We find that S6k1 silencing in diseased mice reverses phospholipid changes induced by activated mTORC1, restores lysosomal activity of retinal-pigmented epithelium cells, and reduces lipoprotein buildup at Bruch's membrane (BM). In pigs, which do not develop disease, we find a similar shift in phospholipids as in mouse, indicating a conserved role for S6k1 in photoreceptor phospholipid metabolism. In aged NHPs with macular drusen, the lipoprotein-rich BM deposits that are a hallmark of human AMD, S6k1 silencing slows drusen growth over a 6-month period. These findings establish S6k1 as modifier of lipoprotein buildup at the BM and support our siRNA platform as a potential treatment modality for AMD and other retinal diseases.}, }
@article {pmid41860312, year = {2026}, author = {Khan, A and Hormel, TT and Gao, M and Guo, Y and Zang, P and Wang, J and Hwang, TS and Bailey, ST and Jia, Y}, title = {Automated Segmentation and Characterization of Retinal Hyperreflective Foci in Age-Related Macular Degeneration.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {3}, pages = {20}, doi = {10.1167/tvst.15.3.20}, pmid = {41860312}, issn = {2164-2591}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Cross-Sectional Studies ; *Macular Degeneration/diagnostic imaging/diagnosis ; Aged ; Female ; Male ; Neural Networks, Computer ; *Retina/diagnostic imaging/pathology ; Aged, 80 and over ; ROC Curve ; Middle Aged ; }, abstract = {PURPOSE: Retinal hyperreflective foci (HRF) are associated with higher risk of progression to advanced age-related macular degeneration (AMD). To enable automated detection, we developed Foci-Net, a convolutional neural network for segmenting HRF in optical coherence tomography (OCT) volumes.<br><br>METHODS: This cross-sectional study included eyes clinically diagnosed with intermediate to advanced AMD and healthy controls. We acquired 6 &#xd7; 6-mm macular-centered scans using 2 OCT systems. Foci-Net modifies the U-Net by replacing the bottleneck with a fine-to-coarse feature extraction block to improve segmentation of both small and large foci. HRF volume was quantified as the proportion of total volume within each retinal layer and characterized by anatomic location. Model performance was evaluated at the count, pixel, eye, and B-scan levels using F1-score, area under the curve (AUC) of the receiver operating characteristic (ROC) curve, precision, sensitivity, and specificity.<br><br>RESULTS: Sixty-one volumetric OCT scans (50 AMD and 11 healthy control eyes) obtained from 50 participants, age 77.65 &#xb1; 9.24 years (mean &#xb1; SD), of whom 72% were women. Foci-Net achieved F1-scores of 73.0 &#xb1; 3.8% counts (based on en face analysis) and 71.6 &#xb1; 29.1% pixels (based on cross-sectional analysis) level relative to the ground truth in 3-fold cross-validation. Diagnostic performance was strong, with an AUC of 100 &#xb1; 0.0% (eye) and 92.7 &#xb1; 0.3% (B-scan) level. HRF was least (2.10%) abundant in the ganglion cell complex and most (55.37%) in the outer nuclear layer.<br><br>CONCLUSIONS: A deep learning approach enables fast HRF segmentation, supporting its role as a biomarker for predicting AMD progression.<br><br>TRANSLATIONAL RELEVANCE: The proposed HRF segmentation method could enhance AMD diagnosis and prognosis.}, }
@article {pmid41860622, year = {2026}, author = {Al-Shammari, YM and AlDhafiri, YM and Ahmad, AK and Alkharraz, BB and Al-Awadhi, MA and Alnabhan, RM}, title = {Clinical efficacy and safety of anti-VEGF biosimilars compared to reference anti-VEGF agents for neovascular age-related macular degeneration: a systematic review, meta-analysis, and meta-regression.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {41860622}, issn = {1573-2630}, mesh = {Humans ; *Biosimilar Pharmaceuticals/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; Visual Acuity ; Treatment Outcome ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Neovascular age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the elderly. Current treatment options include intravitreal anti-VEGF therapy with ranibizumab and aflibercept. These medications are very effective but expensive. Biosimilars of these expensive intravitreal medications have been proposed as less expensive treatment options. However, their clinical equivalence and safety are of concern.<br><br>PURPOSE: The purpose of this study was to assess the efficacy, safety, and immunogenicity of biosimilars of ranibizumab and aflibercept, and their clinical equivalence with their reference biologics, in the treatment of neovascular AMD.<br><br>METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing biosimilar anti-VEGF agents with reference ranibizumab or aflibercept. A comprehensive search of PubMed, Scopus, and Cochrane Library (inception-September 2025) was performed following PRISMA guidelines. Outcomes included change in best-corrected visual acuity (BCVA) at 12&#xa0;weeks and study endpoint, &#x2265;&#x2009;15-letter responder rates, treatment-emergent anti-drug antibodies (ADAs), and ocular/serious ocular adverse events. Risk of bias was assessed using the Cochrane ROB-2 tool.<br><br>RESULTS: Seventeen phase 3 RCTs including 6694 patients were analyzed. Pooled results showed no clinically meaningful differences in BCVA improvement at 12 weeks (MD&#x2009;=&#x2009;-&#x2009;0.42, p&#x2009;=&#x2009;0.17) or at study endpoint (MD&#x2009;=&#x2009;-&#x2009;0.32, p&#x2009;=&#x2009;0.23) between biosimilars and reference biologics. Responder rates (&#x2265;&#x2009;15-letter gain) were comparable (RR&#x2009;=&#x2009;1.06, p&#x2009;=&#x2009;0.36), as were rates of treatment-emergent ADAs (RR&#x2009;=&#x2009;0.89, p&#x2009;=&#x2009;0.40) and ocular adverse events (RR&#x2009;=&#x2009;0.99, p&#x2009;=&#x2009;0.86). The subgroup analysis did not demonstrate significant results for biosimilars of aflibercept compared with the reference aflibercept; however, biosimilars of ranibizumab had slightly less BCVA improvement at the end point (RR 0.53, p 0.02). Heterogeneity was low to moderate, and no publication bias was noted.<br><br>CONCLUSION: Our analysis has demonstrated that biosimilars of ranibizumab and aflibercept have equivalent efficacy, safety, and immunogenicity profiles compared with the reference biologics. Future studies should focus on long-term outcomes, switching studies, and health economics to help determine the long-term success of biosimilar therapy.}, }
@article {pmid41861216, year = {2026}, author = {Lu, F and Zhang, J and Lu, J and Jiang, W and Fei, Z and Xiao, Q and Wang, Z}, title = {Trends, hotspots, and future directions of inflammation in age-related macular degeneration: A 20-year bibliometric study.}, journal = {Medicine}, volume = {105}, number = {12}, pages = {e46598}, pmid = {41861216}, issn = {1536-5964}, mesh = {*Bibliometrics ; Humans ; *Macular Degeneration ; *Inflammation/complications ; *Biomedical Research/trends ; }, abstract = {BACKGROUND: Inflammation significantly impacts the pathogenesis of age-related macular degeneration (AMD), the primary cause of vision loss in the elderly. With the aging global population and increasing incidence of AMD, understanding the inflammation-related mechanisms and identifying potential therapeutic targets have become paramount. This study aims to offer a bibliometric analysis of global research contributions focused on inflammation in AMD, shedding light on research trends, collaborations, and future directions.<br><br>METHODS: We retrieved publications related to inflammation in AMD from 2003 to 2023 from the Web of Science Core Collection database. A total of 2044 articles were analyzed using VOSviewer, CiteSpace, and R-bibliometrix to examine publication trends, influential countries, institutions, authors, and journals, as well as emerging research topics.<br><br>RESULTS: Our analysis revealed a steady global increase in annual publications. The United States and China emerged as leading contributors, demonstrating substantial collaboration and investment in AMD research. Among institutions, the National Eye Institute in the United States and the University of Eastern Finland stood out for their prolific contributions. Key researchers such as Kaarniranta have been central to advancing the field, offering potential collaboration opportunities. Investigative Ophthalmology and Visual Science and Experimental Eye Research were identified as the top journals publishing significant work on inflammation in AMD. Keywords such as "oxidative stress," "complement" "autophagy," "macrophage," and "microglia" were frequently mentioned, highlighting these as current research hotspots.<br><br>CONCLUSION: This analysis underscores the importance of inflammation in AMD and maps the evolution of research, suggesting future directions that may offer new therapeutic strategies.}, }
@article {pmid41861959, year = {2026}, author = {Gale, RP and Loewenstein, A and Zhang, X and Leal, S and Machewitz, T and Sivaprasad, S and Wong, DT and Zeitz, O and Korobelnik, JF and , }, title = {PULSAR: Clinical Outcomes of Aflibercept 8 mg with Extended Dosing and 2 mg in nAMD in Subgroups Defined by Baseline Characteristics.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.02.020}, pmid = {41861959}, issn = {2468-6530}, abstract = {OBJECTIVE: To evaluate the impact of baseline disease severity on clinical outcomes with aflibercept 8 mg with extended dosing intervals versus aflibercept 2 mg in patients with treatment-naïve neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Post hoc descriptive subgroup analysis of PULSAR (NCT04423718), a 96-week, double-masked, randomized, active-controlled clinical trial investigating treatment of nAMD with aflibercept 8 mg with extended dosing intervals or aflibercept 2 mg every 8 weeks. Patients were subgrouped according to severity of baseline disease characteristics, namely best-corrected visual acuity (BCVA), central retinal thickness (CRT), choroidal neovascularization (CNV) lesion type, and CNV area.<br><br>PARTICIPANTS: Patients with nAMD who were randomly assigned to receive aflibercept 8 mg or 2 mg. Overall, 869 patients completed treatment through week 96.<br><br>INTERVENTION: Aflibercept 8 mg was administered every 12 or 16 weeks (8q12 or 8q16) after 3 initial monthly injections. Dosing intervals could be shortened in years 1 and 2 and extended in year 2 based on prespecified disease activity criteria. Aflibercept 2 mg every 8 weeks was administered after 3 initial monthly injections.<br><br>MAIN OUTCOME MEASURES: BCVA and CRT outcomes among subgroups defined by baseline BCVA (&#x2264;54, 55-73, and &#x2265;74 ETDRS letters), CRT (&#x2264;278 &#x3bc;m, 279-343 &#x3bc;m, 344-422 &#x3bc;m, and &#x2265;423 &#x3bc;m), CNV lesion type (minimally classic, occult only, and predominantly classic), and CNV area (<1.3 mm[2], 1.3 to <4 mm[2], 4 to <5 mm[2], and &#x2265;5 mm[2]). Last assigned dosing interval at week 96 for the aflibercept 8q12 and 8q16 treatment arms was also analyzed by disease severity.<br><br>RESULTS: Patients in the aflibercept 8q12 and 8q16 arms achieved visual and anatomic outcomes at week 96 comparable to those in the 2q8 arm within subgroups defined by baseline disease severity. Most patients randomized to the 8q12 and 8q16 arms in each subgroup defined by baseline disease severity had last assigned dosing intervals of &#x2265;12- and &#x2265;16 weeks, respectively, at week 96.<br><br>CONCLUSIONS: Treatment with aflibercept 8 mg can achieve the functional and anatomic benefits observed with aflibercept 2 mg, but with prolonged dosing intervals, regardless of disease severity at initiation.}, }
@article {pmid41862006, year = {2026}, author = {Martyka, A and Bolek, B and Gospodarczyk, N and Czuj, W and Wylęgała, A and Wylęgała, E}, title = {Therapeutic potential of norrin/FZD4/β-catenin signaling in blood-retinal barrier protection.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.03.013}, pmid = {41862006}, issn = {1879-3304}, abstract = {The therapeutic potential of the norrin protein, Frizzled-4 (FZD4) receptor, and the β-catenin signaling pathway is gaining increasing importance in ophthalmology due to their multifaceted effects on the function of the blood-retinal barrier (BRB). Disruption of BRB integrity represents a key mechanism underlying pathological vascular permeability and the progression of diabetic retinopathy and age-related macular degeneration. There remains an unmet need for the development of therapies specifically targeting the protection and regeneration of the BRB, as current treatment strategies primarily focus on symptom alleviation rather than addressing the underlying mechanisms of barrier breakdown. Interest in norrin signaling within the Wnt/β-catenin pathway arises from its crucial role in maintaining BRB integrity through the activation of the Frizzled-4 (FZD4) receptor and LRP5/6 co-receptors, leading to the stabilization of endothelial junctional complexes and the maintenance and restoration of retinal vascular barrier properties, particularly following vascular endothelial growth factor (VEGF)-induced barrier disruptionmodulation of this pthway may represent a novel therapeutic approach aimed at protecting and regenerating the BRB in degenerative retinal diseases. Weidentify current research directions regarding new therapeutic strategies for ophthalmic diseases associated with BRB dysfunction, with particular emphasis on the role of norrin protein, Frizzled-4 (FZD4) receptors, and β-catenin. A comprehensive search was conducted in electronic databases (PubMed, Google Scholar) using the following.}, }
@article {pmid41864469, year = {2026}, author = {Leung, HYE and Zhang, J and Radke, NV and Gan, S and Yao, S and Wang, Z and Li, J and Liu, X and Chong, V and Wang, X and Tan, W and Lam, DSC}, title = {Novel drug development for geographic atrophy.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {100305}, doi = {10.1016/j.apjo.2026.100305}, pmid = {41864469}, issn = {2162-0989}, abstract = {Geographic atrophy (GA), the advanced stage of dry age-related macular degeneration, has transitioned from an untreatable condition to a field of active therapeutic development. This review outlines the key molecular pathways driving GA progression, including complement system dysregulation, oxidative stress, and chronic inflammation. A marked important therapeutic milestone with the first FDA approvals of complement inhibitors, Pegcetacoplan and Avacincaptad pegol, demonstrated a modest but statistically significant slowing of lesion growth. However, these anatomic benefits have not consistently translated into meaningful functional visual improvement, underscoring the need for additional therapeutic strategies. Beyond complement, the therapeutic landscape is rapidly expanding to include oral agents, topical therapies, implant-based delivery systems, subcutaneous injections, and device-based approaches targeting oxidative stress, neuroprotection, mitochondrial dysfunction, lipid metabolism and proteostasis. Emerging modalities, including gene therapy, stem cell-based repair, and bioelectronic implants, aim to move beyond disease slowing toward durable retinal restoration. Despite progress, significant unmet needs persist. Key challenges include treatment burden associated with frequent intravitreal injections, safety considerations, and the persistent disconnect between anatomic endpoints and functional outcomes. These underscore the necessity for future treatments that not only alter disease anatomy but also effectively preserve patients' vision and improve their quality of life.}, }
@article {pmid41866494, year = {2026}, author = {Bhargava, M and Mehta, KN and Parikh, BH and Liu, Z and Su, X}, title = {Advances in retinal pigment epithelium transplantation for age-related macular degeneration: bridging biology to therapeutic frontiers.}, journal = {Stem cell research &amp; therapy}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13287-026-04971-0}, pmid = {41866494}, issn = {1757-6512}, }
@article {pmid41867320, year = {2026}, author = {Lin, Z and Huang, L and Li, D and Yi, S and Weng, J}, title = {Case Report: Maculopathy following standard dose intracameral cefuroxime injection during ICL surgery.}, journal = {Frontiers in ophthalmology}, volume = {6}, number = {}, pages = {1778421}, pmid = {41867320}, issn = {2674-0826}, abstract = {PURPOSE: To describe two rare occurrences of acute toxic maculopathy, specifically Intracameral Cefuroxime Ocular Toxic Syndrome (ICOTS), following uncomplicated posterior-chamber toric phakic implantable collamer lens (TICL) surgery despite the administration of a standard dosage of cefuroxime.<br><br>MATERIALS AND METHODS: This case report identified two patients from a clinical volume of 1,590 eyes treated between 2021 and 2024. Inclusion criteria consisted of patients undergoing bilateral TICL implantation with intracameral cefuroxime who presented with unexpected visual disturbances on postoperative day 1. To isolate cefuroxime as the primary toxic factor, exclusion criteria included systemic comorbidities (such as diabetes mellitus), pre-existing ocular pathologies (including uveitis, macular degeneration, or prior retinal detachment), history of prostaglandin analog use, or baseline structural abnormalities on preoperative optical coherence tomography (OCT). Clinical evaluation included UDVA, BCVA, and SD-OCT imaging.<br><br>RESULTS: Two female patients (aged 29 and 32) underwent bilateral TICL surgery with 0.1 mL of 10 g/L intracameral cefuroxime administered at the conclusion of the procedure. On postoperative day 1, both patients presented with unilateral vision loss (BCVA 20/32 and 20/80, respectively) and reported dim or distorted vision. SD-OCT revealed macular edema and subretinal fluid (SRF). Following conventional postoperative treatment with topical steroids and nonsteroidal anti-inflammatory drugs, complete absorption of SRF was achieved within two weeks to one month, and BCVA improved to 20/16 and 20/20, respectively.<br><br>CONCLUSION: While intracameral cefuroxime is a highly effective prophylactic against endophthalmitis, it may cause sporadic toxic maculopathy even at standard doses during ICL surgery. Unlike typical post-cataract inflammatory edema, ICOTS presents acutely on day 1. Surgeons should maintain a high index of suspicion and utilize early OCT imaging for unexpected postoperative visual disturbances.}, }
@article {pmid41867365, year = {2025}, author = {Gregory-Evans, K and Gregory-Evans, CY}, title = {Molecular insights into foveal hypoplasia: development, genetics, mechanisms, and models.}, journal = {Molecular vision}, volume = {31}, number = {}, pages = {319-343}, pmid = {41867365}, issn = {1090-0535}, mesh = {Humans ; *Fovea Centralis/abnormalities/pathology/growth &amp; development/metabolism ; Animals ; Disease Models, Animal ; Eye Diseases, Hereditary ; Nystagmus, Congenital ; }, abstract = {The fovea is an anatomic specialization of the human retina critical for high visual acuity, color vision, and contrast sensitivity. The molecular and cellular pathways directing this focal topography are still to be determined. Abnormalities of the fovea (e.g., foveal hypoplasia in children) are considered a significant contributor to reduced quality of life. In addition, the fovea is often damaged in common retinal diseases, such as age-related macular degeneration and diabetic retinopathy, with a global economic burden of $500 billion USD. Currently, there are no treatments for foveal defects. Most genes contributing to foveal abnormalities have been identified but are yet to be characterized and studied. This is because common laboratory animals do not have a fovea, and only rare human tissue samples are available during the major phase of foveal maturation, from birth to the end of the fourth year of life. We discuss validation of the anole lizard, which has a foveal structure, for research studies into foveal development. Since foveal development continues after birth, it may be possible to stimulate new foveal maturation where there is developmental damage. From this review, we propose an evidence-based cellular mechanism that offers new possibilities for testing future therapies for foveal defects.}, }
@article {pmid41867749, year = {2026}, author = {Wu, Y and Tong, Y and Byrnes, KG and Zhou, Q and Dong, C and Benjamin, C and Parker, E and Bao, D and Ren, Z and Anderson, CA and Ufret-Vincenty, RL and He, YG and Zhang, Z and Hinkle, D and Ma, J and Wang, S}, title = {Myofibroblast lineage mapping and inhibiting subretinal fibrosis by targeting SMAD3 and MRTF pathways via microRNA-24 functional study.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.03.709397}, pmid = {41867749}, issn = {2692-8205}, abstract = {Subretinal fibrosis underlies the end-stage pathogenesis of retinal diseases including age- related macular degeneration (AMD). It can disrupt retinal structure and eventually lead to legal blindness by generating contractile force, fibrotic scarring, subretinal hemorrhage, and retinal detachment. Myofibroblasts are the predominant cells critically involved in subretinal fibrosis, however, the cellular contribution to myofibroblasts remains unclear. Here we demonstrate that multiple cell lineages, including macrophages, endothelial cells (EC), retinal pigment epithelial (RPE) cells and pericytes, significantly contribute to myofibroblasts in a laser-induced subretinal fibrosis model. We found microRNA miR-24 is significantly downregulated in the plasma of wet AMD patients. Overexpression of miR-24 represses epithelial-mesenchymal transition (EMT), endothelial-mesenchymal transition (EndMT), and the resulting fibrosis by regulating TGF- β/SMAD3 and PAK4/LIMK2/MRTF pathways. Consistently, a combination of SMAD3 and MRTF inhibitors show superior efficacy to individual inhibitors in repressing fibrosis in vitro and laser-induced subretinal fibrosis in vivo . Together, these suggest the contribution of multiple cell-types in myofibroblast transformation in subretinal fibrosis, and repression of miR-24 -regulated TGF-β/SMAD3 and PAK4/LIMK2/MRTF pathways in multiple cell types holds therapeutic potential for treating subretinal fibrosis in AMD and other fibrotic disorders.}, }
@article {pmid41867838, year = {2026}, author = {Little, DR and Shirinifard, A and Lupo, M and Wu, CH and Chen, H and Clemons, MR and Maclean, M and Marola, OJ and Howell, GR and Li, C and Dyer, MA}, title = {Crop-OCT: a Fully Integrated Imageomics Pipeline to Identify Regional and Focal Retinopathy in Murine Models.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.02.27.708333}, pmid = {41867838}, issn = {2692-8205}, abstract = {Imageomics uses machine learning to accelerate our understanding of biological traits and human disease processes. Some of the earliest imageomics applications used deep learning to assess human diseases. For example, retinal fundus images were analyzed to diagnose diabetic retinopathy. The imaging modality optical coherence tomography (OCT) is widely used to diagnose and monitor the progression of retinopathy in patients and preclinical models. The standardized instrumentation and image format of OCT lends itself to imageomics, but generalizable, automated pipelines for segmentation and quantitation of large numbers of OCT images are still in early development. Here, we present the automated, end-to-end pipeline Crop-OCT that extracts features from thousands of OCT images, while preserving their location within the eye. We used the Crop-OCT pipeline on a diverse dataset, including 13 genetic models of retinopathy, with more than 20,000 OCT images, which allowed us to analyze nearly 6 million measured features. The pipeline was generalized on an independent dataset that was analyzed in a blinded manner. The pipeline enabled us to monitor ocular changes associated with aging and progression of diseases, such as retinitis pigmentosa, Leber congenital amaurosis, achromatopsia, Stargardt disease, diabetic retinopathy, and age-related macular degeneration. We also characterized heterogeneity across animals and identified regional and focal lesions. Our pipeline will unify feature extraction for preclinical models of retinal disease and serve as a foundation for future multimodal data integration for artificial intelligence applications based on imageomics.}, }
@article {pmid41868207, year = {2026}, author = {Guo, B and Wang, D and Zhao, Z and Liu, W and Hou, J and Liang, R and Zhang, L}, title = {Evaluation of classification performance for six types of fundus diseases in OCT images based on multi-source training strategy.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1775911}, pmid = {41868207}, issn = {2296-858X}, abstract = {OBJECTIVE: Currently, publicly available Optical Coherence Tomography (OCT) datasets are commonly plagued by limited coverage of disease categories, scarce samples and severe class imbalance, which leads to insufficient generalization ability of deep learning models in real-world clinical settings. This study aims to construct a high-quality OCT dataset encompassing six key types of fundus lesions and normal controls, and to systematically evaluate the improvement effect of training strategies for multi-source data fusion on the performance of multi-class classification.<br><br>METHODS: We integrated local clinical data from Shanxi Eye Hospital with the latest public dataset OCTDL to establish a combined dataset. This dataset consists of 6,165 images, covering seven categories: age-related macular degeneration (AMD), diabetic macular edema (DME), retinal artery occlusion (RAO), retinal vein occlusion (RVO), epiretinal membrane (ERM), vitreomacular interface disease (VID), and normal controls (NO). On this basis, six representative deep learning architectures were selected, and two training paradigms were compared under unified experimental settings: (1) Training exclusively on open-source OCTDL data (S1); (2) Joint training using both local data and OCTDL data (S2). All models were evaluated on the identical OCTDL test set. A comprehensive analysis was conducted using multi-dimensional metrics including accuracy, weighted F1-score, class-specific recall, and area under the curve (AUC), with a particular focus on the misdiagnosis rate.<br><br>RESULTS: The S1 strategy exhibited significantly limited model recognition capability due to the extremely small sample sizes of certain categories. In contrast, the S2 strategy markedly improved the overall performance of the models. Confusion matrix analysis demonstrated that ViT-Base achieved the optimal performance under the S2 strategy: the accuracy reached 93.61%, the misdiagnosis rate of RAO was reduced to 0%, the misdiagnosis rate of AMD was controlled at 1.34%, and the misdiagnosis rate of RVO decreased from 14.89 to 8.51%.<br><br>CONCLUSION: Multi-source data fusion serves as an effective approach to enhance the robustness of OCT multi-category classification models, and it can notably strengthen the recognition capability for certain diseases in particular. This study not only verifies the universal benefits of this strategy but also reveals the critical impact of model selection on the transfer learning effect.}, }
@article {pmid41868220, year = {2026}, author = {Kim, MS and Nam, S and Lee, J and Woo, SJ}, title = {Prevalence, incidence and risk factors of visual disability in patients with exudative age-related macular degeneration: a nationwide population-based study in Korea.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1766076}, pmid = {41868220}, issn = {2296-858X}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss in the elderly. Although anti-vascular endothelial growth factor (VEGF) therapy has improved the visual prognosis of exudative AMD, a considerable proportion of patients still develop severe vision loss. However, real-world data on the prevalence, incidence and risk factors for visual disability among patients with exudative AMD remain limited. This study investigates the prevalence, incidence and risk factors for visual disability among patients with exudative AMD.<br><br>METHODS: This nationwide, population-based retrospective cohort study used Korean National Health Insurance Service data from 2009 to 2023. Patients with newly diagnosed exudative AMD were identified, with a two-year washout period (2009-2010). Prevalence, incidence, hazard ratio (HR) for visual disability were analyzed.<br><br>RESULTS: A total of 147,406 patients with exudative AMD were included. The prevalence of visual disability in 2023 was 4.82% and the overall incidence rate was 12.18 per 1,000 person-years. At 8&#x202f;years, the cumulative incidence probability of monocular visual disability was 4.8% (95% CI, 4.6-5.1), and that of binocular visual disability was 4.4% (95% CI, 4.1-4.7). The mean duration from exudative AMD diagnosis to visual disability was 3.3&#x202f;&#xb1;&#x202f;2.6&#x202f;years. The risk of visual disability increased with older age group (HR, 1.38; 95% CI, 1.35-1.42) and lower income level (HR, 1.06; 95% CI, 1.05-1.08). Female sex (HR, 1.41; 95% CI, 1.35-1.47), diabetic retinopathy (HR, 1.16; 95% CI, 1.08-1.25), glaucoma (HR, 1.10; 95% CI, 1.05-1.15), and severe intraocular hemorrhage requiring vitrectomy (HR, 3.14; 95% CI, 2.63-3.75) were also significant risk factors. A decreasing trend in visual disability incidence was observed among patients who were more recently diagnosed with exudative AMD (-0.25% point per year; p&#x202f;<&#x202f;0.001).<br><br>CONCLUSION: The burden of AMD-related visual disability remains significant, highlighting the need for strategies to improve treatment adherence and ensure equitable access to vision-preserving care. The decreasing trend of visual disability in recent years suggests the practical benefit of improved access to anti-VEGF treatment through lower drug costs and expanded insurance coverage.}, }
@article {pmid41868245, year = {2026}, author = {Xu, W and Zhang, J and Shangguan, Y and Luo, R and Zhu, Y and Bi, Y and Chen, L and Li, B}, title = {Targeting the neurovascular unit in retinal fibrosis: mechanisms and therapeutic perspectives.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1776869}, pmid = {41868245}, issn = {2296-858X}, abstract = {Retinal fibrosis, a severe complication observed in conditions like age-related macular degeneration and diabetic retinopathy, characterized by aberrant myofibroblast activation and excessive extracellular matrix (ECM) deposition, which ultimately led to irreversible visual impairment. Currently, the mechanisms underlying retinal fibrosis remain unclear and existing treatments remain incompletely understood. Thus, a comprehensive understanding of disease mechanisms, together with the development of innovative therapeutic approaches, is essential for advancing effective treatment strategies. This review systematically examines the pathogenesis of retinal fibrosis from the perspective of the neurovascular unit (NVU), with a particular focus on the roles of endothelial cells, pericytes, and glial cells in fibrotic processes. It highlights key fibrotic mechanisms, including epithelial mesenchymal transition (EMT) as well as macrophage and pericyte-to-myofibroblast transitions (MMT/PMT). It further analyzes the molecular mechanisms that regulate myofibroblast activation and extracellular matrix deposition. Additionally, this review outlines potential therapeutic targets for the treatment of retinal fibrosis.}, }
@article {pmid41871654, year = {2026}, author = {Trinh, M and Kalloniatis, M and Jones, BW and Yiu, GC and Borrelli, E and Nivison-Smith, L}, title = {Inner-retinal changes in AMD: Evidence, mechanisms, and future perspectives.}, journal = {Progress in retinal and eye research}, volume = {}, number = {}, pages = {101463}, doi = {10.1016/j.preteyeres.2026.101463}, pmid = {41871654}, issn = {1873-1635}, abstract = {Age-related macular degeneration (AMD) has traditionally been regarded as a disorder of the outer-retina and choroid, characterised by drusen accumulation, retinal pigment epithelium (RPE) dysfunction, and photoreceptor degeneration. However, increasing evidence of inner-retinal involvement across the AMD spectrum, with structural and functional compromise evident from the early stages of disease, challenges this paradigm. Advances in spatially optimised optical coherence tomography (OCT), OCT angiography (OCTA), and high-resolution histology have revealed neuronal, vascular, and glial alterations within the inner-retina that reshape our understanding of AMD pathogenesis. This review synthesises clinical and experimental evidence on inner-retinal changes in AMD, including layer-specific thinning, microvascular rarefaction, impaired neurovascular coupling, and reactive gliosis. Such changes frequently emerge in early AMD, may precede, parallel, or exacerbate outer-retinal degeneration, and are associated with visual dysfunction not fully explained by photoreceptor loss alone. Importantly, mechanistic interactions between inner- and outer-retinal pathology support a bidirectional model of neurodegeneration, wherein region-specific vulnerability is shaped by perfusion dynamics, metabolic demands, and structural connectivity throughout the retina. Recognition of these processes expands the potential for earlier diagnosis, refined monitoring, and novel therapeutic targeting. By integrating structural, functional, and systemic insights, this review reframes AMD as a multi-layer neurovascular disease and underscores the central role of inner-retinal integrity in future AMD research and management.}, }
@article {pmid41872539, year = {2026}, author = {Gurumoorthy, D and Riotto, E and Faes, L and Spooner, K and Fu, DJ}, title = {Infographic: AREDS[1]&amp;AREDS[2]-oral supplementation with antioxidants for age-related macular degeneration (AMD).}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41872539}, issn = {1476-5454}, }
@article {pmid41873297, year = {2026}, author = {Katsanos, A and Benekos, K and Karavasili, M and Gorgoli, K and Kostoulas, C and Gartzonika, K and Christodoulou, DK and Katsanos, K and Georgiou, I}, title = {Intestinal Microbiome of Newly Diagnosed Patients With Neovascular Age-Related Macular Degeneration: A 16S rRNA Gene Sequencing Study.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e103984}, pmid = {41873297}, issn = {2168-8184}, abstract = {BACKGROUND: This study aims to explore differences in the intestinal microbiome between patients with newly diagnosed neovascular age-related macular degeneration (AMD) and controls using 16S rRNA gene sequencing.<br><br>METHODOLOGY: In this cross-sectional study, stool samples from newly diagnosed White patients with neovascular AMD and controls were used for the assessment of the intestinal microbiome. The DNeasy PowerSoil Pro Kit (QIAGEN, Hilden, Germany) was used to extract microbial DNA before sequencing the V3-V4 hypervariable region of the 16S rRNA gene on the Illumina MiSeq system (Illumina, San Diego, CA). Bioinformatic analysis was performed on the Nephele platform using the DADA2 pipeline in R (ClinicalTrials.gov identifier: NCT05757674).<br><br>RESULTS: Thirty-three patients (age: 75 &#xb1; 7 years, 17 women) and 34 age- and sex-matched controls (age: 73 &#xb1; 7 years, 18 women) were analyzed. No differences in height, weight, body mass index, smoking, or systemic comorbidities were noted between the groups. The most prevalent phyla in both groups were Firmicutes, Bacteroidota, Proteobacteria, and Actinobacteria. The most prevalent genus was Bacteroides in both groups. Neither alpha nor beta diversity was different among the groups. The differential abundance analysis using Analysis of Compositions of Microbiomes with Bias Correction 2 (ANCOM-BC2) showed that some Amplicon Sequence Variants (ASVs) from the Coprococcus genus were more abundant in controls than in patients with AMD, whereas several ASVs from Bacteroides were more abundant in the AMD group.<br><br>CONCLUSIONS: In our sample, the intestinal microbiome of newly diagnosed patients with neovascular age-related AMD showed some small but noteworthy differences compared to matched healthy controls. Some Bacteroides ASVs were enriched in AMD patients, while certain Coprococcus ASVs were more abundant in controls.}, }
@article {pmid41874061, year = {2026}, author = {Liu, T and Liao, YF and Liu, JX and Zhang, YP and Yu, YL and Wang, T and Wu, ZX and You, ZP}, title = {Advances in the application of metal-organic frameworks in ophthalmology.}, journal = {Biomaterials science}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5bm01641j}, pmid = {41874061}, issn = {2047-4849}, abstract = {The global burden of vision impairment and blindness caused by eye diseases continues to grow. The eye's inherent physiological barriers-such as the corneal barrier and blood-retinal barrier-lead to challenges in traditional therapies, including low drug bioavailability, poor targeting, and the need for frequent administration. Metal-Organic Frameworks (MOFs), as a class of emerging porous materials, offer promising solutions to overcome these delivery bottlenecks due to their tunable pore structures, high specific surface areas, and ease of functionalization. This review systematically summarizes the latest research advances of MOFs in ophthalmology, focusing on their application as smart carriers for treating various eye diseases including infectious keratitis, bacterial endophthalmitis, glaucoma, age-related macular degeneration, and diabetic retinopathy. It also highlights their innovative use as sensors for tear biomarker detection, intraocular pressure monitoring, and aqueous humor proteomics analysis. Furthermore, this paper delves into ocular delivery strategies for MOFs and systematically analyzes the challenges and future research directions for their clinical translation. It concludes that optimizing material design, strengthening interdisciplinary collaboration, and developing multifunctional integrated platforms are key to advancing this field.}, }
@article {pmid41875412, year = {2026}, author = {Spaide, RF}, title = {Dry Retina Is Not Enough: Re-centering Visual Acuity in Anti-VEGF Therapy for Neovascular AMD.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004841}, pmid = {41875412}, issn = {1539-2864}, abstract = {Anti-vascular endothelial growth factor therapy transformed neovascular age-related macular degeneration, but durability and anatomic drying gradually became proxies for efficacy. Visual acuity gains have plateaued across successive agents. Feedback-driven treatment strategies obscure differences. Future progress should be judged by meaningful improvements in visual function, not extended dosing intervals alone.}, }
@article {pmid41876602, year = {2026}, author = {Steiner, S and Gerendas, BS and Deak, G and Leingang, O and Whitby, A and Bogunovic, H and Reiter, GS and Schmidt-Erfurth, U}, title = {Correlation between human expert macular fluid height assessment and fluid volume quantification in neovascular age-related macular degeneration.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-44982-8}, pmid = {41876602}, issn = {2045-2322}, abstract = {To investigate the association between manually measured retinal fluid heights and AI-quantified retinal fluid volumes and to explore disease activity indicated by fluid volume distributions in neovascular age-related macular degeneration (nAMD) using an approved AI-based algorithm. This retrospective study analyzed baseline OCT data from a multicenter nAMD cohort. Manually measured maximum macular fluid heights on B-scans in the central millimeter (CMM) for intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) were compared with vertical fluid heights and three-dimensional volumes obtained by automated quantification using an AI-based tool (RetInSight Fluid Monitor Version 2). Out of 890 eyes, IRF was identified in the CMM in 328 eyes, SRF in 502 eyes, and PED in 705 eyes. The correlation between manual and AI-based height measurements was strong for IRF (r = 0.87) and PED (r = 0.91), and moderate for SRF (r = 0.67). Manual height-AI volume correlations within the CMM were strong for IRF (r = 0.76) and PED (r = 0.87), and moderate for SRF (r = 0.55). These correlations decreased when total fluid volumes within the central 6 mm were compared with manual CMM height, indicating that CMM height does not represent total nAMD disease activity. In conclusion, AI-derived and manual height measurements showed strong agreement for IRF and PED and moderate agreement for SRF. Maximum fluid height did not reliably reflect overall fluid volume or spatial distribution. AI-based retinal fluid assessment enables quantitative, whole-volume evaluation of retinal fluid and provides a measure of nAMD disease activity.}, }
@article {pmid41876676, year = {2026}, author = {Shenoy, R and Monachan, MT and Gruszka-Goh, M and McKibbin, M}, title = {The Royal College of Ophthalmologists National Ophthalmology Database age-related macular degeneration (AMD) audit: report 1, associations with socio-economic deprivation in neovascular AMD.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41876676}, issn = {1476-5454}, support = {ACF-2023-11-004//DH | National Institute for Health Research (NIHR)/ ; }, abstract = {BACKGROUND: Early diagnosis and treatment of neovascular age-related macular degeneration (NvAMD) improve vision outcomes. This analysis investigates associations of English indices of multiple deprivation 2019 (IMD2019) with baseline characteristics, key care processes and visual acuity (VA) outcomes for NvAMD in the National Ophthalmology Database (NOD).<br><br>METHODS: Eligible eyes started treatment for NvAMD in England between 01/04/2020 and 31/03/2023. Participating centres with &#x2265;25 eyes with baseline VA and IMD2019 data were included.<br><br>RESULTS: Eligible for analysis were 48,583 eyes from 60 English centres. Between decile 1 (most deprived) and decile 10 (least deprived), median age at start of treatment ranged from 79 to 82 years and median baseline VA ranged from 56 to 60 ETDRS letters. After one year of treatment (-28 to +84 days), the median number of injections administered ranged from 7 to 8 across deciles. Loss to follow-up was observed in 13.7% eyes in decile 1, and 11.8% in decile 10. Median VA at 12 months ranged from 61 to 65 ETDRS letters across deciles. A "good" VA outcome (&#x2265;70 ETDRS letters) was achieved by 45.5% in decile 10, compared with 35.9% observed in decile 1 (p&#x2009;<&#x2009;0.001). A "poor" VA outcome (&#x2265;10 ETDRS letter loss from baseline) occurred in 18.4% of eyes in decile 1 versus 14.5% in decile 10 (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: Patients starting NHS-funded treatment in England for NvAMD and living in areas of higher socioeconomic deprivation were typically younger, had lower baseline acuity and achieved worse VA outcomes than those from lower deprivation areas, with little variation in treatment between the deciles.}, }
@article {pmid41877040, year = {2026}, author = {Kocamış, &#xd6;}, title = {Association between optical coherence tomography biomarkers and systemic inflammatory indices in neovascular age-related macular degeneration.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04753-5}, pmid = {41877040}, issn = {1471-2415}, }
@article {pmid41877687, year = {2025}, author = {Hayat, B and Alone, DP}, title = {Unfolded proteins and aggregates: The role of proteostasis in pseudoexfoliation pathology.}, journal = {Molecular vision}, volume = {31}, number = {}, pages = {463-484}, pmid = {41877687}, issn = {1090-0535}, mesh = {Humans ; *Exfoliation Syndrome/metabolism/pathology ; *Proteostasis ; *Unfolded Protein Response ; *Protein Aggregates ; Animals ; Autophagy ; *Protein Aggregation, Pathological/metabolism/pathology ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitin/metabolism ; Endoplasmic Reticulum Stress ; Protein Folding ; Aging/metabolism ; }, abstract = {BACKGROUND: Proteostasis impairment is central to cellular dysfunction in protein aggregation disorders such as Alzheimer disease, Parkinson disease, and age-related macular degeneration. Pseudoexfoliation (PEX), a systemic age-related disorder and a leading cause of secondary glaucoma, is increasingly recognized as a protein aggregation disease. It is characterized by the deposition of pseudoexfoliative material (PEXM) in ocular tissues, leading to elevated intraocular pressure and optic neuropathy.<br><br>OBJECTIVE: This review synthesizes current evidence on the role of proteostasis failure in PEX pathogenesis, with a focus on molecular mechanisms, stress response pathways, and potential therapeutic interventions.<br><br>METHODS: We conducted a comprehensive literature review of studies examining proteostasis mechanisms in PEX. Emphasis was placed on cellular pathways regulating protein synthesis, folding, and degradation, including the unfolded protein response (UPR), ubiquitin-proteasome system (UPS), and autophagy, as well as environmental and aging-related triggers of proteotoxic stress.<br><br>RESULTS: Evidence indicates that chronic proteotoxic stress, arising from aging, oxidative damage, and environmental influences, disrupts the proteostasis network (PN). Dysregulation of ER stress signaling, cytosolic stress responses, and protein degradation pathways contributes to the accumulation of misfolded proteins and extracellular matrix deposits in ocular tissues. These molecular alterations underlie disease onset and progression in PEX syndrome (PEXS) and PEX glaucoma (PEXG).<br><br>CONCLUSIONS: Proteostasis dysfunction plays a pivotal role in PEX pathogenesis by promoting protein misfolding, aggregation, and extracellular deposition. Targeting the proteostasis network, through modulation of stress responses and enhancement of degradation pathways, represents a promising therapeutic strategy for PEXS and PEXG.}, }
@article {pmid41878122, year = {2026}, author = {Gong, J and Wang, P and Xu, Y and Xia, X}, title = {Nanotechnology-Based Treatment for Ophthalmic Diseases.}, journal = {International journal of nanomedicine}, volume = {21}, number = {}, pages = {597696}, doi = {10.2147/IJN.S597696}, pmid = {41878122}, issn = {1178-2013}, mesh = {Humans ; *Eye Diseases/drug therapy/therapy ; *Nanomedicine/methods ; Animals ; Drug Delivery Systems/methods ; *Nanotechnology/methods ; Nanoparticles/chemistry ; Genetic Therapy/methods ; Nanoparticle Drug Delivery System ; }, abstract = {Eye diseases are a major global public health issue causing vision impairment and blindness. The eye's physiological barriers limit traditional drug delivery methods, resulting in low bioavailability, high risks, and poor patient compliance. Nanotechnology offers a revolutionary solution that can enhance the abilities of drugs in corneal retention, barrier penetration, targeted delivery and controlled release to improve efficacy and reduce side effects.This paper reviews the latest advances in nanotechnology for treating ophthalmic diseases. It covers primary nanocarrier systems (lipid, polymeric, carbon-based, and metallic/metallic compound nanoparticles), detailing their characteristics and ocular application potential. It also focuses on specific applications: nanomedicine for anterior segment disorders (cataracts, dry eye, inflammatory conditions) and posterior segment diseases (age-related macular degeneration, diabetic retinopathy, retinal vein occlusion), breakthroughs in delivering anti-VEGF drugs, and innovative applications in treating refractory ocular tumors. Additionally, it explores nanotechnology's prospects in ocular tissue regeneration and retinal gene therapy. Finally, the paper discusses challenges in clinical translation, including standardization, biosafety evaluation, and regulatory approval, and offers an outlook for future development.}, }
@article {pmid41878598, year = {2026}, author = {D'Souza, PR and Sugathan, A}, title = {Charles bonnet syndrome with subsequent depression in acute angle-closure glaucoma: a case report.}, journal = {Oxford medical case reports}, volume = {2026}, number = {3}, pages = {omag024}, doi = {10.1093/omcr/omag024}, pmid = {41878598}, issn = {2053-8855}, abstract = {Charles Bonnet syndrome (CBS) presents with complex visual hallucinations in visually impaired individuals with preserved insight. While most commonly associated with macular degeneration, it may occur in glaucoma. CBS is often under-reported due to stigma and may progress to psychiatric morbidity. A 63-year-old man with bilateral visual loss following acute angle-closure glaucoma experienced vivid hallucinations of animals and snakes. Initially concealed due to embarrassment, the symptoms were revealed during psychiatric assessment. Ophthalmic evaluation confirmed glaucomatous changes; MRI brain was recommended but declined. CBS was diagnosed, and hallucinations resolved with reassurance and low-dose clonazepam. Several weeks later, the patient developed moderate depression (HAM-D = 18), successfully treated with mirtazapine. At three months, he remained asymptomatic. This case is unusual for its association of CBS with angle-closure glaucoma and subsequent depression, underscoring the need for proactive inquiry, de-stigmatization, and integrated ophthalmic-psychiatric care.}, }
@article {pmid41878622, year = {2026}, author = {Zhang, B and Tian, F and Hu, X and Hu, Y and Li, W}, title = {Expression Characteristics of Soluble sCD13 in Wet Age-Related Macular Degeneration and Its Diagnostic Value and Correlation Study.}, journal = {International journal of general medicine}, volume = {19}, number = {}, pages = {553165}, doi = {10.2147/IJGM.S553165}, pmid = {41878622}, issn = {1178-7074}, abstract = {OBJECTIVE: This study explored the level of soluble CD13 (sCD13) and its correlation with angiogenic factors, evaluating the predictive efficacy of sCD13 in wet age-related macular degeneration (wAMD).<br><br>METHODS: 200 patients were included (58 in Non AMD group, 42 in Early AMD group, and 100 in wAMD group). Detailed routine and ophthalmologic examinations were performed on all subjects, and the central retinal thickness (CRT) and ganglion cell-inner plexiform layer (GCIPL) were determined. The concentration of sCD13 was compared. The correlation of sCD13 with PDGF, hsCRP and IL-8 was analyzed. ROC curves were plotted and the diagnostic value of sCD13 was assessed by area under the curve (AUC).<br><br>RESULTS: The sCD13 concentration of patients in the wAMD group (20.41 &#xb1; 5.86 U/mL) was higher. Age, history of smoking, CRT, hsCRP and IL-8 were higher in the wAMD group, while mean GCIPL, BCVA, and PDGF were lower. sCD13 was positively correlated with hsCRP (r = 0.505) and IL-8 (r = 0.193) and negatively correlated with PDGF (r = -0.241). sCD13&#xa0;had predictive efficacy in distinguishing wAMD from non AMD and early AMD, with AUC values of 0.74 and 0.61, respectively (P < 0.05).<br><br>CONCLUSION: sCD13 concentration in the affected eyes of wAMD patients is abnormally elevated and associated with elevated serum hsCRP and IL-8 levels and decreased PDGF. These results suggest that elevated sCD13 may promote the development of wAMD, emphasizing the importance of early control of sCD13 levels.}, }
@article {pmid40323558, year = {2025}, author = {Reiter, GS and Borrelli, E and Dolz-Marco, R and Iezzi, R and Bakri, SJ}, title = {Imaging of Geographic Atrophy: A Practical Approach.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {7}, pages = {1621-1632}, pmid = {40323558}, issn = {2193-8245}, abstract = {Geographic atrophy (GA) secondary to age-related macular degeneration is a chronic degenerative disease involving the retinal pigment epithelium, photoreceptors, and choriocapillaris leading to irreversible loss of visual function. Identification of imaging markers associated with GA development and progression has progressed over the past decades, moving from two-dimensional to three-dimensional imaging, as well as image interpretation using artificial intelligence. However, there is an open discussion about the "must-haves" for GA detection and follow-up as well as complementary imaging. This practical approach provides an overview of the advantages of key imaging modalities for GA and their applicability in clinical and experimental settings.}, }
@article {pmid40324247, year = {2025}, author = {Yang, Z and Cao, W and Qin, H and Lu, X and Wang, Y and Liu, D}, title = {Association between the weight-adjusted waist index and age-related macular degeneration: Results from NHANES 2005-2008.}, journal = {Medicine}, volume = {104}, number = {18}, pages = {e42348}, pmid = {40324247}, issn = {1536-5964}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Body Mass Index ; Cross-Sectional Studies ; *Macular Degeneration/epidemiology/etiology ; Nutrition Surveys ; *Obesity/epidemiology/complications ; Prevalence ; Risk Factors ; United States/epidemiology ; *Waist Circumference ; }, abstract = {The present study aimed to explore the association between weight-adjusted waist index (WWI) levels, a newly proposed indicator for assessing obesity, and the risk of age-related macular degeneration (AMD). A cross-sectional analysis of 20,497 participants was conducted using the National Health and Nutrition Examination Survey (NHANES) 2005-2008 dataset. Trend tests, multivariable logistic regression, and smoothing curve fitting were performed to examine the association between WWI and the risk of AMD. In addition, subgroup analysis and interaction tests were used to test this association in different groups. A total of 5476 participants were included in the study, of whom 420 (7.7%) had AMD. The risk of age-related macular degeneration increased with increasing WWI in all models. In the fully adjusted model, a 55% increase in the prevalence of AMD was observed in the highest tertile (tertile 3: >11.52) of WWI (OR 1.55, 95% CI 1.09, 2.21) compared to the lowest tertile (tertile 1: <10.85). The interaction tests revealed that age, chronic kidney disease, and cardiovascular disease had significant interactions with WWI on AMD risk (P for interaction < .05). This study revealed that higher WWI levels were associated with increased risk of AMD, suggesting that managing obesity according to WWI may reduce AMD risk. However, additional research is warranted to corroborate our results.}, }
@article {pmid40324382, year = {2025}, author = {Butovsky, O and Rosenzweig, N}, title = {Alzheimer's disease and age-related macular degeneration: Shared and distinct immune mechanisms.}, journal = {Immunity}, volume = {58}, number = {5}, pages = {1120-1139}, pmid = {40324382}, issn = {1097-4180}, support = {R01 AG051812/AG/NIA NIH HHS/United States ; R01 AG054672/AG/NIA NIH HHS/United States ; R01 NS088137/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Macular Degeneration/immunology/therapy ; *Alzheimer Disease/immunology/therapy ; Animals ; }, abstract = {Alzheimer's disease (AD) and age-related macular degeneration (AMD) represent the leading causes of dementia and vision impairment in the elderly, respectively. The retina is an extension of the brain, yet these two central nervous system (CNS) compartments are often studied separately. Despite affecting cognition vs. vision, AD and AMD share neuroinflammatory pathways. By comparing these diseases, we can identify converging immune mechanisms and potential cross-applicable therapies. Here, we review immune mechanisms highlighting the shared and distinct aspects of these two age-related neurodegenerative conditions, focusing on responses to hallmark disease manifestations, the opposite role of overlapping immune risk loci, and potential unified therapeutic approaches. We also discuss unique tissue requirements that may dictate different outcomes of conserved immune mechanisms and how we can reciprocally utilize lessons from AD therapeutics to AMD. Looking forward, we suggest promising directions for research, including the exploration of regenerative medicine, gene therapies, and innovative diagnostics.}, }
@article {pmid40326035, year = {2025}, author = {Guo, Y and Zhao, J and Chen, Z}, title = {Circulating Inflammatory Proteins and Age-related Macular Degeneration: New Insights from Mendelian Randomization.}, journal = {Combinatorial chemistry &amp; high throughput screening}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113862073373085250418113858}, pmid = {40326035}, issn = {1875-5402}, abstract = {BACKGROUND: Inflammation is a key mechanism underlying age-related macular degeneration (AMD); however, the specific circulating inflammatory proteins involved remain unclear. This study investigated the causal relationship between 91 circulating inflammatory proteins and AMD using a two-sample Mendelian randomization (MR) approach.<br><br>METHODS: We conducted a two-sample magnetic resonance imaging MR analysis using genomewide association study (GWAS) data. Five MR methodologies were applied, with inverse variance weighting (IVW) as the primary approach. We applied false discovery rate (FDR) correction to mitigate false positives. Sensitivity analyses were performed to assess horizontal pleiotropy and heterogeneity. Additionally, Steiger's test, reverse MR analysis, and linkage disequilibrium score regression (LDSC) were used to validate the results.<br><br>RESULTS: Five inflammatory proteins demonstrated significant associations with overall AMD, including three associated with wet AMD and one associated with dry AMD. LDSC analysis indicated that, except for fibroblast growth factor-19, no genetic correlation confounded the causal relationships. Additionally, the expression of the identified proteins was unaffected by the genetic prediction of AMD.<br><br>CONCLUSION: This study highlights the causal relationship between specific inflammatory proteins and AMD, emphasizing their potential roles in AMD pathogenesis and potential therapeutic targets.}, }
@article {pmid40326420, year = {2025}, author = {Jaggi, D and Berger, LE and Zweifel, S and Becker, MD and Michels, S and Stalder, O and Lincke, JB and Habra, O and Wolf, S and Zinkernagel, MS}, title = {Comparison of treatment routine using aflibercept: Strict vs. relaxed retreatment regimen (TOLERANT study)-A non-inferiority, randomized controlled trial.}, journal = {Acta ophthalmologica}, volume = {103}, number = {6}, pages = {e385-e393}, pmid = {40326420}, issn = {1755-3768}, support = {//Bayer/ ; }, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Intravitreal Injections ; *Visual Acuity ; Female ; Male ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Angiogenesis Inhibitors/administration &amp; dosage ; Retreatment ; Follow-Up Studies ; Fluorescein Angiography ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Fundus Oculi ; Middle Aged ; }, abstract = {PURPOSE: This trial evaluated the noninferiority of a relaxed compared to a strict treat-and-extend treatment strategy in patients with neovascular Age-related macular degeneration (AMD).<br><br>METHODS: Multicenter, randomized, controlled, phase IV, non-inferiority clinical trial. Patients with treatment-na&#xef;ve nAMD were randomized 1:1 to a relaxed or strict treat-and-extend treatment regimen. Aflibercept 2 mg/0.05 mL was used. In the relaxed regimen, up to 100 &#x3bc;m subfoveal subretinal fluid was tolerated, vs. no tolerance of any fluid in the strict regimen. The primary outcome was the change in best corrected visual acuity (BCVA; ETDRS letters) from baseline to the end of the study at week 104 and its difference between the two treatment arms, with a 5-letter non-inferiority margin.<br><br>RESULTS: We randomized 150 patients. The full analysis showed non-inferiority of the relaxed treatment, with a mean difference of -0.12 letters (95%-CI: -3.45 to infinity, H0; mean. diff. &#x2264;&#x2009;5 letters: p =&#x2009;0.008), and a visual acuity gain of 7.3 (4.82; 9.78) vs. 7.01 (3.67; 10.36) letters in the strict vs. relaxed regimen, respectively. Many patients deviated from the protocol due to Covid-19. Per-protocol analysis showed a mean difference of -1.78 letters (95%-CI: -6.61 to infinity, H0; mean. diff. &#x2264;&#x2009;5 letters: p =&#x2009;0.136). Fewer injections were needed in the relaxed regimen, with a mean difference of -2.34 (95%-CI: -4.11 to -0.56, p =&#x2009;0.01).<br><br>CONCLUSION: Tolerating up to 100 &#x3bc;m subfoveal subretinal fluid achieves good visual outcomes in our 24-month follow-up period, in patients treated with aflibercept for nAMD, with significantly fewer injections needed.}, }
@article {pmid40327005, year = {2025}, author = {Chen, C and Lan, Y and Yan, W and Zhang, X and Li, T and Han, J}, title = {Exploring Therapeutic Targets for Age-Related Macular Degeneration From Circulating Proteins to Plasma Metabolites in the European Population.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {5}, pages = {8}, pmid = {40327005}, issn = {2164-2591}, mesh = {Humans ; *Macular Degeneration/genetics/blood ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Blood Proteins/metabolism ; Male ; Quantitative Trait Loci ; Aged ; Female ; Polymorphism, Single Nucleotide ; Europe ; White People/genetics ; White ; }, abstract = {PURPOSE: To explore the causal associations among circulating proteins, plasma metabolites, and age-related macular degeneration (AMD).<br><br>METHODS: We employed Mendelian randomization (MR) analysis and colocalization analysis to discern the causal relationship between proteomes and AMD. This investigation utilized data from protein quantitative trait loci (pQTL) studies in deCODE and the UK Biobank. Additionally, plasma metabolite-related genome-wide association studies (GWAS) data and AMD-related GWAS data were incorporated.<br><br>RESULTS: Our findings confirmed a potential causal relationship between cytoplasmic tryptophanyl-tRNA synthetase 1 (WARS1) and a higher risk of AMD. The observed causal impact of WARS1 on the two subtypes of AMD (dry and wet) align consistently with the aforementioned outcomes. Three plasma metabolites-N-acetyl-kynurenine, N-acetyltyrosine, and caproate (6:0)-were identified as mediators of the causal effect of WARS1 on AMD, and subgroup analysis revealed that N-acetyltyrosine is a specific negative metabolite associated with WARS1 and dry AMD, whereas X-16580 is a specific positive metabolite linked to WARS1 and wet AMD.<br><br>CONCLUSIONS: The outcomes of this study suggest a potential causal role of specific circulating proteins in AMD and identified the mediating role of plasma metabolites between WARS1 and AMD by integrating multiple genetic analyses. Nevertheless, further research is essential to validate and strengthen these conclusions.<br><br>TRANSLATIONAL RELEVANCE: This study establishes the causal role of specific circulating proteins in AMD and identified the mediating role of plasma metabolites between WARS1 and AMD.}, }
@article {pmid40327010, year = {2025}, author = {Thomsen, AK and Steffensen, MA and Nielsen, AT and Vorum, H and Honoré, B and Nissen, MH and Sørensen, TL}, title = {Chemokine System Changes Drive Age-Related Macular Degeneration and Influence Treatment Outcomes.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {5}, pages = {14}, pmid = {40327010}, issn = {1552-5783}, mesh = {Humans ; Female ; Male ; Prospective Studies ; Aged ; *Chemokines/blood ; *Receptors, Chemokine/metabolism/blood ; Flow Cytometry ; Treatment Outcome ; Aged, 80 and over ; Angiogenesis Inhibitors/therapeutic use ; Middle Aged ; *Wet Macular Degeneration/drug therapy/blood ; Monocytes/metabolism ; Tomography, Optical Coherence ; }, abstract = {PURPOSE: The chemokine system is associated with age-related macular degeneration (AMD), shown in previous studies. In this study, we investigate these chemokines and chemokine receptors and their association with treatment response in neovascular AMD (nAMD), and association to intermediate AMD (iAMD).<br><br>METHODS: In this prospective cohort study, patients with nAMD, iAMD, and healthy controls were included. The initial and 1-year treatment response was evaluated in patients with nAMD. Plasma chemokine concentrations of CCL2, CCL3, CCL4, CCL20, CXCL8, and CXCL10 were measured with immunoassays. Chemokine receptor expression levels of CCR1, CCR2, CCR5, CCR6, CXCR2, CXCR3, and CX3CR1 on circulating T cells and monocytes were measured with flow cytometry. Correlation network analyses were performed of the chemokine system. Genotyping for CFH and ARMS2 risk polymorphisms was performed in patients with nAMD.<br><br>RESULTS: Patients with nAMD with poor initial treatment response had significantly lower proportions of CD4+CXCR3+, CCR5+ classical monocytes, and CCR2+ non-classical monocytes compared with good initial responders (all P < 0.05). Patients with nAMD with poor 1-year treatment response had significantly lower CD4+CXCR3+ and CCR2+ non-classical monocytes compared to good 1-year responders (both P < 0.05). Correlation networks revealed a more complex regulation in partial and poor initial treatment responders. Multiple chemokines and chemokine receptors significantly correlated with the risk genotypes of CFH and ARMS2.<br><br>CONCLUSIONS: Patients with nAMD with poor treatment response had dysregulation of the chemokine system. The chemokine system might be a potential target of novel treatment in nAMD. Further studies are needed to clarify the chemokine system's role in nAMD treatment response.}, }
@article {pmid40327408, year = {2025}, author = {Yi, W and Xu, M and Xue, Y and Cao, Y and Yang, Z and Zhou, L and Zhou, Y and Shi, L and Mai, X and Sun, Z and Qing, W and Li, Y and Qing, A and Zhang, K and Ou, L and Chen, S and Duh, EJ and Liu, X}, title = {A spontaneous nonhuman primate model of inherited retinal degeneration.}, journal = {JCI insight}, volume = {10}, number = {12}, pages = {}, pmid = {40327408}, issn = {2379-3708}, support = {R01 EY035549/EY/NEI NIH HHS/United States ; R01 EY035897/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Disease Models, Animal ; Macaca fascicularis ; *Bestrophins/genetics/metabolism ; *Retinal Degeneration/genetics/pathology ; Humans ; Male ; *Vitelliform Macular Dystrophy/genetics/pathology ; Female ; Retinal Pigment Epithelium/pathology ; Mutation ; Retinal Cone Photoreceptor Cells/pathology ; }, abstract = {Inherited retinal degenerations (IRDs) are important causes of progressive, irreversible blindness. Hereditary macular diseases, in particular, are significant in their effect on the specialized, central cone photoreceptor-rich macula responsible for high resolution vision. Autosomal dominant Best vitelliform macular dystrophy (BVMD), caused by variants in the BEST1 gene, is one of the most common inherited macular dystrophies. Gene therapies have emerged as promising treatments for IRDs, but a lack of suitable animal models has hindered progress both in treatments and in understanding the mechanisms underlying macular diseases. Here, we report a Macaca fascicularis carrying a heterozygous potential pathogenic BEST1p.Q327E variant that disrupts the BEST1 ion channel by destabilizing the A195 helix, mirroring the structural perturbations seen in certain human pathological mutants. Longitudinal imaging over 2 years revealed progressive macular changes, including subfoveal cleft enlargement, lipid-rich deposit accumulation, retinal pigment epithelium (RPE) disruption, and central-to-peripheral photoreceptor degeneration, recapitulating early human BVMD pathology. Histopathology demonstrated diminished BEST1 expression, attenuation of the RPE-photoreceptor interface, and 2 distinct types of lipid deposits, including heretofore unappreciated cone mitochondrial-enriched lesions, highlighting selective cone mitochondria vulnerability. This is, to our knowledge, the first nonhuman primate model of inherited macular dystrophy, and it links BEST1 mutations, mitochondrial dysfunction, and progressive macular degeneration, offering new insights into BVMD pathophysiology and highlighting its utility for studying disease progression and potential therapeutic interventions.}, }
@article {pmid40329091, year = {2025}, author = {Scampoli, A and Carlà, MM and Grieco, G and Governatori, L and Catalani, R and Rizzo, S and Caporossi, T}, title = {One-year functional and structural results of faricimab for treatment-naïve neovascular age related macular degeneration: An OCT angiography study.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {263}, number = {8}, pages = {2219-2226}, pmid = {40329091}, issn = {1435-702X}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Female ; Male ; *Visual Acuity ; Prospective Studies ; Angiogenesis Inhibitors/administration &amp; dosage ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Follow-Up Studies ; Aged ; Fundus Oculi ; Treatment Outcome ; *Macula Lutea/pathology ; Aged, 80 and over ; Time Factors ; Dose-Response Relationship, Drug ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To explore the 1-year functional and anatomic outcomes of treatment-naïve neovascular age-related macular degeneration (nAMD) eyes undergoing a treat and extend (TAE) regimen with faricimab, METHODS: Prospective interventional study on 33 eyes with treatment-naïve nAMD undergoing a loading phase of 4 monthly faricimab followed by a TAE regimen. Participants underwent functional assessment and retinal imaging with optical coherence tomography and angiography (OCT/OCTA), at baseline and follow-up visits (V0-V5). Primary outcomes were safety, changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST). Secondary outcomes included changes in OCT biomarkers (intraretinal and subretinal fluid [IRF and SRF], maximum pigment epithelium detachment [PED] height) and vascular densities (VD) in the superficial (SCP) and deep capillary plexuses (DCP).<br><br>RESULTS: Mean follow-up was 14.1&#x2009;&#xb1;&#x2009;2.7&#xa0;months. At the final visit, 36.4% eyes were on a q16w regimen, and 36.4% on q12w. Results showed significant reductions in CST (V0: 334&#x2009;&#xb1;&#x2009;102&#xa0;&#x3bc;m, V5: 227&#x2009;&#xb1;&#x2009;47&#xa0;&#x3bc;m, p&#x2009;<&#x2009;0.001), presence of IRF/SRF and PED height. BCVA improved significantly from 0.51&#x2009;&#xb1;&#x2009;0.23 to 0.36&#x2009;&#xb1;&#x2009;0.26 LogMAR (p&#x2009;=&#x2009;0.03). A dry macula after the loading phase was achieved in 63.7% of cases and correlated with longer inter-injections intervals during TAE. SCP's VD showed a transient decrease in V1-V3 but returned to baseline values at V5, while no significant changes were observed in DCP VD. No cases of intraocular inflammation or adverse events were observed.<br><br>CONCLUSION: Faricimab showed favorable results in treatment-naive nAMD, leading to structural and functional improvements and allowing for extended treatment intervals even in real-world setting.}, }
@article {pmid40329206, year = {2025}, author = {Zhang, L and Luo, Y}, title = {Correlation analysis between OCT evaluation and postoperative visual prognosis of patients with age-related macular degeneration complicated with cataract.}, journal = {BMC ophthalmology}, volume = {25}, number = {1}, pages = {266}, pmid = {40329206}, issn = {1471-2415}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Retrospective Studies ; *Visual Acuity/physiology ; Aged ; Prognosis ; *Cataract/complications/physiopathology ; Aged, 80 and over ; *Macular Degeneration/complications/physiopathology/surgery ; Postoperative Period ; ROC Curve ; Middle Aged ; Phacoemulsification ; *Cataract Extraction ; }, abstract = {OBJECTIVE: To explore the correlation between optical coherence tomography (OCT) evaluations and postoperative visual prognosis in individuals with AMD complicated with cataract, and to investigate the clinical applications of these evaluations for predicting visual outcomes.<br><br>METHODS: We retrospectively analyzed the clinical data of 132 individuals (132 eyes) with AMD complicated by cataract, admitted to our hospital from April 2022 to January 2024. All patients underwent surgical treatment and were categorized into two groups based on their visual prognosis after 6 months: the "good prognosis (GP)" group (best corrected visual acuity decrease < 0.1 logMAR) and the "poor prognosis (PP)" group (best corrected visual acuity decrease &#x2265; 0.1 logMAR). We evaluated OCT parameters including central retinal thickness (CRT), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and total average macular thickness (TR). Pearson correlation analysis was employed to assess the relationship between these OCT parameters and postoperative visual outcomes. Additionally, receiver operating characteristic (ROC) were used to calculate the predictive value of OCT measurements for identifying poor postoperative visual prognosis in this patient cohort.<br><br>RESULTS: Preoperative OCT results showed significantly higher values for CMT, CRT, TR, and SFCT in the PP group compared to the GP group (P < 0.05). Pearson correlation analysis revealed a positive association between postoperative visual acuity and these OCT parameters. Logistic regression modeling identified CMT, CRT, TR, and SFCT as key predictors of poor visual prognosis in AMD patients with cataract. ROC analysis showed that combining these parameters improved the prediction accuracy, with an area under the curve (AUC) of 0.993, sensitivity of 99.87%, and specificity of 95.30%, which were significantly higher compared to single-index evaluations (P < 0.05).<br><br>CONCLUSION: CMT, CRT, TR, SFCT are obviously related to the postoperative visual prognosis in patients with AMD complicated by cataract. The combined evaluation of these OCT parameters demonstrates high predictive efficiency for poor postoperative visual prognosis and can serve as an important assessment index for evaluating the postoperative visual prognosis in this patient population.}, }
@article {pmid40329243, year = {2025}, author = {Abualhasan, H and Beshtawi, IM and Noor, M and Mustafa, O and Hantoli, S}, title = {Predictive factors for adherence to intravitreal anti-vascular endothelial growth factor therapy in Palestinian patients with diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration: a retrospective cohort study.}, journal = {BMC ophthalmology}, volume = {25}, number = {1}, pages = {268}, pmid = {40329243}, issn = {1471-2415}, mesh = {Humans ; Female ; Male ; Retrospective Studies ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Retinal Vein Occlusion/drug therapy/ethnology ; *Diabetic Retinopathy/drug therapy/ethnology ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; *Macular Degeneration/drug therapy/ethnology ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Arabs ; *Bevacizumab/administration &amp; dosage/therapeutic use ; Follow-Up Studies ; Visual Acuity ; Aptamers, Nucleotide ; Aged, 80 and over ; }, abstract = {BACKGROUND: The burden of retinal vascular and degenerative diseases on patients and healthcare systems can be significant if patients do not complete scheduled intravitreal injections. This study aimed to identify the factors that influence adherence with follow-up injections in patients with diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion receiving intravitreal injections of anti-vascular endothelial growth factor treatment.<br><br>METHODS: This study utilized data from patients who received intravitreal anti-vascular endothelial growth factor injections between 2022 and 2023 at An-Najah National University Hospital. Patient information, such as demographic information, number of injections administered, and details of follow-up visits, was obtained from the hospital's electronic records. When electronic records lacked certain information, patients or their relatives were contacted to provide the missing data. Data entry and analysis were performed using chi-square tests and the Statistical Package for Social Sciences. A p-value&#x2009;&#x2264;&#x2009;0.05 indicated statistical significance.<br><br>RESULTS: A total of 107 patients, 43 (40.2%) were adherent, while 64 (59.8%) were non-adherent. Sex was significantly associated with adherence (P&#x2009;=&#x2009;0.035), with females more likely to adhere. Planned number of injections correlated with adherence (P&#x2009;=&#x2009;0.004), as those receiving fewer injections were more adherent. Cost problems negatively impacted adherence (P&#x2009;=&#x2009;0.016), with non-adherent patients more frequently reporting financial barriers. Positive patient expectations for vision improvement were strongly associated with adherence (P&#x2009;=&#x2009;0.003). Mobility problems influenced adherence (P&#x2009;=&#x2009;0.049), as those without mobility issues adhered more. Physical assistance from relatives significantly improved adherence (P&#x2009;=&#x2009;0.036). Factors not significantly influencing adherence included comorbidities, education level, and insurance status.<br><br>CONCLUSION: Our study revealed that 60% of patients did not adhere to intravitreal anti-vascular endothelial growth factor treatment injections. Factors influencing adherence included the planned number of injections, cost problems, indication for injections, sex, need for physical assistance, and mobility problems. It is crucial to increase awareness of these factors to prevent complications such as blindness. Raising awareness could lead to improved adherence rates, better treatment outcomes, and positive impacts on patient and community health.}, }
@article {pmid40329608, year = {2025}, author = {Çalış Karanfil, F and Özmert, E}, title = {Evaluation of the macula pigment optical density by a psychophysical test in dry age-related macular degeneration.}, journal = {European journal of ophthalmology}, volume = {35}, number = {5}, pages = {1675-1685}, doi = {10.1177/11206721251339507}, pmid = {40329608}, issn = {1724-6016}, mesh = {Humans ; Male ; Female ; Prospective Studies ; *Macular Pigment/metabolism ; Aged ; Lutein/administration &amp; dosage/metabolism ; Middle Aged ; Zeaxanthins ; *Geographic Atrophy/metabolism/diagnosis/drug therapy/physiopathology ; Fluorescein Angiography ; Visual Field Tests ; *Macula Lutea/metabolism ; Psychophysics ; Visual Acuity/physiology ; Visual Fields/physiology ; Xanthophylls/administration &amp; dosage ; Aged, 80 and over ; }, abstract = {PurposeTo evaluate the macular pigment optical density (MPOD) in dry age-related macular degeneration (AMD).MethodsThis prospective study included 68 dry AMD patients and, as the control group, 91 healthy volunteers. Age, gender, family history, smoking, alcohol, hypertension, hyperlipidemia, height, weight, dietary lutein intake, and use of lutein-zeaxanthin (L-Z) were questioned. Full ophthalmic examination was performed. Color fundus photography and fundus autofluorescence (FAF) images were recorded. MPOD was measured by color perimetry (CP) every 3 months for 9 months in the dry AMD group, and 1 time at the beginning of the study in the control group. 6 mg/day lutein or 10 mg/day L and 2 mg/day Z were started in non-users.ResultsSmoking, obesity, family history, light iris color, and hyperlipidemia were seen more frequently in the AMD group. Average MPOD values in the AMD group were; 3.69 ± 1.82 (baseline), 4.74 ± 1.29 (3rd month), 4.99 ± 1.27 (6th month), and 5.02 ± 1.35 (9th month) dB, respectively. In the control group, the average MPOD was 4.97 ± 1.27 dB. At the baseline, the MPOD of the AMD group was significantly lower than the control group. Smoking, obesity, poor dietary lutein intake, light iris color, and hyperlipidemia were associated with low MPOD.DiscussionThe relationship between MPOD and AMD is controversial in the literature. Low MPOD and AMD may be related depending on our results. Quit smoking, and having a rich dietary L-Z intake are important for preventing AMD progression. The results of the CP are consistent with the other psychophysical tests.}, }
@article {pmid40330313, year = {2025}, author = {Almpanidou, S and Vachliotis, ID and Goulas, A and Polyzos, SA}, title = {The potential role of adipokines and hepatokines in age-related ocular diseases.}, journal = {Metabolism open}, volume = {26}, number = {}, pages = {100365}, pmid = {40330313}, issn = {2589-9368}, abstract = {Age-related ocular diseases, including diabetic retinopathy (DR), age-related macular degeneration (AMD), cataract and glaucoma may lead to visual impairment and even to blindness. Metabolic diseases, such as obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) have emerged as potential risk factors of age-related ocular diseases, especially DR. Visceral adiposity has been associated with increased risk of DR and AMD in most clinical studies, although body mass index has to-date provided conflicting association with DR and AMD. In addition, obesity is recognized as a risk factor of cataract and glaucoma. Similarly to obesity, MASLD appears to be associated with DR in patients with type 1 diabetes mellitus, but probably not in those with type 2 diabetes mellitus. A potential positive association between MASLD and AMD, glaucoma and cataract is supported by limited evidence to-date, thus needing further investigation. Altered secretion patterns of adipokines (adiponectin, leptin, lipocalin-2, resistin) and hepatokines [adropin, fetuin-A, fibroblast growth factor (FGF)-21, retinol binding protein (RBP)-4] seem to disrupt ocular homeostasis and contribute to the development of age-related ocular diseases in the context of obesity and MASLD. In this regard, novel adipokine-based and hepatokine-based therapies may be added to the treatment options for ocular diseases in the future. This narrative review aimed to summarize evidence on the interconnection of obesity and MASLD with age-related ocular diseases, with a specific focus on the roles of adipokines and hepatokines as mediators of these potential associations.}, }
@article {pmid40330498, year = {2024}, author = {Gong, Q and Hu, L and Liu, G and Yin, X and Zhao, X and Li, Q and Li, Y and Sun, Y and Zhou, Y and Guo, C and Du, Z}, title = {WTAP-mediated N6-methyladenosine mRNA methylation regulates laser-induced macular neovascularization.}, journal = {Molecular vision}, volume = {30}, number = {}, pages = {336-347}, pmid = {40330498}, issn = {1090-0535}, mesh = {Animals ; *Adenosine/analogs &amp; derivatives/metabolism/genetics ; *RNA, Messenger/metabolism/genetics ; Methylation ; Mice ; Disease Models, Animal ; beta Catenin/metabolism/genetics ; Mice, Inbred C57BL ; *Retinal Neovascularization/metabolism/genetics/pathology ; *Choroidal Neovascularization/metabolism/genetics/pathology ; Lasers/adverse effects ; Humans ; *Macular Degeneration/genetics/metabolism/pathology ; RNA, Small Interfering/genetics ; Male ; *Cell Cycle Proteins/metabolism/genetics ; Cell Proliferation ; }, abstract = {PURPOSE: Neovascular age-related macular degeneration (nAMD) is now a major cause of central vision loss in older adults worldwide. The primary characteristic of nAMD is the formation of macular neovascularization (MNV), which is a pathologic form of angiogenesis. Epigenetics plays a role in multiple pathological physiologic processes. N6-methyladenosine (m6A) modification is the most common, abundant, and reversible modification in eukaryotic mRNAs, and it plays a role in various pathological angiogenesis processes. This study intends to reveal the expression and functions of m6A during the macular neovascularization (MNV) process.<br><br>METHODS: A laser-induced MNV mouse model was used in this study. m6A quantitative analysis was performed to detect the expression of m6A. Subsequently, the expression of various m6A writers and erasers was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Immunohistochemistry was used to detect Wilms' tumor 1-associating protein (WTAP) expression in the MNV lesions. Intravitreal injection of WTAP siRNA in MNV mice to silence the WTAP gene. Hematoxylin and eosin (H&amp;E) were used to determine the thickness and length of the MNV. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were examined to measure the leakage area of the MNV. Proliferating cell nuclear antigen (PCNA) expression was detected with a western blot. The mRNA and protein levels of &#x3b2;-catenin were tested with qRT-PCR and western blot.<br><br>RESULTS: We found increased m6A modification levels after laser induction compared with the normal control group. Subsequently, the expression of various m6A writers and erasers was detected. The results showed that WTAP increased in the MNV model in mice. After the injection of WTAP siRNA into the vitreous body, the expression of WTAP significantly decreased, subsequently decreasing the m6A modification levels. The width, breadth, and leakage area of MNV damage markedly decreased, and endothelial cell proliferation was inhibited. After laser-induced MNV, the expression of &#x3b2;-catenin increased, and that of &#x3b2;-catenin significantly decreased after WTAP knockout.<br><br>CONCLUSIONS: In conclusion, this study suggests that WTAP-mediated m6A methylation can regulate pathological angiogenesis during MNV and that WTAP may participate in the formation of MNV through the wingless-related integration site (Wnt) pathway. WTAP may be a potential target for MNV treatment.}, }
@article {pmid40330967, year = {2025}, author = {Ciszewski, P and Drelichowska, A and Pikor, D and Wiśniewska, E and Azierski, M}, title = {Innovative technologies for the treatment of dry age-related macular degeneration (AMD) - modern therapeutic perspectives and their future.}, journal = {Romanian journal of ophthalmology}, volume = {69}, number = {1}, pages = {10-16}, pmid = {40330967}, issn = {2501-2533}, mesh = {Humans ; *Genetic Therapy/methods ; *Quality of Life ; *Geographic Atrophy/therapy ; Tissue Engineering/methods ; }, abstract = {PURPOSE: This review explores modern therapeutic options for the dry form of age-related macular degeneration (AMD), a condition representing one of the most significant challenges in ophthalmology due to its progressive nature and lack of effective treatment. The study discusses innovative approaches, evaluates available methods, and examines the potential of emerging technologies to improve patients' quality of life.<br><br>METHODS: A comprehensive review of current literature was conducted, being focused on therapies for dry AMD, including classical methods such as AREDS/AREDS2 supplementation, molecularly targeted drugs, gene therapy, cell transplants, tissue engineering, nanotechnology, and light-based therapies. Emerging tools leveraging artificial intelligence for personalized treatment and predictive modeling were also evaluated.<br><br>RESULTS: AREDS/AREDS2 therapies effectively slow disease progression but cannot reverse retinal damage. Advances include molecularly targeted therapies (Pegcetacoplan, Avacincaptad Pegol) that reduce inflammation, gene therapy (HMR59) protecting RPE cells, and mitochondria-targeted drugs (SS-31) mitigating oxidative stress. Using scaffolds, nanoparticles, tissue engineering, and nanotechnology enhances RPE regeneration and drug delivery. Light-based therapies (LLLT, adaptive phototherapy) improve mitochondrial function, while AI aids in predicting disease progression and personalizing treatment.<br><br>CONCLUSIONS: Modern therapeutic approaches for dry AMD provide promising avenues to slow disease progression and protect vision. However, further clinical trials are needed to optimize these strategies, assess long-term outcomes, and expand patient access to effective treatments. These advancements have the potential to significantly improve the quality of life for individuals affected by dry AMD.}, }
@article {pmid40331961, year = {2025}, author = {Ochoa Hernández, ME and Lewis-Luján, LM and Burboa Zazueta, MG and Del Castillo Castro, T and De La Re Vega, E and Gálvez-Ruiz, JC and Trujillo-López, S and López Torres, MA and Iloki-Assanga, SB}, title = {Role of Oxidative Stress and Inflammation in Age Related Macular Degeneration: Insights into the Retinal Pigment Epithelium (RPE).}, journal = {International journal of molecular sciences}, volume = {26}, number = {8}, pages = {}, pmid = {40331961}, issn = {1422-0067}, mesh = {Humans ; *Macular Degeneration/metabolism/pathology/etiology ; *Oxidative Stress ; *Retinal Pigment Epithelium/metabolism/pathology ; *Inflammation/metabolism/pathology ; Animals ; Reactive Oxygen Species/metabolism ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide, characterized by the accumulation of extracellular drusen deposits within the macula. The pathogenesis of AMD is multifactorial, involving oxidative stress, chronic inflammation, immune system dysregulation, and genetic predisposition. A key contributor to disease progression is the excessive accumulation of reactive oxygen species (ROS), which damage retinal pigment epithelium (RPE) cells and disrupt cellular homeostasis. Additionally, immunosenescence and chronic low-grade inflammation exacerbate AMD pathology, further impairing retinal integrity. Despite ongoing research, effective therapeutic options remain limited, and there is no definitive cure for AMD. This review explores the intricate molecular mechanisms underlying AMD, including the role of oxidative stress, chronic inflammation, and genetic factors in RPE dysfunction. Furthermore, we highlight potential therapeutic strategies targeting these pathways, as well as the emerging role of bioinformatics and artificial intelligence in AMD diagnosis and treatment development. By improving our understanding of AMD pathophysiology, we can advance the search for novel therapeutic interventions and preventative strategies.}, }
@article {pmid40332323, year = {2025}, author = {Tsou, SH and Luo, KS and Huang, CN and Kornelius, E and Cheng, IT and Hung, HC and Hung, YC and Lin, CL and Hsu, MY}, title = {Liraglutide Attenuates FFA-Induced Retinal Pigment Epithelium Dysfunction via AMPK Activation and Lipid Homeostasis Regulation in ARPE-19 Cells.}, journal = {International journal of molecular sciences}, volume = {26}, number = {8}, pages = {}, pmid = {40332323}, issn = {1422-0067}, support = {CSH-2025-C-049//Chung Shan Medical University Hospital/ ; 112-2320-B-040-003-MY3//National Science and Technology Council of Taiwan/ ; 111-2314-B-040-029-MY3//National Science and Technology Council of Taiwan/ ; 111-2320-B-040-017-MY3//National Science and Technology Council of Taiwan/ ; 113-2314-B-040-009//National Science and Technology Council of Taiwan/ ; NCHU-CSMU-11305//the bilateral project from National Chung Hsing University and Chung Shan Medical University/ ; }, mesh = {*Liraglutide/pharmacology ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Humans ; *AMP-Activated Protein Kinases/metabolism ; Oxidative Stress/drug effects ; *Lipid Metabolism/drug effects ; Cell Line ; Homeostasis/drug effects ; *Fatty Acids, Nonesterified/pharmacology ; Macular Degeneration/metabolism/drug therapy/pathology ; Epithelial-Mesenchymal Transition/drug effects ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly, and it is characterized by oxidative stress, lipid dysregulation, and dysfunction of the retinal pigment epithelium (RPE). A hallmark of AMD is the presence of drusen, extracellular deposits rich in lipids, proteins, and cellular debris, which are secreted by the RPE. These deposits impair RPE function, promote chronic inflammation, and accelerate disease progression. Despite advancements in understanding AMD pathogenesis, therapeutic strategies targeting lipid dysregulation and oxidative damage in RPE cells remain limited. This study evaluated the effects of liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on free fatty acid (FFA)-induced damage in ARPE-19 cells, a widely used in vitro model of RPE dysfunction. FFA treatment induced lipid droplet accumulation, oxidative stress, and epithelial-mesenchymal transition (EMT), which are processes implicated in AMD progression. Liraglutide significantly reduced lipid droplet accumulation, mitigated oxidative stress, and suppressed EMT, as demonstrated by high-content imaging, immunocytochemistry, and molecular assays. Mechanistic analyses revealed that liraglutide activates AMP-activated protein kinase (AMPK), enhancing lipophagy and restoring lipid homeostasis. Furthermore, liraglutide influenced exosome secretion, altering paracrine signaling and reducing EMT markers in neighboring cells. These findings underscore liraglutide's potential to address critical mechanisms underlying AMD pathogenesis, including lipid dysregulation, oxidative stress, and EMT. This study provides foundational evidence supporting the development of GLP-1 receptor agonists as targeted therapies for AMD.}, }
@article {pmid40332382, year = {2025}, author = {Liu, X and Ni, Z and Zhang, J and Lin, X and Wu, C and Wu, Y and Dong, L and Zhang, Z and Chi, ZL}, title = {The Protective Role of DUSP4 in Retinal Pigment Epithelium Senescence and Degeneration.}, journal = {International journal of molecular sciences}, volume = {26}, number = {8}, pages = {}, pmid = {40332382}, issn = {1422-0067}, support = {82271114//National Natural Science Foundation of China/ ; LZ22H120001//the Natural Science Foundation of Zhejiang Province/ ; KYYW202227//research expenses of Wenzhou Medical University/ ; }, mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/pathology ; *Dual-Specificity Phosphatases/metabolism/genetics ; *Cellular Senescence/genetics ; *Mitogen-Activated Protein Kinase Phosphatases/metabolism/genetics ; Mice ; *Macular Degeneration/metabolism/pathology/genetics ; Humans ; Disease Models, Animal ; Mice, Inbred C57BL ; Signal Transduction ; Mice, Knockout ; NF-kappa B/metabolism ; Cell Line ; Protein Tyrosine Phosphatases ; }, abstract = {The retinal pigment epithelium (RPE) serves as a critical guardian of subretinal homeostasis, with its dysfunction implicated in major retinal pathologies, including age-related macular degeneration (AMD) and retinitis pigmentosa. While cellular senescence has emerged as a key driver of RPE degeneration, the molecular mechanisms underlying this process remain incompletely defined. Emerging evidence implicates dual-specificity phosphatase 4 (DUSP4) in cellular stress responses through its antioxidant and anti-inflammatory capacities, yet its role in RPE pathophysiology remains unexplored. Our study reveals a compensatory increase in DUSP4 expression during AMD-associated RPE senescence. To functionally characterize this observation, we knocked down DUSP4 in the RPE of mice via subretinal injection of AAV-shDUSP4. In a sodium iodate-induced dry AMD model, mice with DUSP4 knockdown presented more severe visual impairment than control mice did. To further investigate the molecular mechanism, stable DUSP4-knockout cell lines were constructed via CRISPR/Cas9 technology. The high expression of senescence markers in the DUSP4-knockout cell lines was reversed by DUSP4 overexpression. Furthermore, DUSP4 coordinates the modulation of cell cycle, stress response, and pro-inflammatory signaling by inhibiting the p53, p38, and NF-kB pathways. These findings establish DUSP4 as a multi-functional regulator of RPE senescence. Our work not only elucidates a novel DUSP4-dependent mechanism in AMD pathogenesis but also highlights its therapeutic potential for preserving RPE function in AMD.}, }
@article {pmid40332529, year = {2025}, author = {Moshtaghion, SMM and Locri, F and Reyes, AP and Plastino, F and Kvanta, A and Morillo-Sanchez, MJ and Rodríguez-de-la-Rúa, E and Gutierrez-Sanchez, E and Montero-Sánchez, A and Lucena-Padros, H and André, H and Díaz-Corrales, FJ}, title = {VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human Samples.}, journal = {International journal of molecular sciences}, volume = {26}, number = {8}, pages = {}, pmid = {40332529}, issn = {1422-0067}, support = {PI17/01026, P-FIS: 21/00087//Instituto de Salud Carlos III and the Fondo Europeo de Desarrollo Regional/ ; C2-0009-2020//Junta de Andaluc&#xed;a, Programa Nicol&#xe1;s Monardes/ ; }, mesh = {Animals ; *Vascular Endothelial Growth Factor A/metabolism/genetics ; Humans ; Biomarkers/metabolism ; Mice ; Female ; Disease Models, Animal ; *Macular Degeneration/metabolism/pathology ; *Tears/metabolism ; Male ; Aged ; Retinal Pigment Epithelium/metabolism ; Tomography, Optical Coherence ; Choroidal Neovascularization/metabolism ; Choroid/metabolism ; STAT3 Transcription Factor/metabolism ; Aged, 80 and over ; NF-kappa B/metabolism ; Middle Aged ; }, abstract = {Vascular endothelial growth factor (VEGF) is a key mediator of exudative age-related macular degeneration (eAMD), yet non-invasive biomarkers for disease monitoring remain limited. This study evaluates VEGF levels in human tear fluid as a potential biomarker for eAMD and investigates the molecular dynamics of VEGF in a laser-induced choroidal neovascularization (lCNV) mouse model. Tear VEGF levels were quantified using proximity qPCR immunoassays in eAMD patients (n = 29) and healthy controls (n = 21) and correlated with optical coherence tomography (OCT) findings. Molecular analyses, including immunohistochemistry, gene expression profiling, and phosphorylation assays, were conducted on choroid-retinal pigment epithelium (RPE) and lacrimal gland (LG) tissues from lCNV mice (n = 25). Tear VEGF levels were significantly elevated in eAMD patients, correlating with disease severity. Females exhibited higher VEGF levels, a pattern not replicated in the mouse model. In lCNV mice, VEGF overexpression originated from the choroid-RPE, driven by hypoxic and inflammatory signaling, with no significant LG contribution. Increased VEGF, IL-6, and vimentin expression, along with NF-κB and STAT3 activation, were observed. These findings suggest that tear VEGF is a promising non-invasive biomarker for eAMD, warranting further validation for clinical application in disease monitoring and treatment optimization.}, }
@article {pmid40332908, year = {2025}, author = {Machida, A and Suzuki, K and Nakayama, T and Miyagi, S and Maekawa, Y and Murakami, R and Uematsu, M and Kitaoka, T and Oishi, A}, title = {Glucagon-Like Peptide 1 Receptor Agonist Stimulation Inhibits Laser-Induced Choroidal Neovascularization by Suppressing Intraocular Inflammation.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {5}, pages = {15}, pmid = {40332908}, issn = {1552-5783}, mesh = {Animals ; *Choroidal Neovascularization/metabolism/prevention &amp; control/drug therapy/etiology ; Mice, Inbred C57BL ; Mice ; *Glucagon-Like Peptide-1 Receptor Agonists ; Disease Models, Animal ; Intravitreal Injections ; *Liraglutide/therapeutic use/pharmacology ; Glucagon-Like Peptide-1 Receptor/metabolism ; *Inflammation/prevention &amp; control/metabolism ; Laser Coagulation/adverse effects ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Male ; Immunohistochemistry ; Cytokines/metabolism ; Real-Time Polymerase Chain Reaction ; }, abstract = {PURPOSE: The glucagon-like peptide-1 receptor (GLP-1R), a diabetes therapy target, is expressed in multiple organs and is associated with neuroprotective, anti-inflammatory, and antitumor effects, particularly in cardiac and cerebral tissues. Although GLP-1's role in diabetic and ischemic retinopathies is well-studied, its influence on choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD) remains unclear. This study explored the effects of GLP-1 on CNV using a laser-induced mouse model.<br><br>METHODS: The anti-angiogenic effects of GLP-1 were tested using ex vivo sprouting assays in 3-week-old C57BL/6J mice. In 6-week-old mice, GLP-1R localization in laser-induced CNV lesions was analyzed via immunohistochemistry. Liraglutide, a GLP-1R agonist, was administered subcutaneously for 7 days or by single intravitreal injection post-laser. Eyeballs collected on days 1 to 7 post-laser were analyzed using RT-qPCR for GLP-1R expression and inflammatory cytokines.<br><br>RESULTS: GLP-1R-positive cells were detected in CNV lesions and were expressed in Iba-1-positive activated microglia or macrophages. They also expressed in abnormal retinal pigment epithelial cells and surrounding normal endothelial cells. NOD-like receptor protein 3 (NLRP3) inflammasome signaling was observed near CNV. Liraglutide inhibited angiogenesis in ex vivo assays and significantly reduced CNV formation with both subcutaneous and intravitreal administration. Additionally, Liraglutide inhibited expression of NLRP3, IL-1&#x3b2;, IL-6, and TNF expression compared with healthy controls. Intravitreal GLP-1R antagonist reduced subcutaneous effects.<br><br>CONCLUSIONS: Liraglutide suppresses CNV formation, likely via NLRP3 inflammasome inhibition. Intraocular GLP-1R appears to mediate anti-CNV effects, supporting GLP-1R agonists as potential adjunctive therapy for exudative AMD and warranting further investigation into its safety and clinical feasibility.}, }
@article {pmid40333806, year = {2025}, author = {Chen, MY and Du, J and Do, BK and Ali, MH}, title = {Comparing visual outcomes of nAMD treatment during and after the COVID-19 restrictions period.}, journal = {PloS one}, volume = {20}, number = {5}, pages = {e0323253}, pmid = {40333806}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control ; Male ; Female ; Aged ; Retrospective Studies ; Visual Acuity/drug effects ; Treatment Outcome ; Aged, 80 and over ; SARS-CoV-2 ; Middle Aged ; *Angiogenesis Inhibitors/therapeutic use ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Bevacizumab/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; }, abstract = {MAIN OBJECTIVE: Compare treatment outcomes of newly diagnosed neovascular age-related macular degeneration (nAMD) during and after the COVID-19 restrictions.<br><br>METHODS: This retrospective study at the Retina Group of Washington analyzed nAMD patients treated with anti-VEGF therapy with&#x2009;&#x2265;&#x2009;12 months of follow-up. Two groups were identified: 258 subjects diagnosed between March 2020-March 2022 (Group 1) and 376 subjects diagnosed after (Group 2). Primary outcomes were 12-month and final best-corrected visual acuity (BCVA), and number of injections in the first 12 months.<br><br>RESULTS: Initial mean BCVA was 20/71 and 20/68 in Group 1 and Group 2, with median BCVA of 20/60 and 20/50, respectively. At 12 months, mean BCVA improved to 20/65 and 20/54 in Group 1 and Group 2, respectively (p&#x2009;=&#x2009;0.086). Final mean BCVA was 20/76 for Group 1 and 20/58 for Group 2 (p&#x2009;=&#x2009;0.010). The mean change in LogMAR BCVA from the time of conversion to last follow-up was&#x2009;+&#x2009;0.03 for Group 1 and -0.08 for Group 2 (p&#x2009;=&#x2009;0.007). Group 1 had fewer injections in the first year of therapy (8.67 vs. 9.21, p&#x2009;=&#x2009;0.004). 38.8% of Group 1 reached BCVA &#x2265;20/40 at 12 months, versus 48.9% for Group 2 (p&#x2009;=&#x2009;0.011).<br><br>CONCLUSION: Patients diagnosed during the COVID-19 restrictions period had worse visual outcomes than those diagnosed thereafter. Multiple factors, including, but not limited to reduced treatment frequency, likely contributed to worse visual outcomes.}, }
@article {pmid40335681, year = {2025}, author = {Yu, J and Zhang, Y and Pang, CP and Tham, CC and Yam, JC and Chen, LJ}, title = {Association between leukocyte telomere length and incident glaucoma: A prospective UK biobank study.}, journal = {Eye (London, England)}, volume = {39}, number = {11}, pages = {2176-2182}, pmid = {40335681}, issn = {1476-5454}, mesh = {Humans ; Male ; Female ; *Leukocytes/metabolism/pathology ; Prospective Studies ; United Kingdom/epidemiology ; Middle Aged ; *Glaucoma/epidemiology/genetics ; Aged ; Incidence ; Biological Specimen Banks ; *Telomere/genetics ; Risk Factors ; Intraocular Pressure/physiology ; Follow-Up Studies ; UK Biobank ; }, abstract = {BACKGROUND: Leukocyte telomere length (LTL) has been associated with various diseases, including age-related eye diseases such as cataract and age-related macular degeneration. However, the role of LTL in the longitudinal development of glaucoma is still unknown. Here we prospectively evaluate the association of LTL with glaucoma incidence and related traits, in the UK Biobank cohort.<br><br>METHODS: The study cohort included 419,603 participants with complete baseline data for glaucoma analyses. Multivariable Cox proportional hazards models were used to evaluate the association between LTL and the risk of glaucoma incidence, and multivariable linear regression was employed to test the association between LTL and glaucoma-related traits.<br><br>RESULTS: During a 13.58-year follow-up period, 7385 (1.76%) participants developed glaucoma. No association between LTL and incident glaucoma was found in either Model 1 (adjusted for age, sex, ethnicity and the ancestry components; HR&#x2009;=&#x2009;1.011, 95% CI: 0.990-1.033; P&#x2009;=&#x2009;0.311), or Model 2 (additionally adjusted for smoking status, alcohol consumption, body mass index, systolic blood pressure, education level, Townsend Deprivation Index, polygenic risk score for glaucoma, and history of diabetes and cardiovascular diseases; HR&#x2009;=&#x2009;1.010, 95% CI: 0.988-1.032; P&#x2009;=&#x2009;0.367). Non-significant associations were also observed for glaucoma-related traits, including the retinal nerve fibre layer, ganglion cell-inner plexiform layer, and intraocular pressure with LTL (all P-values&#x2009;>&#x2009;0.05), but LTL was associated with a slightly increased vertical cup-to-disc ratio (P&#x2009;=&#x2009;0.009).<br><br>CONCLUSIONS: This study suggested that LTL is not a major biomarker for incident glaucoma in the UK Biobank population. Further studies in different populations are warranted.}, }
@article {pmid40337864, year = {2025}, author = {Li, W and Zhang, Y and Zhu, H and Su, N and Sun, R and Mao, X and Yang, Q and Yuan, S}, title = {CAVIN3 deficiency promotes vascular normalization in ocular neovascular disease via ERK/JAG1 signaling pathway.}, journal = {JCI insight}, volume = {10}, number = {9}, pages = {}, pmid = {40337864}, issn = {2379-3708}, mesh = {Animals ; Mice ; Humans ; *Choroidal Neovascularization/metabolism/pathology/genetics ; Disease Models, Animal ; Endothelial Cells/metabolism ; *Jagged-1 Protein/metabolism/genetics ; Signal Transduction ; MAP Kinase Signaling System ; Macular Degeneration/metabolism/pathology ; Diabetic Retinopathy/metabolism/pathology/genetics ; Male ; Mice, Inbred C57BL ; Retinal Pigment Epithelium/metabolism/pathology ; *Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Female ; *Neovascularization, Pathologic/metabolism ; Choroid/pathology ; }, abstract = {Multiple members of the caveolae-associated protein (Cavin) family are implicated in angiogenesis. However, the specific role of CAVIN3 in pathological angiogenesis within the eye remains unclear. The present study demonstrated that CAVIN3 knockdown in endothelial cells (ECs) promoted vascular normalization in ocular pathological neovascularization. Elevated CAVIN3 expression was observed in the ECs of retinal pigment epithelium/choroid complexes from patients with neovascular age-related macular degeneration and fibrovascular membranes from patients with proliferative diabetic retinopathy. Additionally, upregulated Cavin3 expression was detected in laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) mouse models. In both OIR and CNV mice, Cavin3 knockdown inhibited pathological neovascularization. Cavin3 deficiency further disrupted EC proliferation and vascular sprouting, thereby promoting vascular normalization by partially restoring microenvironmental hypoxia and reestablishing pericyte-EC interactions. Mechanistically, we demonstrated that zinc finger E-box-binding homeobox 1 (ZEB1) regulated CAVIN3 transcription in ECs under hypoxic conditions. CAVIN3 deficiency modulated pathological vascularization by inhibiting ERK phosphorylation, which downregulated jagged 1 (JAG1) expression. Conclusively, this study elucidated the protective role of endothelial CAVIN3 deficiency in pathological neovascularization models, addressing a gap in understanding the regulatory role of Cavins in angiogenesis. These findings suggested a therapeutic direction for ocular neovascular diseases.}, }
@article {pmid40338383, year = {2025}, author = {Bleidißel, N and Weichenberger, M and Maier, M and Spielberg, N and Feucht, N}, title = {Improved functional and morphological outcomes with faricimab in nAMD eyes with poor response to prior intravitreal anti-VEGF therapy.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {177}, pmid = {40338383}, issn = {1573-2630}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; Intravitreal Injections ; *Visual Acuity ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged, 80 and over ; *Antibodies, Bispecific/administration &amp; dosage ; Treatment Outcome ; Fluorescein Angiography ; Follow-Up Studies ; Ranibizumab/administration &amp; dosage ; Receptors, Vascular Endothelial Growth Factor ; Middle Aged ; Fundus Oculi ; Recombinant Fusion Proteins ; }, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a major cause of vision loss in older adults. While anti-VEGF therapies have improved management by suppressing abnormal blood vessel growth, a substantial subset of patients show poor functional as well as morphological responses and require frequent injections. Faricimab (Vabysmo®), a bispecific inhibitor targeting VEGF-A and angiopoietin-2 (Ang-2), has shown promise in achieving more durable disease control.<br><br>METHODS: This retrospective study included 48 eyes from 47 nAMD patients previously treated with ranibizumab or aflibercept, who were switched to faricimab due to poor treatment response. Evaluations occurred at four time points, assessing best-corrected visual acuity (BCVA), intraretinal (IRF) and subretinal fluid (SRF), subretinal pigment epithelium fluid and fibrosis, central subfield thickness (CST), and central subfield volume (CSV) using spectral-domain OCT. Dosing intervals and patient-reported outcomes were also recorded.<br><br>RESULTS: BCVA improved consistently, with mean logMAR improving from 0.54 to 0.40, reflecting a gain of 1.4 Snellen lines. Dosing intervals extended from a median of 5 to 8&#xa0;weeks, with over one-third of eyes reaching intervals of 10&#xa0;weeks or more. Significant reductions in IRF, SRF, CST as well as CSV were observed (p&#x2009;<&#x2009;0.05) with a quarter of eyes showing no intra- or subretinal fluid at the fourth faricimab injection. Three patients were switched back to their previous anti-VEGF treatment due to a decline in BCVA.<br><br>DISCUSSION: The findings suggest Faricimab as an effective option for nAMD patients who respond inadequately to prior anti-VEGF therapies, offering both functional and anatomical improvements. Extended intervals reduce treatment burden, indicating faricimab's potential to enhance disease control and patient quality of life in real-world settings.}, }
@article {pmid40340707, year = {2025}, author = {Hayakawa, R and Ishii, T and Fushimi, T and Kamei, Y and Yamaguchi, A and Sugimoto, K and Ashida, H and Akagawa, M}, title = {Luteolin protects human ARPE-19 retinal pigment epithelium cells from blue light-induced phototoxicity through activation of Nrf2/Keap1 signaling.}, journal = {Free radical research}, volume = {59}, number = {4}, pages = {356-368}, doi = {10.1080/10715762.2025.2503832}, pmid = {40340707}, issn = {1029-2470}, mesh = {Humans ; *Luteolin/pharmacology ; *NF-E2-Related Factor 2/metabolism ; *Retinal Pigment Epithelium/drug effects/metabolism/radiation effects/pathology ; *Light/adverse effects ; *Kelch-Like ECH-Associated Protein 1/metabolism ; Signal Transduction/drug effects ; Oxidative Stress/drug effects ; Cell Line ; Apoptosis/drug effects ; Blue Light ; }, abstract = {Age-related macular degeneration (AMD), a serious physical and mental health problem worldwide, is the leading cause of irreversible, severe vision impairment and loss in older people. AMD is associated with multiple risk factors, many of which are closely linked to increased oxidative stress. Some studies have suggested that long-term and excessive exposure to blue light may be a potential risk factor for the development or progression of AMD. Recently, we demonstrated that blue light irradiation caused oxidative stress in all-trans-retinal (atRAL)-exposed human ARPE-19 retinal pigment epithelium cells by generating singlet oxygen ([1]O2), leading to apoptotic cell death. Luteolin, a flavonoid found in various edible plants, has been reported to possess divergent health-promoting properties including anti-oxidative and chemopreventive effects by up-regulating anti-oxidative and phase II detoxifying enzymes through activation of Keap1/Nrf2 signaling. Herein, we verified the cytoprotective action of luteolin against blue light irradiation using atRAL-exposed ARPE-19 cells. Our results established that luteolin effectively prevented blue light-induced apoptosis of ARPE-19 cells by mitigating oxidative stress. We also confirmed that luteolin suppressed intracellular accumulation of [1]O2 and formation of atRAL-derived lipofuscin by increased expression of heme oxygenase-1 and aldehyde dehydrogenase 1A1 through activation of Keap1/Nrf2 signaling. Furthermore, our data implied that the luteolin-provoked activation of Keap1/Nrf2 signaling might be due to covalent binding of luteolin o-quinone to the critical cysteinyl thiol in Keap1. The present results suggest that luteolin could be helpful in the prevention and amelioration of blue light-induced retinal degeneration, including AMD.}, }
@article {pmid40341462, year = {2025}, author = {Noh, JH and Lee, MY and Yoo, C and Sung, KR and Kim, JM}, title = {Relationship Between Periodontitis and Open Angle Glaucoma: The Korea National Health and Nutrition Examination Survey.}, journal = {Journal of glaucoma}, volume = {34}, number = {8}, pages = {565-574}, doi = {10.1097/IJG.0000000000002584}, pmid = {40341462}, issn = {1536-481X}, mesh = {Humans ; Male ; Female ; Republic of Korea/epidemiology ; Middle Aged ; Nutrition Surveys ; *Glaucoma, Open-Angle/epidemiology ; *Periodontitis/epidemiology/complications ; Adult ; Aged ; Risk Factors ; Intraocular Pressure/physiology ; Periodontal Index ; Prevalence ; Cross-Sectional Studies ; Young Adult ; Odds Ratio ; }, abstract = {PRCIS: Using Korean National Health and Nutrition Examination Survey (KNHANES) data, this study reveals a significant association between periodontitis and open angle glaucoma.<br><br>PURPOSE: To investigate the relationship between periodontitis and open angle glaucoma.<br><br>METHODS: Data from 17,478 subjects in the KNHANES 2010-2011 were analyzed. We included 6215 subjects aged 19 years or older who underwent both dental and ophthalmological examinations that met International Society of Geographical and Epidemiological Ophthalmology criteria. Exclusions included ocular surgery (eg, refractive, cataract, retina), age-related macular degeneration, those who were pregnant or who were undergoing orthodontic treatment, and those with missing data. The final analysis included 3681 subjects. Periodontal disease was assessed using the Community Periodontal Index (CPI) developed by the WHO.<br><br>RESULTS: Of 3681 subjects, 197 (4.59%) had glaucoma and 3484 (95.41%) did not. Among the 197 glaucoma patients, 80 (39.48%) had periodontitis; among those without glaucoma, 892 (22.20%) had periodontitis (P <0.001). The periodontitis group was more likely to have glaucoma than the nonperiodontitis group [odds ratio (OR), 1.53; 95% CI, 1.06-2.22; adjusted for age, sex, DM, HTN, smoking rate, and drinking rate]. For those older than 40 years, the OR was 1.75 (95% CI, 1.18-2.61), and that for men was 1.65 (95% CI, 1.01-2.70). When comparing the group with and without periodontitis in DM patients, the OR was 2.70 (95% CI, 1.46-5.02).<br><br>CONCLUSION: This study shows a significant association between periodontitis and glaucoma, especially in patients aged 40 and older, men, and those with diabetes. Future follow-up studies are needed to elucidate the mechanism behind this association.}, }
@article {pmid40343286, year = {2025}, author = {Zeng, B and Zhang, C and Liang, Y and Huang, J and Li, D and Liu, Z and Liao, H and Yang, T and Liu, M and Zou, C and Liu, D and Qin, B}, title = {Single-cell RNA sequencing highlights a significant retinal Müller glial population in dry age-related macular degeneration.}, journal = {iScience}, volume = {28}, number = {5}, pages = {112464}, pmid = {40343286}, issn = {2589-0042}, abstract = {The main challenge in dissecting the cells and pathways involved in the pathogenesis of age-related macular degeneration (AMD) is the highly heterogeneous and dynamic nature of the retinal microenvironment. This study aimed to describe the comprehensive landscape of the dry AMD (dAMD) model and identify the key cell cluster contributing to dAMD. We identified a subset of Müller cells that express high levels of Sox2, which play crucial roles in homeostasis and neuroprotection in both mouse models of AMD and patients with dAMD. Additionally, the number of Sox2[+] Müller cells decreased significantly during the progression of AMD, indicating these cells were damaged and underwent cell death. Interestingly, ferroptosis and apoptosis were identified as contributors to the damage of Sox2[+] Müller cells. Our findings are potentially valuable not only for advancing the current understanding of dAMD progression but also for the development of treatment strategies through the protection of Müller cells.}, }
@article {pmid40343605, year = {2025}, author = {Zhao, X and Chen, X and Xin, X}, title = {MiR-6837-3p protected retinal epithelial cells from oxidative stress by targeting E2F6.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {183}, pmid = {40343605}, issn = {1573-2630}, mesh = {*MicroRNAs/genetics/biosynthesis ; *Oxidative Stress ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Humans ; Apoptosis ; *Gene Expression Regulation ; Cell Survival ; Hydrogen Peroxide ; *Macular Degeneration/metabolism/genetics/pathology ; Cell Movement ; Cells, Cultured ; Cell Proliferation ; Reactive Oxygen Species/metabolism ; Flow Cytometry ; Cell Line ; }, abstract = {AIM: The mechanism of age-related macular degeneration (AMD) is a complex illness that is not fully understood. Therefore, the aim of this study was to investigate the expression patterns of miR-6837-3p in retinal epithelial cells.<br><br>METHODS: H2O2 was used to treat ARPE-19 cells for 2, 4 and 6&#xa0;h to mimic the in vivo environment of AMD. MiR inhibitors and mimics were used to inhibit or overexpress miR-6837-3p in H2O2-treated ARPE-19 cells, respectively. Then, CCK8 assay, flow cytometry, and wound healing assays were conducted to assess the effects of miR-6837-3p on the behaviors of ARPE-19 cells, including cell growth, apoptosis, cycle progression, and migration. Finally, microRNA database prediction and luciferase reporter assays were used to demonstrate that miR-6837-3p targets the downstream gene E2F6.<br><br>RESULTS: H2O2 induced a decrease in cell viability and an increase in ROS levels in a time-dependent manner. Additionally, overexpression of miR-6837-3p increased cell viability and suppressed apoptosis in ARPE-19 cells treated with H2O2. Meanwhile, increased miR-6837-3p promoted cell cycle progression and cell migration of ARPE-19 cells. Finally, miR-6837-3p exerted anti-apoptosis and anti-oxidative stress effects by inhibiting the expression of E2F6 in ARPE-19 cells.<br><br>CONCLUSIONS: The MiR-6837-3p/E2F6 axis might be a target for the treatment of AMD to improve ARPE-19 cell function.}, }
@article {pmid40345358, year = {2025}, author = {Eichenbaum, DA and Holekamp, N and Khanani, AM and Pieramici, D and Hershberger, V and Sheth, V and Brunstein, F and Ma, L and Zou, Y and Indjeian, VB and Dere, R and Maia, M and Hsu, JC and Gao, SS and Yaspan, B and Willis, JR and Wiley, H and Lai, P and Chen, H}, title = {Reply to Comment on Phase 2 Study of the Anti-High Temperature Requirement A1 (HtrA1) Fab Galegenimab (FHTR2163) in Geographic Atrophy Secondary to Age-Related Macular Degeneration.}, journal = {American journal of ophthalmology}, volume = {276}, number = {}, pages = {413-414}, doi = {10.1016/j.ajo.2025.04.042}, pmid = {40345358}, issn = {1879-1891}, }
@article {pmid40345486, year = {2025}, author = {Contemori, G and Guenot, J and Cottereau, BR and Trotter, Y and Battaglini, L and Bertamini, M}, title = {Neural and perceptual adaptations in bilateral macular degeneration: an integrative review.}, journal = {Neuropsychologia}, volume = {215}, number = {}, pages = {109165}, doi = {10.1016/j.neuropsychologia.2025.109165}, pmid = {40345486}, issn = {1873-3514}, mesh = {Humans ; *Macular Degeneration/physiopathology/pathology ; *Adaptation, Physiological/physiology ; *Visual Perception/physiology ; *Visual Cortex/physiopathology ; Scotoma/physiopathology ; Animals ; }, abstract = {Bilateral age-related macular degeneration (AMD) results in central vision loss, affecting the fovea-associated cortical regions. This review examines neuroimaging and psychophysical evidence of spontaneous neural adaptation in acquired bilateral central scotoma. Early visual brain areas show reduced cortical thickness and axonal integrity due to postsynaptic (anterograde) degeneration. Contrary to animal models, evidence for spontaneous adaptation in the primary visual cortex (V1) is limited. Activity in the lesion projection zone (LPZ), previously seen as extensive cortical remapping, may result from non-retinotopic peripheral-to-foveal feedback, sharing substrates with healthy retinal feedforward processes. Preferred retinal loci (PRLs) are influenced more by location and task than by residual vision quality. Reduced lateral masking in the PRL may reflect decreased contrast sensitivity from retinal damage, rather than genuine adaptive mechanisms. Weakened crowding in the PRL is explained by transient adaptation in healthy subjects to artificial scotomas, not by long-term plasticity. Higher visual areas may show compensatory mechanisms enhancing complex tasks like symmetry, face, and motion discrimination. Leveraging spontaneous adaptation through perceptual learning-based treatments can preserve residual visual abilities. Because of limited evidence for spontaneous reorganization in AMD, behavioural training and emerging techniques are crucial for optimal treatment efficacy.}, }
@article {pmid40347366, year = {2025}, author = {Watanabe, Y and Koto, T and Takahashi, A and Mizuno, M and Ishida, T and Nakajima, K and Takeuchi, J and Yokoi, T and Nakayama, M and Okada, AA and Inoue, M and Kataoka, K}, title = {Factors predictive of treatment outcomes in submacular hemorrhage secondary to age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {69}, number = {5}, pages = {732-737}, pmid = {40347366}, issn = {1613-2246}, mesh = {Humans ; Retrospective Studies ; Female ; Male ; Tomography, Optical Coherence/methods ; Aged ; *Visual Acuity/physiology ; *Retinal Hemorrhage/etiology/diagnosis/therapy ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Wet Macular Degeneration/complications/diagnosis/drug therapy ; Fluorescein Angiography/methods ; Treatment Outcome ; Fundus Oculi ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Ranibizumab/administration &amp; dosage ; *Endotamponade/methods ; *Macula Lutea/pathology ; }, abstract = {PURPOSE: To identify predictors for visual outcomes of eyes with submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: Clinical data from patients diagnosed with SMH secondary to nAMD and treated with pneumatic displacement were collected. SMH thickness was measured by optical coherence tomography (OCT) at baseline and 1 week. Possible factors associated with best-corrected visual acuity (BCVA) gain at 3 months were analyzed.<br><br>RESULTS: Fifty-six eyes of 56 patients (18 female/38 male; mean age, 77.8 &#xb1; 10.1 years) were analyzed; 34 were treatment-na&#xef;ve and 22 were previously treated with anti-vascular endothelial growth factor agents. Multivariable analysis showed that greater BCVA gain more than 0.3 logMAR at 3 months post-treatment was associated with being treatment-na&#xef;ve (odds ratio [OR], 34.30; 95% confidence interval [CI], 1.38-851.91; P = 0.031), thinner SMH thickness at 1 week after pneumatic displacement (OR, 0.38 per 50-unit increase; CI, 0.18-0.80; P = 0.011), and worse baseline BCVA (OR, 2.58 per 0.1-unit increase; CI, 1.31-5.07; P = 0.006), but not associated with age (OR, 0.50; 95% CI, 0.24-1.06), the time from onset to pneumatic displacement (OR, 1.04; 95%CI, 0.87-1.23), SMH thickness at baseline (OR, 0.92; 95%CI, 0.63-1.36), and the presence of subfoveal hemorrhagic PED (OR, 0.72; 95%CI, 0.08-6.84).<br><br>CONCLUSION: This study identifies novel factors predictive of visual outcomes for pneumatic displacement for SMH due to nAMD. The presence of residual SMH at 1 week following unsuccessful pneumatic displacement may warrant further intervention.}, }
@article {pmid40347367, year = {2025}, author = {Hoshino, J and Matsumoto, H and Numaga, S and Nakamura, K and Akiyama, H}, title = {Two-year outcomes of treat-and-extend regimen with intravitreal faricimab for treatment-naïve neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {69}, number = {4}, pages = {521-528}, pmid = {40347367}, issn = {1613-2246}, mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; *Visual Acuity ; Female ; Male ; Tomography, Optical Coherence ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Fluorescein Angiography ; Follow-Up Studies ; Aged, 80 and over ; Time Factors ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Dose-Response Relationship, Drug ; Antibodies, Bispecific ; }, abstract = {PURPOSE: We previously reported 1-year outcomes of a treat-and-extend (TAE) regimen with intravitreal faricimab (IVF) for treatment-naïve neovascular age-related macular degeneration (nAMD). Herein, we evaluated the second-year results of this TAE regimen with IVF in eyes completing the first-year treatment.<br><br>STUDY DESIGN: Retrospective, interventional case series.<br><br>METHODS: We retrospectively studied 30 eyes with treatment-na&#xef;ve nAMD that had completed the initial year of treatment, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), central choroidal thickness (CCT), total number of injections over 2 years, and intended injection interval at the last visit.<br><br>RESULTS: Twenty-five eyes completed the 2-year IVF treatment. There was no significant difference between pre-treatment and 2 years post-treatment BCVA. FT and CCT both showed significant reductions, maintained during the 2-year study period. The total number of injections was 10.1 &#xb1; 1.2 over the 2 years. The intended injection interval at the last visit was 13.0 &#xb1; 3.4 weeks. Of 5 eyes not completing 2 years of IVF treatment, 4 were switched to other anti-vascular endothelial growth factor (VEGF) agents due to persistent fluids despite IVF at 8-week intervals. In the remaining eye, IVF treatment was discontinued due to suspected faricimab-related intraocular inflammation.<br><br>CONCLUSIONS: The TAE regimen with IVF for treatment-na&#xef;ve nAMD was effective during a 2-year period for improving exudative changes and maintaining visual acuity. Although IVF was found to be a relatively safe treatment for nAMD, there were cases requiring a switch to other anti-VEGF agents due to inadequate fluid control effect.}, }
@article {pmid40347925, year = {2025}, author = {Yang, CC and Jiang, Q and Xue, JS}, title = {Comprehensive multi-omics and pharmacokinetics reveal sclareol's role in inhibiting ocular neovascularization.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {143}, number = {}, pages = {156817}, doi = {10.1016/j.phymed.2025.156817}, pmid = {40347925}, issn = {1618-095X}, mesh = {Animals ; *Diterpenes/pharmacokinetics/pharmacology ; Mice ; *Choroidal Neovascularization/drug therapy ; Mice, Inbred C57BL ; Humans ; Endothelial Cells/drug effects ; Molecular Docking Simulation ; Male ; *Angiogenesis Inhibitors/pharmacology/pharmacokinetics ; Administration, Oral ; *Retinal Neovascularization/drug therapy ; Cell Proliferation/drug effects ; Multiomics ; }, abstract = {BACKGROUND: Ocular neovascularization, a hallmark of several vision-threatening diseases, including retinopathy of prematurity (ROP) and wet age-related macular degeneration (wet AMD), is commonly treated with intravitreal injections of anti-VEGF agents. However, these treatments are limited by invasiveness and drug resistance, highlighting the need for alternative therapies. Sclareol (SCL), a labdane diterpenoid derived from Salvia sclarea, exhibits various biological activities, but its potential role in angiogenesis and pharmacokinetics after oral administration remain unexplored.<br><br>METHODS: Hypoxia-induced endothelial cells (ECs) were used as an in vitro model, while mouse oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) were used as in vivo models. The pharmacokinetics of SCL in plasma, retina, and choroid were analyzed after oral administration in mice. Furthermore, the underlying mechanisms were elucidated through an integrative approach combining transcriptomics, metabolomics, network pharmacology, molecular docking, and molecular dynamics simulation.<br><br>RESULTS: SCL inhibited hypoxia-induced EC proliferation, permeability, migration, tube formation, sprouting, glycolysis, mitochondrial respiration, and oxidative stress by modulating the PI3K-AKT-FOXO1 pathway. Additionally, Oral administration of SCL significantly inhibited OIR and CNV progression in mice, demonstrating enhanced therapeutic efficacy when combined with intravitreal aflibercept (Eylea) injection.<br><br>CONCLUSION: SCL is a promising orally administered natural compound for ocular neovascularization, offering a potential alternative or adjunctive therapy to existing anti-VEGF treatments.}, }
@article {pmid40348352, year = {2025}, author = {Keenan, TDL}, title = {Comment on "Phase 2 Study of the Anti-High Temperature Requirement A1 (HtrA1) Fab Galegenimab (FHTR2163) in Geographic Atrophy Secondary to Age-Related Macular Degeneration".}, journal = {American journal of ophthalmology}, volume = {276}, number = {}, pages = {411-412}, doi = {10.1016/j.ajo.2025.04.044}, pmid = {40348352}, issn = {1879-1891}, }
@article {pmid40348395, year = {2025}, author = {Liu, Z and Huang, Y and Jin, L and Pan, C and Han, X and Zheng, Y}, title = {Validation of a self-administered Home ETDRS visual acuity testing (H-ETDRS) for self-monitoring vision changes in retinal diseases.}, journal = {The British journal of ophthalmology}, volume = {109}, number = {9}, pages = {1012-1019}, doi = {10.1136/bjo-2024-326283}, pmid = {40348395}, issn = {1468-2079}, mesh = {Humans ; *Visual Acuity/physiology ; Male ; Female ; Reproducibility of Results ; Aged ; Middle Aged ; *Vision Tests/methods/instrumentation ; *Diabetic Retinopathy/physiopathology/diagnosis ; *Macular Degeneration/physiopathology/diagnosis ; Aged, 80 and over ; Adult ; }, abstract = {OBJECTIVE: To validate a self-administered Home Early Treatment Diabetic Retinopathy Study (H-ETDRS) visual acuity (VA) test and to assess its accuracy in detecting VA decline in patients with retinal diseases.<br><br>METHODS: A validation group of 156 participants and a testing group of 100 participants with diabetic retinopathy and age-related macular degeneration were recruited. All participants underwent monocular distance best-corrected VA (BCVA) tests in the study eye using the standard ETDRS (S-ETDRS) charts in clinic and the H-ETDRS device in a simulated home setting. Participants in the validation group repeated both methods. H-ETDRS letter scores were compared with S-ETDRS scores, evaluating mean difference and test-retest reliability (TRR). Intraclass correlation coefficients (ICCs) were calculated to measure the agreement. Participants in the testing group repeated both methods with a Bangerter filter density of 0.6 to simulate BCVA change. The performance of H-ETDRS in detecting acuity change was evaluated, with S-ETDRS serving as the standard.<br><br>RESULTS: For the validation group, the mean difference between S-ETDRS and H-ETDRS scores was -1.38 letters (95% limits of agreement (LOA) -6.99 to 4.22). The scores of the two tests were highly correlated with an ICC of 0.98. The mean differences between initial test and retest scores were 0.11 letters (95% LOA -2.62 to 2.84) for S-ETDRS and -0.13 letters (95% LOA -5.64 to 5.38) for H-ETDRS. The ICCs of test-retest letter scores were 1.00 for S-ETDRS and 0.98 for H-ETDRS. For participants in the testing group who showed BCVA decline of one line or more with Bangerter filter, 96.7% were able to detect VA changes using H-ETDRS.<br><br>CONCLUSIONS AND RELEVANCE: The H-ETDRS test demonstrates high TRR and good concordance with S-ETDRS test for retinal patients. The H-ETDRS is viable for self-monitoring VA changes in retinal diseases, however, further validation studies in actual home settings are warranted.}, }
@article {pmid40348918, year = {2025}, author = {Sherif, M and Derradji, Y and Safi, A and Mantel, I}, title = {Long-term outcomes of the observe-and-plan regimen in treating neovascular age-related macular degeneration: a retrospective real-life analysis.}, journal = {Eye (London, England)}, volume = {39}, number = {11}, pages = {2188-2193}, pmid = {40348918}, issn = {1476-5454}, mesh = {Humans ; Retrospective Studies ; Aged ; *Visual Acuity/physiology ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Male ; Female ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Aged, 80 and over ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Follow-Up Studies ; Treatment Outcome ; Tomography, Optical Coherence ; }, abstract = {BACKGROUND/OBJECTIVES: This study aimed to evaluate the long-term (7 years) outcome of visual acuity in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents following the observe-and-plan regimen.<br><br>SUBJECTS/METHODS: A total of 195 eyes from 181 patients with nAMD (mean age 79.5&#x2009;&#xb1;&#x2009;6.9 years), with a mean follow-up duration of 66&#x2009;&#xb1;&#x2009;37 months, treated with intravitreal anti-VEGF (ranibizumab or aflibercept) were included in this retrospective study. The principles of the observe-and-plan regimen were followed, with follow-up exceeding 3 years in real-life settings. Data collected included visual acuity (VA), number of injections and visits, central retinal thickness, and any complications over 7 years from baseline.<br><br>RESULTS: The mean baseline VA was 63&#x2009;&#xb1;&#x2009;17 Early Treatment of Diabetic Retinopathy Study letters (Snellen equivalent 20/63), improving to 73&#x2009;&#xb1;&#x2009;14 at year 1. The initial visual gain was slightly reduced with a final mean VA of 70&#x2009;&#xb1;&#x2009;18 letters (Snellen equivalent 20/40) at year 7. The mean central macular thickness decreased significantly from 375&#x2009;&#xb1;&#x2009;129 at baseline to 276&#x2009;&#xb1;&#x2009;75 at year 1 and to 279&#x2009;&#xb1;&#x2009;87 at year 7. The mean annual number of injections decreased from 8.7&#x2009;&#xb1;&#x2009;3.2 in year 1 to 6.7&#x2009;&#xb1;&#x2009;3.7 in year 2 and to 5.5&#x2009;&#xb1;&#x2009;2.8 in year 7. The mean annual number of visits remained constant throughout, with 4.1&#x2009;&#xb1;&#x2009;1.3 visits in year 1 and 4.7&#x2009;&#xb1;&#x2009;1.7 in year 7.<br><br>CONCLUSIONS: The observe-and-plan regimen was very efficient for treating nAMD in real-life settings, reducing the clinical burden on the medical system and patients, with excellent functional and structural long-term results.}, }
@article {pmid40349982, year = {2025}, author = {London, NJS and Cheung, CMG and Michels, S and Kotecha, A and Margaron, P and Souverain, A and Willis, JR and Lai, TYY}, title = {Outcomes by Faricimab Treatment Interval at Week 48 of TENAYA-LUCERNE Phase III Trials in Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {9}, number = {11}, pages = {1081-1089}, doi = {10.1016/j.oret.2025.05.004}, pmid = {40349982}, issn = {2468-6530}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; Angiopoietin-2/antagonists &amp; inhibitors ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Dose-Response Relationship, Drug ; Double-Blind Method ; Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; Intravitreal Injections ; *Macula Lutea/pathology ; Time Factors ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To assess the visual and anatomic outcomes by individualized treatment intervals at week 48 in patients with neovascular age-related macular degeneration (nAMD) treated with the dual angiopoietin-2/VEGF-A inhibitor faricimab in a post hoc analysis of pooled data from TENAYA/LUCERNE.<br><br>DESIGN: TENAYA/LUCERNE (NCT03823287/NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled, noninferiority phase III trials.<br><br>PARTICIPANTS: Treatment-na&#xef;ve patients &#x2265;50 years of age with nAMD randomized to the faricimab up to every 16 weeks (Q16W; n = 665) arm.<br><br>METHODS: Patients in the faricimab arm received 4 initial doses every 4 weeks through week 12. At weeks 20 and 24, they were assigned to fixed every 8 weeks (Q8W), every 12 weeks (Q12W), or every 16 weeks (Q16W) treatment intervals through week 60, based on prespecified central subfield thickness (CST) or best-corrected visual acuity (BCVA) disease activity criteria or presence of new macular hemorrhage, per investigator clinical examination. The primary analysis was at week 48.<br><br>MAIN OUTCOME MEASURES: Mean changes from baseline in BCVA and CST through week 48 by treatment interval group.<br><br>RESULTS: At week 48, the proportion of faricimab-treated patients on each treatment interval was 45.3% (Q16W), 33.4% (Q12W), and 21.2% (Q8W). The baseline patient characteristics were well balanced across faricimab treatment intervals. However, patients assigned to treatment at Q16W and Q12W had less severe disease at baseline than patients assigned to Q8W. All patients showed sustained BCVA gains and CST reductions through week 48. Mean (95% confidence interval) change from baseline in BCVA was +7.9 letters (6.6 to 9.2), +4.0 letters (2.2 to 5.7), and +5.3 letters (2.4 to 8.2); and that in CST was -142.9 &#x3bc;m (-156.9 to -128.9), -112.5 &#x3bc;m (-131.0 to -94.1), and -165.1 &#x3bc;m (-193.8 to -136.4) for Q16W, Q12W, and Q8W, respectively.<br><br>CONCLUSIONS: Vision and anatomic improvements were achieved and maintained in all faricimab individualized treatment interval groups, with patients treated at longer intervals having more stable outcomes with fewer injections. The clinically relevant disease activity criteria based on vision or anatomy allowed treatment of patients with nAMD to be rapidly extended after the initial dosing phase while maintaining visual gains through week 48 of TENAYA/LUCERNE.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40350849, year = {2025}, author = {Li, B and Guo, S and Zhu, Y and Wang, XS and Wei, DD and Kang, HJ and Zhang, WH and Duan, JA}, title = {[Ameliorative effects of Lycii Fructus-Chrysanthemi Flos at different ratios on retinal damage in mice].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {50}, number = {3}, pages = {732-740}, doi = {10.19540/j.cnki.cjcmm.20240912.701}, pmid = {40350849}, issn = {1001-5302}, mesh = {Animals ; Mice ; *Retina/drug effects/metabolism/injuries ; Male ; *Lycium/chemistry ; *Drugs, Chinese Herbal/administration &amp; dosage ; *Chrysanthemum/chemistry ; NF-kappa B/metabolism/genetics ; Humans ; *Retinal Diseases/drug therapy/genetics/metabolism ; NF-E2-Related Factor 2/genetics/metabolism ; Oxidative Stress/drug effects ; Flowers/chemistry ; Heme Oxygenase-1/metabolism/genetics ; }, abstract = {This study aimed to compare the ameliorative effects of Lycii Fructus and Chrysanthemi Flos at different ratios on retinal damage in mice and to elucidate the underlying mechanisms. A retinal injury model was established by intraperitoneal injection of sodium iodate(NaIO_3) solution. The mice were divided into the following groups: blank group, model group, positive drug(AREDS 2) group, low-and high-dose groups of Lycii Fructus and Chrysanthemi Flos at 1∶1, low-and high-dose groups at 3∶1, and low-and high-dose groups at 1∶3. Administration was carried out 15 days after modeling. The visual acuity of the mice was assessed using the black-and-white box test. The fundus was observed using an optical coherence tomography device, and retinal thickness was measured. HE staining was used to observe the morphology and pathological changes of the retina. The levels of oxidative factors in serum and ocular tissues were measured using assay kits. The levels of inflammatory factors in serum and ocular tissues were detected by enzyme-linked immunosorbent assay(ELISA), and the expression of Nrf2, HO-1, and NF-κB proteins in ocular tissues was analyzed by Western blot. The results showed that after administration of Lycii Fructus and Chrysanthemi Flos at different ratios, the model group showed improved retinal thinning and disordered arrangement of retinal layers, elevated content of SOD and GSH in the serum and ocular tissues, and reduced levels of MDA, TNF-α, IL-1β, and IL-6. Lycii Fructus and Chrysanthemi Flos at 1∶1 and 1∶3 showed better improvement effects. The combination significantly upregulated the expression levels of Nrf2 and HO-1 and downregulated the expression of NF-κB p65. These results indicate that Lycii Fructus and Chrysanthemi Flos at different ratios can improve retinal damage, reduce oxidative stress, and alleviate inflammation in both the body and ocular tissues of mice. The mechanism may be related to the regulation of the Nrf2/HO-1 and NF-κB signaling pathways in ocular tissues. These findings provide a theoretical basis for the clinical application of Lycii Fructus and Chrysanthemi Flos in the treatment of dry age-related macular degeneration.}, }
@article {pmid40353546, year = {2025}, author = {Udom, GJ and Oritsemuelebi, B and Frazzoli, C and Bocca, B and Ruggieri, F and Orisakwe, OE}, title = {[Heavy metals and derangement in carbohydrate metabolism in eye diseases: a systematic review].}, journal = {Vestnik oftalmologii}, volume = {141}, number = {2}, pages = {89-100}, doi = {10.17116/oftalma202514102189}, pmid = {40353546}, issn = {0042-465X}, mesh = {Humans ; *Carbohydrate Metabolism/drug effects ; *Eye Diseases/metabolism/physiopathology ; *Metals, Heavy/adverse effects/toxicity ; Oxidative Stress/drug effects ; }, abstract = {PURPOSE: To uncover the negative impacts of heavy metals on carbohydrate metabolism, their mechanisms and contributory factors, as well as their role on the etiopathogenesis, pathophysiology, and progression of eye diseases.<br><br>MATERIAL AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), various databases were searched (e.g., Scopus, PubMed, etc.) to collect evidence on the link and role of heavy metals in carbohydrate metabolism and pathogenesis of eye diseases. Included studies were appraised for quality using the Critical Appraisal Skills Programme checklists and extracted data were analyzed using the narrative synthesis method.<br><br>RESULTS: Of the 128 papers retrieved, 24 papers met the inclusion criteria. Heavy metals are associated with the onset and progression of diabetes and eye diseases secondary to diabetes (age-related macular degeneration, cataract, and diabetic retinopathy) majorly via toxic interference (induction, inhibition and/or deactivation) of glucose metabolizing enzymes and oxidative stress. The etiology of DR is intricate and includes the simultaneous disruption of several metabolic and signaling mechanisms within the retinal neurovascular unit. The retina is more susceptible to metal-induced toxicities due to the high affinity of heavy metals to melanin content of the retinal epithelium.<br><br>CONCLUSION: This study emphasizes the harmful effects of chronic and intermittent exposure to heavy metals, suggesting no safe exposure levels. To prevent eye diseases secondary to heavy metals-induced altered carbohydrate metabolism, metal chelators, low glycemic diets, and lifestyle modifications should be exploited among vulnerable populations.}, }
@article {pmid40353548, year = {2025}, author = {Voskresenskaya, AA and Sarkizova, MB and Khodzhaev, NS and Kudlay, DA and Kakunina, SA and Borozinets, AY and Pozdeyeva, NA}, title = {[Biosimilars of ranibizumab in retinal diseases: new possibilities in ophthalmology].}, journal = {Vestnik oftalmologii}, volume = {141}, number = {2}, pages = {106-116}, doi = {10.17116/oftalma2025141021106}, pmid = {40353548}, issn = {0042-465X}, mesh = {Humans ; *Ranibizumab/pharmacology/therapeutic use/pharmacokinetics ; *Biosimilar Pharmaceuticals/pharmacology/therapeutic use ; Angiogenesis Inhibitors/pharmacology ; Russia ; *Retinal Diseases/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Ophthalmology/methods ; }, abstract = {The development of biological therapeutic agents has provided new opportunities for treating neovascular age-related macular degeneration (nAMD) using humanized monoclonal antibodies (mAbs) targeting vascular endothelial growth factor A (VEGF-A). The emergence of biosimilars of anti-VEGF agents can significantly improve treatment accessibility and its effectiveness by increasing patient adherence. The development of biosimilars involves comparative studies with the original drug to establish equivalence in physicochemical and biological properties, efficacy, and safety. Biosimilar development programs include extensive analytical and preclinical studies to compare structural and functional components with the original bioproduct, and clinical trials are conducted to prove bioequivalence and therapeutic equivalence. The process of development and registration of the biosimilars is strictly regulated and has no significant differences in Russia, the EU and the US. Currently, more than 10 biosimilars of ranibizumab have been approved worldwide, in Russia it is the drug Laxolan (AO GENERIUM). The introduction of a domestic biosimilar of ranibizumab into clinical practice allows reduction of the costs of retinal disease treatment while maintaining the efficacy and safety of antiangiogenic therapy.}, }
@article {pmid40353550, year = {2025}, author = {Yusef, Y and Plyukhova, AA and Yusef, N}, title = {[Artificial intelligence in assessment of individual risks of age-related macular degeneration progression].}, journal = {Vestnik oftalmologii}, volume = {141}, number = {2}, pages = {123-128}, doi = {10.17116/oftalma2025141021123}, pmid = {40353550}, issn = {0042-465X}, mesh = {Humans ; *Macular Degeneration/diagnosis/physiopathology ; *Artificial Intelligence ; *Tomography, Optical Coherence/methods ; Disease Progression ; Risk Assessment/methods ; Early Diagnosis ; }, abstract = {Age-related macular degeneration (AMD) is a progressive degenerative retinal disease and a leading cause of blindness in older adults worldwide. According to numerous studies, the number of affected individuals reached 196 million in 2020, with projections estimating an increase to 288 million by 2040, including 18.6 million cases of advanced AMD. The advent of optical coherence tomography (OCT) has enabled researchers and clinicians to characterize microstructural changes in different retinal layers at earlier disease stages and improve monitoring strategies. Important steps have been taken to develop algorithms capable of recognizing early signs of AMD, assessing its severity, and predicting progression. These algorithms have formed the basis for artificial intelligence (AI)-driven systems applicable to any hardware or software exhibiting intelligent behavior. OCT imaging allows for the identification of biomarkers whose presence or interaction with other factors predict transition from intermediate to advanced AMD. The obtained data can provide deeper insights into the pathogenesis of intermediate AMD, enhance early diagnosis for timely intervention, and facilitate the search for new treatment options. Artificial intelligence could make this process easier, simpler, less time-consuming, and more accurate by integrating structural OCT data with genetic risk indicators and lifestyle characteristics. However, the results are still inconsistent due to factors leading to limited result reliability, such as database quality, sample sizes, and data acquisition methods.}, }
@article {pmid40354066, year = {2025}, author = {Yang, J and Wu, H and Li, Q and Guo, J and Yao, J and Pan, S and Wu, X and Huang, H and Chen, R and Chen, J and Wang, Y and Peng, Y and Wu, F and Hu, J}, title = {A Simple and Rapid Method for Simultaneous Isolation of Mouse Retina and RPE Wholemounts.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {5}, pages = {14}, pmid = {40354066}, issn = {2164-2591}, mesh = {Animals ; Mice ; *Retinal Pigment Epithelium/cytology ; Mice, Inbred C57BL ; *Retina/cytology ; Tissue Fixation/methods ; }, abstract = {PURPOSE: Retina and retinal pigment epithelium (RPE) wholemounts are important models for studying the pathophysiology of retinal-related ophthalmic diseases, such as age-related macular degeneration and diabetic retinopathy. Currently, there is no method available for simultaneously obtaining retina and RPE wholemounts. The aim of this study is to develop a simple, rapid, and effective technique for the simultaneous isolation of mouse retina and RPE wholemounts.<br><br>METHODS: We developed a novel, streamlined procedure for the efficient isolation of intact retina and RPE wholemounts from mouse eyes. The method involves minimal dissection and uses basic laboratory equipment, allowing the entire process to be completed in approximately 2 to 5&#xa0;minutes per sample. The study also explores the impact of different fixation times on the structural integrity and quality of both retina and RPE wholemounts (3&#xa0;hours in 4% paraformaldehyde [PFA], 30 minutes < 1 &#xd7; phosphate-buffered saline [PBS] < 3 hours).<br><br>RESULTS: The new method consistently yields high-quality, intact retina and RPE wholemounts, with excellent structural integrity suitable for downstream imaging and molecular analyses. The technique significantly reduces preparation time. Optimal fixation conditions were identified, with 3&#xa0;hours of fixation in 4% PFA and PBS incubation times between 30&#xa0;minutes and 3&#xa0;hours yielding the best results. The approach showed higher tissue integrity (80% vs. 45%) and improved staining quality of photoreceptor and ganglion cells. Additionally, the method is highly reproducible and effective for wholemount preparations from both young and older mice (6 and 12&#xa0;months).<br><br>CONCLUSIONS: This study presents a significant advancement in the preparation of retina and RPE wholemounts. The simplicity, speed, and preservation of tissue integrity of the new method make it a valuable tool for ophthalmic disease research. Its potential applications include drug screening, gene therapy, and disease modeling, offering significant advantages in time efficiency, reproducibility, and the quality of morphological analysis.}, }
@article {pmid40354880, year = {2025}, author = {Liaño Sanz-Diez de Ulzurrun, G and Escámez-Fernández, P and Hernáez-Leonato, JM and Son-Camey, B and Rosado-Cerro, I and Arruabarrena, C}, title = {Pigment epithelial detachments in age related macular degeneration.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {100}, number = {6}, pages = {340-350}, doi = {10.1016/j.oftale.2025.05.005}, pmid = {40354880}, issn = {2173-5794}, mesh = {Humans ; *Retinal Detachment/etiology/diagnostic imaging/diagnosis ; *Macular Degeneration/complications ; *Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence ; }, abstract = {Pigment epithelial detachments (PEDs) form a heterogeneous group of lesions of diverse prognosis and treatment that have in common the pathologic elevation of the retinal pigment epithelium plane and its detachment from the underlying layers. Although PEDs are a common finding in age-related macular degeneration, especially in its exudative forms, the diagnostic characterization and prognostic estimation of these lesions is a clinical challenge that necessarily requires a multimodal imaging approach. This review presents the clinical characteristics of the different groups of PED, their diagnostic imaging profile, as well as their natural history.}, }
@article {pmid40355192, year = {2025}, author = {Han, X and Hua, Z and Chen, H and Yang, J}, title = {Cathepsins and age-related macular degeneration: A Mendelian randomization study unveiling causal relationships.}, journal = {Medicine}, volume = {104}, number = {19}, pages = {e42357}, pmid = {40355192}, issn = {1536-5964}, mesh = {Humans ; Mendelian Randomization Analysis ; *Macular Degeneration/genetics ; *Cathepsins/genetics/blood ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Cathepsin B/genetics ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision impairment and blindness in older adults, profoundly affecting millions of individuals worldwide. Cathepsins are a crucial class of proteolytic enzymes that participates in multiple biological process. However, the role of cathepsins in AMD still remains unclear. This study aims to probe into the causal relationship between cathepsins and AMD using a 2-sample Mendelian randomization (MR). Instrumental variables associated with exposure (cathepsins) and the outcome (AMD) were sourced from published genome-wide association studies. To estimate the causal effects, methodologies such as inverse variance weighted, MR-Egger, and weighted median estimation (WM) were employed. Reverse MR and multivariate MR analyses were also performed. The elevated levels of cathepsin B significantly increased the risk of dry AMD, with an odds ratio (OR) of 1.068 (95% CI = 1.007-1.133) and a P-value of .029). Sensitivity analyses confirmed the robustness of these findings, with no evidence of heterogeneity or pleiotropy. Reverse MR analyses indicated that total AMD might elevate levels of cathepsin E (OR = 1.04, P = .029). Multivariate MR analysis showed significant associations between specific cathepsins and AMD subtypes, including cathepsin G and cathepsin O with significantly increasing risk. The study revealed a potential causal effect of cathepsin B on AMD, especially dry AMD. These findings provide potential therapeutic targets for AMD, and further research is needed to understand the underlying mechanisms.}, }
@article {pmid40355704, year = {2025}, author = {Chandak, S and Gurudas, S and Pakeer Muhammed, R and Keskin, A and Thottarath, S and Ghanchi, F and Grabowska, A and Talks, SJ and Pearce, I and McKibbin, M and Kotagiri, A and Menon, G and Burton, BJL and Gale, R and Sivaprasad, S}, title = {Visual outcome following initiation of first injection versus after three monthly doses of aflibercept 2 mg for treatment naïve age-related macular degeneration to inform clinical trial designs: PRECISE Report No. 6.}, journal = {Eye (London, England)}, volume = {39}, number = {11}, pages = {2194-2203}, pmid = {40355704}, issn = {1476-5454}, support = {SIVS1045//Boehringer Ingelheim/ ; }, mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Visual Acuity/physiology/drug effects ; Aged ; Intravitreal Injections ; Male ; Female ; Tomography, Optical Coherence ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/physiopathology ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Drug Administration Schedule ; }, abstract = {PURPOSE: To study the outcome of the first dose versus three monthly doses of 2 mg aflibercept in the initiation phase of neovascular age-related macular degeneration (nAMD) to inform future clinical trial design on novel durable agents. These agents may take time to act and so initial dosing with aflibercept 2 mg is required for immediate effect.<br><br>METHODS: Visual acuity (VA) outcomes and associations with baseline VA and OCT characteristics were analysed using logistic regression via generalised estimating equations. In addition, VA outcomes based on different combinations of eligibility criteria were assessed.<br><br>RESULTS: A total of 1999 eyes of 1862 patients were analysed. The mean age was 79.3 (SD 7.8) years. The mean presenting VA was 58.0 (SD 14.5) ETDRS letter score. A statistical difference in VA was found after first injection (visit 2, 61.6, SD 14.3 ETDRS letter score) and after three monthly injections (visit 4, 62.7, SD 14.9 ETDRS letter score) (P&#x2009;<&#x2009;0.001). Lower baseline VA and OCT features suggestive of structural changes in the fovea are associated with lower VA after both first and post- initiating doses. Eyes with baseline VA&#x2009;>&#x2009;/&#x2009;=&#x2009;54 letters alone had similar VA outcomes to eyes with both VA&#x2009;>&#x2009;/&#x2009;=&#x2009;54 letters and central subfield thickness (CST) of <500 microns.<br><br>CONCLUSION: Mean VA outcomes after three monthly anti-VEGF injections are significantly better than after the first initiating dose. However, baseline OCT characteristics associated with VA in these two timepoints are not clinically different.}, }
@article {pmid40356067, year = {2025}, author = {Zipfel, PF and Heidenreich, K}, title = {The 4 functional segments of Factor H: Role in physiological target recognition and contribution to disease.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {214}, number = {9}, pages = {2150-2164}, doi = {10.1093/jimmun/vkaf065}, pmid = {40356067}, issn = {1550-6606}, support = {SFB 1192//DFG/ ; }, mesh = {Humans ; *Complement Factor H/genetics/immunology/chemistry/metabolism ; Complement Activation/immunology ; Animals ; Complement C3b/metabolism/immunology ; Atypical Hemolytic Uremic Syndrome/immunology ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology/genetics ; }, abstract = {Factor H controls proximal complement activation, and its dysfunction leads to diseases that often manifest in the kidney. Structural and functional analyses have identified 4 distinct functional segments: an N-terminal regulatory unit, a cell binding unit, a segment with combined low-affinity C3b and heparin sites, and a C-terminal recognition or sensor unit with overlapping C3b/C3d and heparin sites. Three segments are linked to diseases. The regulatory segment is affected in C3 glomerulopathy and antineutrophil cytoplasmic antibody-associated vasculitis. The second segment includes the Y402H polymorphism of age-related macular degeneration, is associated with different types of cancer, and is targeted by pathogens. The C-terminal sensor segment is involved in atypical hemolytic uremic syndrome, in FHR1:FHR3 deficient and autoantibody-positive hemolytic uremic syndrome form and is exploited by pathogens. Factor H function is modulated by Factor H like protein 1 and FHR1, 2 plasma proteins that share segments with Factor H. This interplay is critical for fine-tuning local complement. Understanding Factor H's physiological role, as well as the impact of its absence, mutations, or autoantibody targeting, provides insights into disease mechanisms and provides opportunities for therapeutic intervention by using full-length Factor H, its fragments, or complement-modulatory compounds.}, }
@article {pmid40358157, year = {2025}, author = {Kowalczuk, L and Dornier, R and Navarro, A and Jeunet, F and Moser, C and Behar-Cohen, F and Mantel, I}, title = {Adaptive Optics-Transscleral Flood Illumination Imaging of Retinal Pigment Epithelium in Dry Age-Related Macular Degeneration.}, journal = {Cells}, volume = {14}, number = {9}, pages = {}, pmid = {40358157}, issn = {2073-4409}, support = {Project ASSESS retinAI phase contrast imaging for Early diagnoSiS_Activity 20694//European Institute of Innovation and Technology/ ; Project 56126.1 IMPULSE- IRIS Imaging Retinal cells In degenerative diSeases//Innosuisse - Swiss Innovation Agency/ ; }, mesh = {Humans ; *Retinal Pigment Epithelium/diagnostic imaging/pathology ; Aged ; Male ; Female ; Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnostic imaging/pathology ; Middle Aged ; Prospective Studies ; *Geographic Atrophy/diagnostic imaging/pathology ; Aged, 80 and over ; }, abstract = {Adaptive optics-transscleral flood illumination (AO-TFI) is a novel imaging technique with potential for detecting retinal pigment epithelium (RPE) changes in dry age-related macular degeneration (AMD). This single-center prospective study evaluated its ability to visualize pathological features in AMD. AO-TFI images were acquired using the prototype Cellularis[®] camera over six 5 × 5° macular zones in patients with good fixation and no exudative changes. Conventional imaging modalities, including spectral-domain optical coherence tomography (OCT), color fundus photography and fundus autofluorescence, were used for comparison. AO-TFI images were correlated with OCT using a custom method (Fiji software, v. 2.9). Eleven eyes of nine patients (70 ± 8.3 years) with early (n = 5), intermediate (n = 1) and atrophic (n = 5) AMD were analyzed. AO-TFI identified relevant patterns in dry AMD. RPE cell visibility was impaired in affected eyes, but AO-TFI distinguished cuticular drusen with hyporeflective centers and bright edges, large ill-defined drusen and stage 3 subretinal drusenoid deposits as prominent hyperreflective spots. It provided superior resolution for small drusen compared to OCT and revealed crystalline structures and hyporeflective dots in atrophic regions. Atrophic borders remained isoreflective unless RPE displacement was absent, allowing precise delineation. These findings highlight AO-TFI's potential as a sensitive imaging tool for characterizing early AMD and clinical research.}, }
@article {pmid40358170, year = {2025}, author = {Song, YS and Park, S and Fisk, D and Sorenson, CM and Sheibani, N}, title = {Isolation and Characterization of Mouse Choroidal Melanocytes and Their Proinflammatory Characteristics.}, journal = {Cells}, volume = {14}, number = {9}, pages = {}, pmid = {40358170}, issn = {2073-4409}, support = {P30 EY016665/EY/NEI NIH HHS/United States ; EY034646/EY/NEI NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; R01 EY030076/EY/NEI NIH HHS/United States ; AMD Research Award//Arthur and Nancy Nesbit AMD fund/ ; AMD Research Award//Carl Marshall Reeves &amp; Mildred Almen Reeves Foundation/ ; EY030076/EY/NEI NIH HHS/United States ; Endoument//RRF/Daniel Albert Chair/ ; Endoument//Retina Research Foundation/ ; R21 EY034646/EY/NEI NIH HHS/United States ; Unrestricted Award to the Deaprtment of Ophthalmology and visual Sciences//Research to Prevent Blindness/ ; AMD Research Award//Pat and Jay Smith AMD Innovation Fund/ ; }, mesh = {Animals ; *Melanocytes/pathology/metabolism/cytology ; *Choroid/pathology/cytology ; Mice ; *Inflammation/pathology ; Mice, Inbred C57BL ; *Cell Separation/methods ; Cells, Cultured ; }, abstract = {Melanocytes are a major cellular component of the choroid which aids in the maintenance of choroidal integrity and vision. Unfortunately, our knowledge regarding the cell autonomous melanocyte function, in preserving choroidal health and the ocular pathologies associated with choroidal dysfunction, remain largely unknown. The ability to culture melanocytes has advanced our knowledge regarding the origin and function of these cells in choroidal homeostasis and vision. However, the culture of murine choroid melanocytes has not been previously reported. Here, we describe a method for the isolation of melanocytes from the mouse choroid, as well as the delineation of many of their cellular characteristics, including the expression of various cell-specific markers, cell adhesion molecules, melanogenic capacity, and inflammatory responses to various extracellular stressors. Unraveling the molecular mechanisms that regulate melanocyte functions will advance our understanding of their role in choroidal homeostasis and how alterations in these functions impact ocular diseases that compromise vision.}, }
@article {pmid40359333, year = {2025}, author = {Khateb, S and Ghiam, S and Safran, J and Martel, JN and Alabek, M and Nischal, KK and Errera, MH and Eller, AW and Friberg, TR and Chowers, I and Sahel, JA and Banin, E and Rosin, B}, title = {Bilateral Idiopathic Multifocal Pigment Epithelial Detachments: A Case Series and Review of Literature.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004513}, pmid = {40359333}, issn = {1539-2864}, abstract = {PURPOSE: Description of longitudinal follow-up of 13 patients diagnosed with Idiopathic Multifocal Pigment Epithelial Detachments (IMPED), a rare condition first described by Gass et al., in 2005.<br><br>METHODS: This retrospective case series included 13 patients in the first to sixth decades of life who presented with multiple bilateral PEDs, confirmed by Optical Coherence Tomography. Ancillary imaging included fundus autofluorescence and angiography to exclude alternative diagnoses such as Central Serous Chorioretinopathy and Polypoidal Choroidovasculopathy. Electrophysiology testing, including full-field electroretinography (FFERG) and electrooculography (EOG), assessed both retinal and pigment epithelium function. Visual acuity (VA) was documented over a mean follow-up of 6.5 years (range: 0.1-26.4 years).<br><br>RESULTS: All patients demonstrated stable VA during follow-up. Electrophysiology was normal in tested patients (FFERG: 9/13, EOG: 7/13). Genetic testing (10/13) was non-diagnostic. Two patients (including a patient previously receiving anti-VEGF without exudation) exhibited outer retinal atrophy. One patient developed a choroidal neovascularization (CNV) during follow-up, which resolved with intravitreal aflibercept.<br><br>CONCLUSION: IMPED should remain a diagnosis of exclusion, confirmed after sufficient follow-up demonstrating no progression. While our study implies a generally favorable prognosis, continuous monitoring is necessary to assess long-term risks, including potential complications such as the development of CNV and/or atrophy.}, }
@article {pmid40359463, year = {2025}, author = {Cozzi, M and Trinco, A and Romano, F and Zweifel, SA and Staurenghi, G and Invernizzi, A}, title = {Assessing Reliability and Agreement in Topographic Measurement of Reticular Pseudodrusen Area: A Multimodal Imaging Approach.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {9}, pages = {1701-1711}, pmid = {40359463}, issn = {1539-2864}, abstract = {PURPOSE: This study aims to assess the reliability and agreement of fundus autofluorescence (FAF), near-infrared reflectance (NIR), and a combination of NIR and dense structural optical coherence tomography (OCT) scans (OCT+NIR) in delineating the areas of reticular pseudodrusen (RPD) in eyes affected by age-related macular degeneration (AMD).<br><br>METHODS: This was a single-center, cross-sectional study. Patients with non-advanced AMD exhibiting signs of RPD on multimodal imaging were enrolled. Two independent masked graders manually delineated the margins of the area occupied by RPD using the three distinct imaging techniques.<br><br>RESULTS: The study included 60 eyes from 51 patients, with a mean age of 81.5 (&#xb1;7.1) years.The intraclass correlation coefficient between the two graders across all imaging modalities was 0.96 for FAF, 0.92 for NIR, and 0.98 for OCT+NIR. The narrowest limits of agreement were observed with OCT+NIR (-4.38 +5.17 mm 2). Foveal involvement and age were significantly correlated with larger RPD area (p =0.036 and p=0.019 respectively). Pairwise comparisons of square root-transformed RPD areas indicated that FAF detected a significantly larger RPD area compared to other methods (p <0.001).<br><br>CONCLUSIONS: These findings validate OCT+NIR as a reliable approach for measuring RPD areas, potentially serving as a critical biomarker for AMD in future clinical trials.}, }
@article {pmid40360203, year = {2025}, author = {Overbey, K and Romano, F and Ding, X and Bennett, CF and Stettler, I and Garg, I and Ploumi, I and Vingopoulos, F and Yuan, M and Razavi, P and Finn, M and Laíns, I and Patel, NA and Kim, L and Wu, D and Eliott, D and Husain, D and Vavvas, D and Miller, JW and Miller, JB}, title = {Choriocapillaris impairment in dry AMD: insights from swept-source OCT angiography and associations with structural biomarkers.}, journal = {The British journal of ophthalmology}, volume = {109}, number = {9}, pages = {1020-1027}, doi = {10.1136/bjo-2024-326416}, pmid = {40360203}, issn = {1468-2079}, support = {R01 EY030088/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Cross-Sectional Studies ; *Tomography, Optical Coherence/methods ; Male ; Female ; *Choroid/blood supply/diagnostic imaging ; *Fluorescein Angiography/methods ; Aged ; *Geographic Atrophy/physiopathology/diagnosis/diagnostic imaging ; Middle Aged ; Biomarkers ; Retinal Pigment Epithelium/pathology ; Aged, 80 and over ; Fundus Oculi ; Capillaries/pathology ; Visual Acuity ; }, abstract = {AIMS: To assess choriocapillaris flow deficit percentage (CCFD%) across stages of dry age-related macular degeneration (AMD) using swept-source optical coherence tomography angiography (SS-OCTA).<br><br>METHODS: This cross-sectional, observational study included 270 eyes (182 patients), classified as early (70 eyes), intermediate (121 eyes) and geographic atrophy (GA, 79 eyes).Participants underwent a complete examination including macular 6&#xd7;6&#x2009;mm SS-OCTA scans (PLEX Elite 9000). Scans were reviewed and analysed for subretinal drusenoid deposits (SDDs), retinal pigment epithelium (RPE) atrophy size, incomplete RPE and outer retinal atrophy (iRORA) and drusen volume (3&#x2009;mm). CCFD% was calculated after compensation and binarisation using Phansalkar's method (r=4-15 pixels) in various early treatment for diabetic retinopathy study sectors. Linear mixed-effects models adjusted for age evaluated associations with AMD stages and other imaging biomarkers.<br><br>RESULTS: CCFD% progressively increased with advancing dry AMD stages. Intermediate AMD eyes showed higher CCFD% than early AMD ones across all regions (p<0.001). GA eyes exhibited significantly higher CCFD% compared with early (p<0.001) and intermediate AMD eyes (p<0.001).SDDs were significantly associated with higher CCFD% in early (p<0.01) and intermediate AMD (p<0.05) for almost all regions examined, but not in GA (p>0.05). iRORA presence in iAMD and larger RPE atrophy in GA correlated with increased CCFD% (p<0.001).<br><br>CONCLUSIONS: This study provides a comprehensive reference database for CCFD% across the stages of dry AMD using SS-OCTA. CCFD% increased with AMD severity, iRORA, SDDs, particularly in early and intermediate stages, and RPE atrophy size. Our findings support CCFD% as a valuable biomarker for clinical and research applications, warranting longitudinal studies to validate its prognostic value.}, }
@article {pmid40360847, year = {2025}, author = {Wu, KY and Dave, A and Nirwal, GK and Giunta, M and Nguyen, VDH and Tran, SD}, title = {Exosome Innovations in Ophthalmology and Sjögren's Syndrome.}, journal = {Advances in experimental medicine and biology}, volume = {1488}, number = {}, pages = {103-131}, pmid = {40360847}, issn = {0065-2598}, mesh = {Humans ; *Sjogren's Syndrome/therapy/metabolism/pathology ; *Exosomes/transplantation/metabolism ; Animals ; *Ophthalmology/methods/trends ; Mesenchymal Stem Cells/metabolism ; }, abstract = {Exosomes, a subset of extracellular vesicles, have emerged as potential therapeutic agents in ophthalmology due to their ability to modulate immune responses, facilitate cellular communication, and promote tissue repair. This chapter explores the potential applications of exosome-based therapies in corneal and anterior segment disorders, retinal diseases, glaucoma, and Sjögren's syndrome. In corneal disorders, mesenchymal stem cell (MSC)-derived secretomes have shown promise in accelerating wound healing, reducing fibrosis, and modulating inflammation, with hydrogel encapsulation strategies potentially enhancing their efficacy. In retinal diseases, exosomes may provide neuroprotective effects in age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa by modulating oxidative stress and inflammation. In glaucoma, secretome-based therapies could support retinal ganglion cell survival and optic nerve regeneration, though their impact on intraocular pressure via the trabecular meshwork remains uncertain. Additionally, exosomal biomarkers in aqueous humor are being investigated as potential diagnostic tools. In Sjögren's syndrome, exosomal biomarkers may facilitate earlier detection, while stem cell-derived exosomes hold promise in modulating immune responses and restoring glandular function. Despite encouraging preclinical and early clinical findings, standardization, scalability, and long-term safety must be addressed before clinical translation. Future research will focus on optimizing exosome-based therapies and exploring their feasibility for ophthalmic applications.}, }
@article {pmid40361958, year = {2025}, author = {Nurjanah, T and Patel, M and Mar, J and Holden, D and Barrett, SC and Yannuzzi, NA}, title = {Expanding Application of Optical Coherence Tomography Beyond the Clinic: A Narrative Review.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {9}, pages = {}, pmid = {40361958}, issn = {2075-4418}, abstract = {Since its introduction, optical coherence tomography (OCT) has significantly progressed in addressing its limitations. By integrating artificial intelligence and multimodal imaging, OCT enhances both speed and image quality while reducing its size. OCT continues to advance, offering new possibilities beyond the in-office setting, including intraoperative applications. This review will explore the different types of home OCT and intraoperative OCT, as well as the uses of each device and their future potential in ophthalmology.}, }
@article {pmid40362317, year = {2025}, author = {Khan, I and Ramzan, F and Tayyab, H and Damji, KF}, title = {Rekindling Vision: Innovative Strategies for Treating Retinal Degeneration.}, journal = {International journal of molecular sciences}, volume = {26}, number = {9}, pages = {}, pmid = {40362317}, issn = {1422-0067}, mesh = {Humans ; *Retinal Degeneration/therapy ; Genetic Therapy/methods ; Animals ; Stem Cell Transplantation/methods ; Gene Editing ; Regenerative Medicine/methods ; }, abstract = {Retinal degeneration, characterized by the progressive loss of photoreceptors, retinal pigment epithelium cells, and/or ganglion cells, is a leading cause of vision impairment. These diseases are generally classified as inherited (e.g., retinitis pigmentosa, Stargardt disease) or acquired (e.g., age-related macular degeneration, diabetic retinopathy, glaucoma) ocular disorders that can lead to blindness. Available treatment options focus on managing symptoms or slowing disease progression and do not address the underlying causes of these diseases. However, recent advancements in regenerative medicine offer alternative solutions for repairing or protecting degenerated retinal tissue. Stem and progenitor cell therapies have shown great potential to differentiate into various retinal cell types and can be combined with gene editing, extracellular vesicles and exosomes, and bioactive molecules to modulate degenerative cellular pathways. Additionally, gene therapy and neuroprotective molecules play a crucial role in enhancing the efficacy of regenerative approaches. These innovative strategies hold the potential to halt the progression of retinal degenerative disorders, repair or replace damaged cells, and improve visual function, ultimately leading to a better quality of life for those affected.}, }
@article {pmid40364054, year = {2025}, author = {Frizziero, L and Midena, G and Danieli, L and Torresin, T and Perfetto, A and Parrozzani, R and Pilotto, E and Midena, E}, title = {Hyperreflective Retinal Foci (HRF): Definition and Role of an Invaluable OCT Sign.}, journal = {Journal of clinical medicine}, volume = {14}, number = {9}, pages = {}, pmid = {40364054}, issn = {2077-0383}, abstract = {Background: Hyperreflective retinal foci (HRF) are small, discrete, hyperreflective elements observed in the retina using optical coherence tomography (OCT). They appear in many retinal diseases and have been linked to disease progression, treatment response, and prognosis. However, their definition and clinical use vary widely, not just between different diseases, but also within a single disorder. Methods: This perspective is based on a review of peer-reviewed studies examining HRF across different retinal diseases. The studies included analyzed HRF morphology, distribution, and clinical relevance using OCT. Particular attention was given to histopathological correlations, disease-specific patterns, and advancements in automated quantification methods. Results: HRF distribution and features vary with disease type and even within the same disease. A variety of descriptions have been proposed with different characteristics in terms of dimensions, reflectivity, location, and association with back shadowing. Automated OCT analysis has enhanced HRF detection, enabling quantitative analysis that may expand their use in clinical practice. However, differences in software and methods can lead to inconsistent results between studies. HRF have been linked to microglial cells and may be defined as neuro-inflammatory cells (Inflammatory, I-HRF), migrating retinal pigment epithelium cells (Pigmentary, P-HRF), blood vessels (Vascular, V-HRF), and deposits of proteinaceous or lipid elements leaking from vessels (Exudative, E-HRF). Conclusions: HRF are emerging as valuable imaging biomarkers in retinal diseases. Four main types have been identified, with different morphological features, pathophysiological origin, and, therefore, different implications in the management of retinal diseases. Advances in imaging and computational analysis are promising for their incorporation into personalized treatment strategies.}, }
@article {pmid40364109, year = {2025}, author = {Raju, P and Yu, M}, title = {Clinical Applications of the Cone Contrast Test in Ophthalmology and Neurology.}, journal = {Journal of clinical medicine}, volume = {14}, number = {9}, pages = {}, pmid = {40364109}, issn = {2077-0383}, support = {P30-EY025585/NH/NIH HHS/United States ; }, abstract = {Color vision is a critical aspect of human visual perception, yet traditional assessments often lack quantitative precision. The Rabin Cone Contrast Test and its successors offer objective, standardized measurements of cone-specific contrast sensitivity. These tests improve the detection and classification of color vision deficiencies and can facilitate the monitoring of color vision deficits in inherited retinal diseases, cone dystrophies, optic neuropathies, and brain injuries. Integrating quantitative color vision testing into clinical practice presents a more reliable, reproducible, and functionally relevant evaluation, highlighting its value in disease diagnosis, characterization, and management.}, }
@article {pmid40364185, year = {2025}, author = {Ota, H and Takeuchi, J and Nonogaki, R and Tamura, K and Kominami, T}, title = {Pneumatic Displacement and Anti-VEGF Therapy for Submacular Hemorrhage in Neovascular Age-Related Macular Degeneration: A Retrospective Study.}, journal = {Journal of clinical medicine}, volume = {14}, number = {9}, pages = {}, pmid = {40364185}, issn = {2077-0383}, abstract = {Background/Objectives: Submacular hemorrhage (SMH) associated with neovascular age-related macular degeneration (nAMD) can lead to significant vision loss, and the optimal management strategy remains uncertain. This study aimed to evaluate the efficacy and safety of pneumatic displacement (PD) without tissue plasminogen activator (t-PA) for SMH secondary to nAMD. Methods: A retrospective analysis was conducted on 22 eyes with SMH secondary to nAMD treated with PD without t-PA. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), number of intravitreal injections, and postoperative complications were assessed at baseline and follow-up. Multiple logistic regression analyses were used to identify factors associated with visual outcomes. Results: In the 22 eyes that completed the 6-month follow-up, BCVA (logMAR) was 0.88 ± 0.46 at baseline and 0.76 ± 0.63 at 6 months (p = 0.24). In the 15 eyes with 12-month follow-up, BCVA improved significantly from 0.92 ± 0.47 at baseline to 0.56 ± 0.51 at 12 months (p = 0.01). CRT significantly decreased at 3 months (p < 0.01). During this period, patients received an average of 8.13 ± 2.90 intravitreal anti-vascular endothelial growth factor (VEGF) injections. A shorter duration from symptom onset to treatment was associated with better visual outcomes (p = 0.02). Postoperative vitreous hemorrhage occurred in 31.8% of cases. Conclusions: PD without t-PA, in combination with anti-VEGF therapy, improved visual outcomes over 12 months. Early intervention and continuous anti-VEGF administration appear to be key factors in optimizing treatment outcomes. Further studies are needed to establish standardized treatment protocols for SMH associated with nAMD.}, }
@article {pmid40364275, year = {2025}, author = {Saito, M and Mitamura, M and Ito, Y and Endo, H and Katsuta, S and Ishida, S}, title = {Inter-Relationships Between the Deep Learning-Based Pachychoroid Index and Clinical Features Associated with Neovascular Age-Related Macular Degeneration.}, journal = {Journal of clinical medicine}, volume = {14}, number = {9}, pages = {}, pmid = {40364275}, issn = {2077-0383}, abstract = {Background/Objectives: To investigate the impact of pachychoroid on the clinical features of neovascular age-related macular degeneration (nAMD) in Japan using the deep learning-based Hokkaido University pachychoroid index (HUPI), which has a high discriminative ability for pachychoroid. Methods: This retrospective observational study examined 124 eyes of 111 treatment-naïve nAMD patients, including 44 eyes with type 1 macular neovascularization (MNV), 26 eyes with type 2 MNV, and 54 eyes with polypoidal choroidal vasculopathy (PCV). HUPI was calculated for each eye from EDI-OCT choroidal images using our modified LeNet that had learned the image patterns of pachychoroid. Differences in HUPI between nAMD types and inter-relationships between nAMD parameters, including HUPI, were evaluated. Results: The mean HUPI was 0.53 ± 0.30 for type 1 MNV, 0.33 ± 0.23 for type 2 MNV, and 0.61 ± 0.3 for PCV, with significant differences between any two of the three groups (p < 0.05, for each). Round-robin multiple regression analysis for nAMD parameters showed the close associations of the HUPI with choroidal vascular hyperpermeability (CVH) and subretinal fluid (SRF) (p = 0.017 and p < 0.001 for each) and the clear division of nAMD parameters into the following two groups: one including intraretinal fluid and type 1 and type 2 MNV and the other including SRF, CVH, polypoidal lesions, and HUPI. Conclusions: HUPI revealed that eyes with type 1 MNV and PCV had more pachychoroid-like features than eyes with type 2 MNV. HUPI was tightly associated with CVH and SRF but not MNV per se in nAMD parameters, reinforcing the pathoetiological concept of differentiating pachychoroid from typical nAMD.}, }
@article {pmid40364630, year = {2026}, author = {de Lima-Vasconcellos, TH and Bovi Dos Santos, G and Móvio, MI and Donnici, GK and Badin, GM and de Araujo, DR and Kihara, AH}, title = {Neuroprotection provided by polyphenols and flavonoids in photoreceptor degenerative diseases.}, journal = {Neural regeneration research}, volume = {21}, number = {3}, pages = {908-922}, pmid = {40364630}, issn = {1673-5374}, abstract = {The intricate landscape of neurodegenerative diseases complicates the search for effective therapeutic approaches. Photoreceptor degeneration, the common endpoint in various retinal diseases, including retinitis pigmentosa and age-related macular degeneration, leads to vision loss or blindness. While primary cell death is driven by genetic mutations, oxidative stress, and neuroinflammation, additional mechanisms contribute to disease progression. In retinitis pigmentosa, a multitude of genetic alterations can trigger the degeneration of photoreceptors, while other retinopathies, such as age-related macular degeneration, are initiated by combinations of environmental factors, such as diet, smoking, and hypertension, with genetic predispositions. Nutraceutical therapies, which blend the principles of nutrition and pharmaceuticals, aim to harness the health benefits of bioactive compounds for therapeutic applications. These compounds generally possess multi-target effects. Polyphenols and flavonoids, secondary plant metabolites abundant in plant-based foods, are known for their antioxidant, neuroprotective, and anti-inflammatory properties. This review focuses on the potential of polyphenols and flavonoids as nutraceuticals to treat neurodegenerative diseases such as retinitis pigmentosa. Furthermore, the importance of developing reliable delivery methods to enhance the bioavailability and therapeutic efficacy of these compounds will be discussed. By combining nutraceuticals with other emerging therapies, such as genetic and cell-based treatments, it is possible to offer a more comprehensive approach to treating retinal degenerative diseases. These advancements could lead to a viable and accessible option, improving the quality of life for patients with retinal diseases.}, }
@article {pmid40365539, year = {2025}, author = {Xiaodong, L and Xia, C and Xuewei, Q and Dandan, W and Yi, Y and Zhilin, L}, title = {Sustainable Practices in Anti-VEGF Therapy: A 15-Year Bibliometric Analysis of Ranibizumab for Age-Related Macular Degeneration.}, journal = {Journal of ophthalmology}, volume = {2025}, number = {}, pages = {8891531}, pmid = {40365539}, issn = {2090-004X}, abstract = {Objective: A bibliometric analysis was performed in the domain of ranibizumab and age-related macular degeneration (AMD) to delineate current trends in international research dynamics and to provide a visual representation of research hotspots and challenges associated with ophthalmic drugs over the past 15 years. This study also evaluates the sustainability of ranibizumab therapy through reduced injection burden, cost-effectiveness compared to alternative treatments, and long-term outcomes that minimize healthcare resource utilization. Method: In this cross-sectional study, bibliometrics analyzed data retrieved and extracted from the Web of Science Core Collection (WOSCC) database to analyze the evolution and thematic trends in the delivery of studies from January 1, 2008, to September 2, 2023, for ranibizumab and AMD studies. A total of 2691 articles on the field were assessed for specific characteristics such as the year of publication, journal, author, institution, country/region, citation, and keywords. Co-authorship analysis, co-occurrence analysis, co-citation analysis, and network visualization were constructed using VOSviewer. Some important subtopics identified by bibliometric characterization were further discussed and reviewed. Results: From 2008 to 2023, the cumulative number of articles published globally increased from 1 to 2,691, with the highest number of articles published in 2020 (255 papers). RETINA THE JOURNAL OF RETINAL AND VITREOUS DISEASES published the most manuscripts (285 papers) and was cited (6496 citations), followed by OPHTHALMOLOGY (193 papers) and GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY (163 papers). OPHTHALMOLOGY was the most cited (20,865 citations), with the United States (786 papers, 38,014 citations), Univ Sydney (98 papers, 5245 citations), and Kim, Jong Woo (56 papers, 550 citations) being the most productive and influential institutions, countries, and authors, respectively. Five clusters were formed by summarizing the top 100 keywords, which marked the emerging frontier of ranibizumab and AMD-related research. Further discussion of the five clusters of research is to assist the researcher in determining the scope of the research topic and planning the direction of the research. Conclusion: Over the past two decades, there has been a notable increase in the number of publications and citations pertaining to ranibizumab and AMD across various countries, institutions, and authors. This study elucidates current trends, global collaboration patterns, foundational knowledge, research hotspots, and developmental trajectories within the realm of ranibizumab-related AMD research. Key advancements in AMD treatment with ranibizumab over the last 15 years have centered on less frequent injection schedules, extended drug efficacy, and enhanced safety profiles.}, }
@article {pmid40365784, year = {2025}, author = {Oertel, J and Fischer, D and Tarhan, M and Meller, D and Hammer, M}, title = {Fundus autofluorescence lifetimes in age-related macular degeneration versus healthy controls in a pseudophakic population.}, journal = {Acta ophthalmologica}, volume = {103}, number = {6}, pages = {e394-e400}, pmid = {40365784}, issn = {1755-3768}, support = {HA 4430/5-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; Male ; Female ; Aged ; *Pseudophakia/complications/diagnosis ; *Fluorescein Angiography/methods ; Aged, 80 and over ; *Ophthalmoscopy/methods ; Fundus Oculi ; *Macular Degeneration/diagnosis ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; Retrospective Studies ; }, abstract = {PURPOSE: To check whether prolonged fundus autofluorescence (FAF) lifetimes in age-related macular degeneration (AMD) could be an artefact resulting from lens fluorescence.<br><br>METHODS: Fluorescence lifetime imaging ophthalmoscopy (FLIO) was performed in pseudophakic intermediate AMD as well as healthy controls. The median values of FAF lifetimes in the centre, the inner and the outer ring of the ETDRS grid, obtained as amplitude-weighted mean of the lifetimes from a three-exponential fit of the fluorescence decay over time in two spectral channels, as well as peak emission wavelengths (PEW) were compared between patients and controls. The age dependence of FAF lifetime was checked per group. In the patient cohort, FAF lifetimes of individuals with and without subretinal drusenoid deposits (SDD) were compared.<br><br>RESULTS: Forty-four AMD patients (mean age 80.0&#x2009;&#xb1;&#x2009;6.0&#x2009;years) and 26 controls (mean age 73.0&#x2009;&#xb1;&#x2009;10.2&#x2009;years) were included. The FAF lifetimes of a subgroup of patients (N&#x2009;=&#x2009;25, mean age 76.3&#x2009;&#xb1;&#x2009;5.6&#x2009;years), age-matched to the controls, were significantly longer than those of the controls (all grid areas and spectral channels p&#x2009;<&#x2009;0.001). FAF lifetimes increased with age in the controls (p&#x2009;=&#x2009;0.006-0.03), but not in the patients. Patients with SDD had longer FAF lifetimes than those without (p&#x2009;=&#x2009;0.003-0.068). PEW neither showed significant group differences nor age dependence.<br><br>CONCLUSIONS: Although long fluorescence lifetimes of the lens can affect FAF lifetime measurements, prolonged FAF lifetimes in AMD are specific to the disease and not a lens artefact as shown in pseudophakic eyes. The effect of AMD on the lifetimes outweighs that of age. Patients with SDD, who have a higher risk of AMD progression, also show longer FAF lifetimes.}, }
@article {pmid40371970, year = {2025}, author = {Ali, FS and Tabano, DC and Borkar, DS and Leng, T and Garmo, V and Ahmed, A and Myers, R and Shaia, JK and Barteselli, G and Singh, RP}, title = {Early Outcomes After Initiation of Faricimab for Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {56}, number = {8}, pages = {468-477}, doi = {10.3928/23258160-20250304-02}, pmid = {40371970}, issn = {2325-8179}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; Intravitreal Injections ; *Visual Acuity ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; Aged, 80 and over ; Tomography, Optical Coherence ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography ; Middle Aged ; Time Factors ; Antibodies, Bispecific ; }, abstract = {BACKGROUND AND OBJECTIVE: This study assessed treatment patterns and early outcomes among patients with neovascular age-related macular degeneration (nAMD) initiating faricimab in routine clinical practice in the United States.<br><br>PATIENTS AND METHODS: FARETINA-AMD is a retrospective study among patients with nAMD initiating faricimab from February 2022 to June 2023 identified from the US IRIS[&#xae;] Registry.<br><br>RESULTS: Included were 21,508 patients previously treated with anti-vascular endothelial growth factor (anti-VEGF) (25,784 eyes) and 1,836 treatment-na&#xef;ve patients (1,982 eyes) with nAMD. Among previously treated eyes, visual acuity remained stable with faricimab. In treatment-na&#xef;ve eyes, mean &#xb1; SD visual acuity improved from 56.7 &#xb1; 24.1 letters at index to 61.4 &#xb1; 22.3 after faricimab injection 4 (P < 0.01). Mean &#xb1; SD central subfield thickness improved from 315.2 &#xb1; 80.0 (index) to 264.9 &#xb1; 60.1 &#x3bc;m (injection 4) in treatment-na&#xef;ve eyes and 296.2 &#xb1; 95.5 to 273.0 &#xb1; 81.4 &#x3bc;m in previously treated eyes (both P < 0.01).<br><br>CONCLUSIONS: Among patients with nAMD receiving faricimab, visual acuity improved in treatment-na&#xef;ve eyes, and both previously treated and treatment-na&#xef;ve eyes experienced anatomical improvement.}, }
@article {pmid40371972, year = {2025}, author = {Goldberg, RA and Boyer, DS and Holz, FG and MacCumber, MW and Garg, SJ and Brown, DM and Lad, EM and Steinle, N and Rishi, PS and Pearce, I and Ach, T and Ribeiro, R and Li, C and Jones, D and Tsuboi, M and Ferrone, PJ and Baumal, CR and Wykoff, CC}, title = {Pegcetacoplan for Geographic Atrophy Over 30 Months: Data From OAKS, DERBY, and the GALE Long-Term Extension Study.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {56}, number = {7}, pages = {398-406}, doi = {10.3928/23258160-20250217-01}, pmid = {40371972}, issn = {2325-8179}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; *Geographic Atrophy/diagnosis/drug therapy/etiology ; Intravitreal Injections ; Time Factors ; Tomography, Optical Coherence/methods ; Treatment Outcome ; *Visual Acuity ; }, abstract = {BACKGROUND AND OBJECTIVE: This study will report safety and efficacy of pegcetacoplan for geographic atrophy (GA) secondary to age-related macular degeneration (AMD).<br><br>PATIENTS AND METHODS: GALE is a phase 3, open-label, multicenter, 36-month extension of the OAKS and DERBY studies. Patients who received pegcetacoplan monthly (PM) or every other month (PEOM) in OAKS or DERBY continued the same regimen in GALE (PM-PM and PEOM-PEOM); sham-observed patients initiated pegcetacoplan, maintaining the same interval.<br><br>RESULTS: In the first 6 months of GALE, 3.0% of study eyes developed exudative AMD, 1.3% intraocular inflammation, 0.1% ischemic optic neuropathy, and none endophthalmitis. Pegcetacoplan reduced GA growth rate by 39% (PM-PM) and 32% (PEOM-PEOM), with increasing efficacy over time across GA subtypes. In eyes with nonsubfoveal GA, pegcetacoplan reduced GA growth rate by 45% (PM-PM) and 33% (PEOM-PEOM).<br><br>CONCLUSION: Pegcetacoplan reduced GA growth rate up to 45% with increasing efficacy over 30 months and demonstrated a favorable safety profile. [Ophthalmic Surg Lasers Imaging Retina 2025;56:398-406.].}, }
@article {pmid40372291, year = {2026}, author = {,  and , }, title = {Prevalence of Vision Loss in High-Income Countries and in Eastern and Central Europe in 2020: Magnitude and Temporal Trends.}, journal = {Ophthalmic epidemiology}, volume = {33}, number = {1}, pages = {54-67}, doi = {10.1080/09286586.2025.2486461}, pmid = {40372291}, issn = {1744-5086}, mesh = {Humans ; Prevalence ; *Blindness/epidemiology ; *Developed Countries/statistics &amp; numerical data ; Europe/epidemiology ; Male ; Female ; Europe, Eastern/epidemiology ; Middle Aged ; Sex Distribution ; Aged ; *Persons with Visual Disabilities/statistics &amp; numerical data ; }, abstract = {PURPOSE: To estimate the prevalence of vision loss for 2020 in high-income countries (HICs) and Central/Eastern Europe and analyse evolving trends since 1990.<br><br>METHODS: Based on a systematic review of medical literature, prevalence of blindness, moderate and severe vision impairment (MSVI), mild vision impairment (VI), moderate VI and presbyopia were estimated for 1990, 2000, 2010, and 2020.<br><br>RESULTS: The study included 68 population-based studies. In the whole study region, the age-standardized prevalence (all ages) of blindness, MSVI, moderate VI, severe VI, mild VI, and presbyopia-related VI was 0.17% (95% CI:0.15-0.19), 2.27% (2.05-2.49), 2.06% (1.84-2.29), 0.21% (0.18-0.23), 1.79% (1.62-1.99), and 2.61% (1.88-3.48) respectively, with slightly higher rates for women than men. The prevalence rates were higher in Central/Eastern Europe than in the HIC, and lower than the global rates. Stratified between Australasia, high-income Asia Pacific region, high-income North America, Western Europe, Central Europe, and Eastern Europe, the age-standardized prevalence of blindness changed between 2000 and 2020 for men aged 50+&#xa0;years by -7.95% (-8.11/-7.78), -14.51% (-14.64/-14.38), +13.18% (+13.00/+13.36), -12.07% (-12.23/-11.91), -14.39% (-14.54/-14.23), and -23.59% (-23.72/-23.46), respectively, without significant sex-related differences. Highest increase was in high-income North America (+13.18% (+13.00/+13.36)) and most marked reduction in Eastern Europe (-23.59% (-23.72/-23.46)). Estimated blind individuals were stratified as follows: Australasia, 68,866 (54,913-84,527), high-income Asia Pacific region, 535,124 (439,912-640,330), high-income North America, 711,990 (575,977-867,402), Western Europe, 1,533,752 (1,218,371-1,898,343), Central Europe, 327,352 (264,513-398,083) and Eastern Europe, 789,618 (663,130-923,121).<br><br>CONCLUSIONS: Age-standardized prevalence of blindness and MSVI have further decreased in HIC and Eastern/Central Europe (except for high-income North America with an increase).}, }
@article {pmid40372516, year = {2025}, author = {Zimmermann, ME and Thanner, V and Helbig, H and Stark, KJ and Heid, IM and Brandl, C}, title = {[Awareness for age-related macular degeneration in the population-based AugUR study : Comparison of participant self-report with medical records data from treating ophthalmologists].}, journal = {Die Ophthalmologie}, volume = {122}, number = {8}, pages = {612-618}, pmid = {40372516}, issn = {2731-7218}, support = {01ER1206//BMBF/ ; 01ER1507//BMBF/ ; HE3690/7-1//DFG/ ; HE3690/5-1//DFG/ ; BR 6028/2-1//DFG/ ; R01 EY RES 511967/GF/NIH HHS/United States ; R01 EY RES 516564/GF/NIH HHS/United States ; }, mesh = {Humans ; Aged ; *Macular Degeneration/epidemiology/diagnosis/psychology ; *Self Report ; Male ; Female ; Aged, 80 and over ; *Ophthalmologists/statistics &amp; numerical data ; Germany/epidemiology ; *Medical Records/statistics &amp; numerical data ; *Health Knowledge, Attitudes, Practice ; Awareness ; }, abstract = {BACKGROUND: Limited awareness of existing age-related macular degeneration (AMD) can negatively affect the use of appropriate healthcare. This is particularly true for the older population, who are most commonly affected by AMD.<br><br>OBJECTIVES: Analyzing the awareness of an existing AMD diagnosis in the older population. We evaluated AMD self-reports of participants of the population-based AugUR study aged &#x2265;&#x202f;70&#xa0;years in and around Regensburg using the records of treating ophthalmologists (BAA).<br><br>MATERIALS AND METHODS: AMD self-reports of the AugUR participants were collected at study inclusion using interview-based questionnaires. An AMD diagnosis documented by the BAA was recorded by the BAA using an online questionnaire. Consensus or dissent of the available information was determined by creating a&#xa0;timeline for the date of study inclusion, the date of the first documented AMD diagnosis by the BAA and the date of the last visit to the BAA.<br><br>RESULTS: Self-report and BAA records on AMD were available for 1473 AugUR participants. Consensus was reached for 1270 individuals (86%). Of the 262 individuals with an existing BAA AMD diagnosis prior to study inclusion, 166 (63%) reported that they did not have AMD. In 137 of these 166 "underreporters", early stages of AMD were documented by the BAA.<br><br>CONCLUSION: Our results suggest that 63% of the older population with a&#xa0;BAA-AMD diagnosis are unaware of their AMD diagnosis. Most of these diagnoses represent early stages of AMD, which may not be communicated to patients as "AMD". Improved awareness, including early forms of AMD, could support preventative behavior by those affected.}, }
@article {pmid40373229, year = {2025}, author = {Ong, C and Sun, C and Mathur, R and Chan, CM and Yeo, I and Sim, S and Teo, K and Cheung, G}, title = {Fundus Autofluorescence (FAF) Alteration in Polypoidal Choroidal Vasculopathy (PCV) and Typical Neovascular Age Related Macular Degeneration (tAMD).}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {9}, pages = {1727-1737}, pmid = {40373229}, issn = {1539-2864}, abstract = {PURPOSE: To characterize and evaluate differences in fundus autofluorescence (FAF) alteration in polypoidal choroidal vasculopathy (PCV) and typical neovascular age related macular degeneration (tAMD).<br><br>METHODS: We used multimodal imaging to delineate the area of macular neovascularization (MNV) and extent of subretinal fluid (SRF). Macular FAF alteration was categorized to those limited to the area of the neovascular lesion (zone 1), area beyond zone 1 affected by subretinal fluid or pigment epithelial detachment (zone 2), and area beyond zone 2 (zone 3). Loss of FAF signal that correlated with complete outer retina and RPE loss (c-RORA) was documented.<br><br>RESULTS: We included 94 eyes from 94 patients (48 with diagnosis of PCV; 46 with diagnosis of tAMD). PCV eyes had greater subfoveal choroidal thickness (250 &#xb1; 92 &#x3bc;m vs 178 &#xb1; 86 &#x3bc;m, p<0.001) compared to tAMD. FAF alteration was seen in all eyes in Zone 1 and 2. Polypoidal lesion(s) appear as hyper-AF, iso-AF or hypo-AF round lesions. FAF alteration extending to zone 3 was observed in 41.7% of PCV eyes and 19.6% of tAMD eyes (p=0.02), in which hyper-AF pattern was predominant. Furthermore, zone 3 FAF alteration was associated with choroidal vascular hyperpermeability in eyes with PCV but not in tAMD (40% vs 0%, p=0.03).<br><br>CONCLUSION: These findings highlight RPE dysfunction may affect widespread areas in PCV, and may be the effect of choroidal congestion.}, }
@article {pmid40373839, year = {2025}, author = {Zou, R and Wu, X and Chen, H and Yuan, F and Yuan, Y}, title = {CLK2-SOX3 combination promotes choroidal neovascularization by SGLT1 inducing endothelial cell metabolic reprogramming.}, journal = {Cellular signalling}, volume = {133}, number = {}, pages = {111865}, doi = {10.1016/j.cellsig.2025.111865}, pmid = {40373839}, issn = {1873-3913}, mesh = {Animals ; *Endothelial Cells/metabolism ; Mice ; *SOXB1 Transcription Factors/metabolism/genetics ; *Choroidal Neovascularization/metabolism/pathology/genetics ; *Sodium-Glucose Transporter 1/metabolism/genetics ; *Protein Serine-Threonine Kinases/metabolism/genetics ; Mice, Inbred C57BL ; Humans ; Cellular Reprogramming ; Metabolic Reprogramming ; }, abstract = {Choroidal neovascularization (CNV) is one of the main causes of visual loss. Endothelial cell metabolic reprogramming is an important mechanism in regulating pathological neovascularization. However, how endothelial cell metabolic reprogramming is regulated in CNV is not yet clear. In this study, we constructed CNV mouse model by laser injury and in vitro cell model by hypoxia-induced mouse brain microvascular endothelial cells (BMECs). We identified glucose transporter Sodium-Dependent Glucose Transporter 1 (SGLT1) regulating endothelial cell metabolic reprogramming by siRNA transfection and metabolomics analysis. Mechanistically, we manifested the TCTTTGTCTG and ATTGCCTC sequences in the sglt1 promoter was targeted by SRY-box transcription factor 3 (SOX3). Furtherly, the function of SOX3 was induced by its Ser97 site combining with CDC-like kinase 2 (CLK2). Our results show that the CLK2-SOX3 combination targets sglt1, thereby inducing metabolic reprogramming of endothelial cells and promoting CNV.}, }
@article {pmid40374301, year = {2025}, author = {Del-Cura, MP and Jimeno Anaya, L and Sastre Ibáñez, M and Quijada-Angeli, S and Martín-Herrero, A and Pastora-Salvador, N and Sánchez Marugán, B and Martínez Sánchez, M and Castaño Martín, B and Crespo-Carballés, MJ}, title = {Adherence and Awareness of Patients with Age-Related Macular Degeneration to AREDS 2 Recommended Nutritional Supplements.}, journal = {Journal of nutrition in gerontology and geriatrics}, volume = {44}, number = {2}, pages = {123-132}, doi = {10.1080/21551197.2025.2504911}, pmid = {40374301}, issn = {2155-1200}, mesh = {Humans ; Female ; *Dietary Supplements ; Male ; *Macular Degeneration ; Aged ; *Health Knowledge, Attitudes, Practice ; *Patient Compliance ; Middle Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Vitamins/therapeutic use/administration &amp; dosage ; Surveys and Questionnaires ; }, abstract = {BACKGROUND &amp; AIMS: Age-related macular degeneration (AMD) stands as the leading cause of visual impairment and blindness in developed nations. The Age-Related Eye Disease Study 2 (AREDS 2) conclusively demonstrated the advantages of vitamin and mineral supplementation in either preventing or slowing down the progression of AMD. This survey was crafted to evaluate the utilization of nutritional supplements and to gauge the knowledge, attitudes, and practices of patients with AMD. The aim was to identify factors predicting adherence and explore the public health implications.<br><br>METHODS: A cross-sectorial study was conducted involving 148 patients through a survey carried out at a tertiary-level hospital. The survey focused on patients with AMD who were candidates for nutritional supplements.<br><br>RESULTS: The primary outcome was the rate of adherence to AREDS recommendations, which was found to be 83%. Female gender (P&#x2009;=&#x2009;0.038), effective medication regimen management (P&#x2009;<&#x2009;0.01), and higher levels of education (P&#x2009;<&#x2009;0.01) emerged as independent factors significantly associated with adherence.<br><br>CONCLUSIONS: While ophthalmologists play a crucial role in addressing neovascular complications of AMD, they also bear the responsibility of promoting patient adherence to AREDS supplements. Achieving optimal compliance requires addressing the multifaceted factors identified in this study, with specific attention to patients' educational backgrounds and informational requirements.}, }
@article {pmid40374310, year = {2026}, author = {Gouliopoulos, N and Bouratzis, N and Kympouropoulos, S and Datseris, I and Georgalas, I and Theodossiadis, P and Rouvas, A}, title = {Mental Health Consequences of Age-Related Macular Degeneration: Exploring Depression Prevalence and Severity in Wet and Dry Forms.}, journal = {Clinical gerontologist}, volume = {49}, number = {1}, pages = {168-176}, doi = {10.1080/07317115.2025.2506768}, pmid = {40374310}, issn = {1545-2301}, mesh = {Humans ; Female ; Male ; Cross-Sectional Studies ; Aged ; Prevalence ; *Depression/epidemiology/psychology/etiology ; Severity of Illness Index ; Quality of Life/psychology ; *Macular Degeneration/psychology/complications ; Greece/epidemiology ; Middle Aged ; Visual Acuity ; *Wet Macular Degeneration/psychology/complications ; Aged, 80 and over ; Psychiatric Status Rating Scales ; Mental Health ; }, abstract = {OBJECTIVES: Age-related macular degeneration (AMD) is a leading cause of vision loss, affecting quality of life. Although AMD is associated with an increased risk of depression, differences between dry and wet forms are not well understood. This study examined depressive symptoms in Greek patients with dry and wet AMD compared to healthy-controls using the Zung Self-Rating Depression Scale (SDS).<br><br>METHODS: A cross-sectional study included 146 AMD patients (74 dry, 72 wet) and 60 controls. Depressive symptoms were assessed using the Zung SDS. Demographic and clinical data were collected. Statistical analyses compared depression severity and prevalence between groups, adjusting for potential confounders.<br><br>RESULTS: Wet AMD patients had significantly higher Zung SDS scores (50.4&#x2009;&#xb1;&#x2009;7.81) than dry AMD (44.8&#x2009;&#xb1;&#x2009;6.75) and controls (41.4&#x2009;&#xb1;&#x2009;7.85, p&#x2009;<&#x2009;.001). Depression prevalence was 56% in wet, 27% in dry AMD, and 20% in controls. After adjusting for visual acuity, age, sex, and other factors, wet AMD remained significantly associated with greater depression severity (p&#x2009;<&#x2009;.001).<br><br>CONCLUSIONS: Wet AMD is associated with higher depression severity compared to dry AMD, emphasizing the need for integrated ophthalmologic and mental health care.<br><br>CLINICAL IMPLICATIONS: Depression is common among AMD patients, particularly those with wet AMD. Screening and psychological support should be incorporated into AMD management.}, }
@article {pmid40374738, year = {2025}, author = {Wang, L and Wang, LX and Li, MY and Zhang, R and Zhou, GH}, title = {Clinical characterization of CCT2 and its role in autophagy regulation during age-related macular degeneration.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {16849}, pmid = {40374738}, issn = {2045-2322}, support = {2022L203//Technology Innovation Project of Colleges and Universities in Shanxi Province/ ; No201903D321117//Major Research and Development Program of Shanxi/ ; No2020RC22//Medical major Research program of Shanxi/ ; No. 2020-195//Scientific Research Foundation for the Returned Overseas Chinese Scholars/ ; }, mesh = {Humans ; *Macular Degeneration/genetics/metabolism/pathology ; *Autophagy/genetics ; Male ; Female ; Aged ; *Chaperonin Containing TCP-1/genetics/metabolism ; Retina/metabolism/pathology ; Retinal Pigment Epithelium/metabolism/pathology ; Transcriptome ; Gene Expression Profiling ; Middle Aged ; Aged, 80 and over ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly, and the role of chaperonin containing TCP1 subunit 2 (CCT2) remains unclear. This study aims to elucidate the mechanistic link between CCT2 and AMD, contributing to improved understanding and potential therapeutic strategies. Retinal and RPE-Choroid transcriptome array data from 130 AMD patients and 121 normal donors (GSE29801 dataset) were reanalyzed to assess CCT2 expression across different AMD subtypes, age groups, and genders. Single-sample gene set enrichment analysis was performed to explore correlations with autophagy-related genes and other established AMD causes. Additionally, CCT2 expression was validated in sodium iodate (NaIO3)-induced 661 W cells (photoreceptor-like cells) using quantitative real-time PCR (qRT-PCR). CCT2 was significantly enriched in advanced AMD retinas compared to intermediate stages in retina (both macular and extramacular) and early stages in extramacular retina (p < 0.05). NaIO3-treated 661 W cells exhibited a similar expression trend, confirming transcriptomic findings. CCT2 is significantly upregulated in advanced AMD and may contribute to drusen degradation. It shows potential as both a biomarker and an independent diagnostic indicator, particularly for advanced-stage AMD.}, }
@article {pmid40374798, year = {2025}, author = {Shi, L}, title = {Enhancing medical explainability in deep learning for age-related macular degeneration diagnosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {16975}, pmid = {40374798}, issn = {2045-2322}, mesh = {Humans ; *Macular Degeneration/diagnosis/diagnostic imaging ; *Deep Learning ; }, abstract = {Deep learning models hold significant promise for disease diagnosis but often lack transparency in their decision-making processes, limiting trust and hindering clinical adoption. This study introduces a novel multi-task learning framework to enhance the medical explainability of deep learning models for diagnosing age-related macular degeneration (AMD) using fundus images. The framework simultaneously performs AMD classification and lesion segmentation, allowing the model to support its diagnoses with AMD-associated lesions identified through segmentation. In addition, we perform an in-depth interpretability analysis of the model, proposing the Medical Explainability Index (MXI), a novel metric that quantifies the medical relevance of the generated heatmaps by comparing them with the model's lesion segmentation output. This metric provides a measurable basis to evaluate whether the model's decisions are grounded in clinically meaningful information. The proposed method was trained and evaluated on the Automatic Detection Challenge on Age-Related Macular Degeneration (ADAM) dataset. Experimental results demonstrate robust performance, achieving an area under the curve (AUC) of 0.96 for classification and a Dice similarity coefficient (DSC) of 0.59 for segmentation, outperforming single-task models. By offering interpretable and clinically relevant insights, our approach aims to foster greater trust in AI-driven disease diagnosis and facilitate its adoption in clinical practice.}, }
@article {pmid40374931, year = {2025}, author = {Lim, JI and Ko, S and McAllister, M and Faux, N and Bawa, K and Mearns, E and Patel, S and Spicer, G and Martinez, A and Tabano, D}, title = {Systematic review of clinical practice guidelines for the management of neovascular age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {39}, number = {11}, pages = {2223-2230}, pmid = {40374931}, issn = {1476-5454}, support = {N/A//Genentech (Genentech, Inc.)/ ; }, mesh = {Humans ; *Practice Guidelines as Topic ; *Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/diagnosis/therapy/drug therapy ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; *Disease Management ; }, abstract = {BACKGROUND/OBJECTIVES: To assess geographically global clinical practice guidelines (CPGs) for neovascular age-related macular degeneration (nAMD) management.<br><br>METHODS: A systematic literature review (SLR) of CPGs for nAMD management was conducted using Embase and MEDLINE databases, Guideline Central, Health Technology Assessment bodies, professional ophthalmology associations, and backwards citation tracking. CPGs published between January 2010-October 2023 were included and independently assessed by four reviewers using the Appraisal of Guidelines for Research and Evaluation II (AGREE II). CPGs were qualitatively assessed for anatomical measurements (optical coherence tomography [OCT] and visual acuity [VA]). PROSPERO identification is CRD42023473223.<br><br>RESULTS: Nine of 147 identified global CPGs were included in the SLR for diagnosis, treatment, and disease monitoring for nAMD. Overall AGREE II scores were 62-95 (mean [standard deviation] score 75 [10.6]). Strongest domains were Scope and Purpose (86.6 [11.0]), Clarity of Presentation (84.3 [13.0]), and Editorial Independence (89.1 [15.4]); Stakeholder Involvement (63.4 [16.6]), Applicability (73.0 [12.6]), and Rigor of Development (55.4 [25.9]) were lowest. 4/9 CPGs were "Recommended" by reviewers, and 5/9 were "Recommended with Modifications". All CPGs recommended OCT for initial diagnosis. 2/9 CPGs did not mention VA. For managing pharmacological interventions, 4/9 CPGs recommended using VA, and three recommended OCT. Eight CPGs recommended using either VA or OCT for disease monitoring while on anti-vascular endothelial growth factor (VEGF) treatment. 6/9 CPGs recommended screening for VA and 7/9 CPGs recommended using OCT to change anti-VEGF intervals.<br><br>CONCLUSION: CPG methods, recommendations on applicability in resource-constrained systems, and patient advocacy/perspectives will improve CPG trustworthiness and transparency.}, }
@article {pmid40374933, year = {2025}, author = {Sadeghi, E and Schulman, A and Vupparaboina, SC and Singh, SR and Hasan, N and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Eller, AW and Chhablani, J}, title = {Correlation of retino-choroidal thickness and vascular metrics with drusen volume as a severity marker of age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {39}, number = {11}, pages = {2231-2237}, pmid = {40374933}, issn = {1476-5454}, mesh = {Humans ; Aged ; Male ; Female ; *Choroid/pathology/blood supply/diagnostic imaging ; Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnosis/pathology/physiopathology ; Fluorescein Angiography/methods ; *Retinal Vessels/pathology/diagnostic imaging ; Visual Acuity/physiology ; Severity of Illness Index ; Aged, 80 and over ; Middle Aged ; *Retina/pathology ; *Macular Degeneration/diagnosis/physiopathology ; Biomarkers ; Cross-Sectional Studies ; }, abstract = {PURPOSE: To assess retinal vascular perfusion and choroidal vascularity biomarkers correlated with drusen volume and severity of age-related macular degeneration (AMD).<br><br>METHODS: Patients underwent swept-source optical coherence tomography angiography (SS-OCTA) (PlexElite-9000). Eyes with geographic atrophy or neovascular AMD were excluded. Retinal thickness, retinal perfusion including superficial (SCP) and deep capillary plexuses (DCP), foveal avascular zone (FAZ), drusen volume, choroidal thickness (ChT) and choroidal vascularity index (CVI) were assessed through the Advanced Research and Innovation Network. Linear mixed model and Spearman test were used for statistical analysis.<br><br>RESULTS: We assessed 81 eyes from 57 subjects (34 early-stage, 47 intermediate-stage AMD). The mean age was 74.95&#x2009;&#xb1;&#x2009;8.79 years. The mean LogMar visual acuity (VA) was 0.16&#x2009;&#xb1;&#x2009;0.18 (early-stage:&#xa0;0.12&#x2009;&#xb1;&#x2009;0.17, intermediate-stage:&#xa0;0.19&#x2009;&#xb1;&#x2009;0.18, P&#x2009;=&#x2009;0.122). Between early and intermediate AMD, no significant differences were seen in SCP and DCP vascular perfusion (P&#x2009;=&#x2009;0.368, 0.859, respectively), FAZ (p&#x2009;=&#x2009;0.836) and retinal thickness within the 6-mm area (P&#x2009;=&#x2009;0.680). Drusen volume showed a significant difference (early-stage:&#xa0;0.0706&#x2009;&#xb1;&#x2009;0.1272, intermediate-stage:&#xa0;0.2102&#x2009;&#xb1;&#x2009;0.2211mm[3], P&#x2009;<&#x2009;0.01). Intermediate-stage AMD had significantly lower mean ChT (266.40&#x2009;&#xb1;&#x2009;115.55 vs. 204.97&#x2009;&#xb1;&#x2009;70.69&#x2009;&#xb5;m, P&#x2009;=&#x2009;0.038) and CVI (0.605&#x2009;&#xb1;&#x2009;0.021 vs. 0.591&#x2009;&#xb1;&#x2009;0.015, P&#x2009;=&#x2009;0.004) within the 5-mm area. Drusen volume was negatively correlated with ChT (r&#x2009;=&#x2009;-0.198, P&#x2009;=&#x2009;0.017) and CVI (r&#x2009;=&#x2009;-0.209, P&#x2009;=&#x2009;0.029). No significant correlation was found between drusen volume and VA (r&#x2009;=&#x2009;0.051, P&#x2009;=&#x2009;0.143), retinal thickness (-0.03, P&#x2009;=&#x2009;0.393), FAZ (r&#x2009;=&#x2009;-0.023, P&#x2009;=&#x2009;0.150), SCP (r&#x2009;=&#x2009;-0.011, P&#x2009;=&#x2009;0.307), and DCP (r&#x2009;=&#x2009;-0.022, P&#x2009;=&#x2009;0.190).<br><br>CONCLUSION: Drusen volume, a key AMD severity marker, correlates more strongly with choroidal parameters like ChT and CVI than retinal thickness and perfusion. It may serve as a biomarker for dry AMD severity, with choroidal biomarkers showing earlier disease changes.}, }
@article {pmid40376545, year = {2025}, author = {Renton, AI and Klein, DJ and Livezey, JA and Nemrodov, D and Wolfer, S and Hanina, A and Van De Ville, D}, title = {Video-evoked neuromarkers of visual function in age-related macular degeneration.}, journal = {Frontiers in human neuroscience}, volume = {19}, number = {}, pages = {1569282}, pmid = {40376545}, issn = {1662-5161}, abstract = {Neural markers of visual function in age-related macular degeneration (AMD) allow clinicians and researchers to directly evaluate the functional changes in visual processing which occur as a result of the progressive loss of afferent input from the macula. Unfortunately, few protocols exist that elicit such neural markers, and most of these are poorly adapted to AMD. Here, we propose a novel method of embedding frequency tags into full color and motion videos by periodically manipulating the contrast of visual information of different spatial frequencies at different temporal frequencies. These videos elicit steady-state visual evoked potentials (SSVEPS) in viewers which, when measured using electrophysiological neuroimaging methods, independently represent the responses of populations of neurons tuned to the tagged spatial frequencies. We used electroencephalography (EEG) to record the SSVEPs of 15 AMD patients and 16 age-matched healthy controls watching a 6-min series of natural scene videos filtered with this spatial frequency tagging method. Compared with healthy controls, AMD patients showed a lower SSVEP to high spatial frequency information, and a stronger response to the low spatial frequency information in the video set. The ratio of the SSVEP to lower relative to higher spatial frequency information was strongly predictive of both visual acuity and contrast sensitivity, and the topographic distributions of these responses suggested retinotopic reorganization of the neural response to spatial frequency information.}, }
@article {pmid40379195, year = {2025}, author = {Zhang, P and Duan, J and Wang, C and Li, X and Su, J and Shang, Q}, title = {Predicting response to anti-VEGF therapy in neovascular age-related macular degeneration using random forest and SHAP algorithms.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {53}, number = {}, pages = {104635}, doi = {10.1016/j.pdpdt.2025.104635}, pmid = {40379195}, issn = {1873-1597}, mesh = {Humans ; Retrospective Studies ; Aged ; Tomography, Optical Coherence/methods ; Male ; Algorithms ; Female ; *Angiogenesis Inhibitors/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Macular Degeneration/drug therapy/diagnostic imaging ; Machine Learning ; Aged, 80 and over ; Choroidal Neovascularization/drug therapy ; *Photochemotherapy/methods ; Middle Aged ; *Wet Macular Degeneration/drug therapy/diagnostic imaging ; Random Forest ; }, abstract = {PURPOSE: This study aimed to establish and validate a prediction model based on machine learning methods and SHAP algorithm to predict response to anti-vascular endothelial growth factor (VEGF) therapy in neovascular age-related macular degeneration (AMD).<br><br>METHODS: In this retrospective study, we extracted data including demographic characteristics, laboratory test results, and imaging features from optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Eight machine learning methods, including Logistic Regression, Gradient Boosting Decision Tree, Random Forest, CatBoost, Support Vector Machine, XGboost, LightGBM, K Nearest Neighbors were employed to develop the predictive model. The machine learning method with optimal performance was selected for further interpretation. Finally, the SHAP algorithm was applied to explain the model's predictions.<br><br>RESULTS: The study included 145 patients with neovascular AMD. Among the eight models developed, the Random Forest model demonstrated general optimal performance, achieving a high accuracy of 75.86 % and the highest area under the receiver operating characteristic curve (AUC) value of 0.91. In this model, important features identified as significant contributors to the response to anti-VEGF therapy in neovascular AMD patients included fractal dimension, total number of end points, total number of junctions, total vessels length, vessels area, average lacunarity, choroidal neovascularization (CNV) type, age, duration and logMAR BCVA. SHAP analysis and visualization provided interpretation at both the factor level and individual level.<br><br>CONCLUSION: The Random Forest model for predicting response to anti-VEGF therapy in neovascular AMD using SHAP algorithm proved to be feasible and effective. OCTA imaging features, such as fractal dimension, total number of end points et al., were the most effective predictive factors.}, }
@article {pmid40379450, year = {2025}, author = {Mehta, NN and Nagel, ID and Agnihotri, A and Kalaw, FGP and Heinke, A and Cheng, L and Bartsch, DU and Freeman, WR}, title = {Anti-VEGF injections and macular atrophy progression in patients with neovascular age-related macular degeneration in remission.}, journal = {The British journal of ophthalmology}, volume = {109}, number = {9}, pages = {1028-1035}, pmid = {40379450}, issn = {1468-2079}, support = {P30 EY022589/EY/NEI NIH HHS/United States ; R01 EY033847/EY/NEI NIH HHS/United States ; R01 EY035262/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Retrospective Studies ; Female ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Disease Progression ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Tomography, Optical Coherence ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Aged, 80 and over ; Visual Acuity/physiology ; Fluorescein Angiography ; Bevacizumab/administration &amp; dosage ; *Macula Lutea/pathology ; Remission Induction ; Follow-Up Studies ; Middle Aged ; Atrophy ; }, abstract = {AIMS: To determine the effect of continuing anti-vascular endothelial growth factor (VEGF) injections on the progression of macular atrophy (MA) during remission of neovascular age-related macular degeneration (nAMD).<br><br>METHODS: In this retrospective cohort study, 59 eyes with nAMD with at least 6-month remission (disease inactivity) were analysed and were grouped into two. In group 1, anti-VEGF injections were stopped after remission (holiday). In group 2, injections were continued despite inactivity (maintenance).Using blue autofluorescence images via Heidelberg Spectralis, MA area was measured at initial injection, remission onset and the latest available remission point. The absence of subretinal haemorrhage, intraretinal fluid, subretinal fluid or subretinal hyper-reflective material associated with fluid on serial spectral domain optical coherence tomography scans was used to confirm the inactivity of the disease (remission). The rate of progression of MA during the period of remission was measured for the two groups.<br><br>RESULTS: In group 1, 30 eyes received a mean of 16.97 injections over 39.2 months, followed by 21 months of drug holiday. In group 2, 29 eyes received a mean of 27.1 injections over 62.16 months, followed by a mean of 11.59 injections over 19.32 months for maintenance. The MA in the maintenance group progressed faster than the holiday group during remission (p=0.03).<br><br>CONCLUSIONS: Maintenance injections for nAMD in remission significantly increase progression of MA.}, }
@article {pmid40380672, year = {2025}, author = {Feretzakis, G and Karakosta, C and Gkoulalas-Divanis, A and Bisoukis, A and Boufeas, IZ and Bazakidou, E and Sakagianni, A and Kalles, D and Verykios, VS}, title = {Leveraging Vision Transformers in Multimodal Models for Retinal OCT Analysis.}, journal = {Studies in health technology and informatics}, volume = {327}, number = {}, pages = {1135-1139}, doi = {10.3233/SHTI250567}, pmid = {40380672}, issn = {1879-8365}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Deep Learning ; Neural Networks, Computer ; *Retina/diagnostic imaging ; *Retinal Diseases/diagnostic imaging ; *Image Interpretation, Computer-Assisted/methods ; Macular Degeneration/diagnostic imaging ; }, abstract = {Optical Coherence Tomography (OCT) has become an indispensable imaging modality in ophthalmology, providing high-resolution cross-sectional images of the retina. Accurate classification of OCT images is crucial for diagnosing retinal diseases such as Age-related Macular Degeneration (AMD) and Diabetic Macular Edema (DME). This study explores the efficacy of various deep learning models, including convolutional neural networks (CNNs) and Vision Transformers (ViTs), in classifying OCT images. We also investigate the impact of integrating metadata (patient age, sex, eye laterality, and year) into the classification process, even when a significant portion of metadata is missing. Our results demonstrate that multimodal models leveraging both image and metadata inputs, such as the Multimodal ResNet18, can achieve competitive performance compared to image-only models, such as DenseNet121. Notably, DenseNet121 and Multimodal ResNet18 achieved the highest accuracy of 95.16%, with DenseNet121 showing a slightly higher F1-score of 0.9313. The multimodal ViT-based model also demonstrated promising results, achieving an accuracy of 93.22%, indicating the potential of Vision Transformers (ViTs) in medical image analysis, especially for handling complex multimodal data.}, }
@article {pmid40381862, year = {2025}, author = {Chen, XN and Zhang, Y and Kam, KW and Au, SCL and Zhang, XJ and Ng, MPH and Yip, WW and Ip, P and Wong, ICK and Young, AL and Pang, CP and Tham, CC and Chen, LJ and Yam, JC}, title = {Genetic association of attention-deficit/hyperactivity disorder with thirteen ocular disorders.}, journal = {Journal of affective disorders}, volume = {385}, number = {}, pages = {119422}, doi = {10.1016/j.jad.2025.119422}, pmid = {40381862}, issn = {1573-2517}, mesh = {Humans ; *Attention Deficit Disorder with Hyperactivity/genetics/complications/epidemiology ; Mendelian Randomization Analysis ; *Eye Diseases/genetics/epidemiology ; Male ; Genetic Predisposition to Disease/genetics ; Female ; Linkage Disequilibrium/genetics ; Polymorphism, Single Nucleotide/genetics ; Child ; }, abstract = {PURPOSE: Although attention deficit hyperactivity disorder (ADHD) is linked to elevated risk of various ocular disorders, their genetic association and causality remain unclear.<br><br>METHODS: This study performed linkage disequilibrium score regression (LDSC) and pleiotropic analysis under composite null hypothesis (PLACO) to explore genetic associations, and bidirectional mendelian randomization (MR) to assess the causality between ADHD and thirteen ocular disorders.<br><br>RESULTS: LDSC showed ADHD genetically correlated with corneal ulcer, keratitis, blepharochalasis, lacrimal system disorders, senile cataract, retinal vascular occlusion, and age-related macular degeneration. MR revealed genetic liability to ADHD increased the risk of corneal ulcer (OR&#xa0;=&#xa0;1.18, FDR adjusted P&#xa0;=&#xa0;0.01), keratitis (OR&#xa0;=&#xa0;1.13, P&#xa0;=&#xa0;0.007), blepharochalasis (OR&#xa0;=&#xa0;1.23, P&#xa0;=&#xa0;0.002), and lacrimal system disorders (OR&#xa0;=&#xa0;1.09, P&#xa0;=&#xa0;0.04), while decreasing the risk of primary open-angle glaucoma (OR&#xa0;=&#xa0;0.83, P&#xa0;=&#xa0;0.003), exfoliation glaucoma (OR&#xa0;=&#xa0;0.71, P&#xa0;=&#xa0;0.001), and normotensive glaucoma (OR&#xa0;=&#xa0;0.79, P&#xa0;=&#xa0;0.02). Conversely, genetic liability to strabismus increased ADHD risk (OR&#xa0;=&#xa0;1.09, P&#xa0;=&#xa0;0.03). The identification of pleiotropic loci using PLACO suggested that genetic factors played a role in the associations between ADHD and ocular diseases.<br><br>CONCLUSIONS: This study revealed genetic associations between ADHD and multiple ocular disorders, identifying causal effects of ADHD on an increased risk of corneal ulcer, keratitis, blepharochalasis, and lacrimal system disorders, while showing a protective effect against glaucoma. Conversely, genetic liability to strabismus increased ADHD risk.}, }
@article {pmid40383690, year = {2025}, author = {Ko, MY and Talebi, R and Yu, F and Tseng, VL and Coleman, AL and Hosseini, H}, title = {Socioeconomic Disparities in Intravitreal Injection Use and Anti-VEGF Agent Selection: Aflibercept/Ranibizumab Versus Bevacizumab.}, journal = {Clinical therapeutics}, volume = {47}, number = {8}, pages = {559-565}, doi = {10.1016/j.clinthera.2025.04.010}, pmid = {40383690}, issn = {1879-114X}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use/economics ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Bevacizumab/administration &amp; dosage ; Intravitreal Injections ; Male ; Female ; Aged ; Cross-Sectional Studies ; Ranibizumab/administration &amp; dosage ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Socioeconomic Factors ; Diabetic Retinopathy/drug therapy ; United States ; *Healthcare Disparities/statistics &amp; numerical data/economics ; Macular Edema/drug therapy ; Retinal Vein Occlusion/drug therapy ; Databases, Factual ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use ; Socioeconomic Disparities in Health ; }, abstract = {PURPOSE: There is a paucity of research on socioeconomic factors associated with intravitreal injection use or type of anti-vascular endothelial growth factor (anti-VEGF) use. The purpose of this cross-sectional analysis is to examine the association between demographic and socioeconomic factors and intravitreal injections and type of anti-VEGF (bevacizumab, aflibercept, and ranibizumab) use for patients with diabetic macular edema, proliferative diabetic retinopathy, retinal vein occlusion, and wet age-related macular degeneration in the AllofUs Database, which is a nationwide health database initiative conducted by the National Institutes of Health in the United States to enroll participants from groups that are considered to be historically underrepresented in biomedical research.<br><br>METHODS: The study population included patients diagnosed with diabetic macular edema, proliferative diabetic retinopathy, retinal vein occlusion, or wet age-related macular degeneration based on the International Classification of Diseases Ninth/10th Revision, Clinical Modification diagnosis codes. Exposures included age, sex, race/ethnicity, income, and education. Outcomes included IVI use based on the Current Procedural Terminology 4 codes and anti-VEGF type based on RxNorm codes.<br><br>FINDINGS: Of 3010 participants, 25.9% ever had IVI use. In multivariate logistic regression analyses, those with older age (adjusted odds ratio [aOR] = 1.27; 95% CI, 1.18-1.37) and income >$150,000 (aOR = 1.71; CI, 1.27-2.32) were more likely to have had IVI use. Those with older age (aOR = 1.46; CI, 1.22-1.75), Asian/other race/ethnicity (aOR = 3.81; CI, 1.09-13.34), Hispanic race/ethnicity (aOR = 3.16; CI, 1.59-6.26), income >$150,000 (aOR = 3.20; CI, 1.45-7.06), and college graduate/advanced degree (aOR = 1.83; CI, 1.01-3.31) were more likely to have aflibercept/ranibizumab only versus bevacizumab use.<br><br>IMPLICATIONS: Interventions are needed to increase health literacy and access to IVI for at-risk, low-income populations. Future research should investigate patient and provider decision-making for anti-VEGF drug choice, which may have implications for cost-saving measures and policies.}, }
@article {pmid40384191, year = {2025}, author = {Borodi, PG and Slevin, M}, title = {Exploring the role of inflammation in age-related macular degeneration: new insights and implications for future therapies.}, journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie}, volume = {66}, number = {1}, pages = {51-59}, pmid = {40384191}, issn = {2066-8279}, mesh = {Humans ; *Macular Degeneration/therapy/pathology/complications ; *Inflammation/pathology/complications ; }, abstract = {The retina consists of one of the body's most delicate organs, being sensitive to various metabolic disturbances, vascular abnormalities and inflammatory processes. Age-related macular degeneration (AMD) impacts millions of people worldwide and represents a notable cause of blindness. Chronic inflammation, implicated in several degenerative diseases including Parkinson's and Alzheimer's diseases, as well as atherosclerosis, has been linked to AMD. Both histopathological and genetic investigations have underscored the immune system's role in AMD progression. The objective of this literature review was to summarize the actual knowledge, identify research gaps and to serve as a basis for future studies regarding the correlations between inflammation and AMD. We conducted a thorough search of the primary databases (Web of Science, Cochrane Library, PubMed/MEDLINE), using keywords such as 'age-related macular degeneration', 'inflammation', 'neurodegeneration', and 'C-reactive protein'. We included systematic reviews and meta-analyses that offer the most relevant results in this research area. We also included the results from recent studies that have not yet been widely approached. Our strategy also consisted of looking for relevant articles in the reference list.}, }
@article {pmid40385108, year = {2025}, author = {Yuan, LY and Li, LP and Hua, X and Yuan, XY}, title = {Tracing global progress: two decades of age-related macular degeneration research.}, journal = {International journal of ophthalmology}, volume = {18}, number = {5}, pages = {925-936}, pmid = {40385108}, issn = {2222-3959}, abstract = {AIM: To conduct a comprehensive bibliometric analysis of age-related macular degeneration (AMD) research from 2002 to 2022, identifying key contributing countries, institutions, authors, journals, and research hotspots to inform future research directions.<br><br>METHODS: Publications related to AMD were retrieved from the Web of Science Core Collection (WoSCC) database for the period January 1, 2002, to December 31, 2022. The search was limited to English-language articles and reviews. Bibliometric analysis was performed using Microsoft Excel 2021 for data management and annual publication analysis. Visualization and network analyses were conducted using VOSviewer, CiteSpace, and the Bibliometrix package in R. Collaboration networks among countries, institutions, authors, and journals were mapped. Keywords were analyzed for co-occurrence to identify research hotspots. Metrics such as H-index, total link strength (TLS), and citation counts were used to assess impact.<br><br>RESULTS: A total of 16 715 publications were analyzed, showing a consistent increase in AMD research output over the past 20y, peaking at 1445 publications in 2021. The United States was the leading contributor with 31.8% of total publications, followed by China and the United Kingdom. The University of Melbourne emerged as the most productive institution with the highest TLS, indicating strong international collaborations. Professor Frank G. Holz was identified as the most influential author based on H-index and publication count. Investigative Ophthalmology &amp; Visual Science was the most prolific journal and had the highest citation impact. Keyword co-occurrence analysis revealed four main research clusters: pathogenesis, therapy, epidemiology, and diagnosis. Emerging research hotspots included anti-vascular endothelial growth factor (VEGF) therapies, optical coherence tomography angiography, and artificial intelligence (AI) applications in diagnosis.<br><br>CONCLUSION: The bibliometric analysis highlights significant growth and collaborative efforts in AMD research globally. Key contributors have advanced understanding in pathogenesis, therapeutic strategies, epidemiology, and diagnostic technologies. Future research should focus on interdisciplinary collaborations, novel therapeutic targets, personalized medicine, and technological innovations such as AI to effectively address the challenges posed by AMD.}, }
@article {pmid40385500, year = {2025}, author = {Rajagopal, S and Ahuja, P and Quach, V and Luong, C and Raji, MA}, title = {Repurposing Alzheimer's disease medications-systemic cholinesterase inhibitors-for the treatment of dry eye syndrome, glaucoma, and age-related macular degeneration.}, journal = {Therapeutic advances in ophthalmology}, volume = {17}, number = {}, pages = {25158414251341022}, pmid = {40385500}, issn = {2515-8414}, }
@article {pmid40386394, year = {2025}, author = {Chiu, CJ and Chiu, E and Chang, ML}, title = {Interaction between Infection of Porphyromonas gingivalis, A Keystone Microbe of Oral Microbiome, and Serum Levels of Lutein/Zeaxanthin Is Associated with Risk for Age-related Macular Degeneration.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {40386394}, issn = {2693-5015}, support = {R01 EY021826/EY/NEI NIH HHS/United States ; R21 EY028209/EY/NEI NIH HHS/United States ; }, abstract = {UNLABELLED: Porphyromonas gingivalis (P. gingivalis) functions as a catalyst bacterium in the development of periodontitis, and the serum antibody level against P. gingivalis is considered a surrogate marker for the activity level of periodontopathic microbiome. The chronic systemic inflammation induced by P. gingivalis elevates the risk of various systemic and neurodegenerative disorders, including atherosclerosis, diabetes, and Alzheimer's disease. Although the connection between human microbiome and age-related macular degeneration (AMD) remains relatively unexplored, it is noteworthy that AMD shares risk factors and etiological mechanisms with diseases related to P. gingivalis. To investigate the potential association between periodontopathic microbiome and AMD occurrence, we conducted a candidate microbe approach case-control study. Our hypothesis was tested by examining the correlation between serum P. gingivalis immunoglobulin G (IgG) levels and AMD. Comparing the lowest IgG category (≤ 57 enzyme-linked immunosorbent assay units (EU)) with higher categories revealed escalating risks: the second higher category (58-65 EU) conferred almost a 30% increased risk (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.17 to 1.4), the third higher category (66-119 EU) conferred nearly a 60% increase (OR = 1.58, 95% CI: 1.46 to 1.72), and the highest category (> 119 EU) conveyed over a two-fold risk (OR = 2.04, 95% CI: 1.62 to 2.58) of early AMD. Aligning with the notion that the microbiome composition is significantly shaped by the host's diet, our analysis indicates that sustaining elevated serum levels of lutein/zeaxanthin (≥ 0.35 μmol/L or ≥ 20 μg/dL) might potentially mitigate the P. gingivalis-related AMD risk by as much as 35% (P for interaction < 0.0001). Although the precise mechanism requires additional exploration, these findings suggest a connection between nutrition and oral microbiome, emphasizing their collective role in maintaining eye health.<br><br>SIGNIFICANCE STATEMENT: While our oral microbiome may impact eye health, nutritional factors could play a modulatory role in mitigating the associated risk.}, }
@article {pmid40386979, year = {2025}, author = {Cheong, KX and Chi, M and Pan, W and Lee, YQ and Zhang, Y and Hu, Z and Htoon, HM and Hoang, QV and Chong, MF and Lan, W and Saw, SM and Lamoureux, EL}, title = {Diet and myopic macular degeneration in the Aier-SERI high myopia adult cohort study.}, journal = {Acta ophthalmologica}, volume = {103}, number = {8}, pages = {891-899}, doi = {10.1111/aos.17528}, pmid = {40386979}, issn = {1755-3768}, support = {JRDUKY004900//Duke-NUS Medical School Distinguished Professorship Fund/ ; 2024RC5002//Science and Technology Innovation Program of Hunan Province/ ; 2023RC1079//Science and Technology Innovation Program of Hunan Province/ ; }, mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; Prospective Studies ; Adult ; *Diet/adverse effects ; China/epidemiology ; Middle Aged ; *Myopia, Degenerative/epidemiology/complications/physiopathology/diagnosis ; *Refraction, Ocular/physiology ; *Macular Degeneration/epidemiology/etiology/diagnosis/physiopathology ; Follow-Up Studies ; Risk Factors ; *Feeding Behavior ; *Visual Acuity ; *Population Surveillance ; Surveys and Questionnaires ; }, abstract = {PURPOSE: We investigated relationships between two dietary composite scores and myopic macular degeneration (MMD) in a high myopia adult cohort, as there is a knowledge gap regarding the role of diet in MMD.<br><br>METHODS: This is a cross-sectional analysis of a population-based prospective cohort, the Aier-Singapore Eye Research Institute (SERI) high myopia cohort study of Chinese adults, in Changsha, central China. Systemic and ocular (including cycloplegic spherical equivalent [SE] and axial length [AL]) assessments were carried out. A self-administered food frequency questionnaire was used to assess the dietary intake. Dietary intake was categorised into 13 food groups (refined grains, whole grains, meat, fish, processed/unhealthy meat, plant-based protein, fruits, vegetables, fast food and savoury snacks, dairy products, desserts and sweet snacks, sugar-sweetened beverages, and alcohol). Using exploratory factor analysis, two dietary patterns (Dietary Pattern 1 [less healthy] and 2 [healthier]) were identified. Multivariable logistic regression analyses with Bonferroni corrections were performed to assess associations between diet and MMD.<br><br>RESULTS: Of 445 participants, 71 (16.0%) had MMD. The participants had an overall mean age of 42.3&#x2009;&#xb1;&#x2009;7.3&#x2009;years, SE of -9.5&#x2009;&#xb1;&#x2009;4.3 dioptres (D) and AL of 27.3&#x2009;&#xb1;&#x2009;11.86&#x2009;mm. In the multivariable analyses, none of the 13 food groups (p&#x2009;>&#x2009;0.004 for all) or 2 dietary patterns (p&#x2009;>&#x2009;0.05 for both) were associated with MMD, after adjusting for age, sex, education, SE and AL.<br><br>CONCLUSION: We did not find associations between diet and MMD in a cohort of highly myopic adults. There is currently no dietary advice to prevent MMD. Larger and prospective studies conducted over multiple time points are required.}, }
@article {pmid40388106, year = {2025}, author = {Sadda, S and Hatcher, KA and Shah, BK and Kondapalli, SS and Li, C and Baumal, CR}, title = {Outer Retinal Tubulation and Geographic Atrophy: A Natural History Analysis of Sham Observed Eyes from the OAKS and DERBY Trials.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {7}, pages = {1611-1619}, pmid = {40388106}, issn = {2193-8245}, abstract = {INTRODUCTION: Retrospective, longitudinal analysis of sham observed eyes from the phase 3 OAKS and DERBY trials evaluated the relationship between geographic atrophy (GA) growth and the presence or absence of outer retinal tubulation (ORT).<br><br>METHODS: Prevalence rates of ORT were calculated, and analysis of GA growth was performed using fundus autofluorescence and optical coherence tomography (OCT).<br><br>RESULTS: ORT prevalence rates were 32%, 37.5%, and 43% at baseline, month&#xa0;12, and month&#xa0;24, respectively. Eyes with a fully formed ORT at baseline had 23.6% less GA area growth over 24&#xa0;months compared with GA without ORT present at baseline.<br><br>CONCLUSION: The presence of ORT at baseline on OCT may be reflective of slower growth of GA, irrespective of GA location, as was noted in this series. The potential diagnostic impact of ORT should be considered when designing clinical studies for GA and when analyzing the results of such studies.<br><br>TRIAL REGISTRATION: OAKS: ClinicalTrials.gov identifier NCT03525613 (registered May&#xa0;15, 2018); EudraCT identifier 2018-001435-52 (registered September 27, 2018).<br><br>DERBY: ClinicalTrials.gov identifier NCT03525600 (registered May&#xa0;15, 2018); EudraCT identifier 2018-001436-22 (registered September 21, 2018).}, }
@article {pmid40388717, year = {2025}, author = {Lishinsky-Fischer, N and Chowers, I and Levy, J}, title = {The effects of immunosuppressive therapy for immune-mediated inflammatory disease on the risk of age-related macular degeneration.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004531}, pmid = {40388717}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate the effects of immunosuppressive therapy on the development and progression of age-related macular degeneration (AMD) in patients with an immune-mediated inflammatory disease (IMID).<br><br>METHODS: This is a retrospective cohort study. Data were obtained from TriNetX, a global database of electronic medical records. The analysis utilized the largest network in TriNetX, comprised of 171,583,261 patients from 18 countries. Kaplan-Meier analysis was used to estimate the probability of predefined AMD subcategories between patients with IMID who were prescribed an immunosuppressants and patients who were not.<br><br>RESULTS: After 1:1 propensity score matching, equal-sized cohorts of patients in each group were generated for predefined IMIDs. We found that AMD was more prevalent in patients who received an immunosuppressant for systemic lupus erythematosus (SLE), Crohn's disease, rheumatoid arthritis, sarcoidosis, Sjogren's syndrome, giant cell arteritis and all IMIDs combined.<br><br>CONCLUSIONS: The use of immunosuppressants in patients with some IMIDs appears to be associated with an increased risk of AMD. Further research is warranted in order to fully understand the complex relationship between immunosuppressive therapy and AMD.}, }
@article {pmid40389215, year = {2025}, author = {Lommatzsch, AP and Faatz, H}, title = {[Age-related macular degeneration - Part 2: therapeutic options for AMD].}, journal = {Klinische Monatsblatter fur Augenheilkunde}, volume = {242}, number = {8}, pages = {855-867}, doi = {10.1055/a-2515-9138}, pmid = {40389215}, issn = {1439-3999}, mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Macular Degeneration/drug therapy/diagnosis ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Intravitreal Injections ; Evidence-Based Medicine ; }, abstract = {Currently, intravitreal anti-VEGF therapy is the only way to maintain function with continuous monitoring in neovascular AMD. Several robust morphological biomarkers, such as intraretinal and subretinal fluid, are important to guide treatment decisions at baseline and during the course of the disease. Higher concentrations of anti-VEGF agents and the development of bispecific antibodies combining anti-VEGF and anti-angiopoietin-2 antibodies have been shown to prolong the duration of action in pivotal trials. In particular, a longer duration of action may improve patient adherence by reducing the treatment burden. Several ranibizumab biosimilars are also approved and available for the treatment of neovascular AMD. In addition, bevacizumab is now approved in its originator form for the treatment of neovascular AMD in Europe. For the treatment of geographic atrophy, the intravitreal complement inhibitors approved in the US are not approved in Europe. With these drugs, continuous monthly or bimonthly injections were associated with significantly slower growth of the atrophic area in registration studies. Visual function after two years of treatment showed no difference compared to untreated eyes. In a post-hoc analysis of the largest supplementation studies AREDS and AREDS2, a significantly slower increase in RPE atrophy from the atrophic edge to the fovea was observed compared to placebo (AREDS [n = 208]: p = 0.012; AREDS2 [n = 392]: p = 0.011). This effect needs to be confirmed in controlled randomised trials.}, }
@article {pmid40391124, year = {2025}, author = {Günter, A and Jarboui, MA and Mühlfriedel, R and Seeliger, MW}, title = {Exploration of the visual streak of the Mongolian gerbil as a model for the human central retina.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1562437}, pmid = {40391124}, issn = {2296-858X}, abstract = {INTRODUCTION: The Mongolian gerbil (MG), a day-active rodent, features a particular retinal region of high visual acuity, the visual streak (VS). Optimized for vision in desert-like environments, the VS allows for a perfect view of the horizon between the projection areas of the sky and the ground. Here, we assess the structural basis of this specialized region and compare the findings to the conditions at the human retinal center.<br><br>METHODS: The VSs of MG retinas (n&#x202f;=&#x202f;5) were evaluated morphologically with immunohistochemistry for cone, rod, and RPE cell-specific markers in dorsoventral cross-sections, and the results were compared to data from the near (adjacent) and far periphery. Mass spectrometry of the VS and peripheral retina/RPE was used to analyze the proteomic differential expression between these regions.<br><br>RESULTS: In the VS of the MG, we found an increased density of cones, elongated photoreceptor outer segments (OSs), and a rod-to-cone ratio lying within the zone of descent between the border of the macula and the fovea (macular shoulder). Similarly, the base area of retinal pigment epithelium (RPE) cells in the VS was significantly reduced, while cells were taller than those in the periphery. Accordingly, proteomic data provided evidence for an enhanced abundance of key proteins relevant to photoreceptor and RPE function and pathophysiology of macular diseases in the VS.<br><br>CONCLUSION: The high degree of conformance between the VS data of the MG and the human central retina renders the MG a promising rodent, non-primate model of the central human retina.}, }
@article {pmid40393567, year = {2025}, author = {Zhang, J and Qian, Y and Shangguan, Y and Gong, Y and Shu, Y and Wang, Y}, title = {Bibliometric and visual analysis of retinal fibrosis research from 1993 to 2023.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {54}, number = {}, pages = {104636}, doi = {10.1016/j.pdpdt.2025.104636}, pmid = {40393567}, issn = {1873-1597}, mesh = {Humans ; *Bibliometrics ; Fibrosis ; *Retinal Diseases/pathology/diagnosis ; Tomography, Optical Coherence ; *Retina/pathology ; }, abstract = {BACKGROUND: Retinal fibrosis, a common pathological feature of various retinal diseases, significantly impairs vision. The mechanisms of retinal fibrosis are complex, with cytokine involvement playing a pivotal role. This article aims to elucidate the current research trends and key areas of focus in the study of retinal fibrosis.<br><br>METHODS: Publications from "Web of Science core collection", "PubMed" and "Scopus" were analyzed using R Studio ("Bibliometrix" and "ggplot2" packages) for publication counts, geographic distribution, and collaborations, while "CiteSpace" and "VOSviewer" visualized institutional partnerships and keyword co-occurrence. The methodology follows the PRISMA 2020 guidelines strictly.<br><br>RESULTS: In this analysis, a total of 1985 studies were analyzed. Key topics included "vitrectomy", "epiretinal membrane", "optical coherence tomography (OCT)", "macular membrane", and "macular hole". Keyword co-occurrence analysis emphased macular disease, fibrosis diagnosis, pharmacological treatment, and prognosis across various groups with cytokines as prominent research topics. Additionally, the findings suggested future research would focus on elucidating fibrosis mechanisms, advancing diagnostic techniques, and identifying potential drug targets. The journal "Retina" had the highest citation count for retinal fibrosis. The United States showed the greatest collaboration in retinal fibrosis research, particularly with China.<br><br>CONCLUSIONS: Current retinal fibrosis research focused on OCT diagnostics, cytokine mechanisms, and associated diseases such as diabetic retinopathy and macular degeneration. Future research will explore the integration of artificial intelligence in treatment strategies and the mechanisms underlying post-anti-vascular endothelial growth factor (VEGF) injection fibrosis.}, }
@article {pmid40394320, year = {2026}, author = {Masalkhi, M and Sporn, K and Kumar, R and Ong, J and Nguyen, T and Waisberg, E and Zaman, N and Lee, AG and Tavakkoli, A}, title = {Ophthalmic Image Synthesis and Analysis with Generative Adversarial Network Artificial Intelligence.}, journal = {Journal of imaging informatics in medicine}, volume = {39}, number = {1}, pages = {732-754}, pmid = {40394320}, issn = {2948-2933}, mesh = {Humans ; Tomography, Optical Coherence ; *Artificial Intelligence ; Algorithms ; *Neural Networks, Computer ; *Eye Diseases/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Generative Adversarial Networks ; }, abstract = {Generative adversarial networks (GANs), introduced by Ian Goodfellow in 2014, have revolutionized adversarial machine learning, particularly in data synthesis. This manuscript explores their application in ophthalmic diagnostics, addressing the scarcity of annotated datasets and the need for improved early disease detection. By leveraging GAN architectures, the goal is to enhance the quality of synthetic ophthalmic images, ultimately improving diagnostic algorithm training. A systematic review was conducted from January to April 2024 across PubMed, Embase, and Scopus. Search terms included "Generative Adversarial Networks" and "ophthalmic image synthesis." Articles were selected based on relevance to retinal image generation and diagnostic improvement in ophthalmology. GANs show considerable promise in generating high-resolution retinal and optical coherence tomography (OCT) images. Models like DR-GAN and Pix2Pix have successfully synthesized images that resemble real diagnostic data, proving valuable when annotated datasets are scarce. GAN-generated images enhance training for algorithms detecting diseases such as diabetic retinopathy, glaucoma, and age-related macular degeneration. Recent advances, including conditional GANs and CycleGANs, have enabled disease-specific image generation, boosting the diversity of training datasets, particularly in resource-limited settings. Integrating GANs into ophthalmic diagnostics represents a significant leap in medical AI, offering high-quality synthetic images to improve diagnostic algorithms. Despite their potential, challenges such as the need for larger datasets, improved image interpretability, and noise reduction must be addressed. Future research should focus on optimizing these models and incorporating multi-modal data to enhance diagnostic accuracy in clinical settings.}, }
@article {pmid40394614, year = {2025}, author = {Hushmandi, K and Lam, HY and Wong, WM and Tan, W and Daryabari, SH and Reiter, RJ and Farahani, N and Kumar, AP}, title = {Gene therapy for age-related macular degeneration: a promising frontier in vision preservation.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {233}, pmid = {40394614}, issn = {1478-811X}, support = {NUHSRO/2023/039/RO5+6/Seed-Mar/04//National University of Singapore/ ; }, mesh = {Humans ; *Macular Degeneration/therapy/genetics ; *Genetic Therapy/methods ; Animals ; *Vision, Ocular ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of central vision loss, progressively impairing the retina and affecting millions worldwide. By 2040, global cases of AMD are projected to reach 300 million, posing a significant public health challenge. While early AMD may only cause mild visual impairment, advanced stages, particularly neovascular (wet) and non-neovascular (dry) AMD, can lead to severe vision loss or legal blindness, substantially affecting daily life. The introduction of anti-angiogenic therapies has revolutionized wet AMD treatment, offering a high probability of preserving or improving vision. However, these therapies do not halt AMD progression, and no definitive treatments exist for dry AMD. The limitations of current therapies, such as frequent injections and treatment resistance, underscore the urgent need for novel strategies. Gene therapy, which has shown success in treating other hereditary retinal diseases, offers a promising long-term solution for AMD by targeting retinal cells to produce therapeutic proteins. This review explores the potential of gene therapy for AMD, examining recent clinical trials and future treatment directions.}, }
@article {pmid40395179, year = {2025}, author = {Zou, Y and Jiang, J and Li, Y and Ding, X and Tong, Q and Shi, Y and Xiao, L and Chen, L}, title = {Immune Checkpoint PD-L1 Modulates Retinal Microglial Activation to Alleviate Vascular Leakage in Choroidal Neovascularization via ERK.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {23}, pages = {e2400747}, pmid = {40395179}, issn = {2198-3844}, support = {81371042//National Natural Science Foundation of China/ ; 81870660//National Natural Science Foundation of China/ ; 22Y11910500//Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission/ ; 202305AC160073//Yunnan Provincial Young and Middle - Aged Academic and Technical Leaders Reserve Talents Project/ ; 202401AY070001-172/174//Yunnan Provincial Department of Science and Technology - Kunming Medical University Joint Fund for Applied Basic Research/ ; }, mesh = {Animals ; *Microglia/metabolism/immunology ; *B7-H1 Antigen/metabolism/genetics ; *Choroidal Neovascularization/metabolism/immunology ; Mice ; Disease Models, Animal ; *Retina/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; *Macular Degeneration/metabolism ; Humans ; MAP Kinase Signaling System ; }, abstract = {Neovascular age-related macular degeneration (NVAMD) is a common retinal disease causing vision loss in the elderly. Neuroinflammation significantly contributes to NVAMD's etiology. This study explores the role of Programmed cell death ligand 1 (PD-L1), an immune checkpoint (ICP) in microglia, known for limiting neuroinflammation in neurodegenerative diseases, and its potential function in NVAMD. This work finds increased PD-L1 expression in retinal microglia following laser injury. PD-L1 knockout (KO) or inhibitory PD-L1 antibody treatment worsens vascular leakage and neoangiogenesis in a laser-induced NVAMD mouse model, effects reversible by microglia depletion with PLX5622. This study underscores that choroidal neovascularization (CNV) may be regulated by multiple mechanisms, with PD-L1 modulation representing one of these pathways. Blocking PD-L1 elevated proinflammatory factors and p-ERK levels, indicating microglial overactivation in NVAMD. Conversely, enhancing PD-L1 signaling reduced neuroinflammation and neovascularization via ERK. These findings highlight PD-L1's role in neoangiogenesis and neuroinflammation in NVAMD, suggesting its potential as a target for immunomodulatory treatment in NVAMD.}, }
@article {pmid40396232, year = {2025}, author = {Chin, CH and Chien, CC and Huang, CJ and Ke, CY and Lee, YJ}, title = {Differential Transcription Factor Activator Protein-2 Delta Genotypes Affect the Levels of Interleukin-1 Beta, Interleukin 8, and Vascular Endothelial Growth Factor-C in the Retinal Pigment Epithelial Cells after Long-term Light Exposure.}, journal = {Journal of physiological investigation}, volume = {68}, number = {4}, pages = {218-228}, doi = {10.4103/ejpi.EJPI-D-24-00107}, pmid = {40396232}, issn = {2950-6344}, mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/radiation effects ; Rats ; *Transcription Factor AP-2/genetics/metabolism ; *Interleukin-8/metabolism/genetics ; *Interleukin-1beta/metabolism/genetics ; Genotype ; Male ; *Light/adverse effects ; Rats, Sprague-Dawley ; }, abstract = {Retinal degeneration accompanied by abnormal neovascularization from the choroid in the macular area is a critical disease to cure. Retinal cell apoptosis or inflammation in the macula can lead to neovascularization in that area. Some environmental factors such as long-term light exposure, particularly the blue end of the light spectrum, can damage the retina, causing such a disease. Improved understanding of genetic molecules has indicated that certain genes may be potential biomarkers of neovascular macular degeneration. This study aimed to investigate the expression of transcription factor activator protein-2 δ (TFAP-2D) in the retina and explore its role in the pathogenesis of retinal degeneration. For this, a long-term light exposure animal model was used to evaluate TFAP-2D expression in the retina. In addition, two vectors overexpressing different genotypes of TFAP-2D were transfected into retinal pigment epithelial (RPE) cells, and the expression of angiogenesis molecules was investigated. It was found that TFAP-2D expression was observed in the RPE area of the retina in long-term light-exposed rats; however, no TFAP-2D expression was detected in the retina of control (normal) rats. Interleukins (ILs) 1B, IL8, vascular endothelial growth factor (VEGF)-C, and one VEGF receptor (kinase insert domain receptor) were significantly upregulated in RPE cells with TFAP-2D with a C allele at rs78648104 (TFAP-2D-C) overexpression. In conclusion, experiments with different TFAP-2D genotypes revealed that long-term light exposure upregulated TFAP-2D expression in the RPE cells of the retina. In addition, overexpression of TFAP-2D-C induced the release of IL1B, IL8, and VEGF-C, which may lead to neovascularization in the choroid and retina.}, }
@article {pmid40396593, year = {2025}, author = {Li, C and Wang, B}, title = {Role of P2X7R in Retinal Diseases: A Review.}, journal = {Immunity, inflammation and disease}, volume = {13}, number = {5}, pages = {e70203}, pmid = {40396593}, issn = {2050-4527}, support = {//This study was supported by the Natural Science Foundation of Gansu Province (22JR5RA971)./ ; }, mesh = {Humans ; *Receptors, Purinergic P2X7/metabolism ; Animals ; *Retinal Diseases/metabolism ; Macular Degeneration/metabolism ; Retinitis Pigmentosa/metabolism ; Diabetic Retinopathy/metabolism ; }, abstract = {BACKGROUND: P2X purinoceptor 7 receptor (P2X7R) is an ATP-gated ion channel that, upon activation by ATP, triggers the release of inflammatory mediators and induces apoptosis in cells. This channel plays a crucial role in the onset and progression of various diseases. Recently, there has been a growing body of research focused on the function of P2X7R receptors in ophthalmic conditions, particularly concerning retinal diseases such as age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa.<br><br>OBJECTIVE: This article is to provide a comprehensive review of the advancements in the study of P2X7R and its association with retinal diseases, elucidating its role in these conditions and identifying potential avenues for future research.<br><br>METHODS: Electronic databases, including PubMed, Web of Science, and Wan fang Data were searched for relevant literature. The following keywords were used: "P2X7R", Age-related macular degeneration", "Diabetic retinopathy", "Retinitis pigmentosa". Both preclinical and clinical studies were included to provide a holistic understanding of P2X7R's role in retinal pathology.<br><br>RESULTS: P2X7R activation exacerbates retinal diseases by promoting inflammation and apoptosis. However, its role in disease progression and homeostasis complicates therapeutic targeting, highlighting the need for selective inhibitors and further research into its context-dependent functions.<br><br>CONCLUSION: P2X7R plays a critical role in the pathogenesis of retinal diseases. At the same time, preclinical studies suggest that P2X7R inhibition holds promise as a therapeutic strategy. Future research should focus on developing selective P2X7R inhibitors, elucidating the receptor's role in different disease stages, and identifying biomarkers to guide personalized treatment. Addressing these challenges will be essential for translating P2X7R-targeted therapies into clinical practice and improving outcomes for patients with retinal diseases.}, }
@article {pmid40396905, year = {2025}, author = {Chen, Z and Zhu, X and Lu, MM and Ou, Q and Wang, X and Zhao, Z and Shen, Q and Wang, Q and Wang, Z and Xu, JY and Jin, C and Gao, F and Wang, J and Zhang, J and Zhang, J and Jin, X and Bi, Y and Lu, L and Xu, GT and Tian, H}, title = {PHOSPHO1 Suppresses Ferroptosis in Retinal Pigment Epithelial Cells by Reducing the Levels of Phosphatidylethanolamine Molecular Species.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {28}, pages = {e2505359}, pmid = {40396905}, issn = {2198-3844}, support = {2023YFC2506100//Ministry of Science and Technology of China/ ; 24ZR1470100//Natural Science Foundation of Shanghai/ ; 20234Y0113//Shanghai Municipal Health Commission/ ; 82471073//National Natural Science Foundation of China/ ; 82271108//National Natural Science Foundation of China/ ; }, mesh = {*Ferroptosis/physiology/genetics ; *Retinal Pigment Epithelium/metabolism ; *Phosphatidylethanolamines/metabolism ; Animals ; Rats ; Humans ; Lipid Peroxidation ; Macular Degeneration/metabolism ; Autophagy ; Epithelial Cells/metabolism ; *Phosphoric Monoester Hydrolases/metabolism/genetics ; Iron/metabolism ; Disease Models, Animal ; }, abstract = {Iron-induced lipid peroxidation of phosphatidylethanolamine (PE) species is a key driver of ferroptosis in retinal pigment epithelial (RPE) cells, a process closely associated with age-related macular degeneration (AMD). The previous studies have demonstrated that induced retinal pigment epithelial (iRPE) cells generated by transcription factor-mediated reprogramming exhibit superior therapeutic efficacy in treating AMD. In this study, it is found that these iRPE cells are resistant to ferroptosis and further identified phosphoethanolamine/phosphocholine phosphatase 1 (PHOSPHO1) as a critical regulator underlying ferroptosis resistance. Mechanistically, PHOSPHO1 inhibits ferroptosis through two distinct mechanisms. First, it reduces PE levels in the endoplasmic reticulum, thereby limiting PE-derived lipid peroxidation. Second, it suppresses autophagy and ferritinophagy, leading to a reduction in intracellular free iron accumulation. Experiments using an in vivo rat model confirm that PHOSPHO1 effectively protects RPE cells from ferroptotic damage. These findings highlight PHOSPHO1 as a potential therapeutic target for AMD, providing insights into novel ferroptosis-based intervention strategies.}, }
@article {pmid40397174, year = {2025}, author = {Heimes-Bussmann, B and Bellenbaum, R and Njoo, C and Liakopoulos, S and Schmitz-Valckenberg, S and Zortel, M and Rothaus, K and Leemhuis, J and Mussinghoff, P and Lommatzsch, A}, title = {[Faricimab in previously treated neovascular age-related macular degeneration : Study design of the prospective noninterventional study PASSENGER].}, journal = {Die Ophthalmologie}, volume = {122}, number = {9}, pages = {693-699}, pmid = {40397174}, issn = {2731-7218}, mesh = {Humans ; Prospective Studies ; *Wet Macular Degeneration/drug therapy ; Visual Acuity/drug effects ; Aged ; Middle Aged ; Male ; Female ; Quality of Life ; Treatment Outcome ; Germany ; Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; Antibodies, Bispecific ; }, abstract = {BACKGROUND: Faricimab was approved in the European Union in 9/2022 as the first bispecific antibody for the treatment of neovascular age-related macular degeneration (nAMD), visual impairment due to diabetic macular oedema (DME) or retinal vein occlusion. To date, the efficacy profile of faricimab has been investigated under pivotal clinical phase 3 study conditions in treatment-naïve nAMD patients. The prospective noninterventional study (NIS) PASSENGER is a multicentre study that aims at contributing to a better understanding of the effectiveness, safety and impact of faricimab on quality of life in previously treated patients with nAMD under real-world conditions in Germany.<br><br>METHODS: The planned observation period per patient is 24&#xa0;months. Patients (n&#x202f;=&#x2009;620) aged &#x2265;&#x202f;50&#xa0;years with nAMD who switched to faricimab no longer than 12&#xa0;weeks prior to enrolment in the study, were previously treated with a&#xa0;vascular endothelial growth factor (VEGF) inhibitor for a&#xa0;maximum of 36&#xa0;months, and had a&#xa0;best corrected visual acuity (BCVA) of 30-80 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale at the start of therapy with faricimab are eligible to participate. The primary outcome measure is the change in BCVA from baseline after 52&#xa0;weeks. In addition, central subfield thickness, intraretinal, subretinal and subpigment epithelial fluid over time as well as patient-reported outcomes, adherence and adverse events are recorded.<br><br>RESULT: The first patient was enrolled in June 2023. According to the current schedule, recruitment (24&#xa0;months) will be completed by June 2025 and the last patient visit is anticipated in Q2/2027.<br><br>CONCLUSION: Data from the PASSENGER study are intended to contribute to a&#xa0;better understanding of therapy management in daily practice in Germany.}, }
@article {pmid40397903, year = {2025}, author = {Wang, P and Hu, Z and Haider, M and Hopman, W and Sharma, E and Sharma, S}, title = {The Association Between Hepatic Steatosis and Age-Related Macular Degeneration: A Cross-Sectional Study.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004526}, pmid = {40397903}, issn = {1539-2864}, abstract = {PURPOSE: The primary aim of this study is to estimate the association of hepatic steatosis in patients diagnosed with Age-Related Macular Degeneration (AMD).<br><br>METHODS: Patients with AMD and without secondary causes of chronic liver disease, alongside age- and sex-matched controls were recruited. Hepatic steatosis was determined via ultrasound imaging, and metabolic risk factors were collected using standardized surveys.<br><br>RESULTS: A total of 98 patients were recruited (49 cases, 49 controls). Hepatic steatosis was observed in 51.0% of the AMD group compared to 30.6% in controls, a statistically significant difference (&#x3c7;2(1) = 4.224, p = 0.040). In multivariable models, dyslipidemia and diabetes were the strongest predictors, with association of steatosis attenuated but still significant (OR 2.36, 95% CI 1.03-5.40, p = 0.049).<br><br>CONCLUSION: This study suggests an association between AMD and the prevalence of hepatic steatosis, after controlling for metabolic risk factors.}, }
@article {pmid40397942, year = {2025}, author = {Osei Duah Junior, I and Akuffo, KO and Ampong, J and Owiredu, D and Boateng, BS and Danso-Appiah, A}, title = {Dietary factors and predominant eye diseases in sub-Saharan African populations: A systematic review protocol.}, journal = {PloS one}, volume = {20}, number = {5}, pages = {e0320030}, pmid = {40397942}, issn = {1932-6203}, mesh = {Humans ; Systematic Reviews as Topic ; Africa South of the Sahara/epidemiology ; *Eye Diseases/epidemiology/etiology ; *Diet/adverse effects ; }, abstract = {Evidence linking diet and ocular diseases is growing, yet variations persist, with a paucity of data in sub-Saharan Africa. The proposed review will systematically synthesize evidence on dietary factors associated with predominant eye disorders (cataracts, refractive error, glaucoma, diabetic retinopathy, age-related macular degeneration, and dry eye disease) in the sub-Saharan African population. The systematic review protocol will follow PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols) for transparency in reporting. All relevant published studies in the English Language will be identified from PubMed, Scopus, Web of Science, Embase, Health Inter-Network Access to Research Initiative (HINARI), Cumulative Index to Nursing and Allied Health Literature (CINAHL), African Journal of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) using medical subject headings (MeSH) and controlled vocabulary without date restrictions. The reference lists of all retrieved studies will be checked and experts will be contacted for additional relevant studies. The risk of bias for observational studies will be assessed using ROBINS-E (Risk of Bias in Non-Randomized Studies - of Exposure) and for non-interventional and randomized studies ROBINS-V2 (Risk of Bias in Non-Randomized Studies version 2) and ROB2 (Cochrane Risk of Bias 2) will be employed respectively. Study quality will be assessed using the National Heart Lung and Blood Institutes Quality Assessment (NHLBI) tool for Observational Cohort and Cross-Sectional Studies and Controlled Interventional Studies. Meta-analysis will not be considered because of the wide range of dietary factors and the susceptibility to high heterogeneity. Patterns of association between dietary factors and the specific eye diseases will be consolidated by Synthesis Without Meta-analysis (SWiM).}, }
@article {pmid40398512, year = {2025}, author = {Huang, A and Wu, Z and Ansari, G and Von Der Emde, L and Pfau, M and Schmitz-Valckenberg, S and Fleckenstein, M and Keenan, TDL and Sadda, SR and Guymer, RH and Cheung, CMG and Chakravarthy, U}, title = {Geographic atrophy: Understanding the relationship between structure and function.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {14}, number = {3}, pages = {100207}, pmid = {40398512}, issn = {2162-0989}, support = {ZIA EY000514/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; *Geographic Atrophy/physiopathology/diagnosis ; *Tomography, Optical Coherence/methods ; *Visual Acuity/physiology ; Fluorescein Angiography/methods ; *Visual Fields/physiology ; Disease Progression ; Visual Field Tests ; }, abstract = {PURPOSE: This review explores the complex relationship between anatomical alterations and functional consequences in geographic atrophy (GA), the advanced non-neovascular form of age-related macular degeneration. We examine the natural history, progression patterns, structural biomarkers, functional assessments, and structure-function correlations in GA.<br><br>METHODS: Experts contributed specialized knowledge on GA pathophysiology, imaging biomarkers, and functional assessment methods. We synthesized an understanding of the relationship between structural changes (including fundus autofluorescence patterns, optical coherence tomography markers, and novel biomarkers) and functional outcomes (visual acuity, microperimetry, reading performance, and patient-reported outcomes), drawing from authors' research expertise and relevant literature.<br><br>RESULTS: While GA is defined by visible areas of outer retinal atrophy, the structure-function relationship is complex and often discordant. Visual acuity incompletely reflects the functional impact of GA, as it may remain preserved until foveal involvement occurs. Microperimetric assessments reveal functional deficits extending beyond visible atrophic borders, with varying degrees of correlation between structural and functional metrics. Different fundus autofluorescence patterns demonstrate distinct functional implications and progression rates. Recent innovations in imaging and visual function testing offer enhanced characterization of disease progression.<br><br>CONCLUSIONS: The complex relationship between structural and functional measures in GA reflects underlying pathophysiological mechanisms and has important implications for clinical trial endpoints and patient management. Multimodal assessment incorporating both structural and functional parameters is essential for the comprehensive evaluation and management of GA, particularly as novel therapeutic approaches emerge.}, }
@article {pmid40400877, year = {2025}, author = {Chujo, S and Matsubara, H and Mase, Y and Kato, K and Kondo, M}, title = {Successful Response to Intravitreal Faricimab Injections in a Case of Neovascular Age-Related Macular Degeneration in Vitrectomized Eyes.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e82709}, pmid = {40400877}, issn = {2168-8184}, abstract = {The half-life of anti-vascular endothelial growth factor (anti-VEGF) drugs shortens significantly after vitrectomy due to an increased intraocular pharmacokinetic clearance caused by the absence of the vitreous gel. This reduced half-life can limit the therapeutic effect of these intravitreal agents and complicate the management of conditions such as neovascular age-related macular degeneration (nAMD). We report a case of nAMD in a vitrectomized eye that showed inadequate response to both aflibercept and brolucizumab, but experienced effective suppression of exudation following intravitreal administration of faricimab. This case suggests that faricimab may offer a therapeutic benefit in managing exudative changes in vitrectomized eyes with nAMD.}, }
@article {pmid40401519, year = {2025}, author = {Gupta, R and Bunea, I and Alvisio, B and Barone, F and Gupta, R and Baker, D and Qian, H and Daniele, E and Contreary, CG and Montford, J and Sharma, R and Maminishkis, A and Singh, MS and Magone De Quadros Costa, MT and Kashani, AH and Amaral, J and Bharti, K}, title = {iPSC-RPE patch restores photoreceptors and regenerates choriocapillaris in a pig retinal degeneration model.}, journal = {JCI insight}, volume = {10}, number = {10}, pages = {}, pmid = {40401519}, issn = {2379-3708}, mesh = {Animals ; Swine ; *Induced Pluripotent Stem Cells/transplantation/cytology ; Disease Models, Animal ; *Retinal Pigment Epithelium/cytology/transplantation ; Tomography, Optical Coherence ; *Retinal Degeneration/therapy/pathology ; *Choroid ; Polylactic Acid-Polyglycolic Acid Copolymer ; Regeneration ; Tissue Scaffolds ; }, abstract = {Dry age-related macular degeneration (AMD) is a leading cause of untreatable vision loss. In advanced cases, retinal pigment epithelium (RPE) cell loss occurs alongside photoreceptor and choriocapillaris degeneration. We hypothesized that an RPE-patch would mitigate photoreceptor and choriocapillaris degeneration to restore vision. An induced pluripotent stem cell-derived RPE (iRPE) patch was developed using a clinically compatible manufacturing process by maturing iRPE cells on a biodegradable poly(lactic-co-glycolic acid) (PLGA) scaffold. To compare outcomes, we developed a surgical procedure for immediate sequential delivery of PLGA-iRPE and/or PLGA-only patches in the subretinal space of a pig model of laser-induced outer retinal degeneration. Deep learning algorithm-based optical coherence tomography (OCT) image segmentation verified preservation of the photoreceptors over the areas of PLGA-iRPE-transplanted retina and not in laser-injured or PLGA-only-transplanted retina. Adaptive optics imaging of individual cone photoreceptors further supported this finding. OCT-angiography revealed choriocapillaris regeneration in PLGA-iRPE- and not in PLGA-only-transplanted retinas. Our data, obtained using clinically relevant techniques, verified that PLGA-iRPE supports photoreceptor survival and regenerates choriocapillaris in a laser-injured pig retina. Sequential delivery of two 8 mm2 transplants allows for testing of surgical feasibility and safety of the double dose. This work allows one surgery to treat larger and noncontiguous retinal degeneration areas.}, }
@article {pmid40402186, year = {2025}, author = {Schloesser, L and Ziemssen, F and Schuster, AK and Hasan, S and Finger, RP}, title = {[Screening recommendations for glaucoma, age-related macular degeneration and diabetic eye diseases].}, journal = {Die Ophthalmologie}, volume = {122}, number = {7}, pages = {518-523}, pmid = {40402186}, issn = {2731-7218}, mesh = {Humans ; *Glaucoma/diagnosis/epidemiology ; *Macular Degeneration/diagnosis/prevention &amp; control/epidemiology ; *Diabetic Retinopathy/diagnosis ; *Mass Screening/standards ; Germany ; *Practice Guidelines as Topic ; *Ophthalmology/standards ; }, abstract = {BACKGROUND: The main causes of blindness, age-related macular degeneration (AMD), glaucoma and diabetic eye diseases (DED), are becoming increasingly more important in terms of health economics due to the demographic developments.<br><br>OBJECTIVE: The current screening recommendations for these diseases and the underlying evidence are presented.<br><br>MATERIAL AND METHODS: A&#xa0;detailed literature search was conducted and the recommendations of the relevant guidelines of the Association of the Scientific Medical Societies in Germany (AWMF) were summarized.<br><br>RESULTS: There are current screening recommendations for glaucoma and DED but there is still no consensus with respect to AMD. Screening for DED is financed by the statutory health insurance (SHI) and offered as part of routine care. Glaucoma screening is only covered by the SHI if certain risk factors are present and is not yet implemented across the board.<br><br>CONCLUSION: There are established screening programs for DED that are financed by the SHI; however, there are AWMF recommendations for glaucoma but no SHI-financed screening programs and there are still no AWMF screening recommendations for AMD. Whether and to what extent screening programs are used by the respective target populations should be further investigated in studies.}, }
@article {pmid40402519, year = {2025}, author = {Luo, T and Li, C and Zhou, L and Sun, H and Yang, MM}, title = {Protein Acetylation in Age-Related Macular Degeneration: Mechanisms, Roles, and Therapeutic Perspectives.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {5}, pages = {30}, pmid = {40402519}, issn = {1552-5783}, mesh = {Humans ; *Macular Degeneration/metabolism/drug therapy ; Acetylation ; Oxidative Stress/physiology ; Choroidal Neovascularization/metabolism ; Cellular Senescence/physiology ; }, abstract = {Age-related macular degeneration (AMD) is a top cause of severe vision loss and blindness in older adults globally. This multifactorial disease arises from genetic, environmental, and age-related factors. Protein acetylation modification plays a key role in AMD progression through both epigenetic and non-epigenetic pathways. This review comprehensively discusses the multidimensional impacts of protein acetylation in AMD, particularly its dynamic regulation of angiogenesis, oxidative stress, inflammatory responses, and cellular senescence. Recent evidence shows that histone acetylation modification inhibits choroidal neovascularization (CNV) formation by regulating vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF-1α) expression, while upregulating the complement inhibitor clusterin to maintain Bruch's membrane integrity. Additionally, the NAD+-dependent deacetylase SIRT1 modulates the deacetylation of transcription factors such as PGC-1α, NF-κB, and FOXO3, enhancing mitochondrial antioxidant function and suppressing inflammatory cascades to disrupt the vicious cycle of oxidative stress and chronic inflammation. In terms of cellular senescence, histone hypoacetylation and hyperacetylation of non-histone proteins (e.g., p53, E2F1) jointly cause retinal pigment epithelial (RPE) cell-cycle arrest and autophagy imbalance, accelerating AMD progression. Genetic evidence further reveals subtype-specific expression changes and epigenetic regulatory mechanisms of histone deacetylases (HDACs), such as HDAC11 and HDAC1/3, in AMD. This article explores the clinical significance of these findings and proposes a novel combined therapeutic strategy. It involves synergistically targeting acetylation homeostasis with HDAC inhibitors (e.g., TSA, AN7) and SIRT1 activators while inhibiting abnormal angiogenesis, repairing metabolic disorders, and restoring autophagy function. This dual-targeting approach may overcome current anti-VEGF therapy limitations and open new precision management avenues for AMD.}, }
@article {pmid40403167, year = {2025}, author = {Marks, V and Golos, AM and Gill, M and Henick, D and Li, K and DeBroff, B and Kombo, N}, title = {Persistent Anterior Uveitis Following Cataract Surgery.}, journal = {Ocular immunology and inflammation}, volume = {33}, number = {8}, pages = {1618-1623}, doi = {10.1080/09273948.2025.2509716}, pmid = {40403167}, issn = {1744-5078}, mesh = {Humans ; Female ; Retrospective Studies ; *Uveitis, Anterior/epidemiology/etiology/diagnosis/drug therapy ; Male ; Aged ; Middle Aged ; Risk Factors ; Incidence ; *Cataract Extraction/adverse effects ; *Postoperative Complications ; Aged, 80 and over ; Visual Acuity ; Connecticut/epidemiology ; Follow-Up Studies ; Adult ; }, abstract = {PURPOSE: To determine the incidence of and risk factors for persistent anterior uveitis following cataract surgery.<br><br>METHODS: This was a retrospective cohort study of patients who underwent cataract surgery at a tertiary referral center in Connecticut, USA. Those with prior uveitis, complex ocular pathology, concurrent procedures, and surgical complications were excluded. The outcome was development of persistent anterior uveitis, defined as anterior chamber cell grade&#x2009;&#x2265;&#x2009;0.5+ and steroid treatment beyond two months. Patients who did and did not develop persistent anterior uveitis were compared using univariate and multivariate analysis.<br><br>RESULTS: Of 3341 patients (5419 eyes), 45 (61) developed persistent anterior uveitis (1.1% incidence). Cases were significantly younger (64.6&#x2009;years vs. 69.6&#x2009;years, p&#x2009;<&#x2009;0.001), and there were significantly higher proportions of female (73.8% compared to 58.5%, p&#x2009;=&#x2009;0.016) and Black or African American (54.1% vs. 15.5%, p&#x2009;<&#x2009;0.001) patients, as well as those with age-related macular degeneration (9.8% vs. 1.5%, p&#x2009;<&#x2009;0.001), previous intravitreal injections (14.8% vs. 6.0%, p&#x2009;=&#x2009;0.004), and diabetes (18.0% vs. 8.9%, p&#x2009;=&#x2009;0.013). In multivariate analysis, older age was associated with a significantly lower likelihood of persistent anterior uveitis (adjusted odds ratio (AOR)&#x2009;=&#x2009;0.963, 95% confidence interval (CI)=[0.942, 0.984]), whereas Black race (AOR&#x2009;=&#x2009;9.102, 95% CI&#x2009;=&#x2009;[4.836, 17.133]) and wet age-related macular degeneration (AOR&#x2009;=&#x2009;37.700, 95% CI&#x2009;=&#x2009;[6.408, 221.792]) were associated with a significantly higher likelihood.<br><br>CONCLUSIONS: In this study, 1.1% of eyes developed persistent anterior uveitis following cataract surgery. Younger age, Black race, and wet age-related macular degeneration should be investigated as potential risk factors to improve its prophylaxis, identification, and management.}, }
@article {pmid40407506, year = {2025}, author = {Poveda, JL and Arnáiz, P and López, S and Muñoz, B and Fernández-Ferreiro, A}, title = {Preferences of Hospital Pharmacists for the Different Attributes of Intravitreal Treatments for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema in Spain: The SEEKING Study.}, journal = {Pharmacy (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, pmid = {40407506}, issn = {2226-4787}, support = {//Roche Farma S.A./ ; }, abstract = {The process of evaluation and selection of drugs in Spain is currently changing, with hospital pharmacists (HPs) having a growing relevance. This cross-sectional observational study aimed to assess HPs' preferences for different hypothetical intravitreal treatments for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Best corrected visual acuity (BCVA), ocular adverse events (AE), annual drug cost, available presentation, and mechanisms of action (MoA) were the selected attributes. A conjoint analysis was used. Ninety-one HPs completed the study. The mean (SD) age was 39.2 (10.2) years, 60.4% were female, and the mean (SD) time of experience as HP was 12.6 (8.3) years. For nAMD treatments, BCVA (38.6%) and ocular AE (27.3%) were the most important attributes, while annual drug cost (16.3%), available presentation (11.1%), and MoA (6.7%) were not as important. For DME drugs, BCVA (44.6%) and ocular AE (25.5%) were the most significant factors; annual drug cost (17.9%), the drug's available presentation (7.3%), and MoA (4.8%) were not considered to be as crucial. Preferences were comparable independent of HP experience. Effectiveness and safety were the most important attributes when choosing a drug. Comprehending the significant characteristics for HPs could potentially improve their collaborative function within multidisciplinary teams involved in intravitreal treatments.}, }
@article {pmid40407556, year = {2025}, author = {Udomwech, L and Eden, C and Tawanwongsri, W}, title = {Relationship Between Facial Melasma and Ocular Photoaging Diseases.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {13}, number = {2}, pages = {}, pmid = {40407556}, issn = {2076-3271}, mesh = {Humans ; *Melanosis/epidemiology/complications/etiology/pathology ; Female ; Middle Aged ; Aged ; Male ; Adult ; Cross-Sectional Studies ; Aged, 80 and over ; Ultraviolet Rays/adverse effects ; Face/pathology ; Thailand/epidemiology ; Sunlight/adverse effects ; *Eye Diseases/etiology/epidemiology ; Cataract/epidemiology/etiology ; }, abstract = {Background/Objectives: Facial melasma is a common, chronic, and relapsing hyperpigmentation disorder, affecting up to 40% of adult women in Southeast Asia. Although most cases are mild, the condition may have a considerable psychological impact. Ocular photoaging diseases are also common and have been increasingly recognized in aging populations exposed to chronic sunlight. Ultraviolet (UV) radiation is implicated in both melasma and ocular photoaging; however, their relationship remains unclear. Methods: This cross-sectional study investigated the association between facial melasma and UV-induced ocular conditions among 315 participants aged 30-80 years at Walailak University Hospital, Thailand. Facial melasma was diagnosed clinically and dermoscopically, with severity assessed using the modified Melasma Area Severity Index. Ophthalmological examinations evaluated UV-related ocular conditions, including pinguecula, pterygium, climatic droplet keratopathy, cataracts, and age-related macular degeneration. Logistic regression analyses were performed, adjusting for age, sex, and sun exposure. Results: Facial melasma was identified in 66.0% of participants (n = 208), and nuclear cataracts were significantly associated with melasma (adjusted odds ratio, 2.590; 95% confidence interval, 1.410-4.770; p = 0.002). Additionally, melasma severity correlated with nuclear cataract severity (ρ = 0.186, p = 0.001). Other ocular conditions were not significantly associated with melasma. Conclusions: These findings suggest a shared UV-related pathogenesis between facial melasma and nuclear cataracts. Sun protection measures, including regular sunscreen use, UV-blocking eyewear, and wide-brimmed hats, may help mitigate the risk of both conditions. Further multicenter studies are warranted to confirm these findings and explore the underlying mechanisms.}, }
@article {pmid40407849, year = {2025}, author = {Ridano, ME and Hanke-Gogokhia, C and Lehmann, GL and Caceres, PS and Vaglienti, MV and Ceschin, D and Schreiner, R and Croci, DO and Torroja-Fungairiño, C and Rodriguez-Boulan, E and Benedicto, I and Rabinovich, GA and Sánchez, MC}, title = {Stromal-Like Cells and Retinal Pigment Epithelium Modulate Choroidal Sprouting Through Galectin-1-Dependent and Independent Pathways.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {10}, pages = {e70671}, pmid = {40407849}, issn = {1530-6860}, support = {01586//agenciaidiar | Fondo para la Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica (FONCYT)/ ; 033805-I//MEC | Agencia Estatal de Investigaci&#xf3;n (AEI)/ ; 137111OA-I00//MEC | Agencia Estatal de Investigaci&#xf3;n (AEI)/ ; 1314//agenciaidiar | Fondo para la Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica (FONCYT)/ ; R01 EY08531//Foundation for the National Institutes of Health (FNIH)/ ; U54 CA221208/CA/NCI NIH HHS/United States ; 2440//agenciaidiar | Fondo para la Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica (FONCYT)/ ; }, mesh = {*Galectin 1/metabolism/genetics ; *Retinal Pigment Epithelium/metabolism/cytology ; Animals ; *Choroid/metabolism/blood supply ; Mice ; *Stromal Cells/metabolism ; Mice, Knockout ; Mice, Inbred C57BL ; Choroidal Neovascularization/metabolism ; Humans ; Macular Degeneration/metabolism ; }, abstract = {Outer retinal function depends on two supporting tissues: the retinal pigment epithelium (RPE) and the choroid. Limited molecular information is available on the intercellular networks that sustain RPE/choroid tissue in both healthy and pathological states. Galectin-1 (Gal1), a β-galactoside-binding lectin, has recently emerged as a key regulator of angiogenesis and a potential therapeutic target in vascular pathologies, including age-related macular degeneration. Here, we studied the expression of Gal1 in the outer retina and its regulatory role in the RPE/choroid under physiological and pathological conditions. Our findings indicate that Gal1 is predominantly associated with stromal cells in the RPE/choroid. In Gal1-deficient (Lgals1[-/-]) mice, the RPE/choroid ultrastructure and gene expression profiles were altered, and choroidal explants exhibited reduced sprouting compared to those of wild-type mice. Consistently, recombinant Gal1 promoted choroidal sprouting under hypoxic conditions, and stromal-like cells modulated pro-angiogenic and antiangiogenic gene expression in vitro under pathological conditions. Interestingly, Gal1 was also expressed by the RPE, with apical secretion under normoxia that shifted toward a basolateral phenotype under hypoxia. These findings identify stromal-like cells and RPE as key sources of Gal1 in the choroid, highlighting its distinct roles in maintaining RPE/choroid homeostasis in healthy or pathological microenvironments.}, }
@article {pmid40409337, year = {2025}, author = {Zhang, N and Ma, C and Shao, F and Wang, H and Ma, X}, title = {Fib@PEGDA/GelMA hydrogel as a light-curing thin-layer matrix for RPE cell growth and function.}, journal = {Biomedical materials (Bristol, England)}, volume = {20}, number = {4}, pages = {}, doi = {10.1088/1748-605X/addcab}, pmid = {40409337}, issn = {1748-605X}, mesh = {*Retinal Pigment Epithelium/cytology ; *Hydrogels/chemistry ; *Polyethylene Glycols/chemistry ; Humans ; Tissue Engineering/methods ; Cell Proliferation ; Cell Survival ; Biocompatible Materials/chemistry ; Tissue Scaffolds/chemistry ; Light ; Printing, Three-Dimensional ; Materials Testing ; Cell Line ; Animals ; }, abstract = {Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, are leading causes of blindness globally, characterized by progressive degeneration of retinal pigment epithelium (RPE) and photoreceptor (PR) cells. Despite advancements, current therapies have not substantially arrested disease progression. Cell replacement therapy using healthy RPE and PR cells holds promise but faces obstacles such as poor cell survival, inadequate integration, and transplantation difficulties. To address these issues, tissue engineering combined with 3D printing has become a focal point. This study investigates the use of four hydrogels-GelMA, HAMA, AlgMA, and PEGDA-and their various crosslinked combinations for creating hydrogel thin-layer matrices conducive to RPE cell growth. PEGDA/GelMA hydrogel demonstrated optimal support for cell spreading and proliferation, which is not achievable with hydrogels matrices of other formulations. The relationship between the mechanical properties of PEGDA/GelMA hydrogels and cell growth was further refined. PEGDA600-20 hydrogel with a compressive modulus of 1245.07 ± 20.79 kPa was selected based on time-course viability assays, leading to the development of the optimized Fib@PEGDA/GelMA hydrogel exhibited exceptional biocompatibility. Compared to PEGDA/GelMA, CCK-8 assays demonstrated significantly improved relative cell viability at 24 h, 48 h, and 72 h, with increases of 17.73 ± 1.22%, 14.54 ± 3.63%, and 19.04 ± 2.31%, respectively on Fib@PEGDA/GelMA matrix. qRT-PCR results indicated a mitigation of epithelial-mesenchymal transition (EMT), as evidenced by downregulation of EMT markers (CDH2, COL1A1, and FN1), accompanied by reduced IL-6 levels. Fib@PEGDA/GelMA hydrogel enhanced phagocytic activity in ARPE-19 cells and promoted functional expression in hiPSC-RPEs. Additionally, the hydrogel showed favorablein vivobiocompatibility following subcutaneous implantation of RCS rats at 1, 2, and 4 weeks post-implantation evidenced by HE and Masson's staining. This system offers a promising bioink for 3D-printed retinal cell scaffolds and paves the way for future advancements in cell replacement therapies for retinal degenerative diseases.}, }
@article {pmid40409801, year = {2025}, author = {García, DM}, title = {Retinal physiology in metabolic syndrome.}, journal = {Advances in genetics}, volume = {113}, number = {}, pages = {76-101}, doi = {10.1016/bs.adgen.2024.11.002}, pmid = {40409801}, issn = {0065-2660}, mesh = {Humans ; *Metabolic Syndrome/physiopathology/complications/metabolism/pathology ; *Retina/physiopathology/metabolism/pathology ; *Diabetic Retinopathy/physiopathology/pathology/metabolism ; *Obesity/complications/physiopathology/metabolism ; Oxidative Stress ; Insulin Resistance ; Animals ; Glaucoma ; }, abstract = {Obesity is increasingly recognized not only for its systemic health impacts but also for its association with visual defects and eye diseases. This chapter explores the relationship between obesity and ocular health, highlighting the mechanisms by which metabolic dysregulation influences visual outcomes. Obesity exacerbates risk factors such as hypertension, dyslipidemia, and insulin resistance, which compromise retinal and optic nerve health. Conditions like diabetic retinopathy, age-related macular degeneration, and glaucoma are discussed in the context of obesity-related inflammation, oxidative stress, and altered vascular function, focusing on the retina as one of the body's most metabolically demanding tissues. Key pathways include adipose-derived cytokines that disrupt retinal homeostasis, and the effects of insulin resistance on retinal cells and vasculature. Furthermore, this chapter covers emerging evidence on the advances of genetic factors linking diabetic retinopathy to retinal impairments. By elucidating these interactions, we aim to provide insight into preventive and therapeutic strategies that could mitigate vision loss among individuals with obesity.}, }
@article {pmid40409921, year = {2025}, author = {Taylor, DJ and Enoch, J and Jones, L and Higgins, B and Binns, A and Crabb, DP}, title = {An overview of quality of life and visual outcomes in AMD.}, journal = {Progress in brain research}, volume = {292}, number = {}, pages = {203-229}, doi = {10.1016/bs.pbr.2025.03.007}, pmid = {40409921}, issn = {1875-7855}, mesh = {Humans ; *Quality of Life/psychology ; *Macular Degeneration/psychology/physiopathology/complications ; *Visual Acuity/physiology ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in high income countries and third most common cause of blindness worldwide. This chapter provides an overview of existing literature pertaining to the ways in which AMD impacts clinical measures of visual function, quality of life, and performance of everyday tasks. As well as being used in clinics, some of the tests described in this chapter have the potential to be piloted in patients' homes as self-monitoring tools, or as patient-centred outcome measures in clinical trials for new treatments in AMD. Moreover, the research findings reported in this literature review should help clinicians with patient management and expectations, and should to inform future patient, public and professional education on AMD.}, }
@article {pmid40410947, year = {2025}, author = {Cleveland, SD and Baker, MJ and Erdman, AG and Nazari, H}, title = {Current and future directions for the use of handheld fundus cameras in telehealth.}, journal = {Expert review of medical devices}, volume = {22}, number = {7}, pages = {657-665}, doi = {10.1080/17434440.2025.2508877}, pmid = {40410947}, issn = {1745-2422}, mesh = {Humans ; *Telemedicine/instrumentation ; *Fundus Oculi ; Artificial Intelligence ; *Photography/instrumentation ; *Retinal Diseases/diagnosis/diagnostic imaging ; Machine Learning ; }, abstract = {INTRODUCTION: A shortage of trained retinal specialists has created a growing need for a telehealth retinal screening alternative. Recent developments in handheld fundus cameras, enhanced by artificial intelligence (AI) and machine learning (ML) methods, have created a promising avenue to satisfy the unmet need for efficient retinal disease screening. This paper discusses the state of current handheld fundus cameras as well as promising future directions.<br><br>AREAS COVERED: Commercially available handheld fundus cameras and the current and future developments in telehealth retinal screenings using these cameras are discussed. Relevant literature encompassing handheld fundus cameras, diagnostic accuracy, and AI in grading were included. Commercial handheld fundus cameras were targeted in the literature and from their company websites. Additional information was obtained through dialogs with company representatives.<br><br>EXPERT OPINION: Handheld fundus cameras utilized for telehealth retinal screening have shown success in multiple small-scale studies. To make their usage more widespread, multiple technical, technological, and methodical barriers must be addressed. This can be accomplished by improving the technology, utilizing AI, and developing telehealth guidelines.}, }
@article {pmid40411432, year = {2025}, author = {Spooner, K and Broadhead, G and Fraser-Bell, S and Hong, T and Wong, JG and Chang, AA}, title = {Real-World 10-Year Outcomes of Anti-VEGF Therapy for Neovascular Age-Related Macular Degeneration: A Meta-Analysis.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {53}, number = {7}, pages = {773-790}, pmid = {40411432}, issn = {1442-9071}, mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity/physiology ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Bevacizumab/therapeutic use ; Treatment Outcome ; Ranibizumab/therapeutic use ; }, abstract = {BACKGROUND: This study examines the long-term effectiveness of anti-VEGF therapy in managing neovascular age-related macular degeneration (nAMD). Despite the well-established short-term improvements of anti-VEGF therapy, there is limited data on its continued efficacy over extended periods. This meta-analysis synthesises real-world data to evaluate anti-VEGF therapy's long-term outcomes systematically.<br><br>METHODS: We conducted a comprehensive literature review across PubMed, EMBASE and Cochrane databases, focusing on studies that reported outcomes of anti-VEGF treatment for nAMD over a decade. The analysis included pooling baseline patient characteristics, study designs, sample sizes and changes in visual acuity (VA) over 10&#x2009;years.<br><br>RESULTS: Our search produced 12 observational studies encompassing 7509 eyes, with 1274 completing 10-years of follow-up. The most substantial improvement in VA was observed in the first year following the initiation of anti-VEGF therapy. On average, there was a decline of 8.11 letters in VA after 10&#x2009;years from baseline (95% CI -10.83 to -5.39, p&#x2009;<&#x2009;0.01). In some cases, VA reverted to baseline levels after 10&#x2009;years; in others, it declined significantly below baseline. Meta-regression showed that mean VA change was greater in those with a lower baseline VA and those treated with a higher number of injections over 10-years(p&#x2009;<&#x2009;0.01).<br><br>CONCLUSION: Our findings suggest that the mean visual acuity of eyes treated for nAMD deteriorates progressively over the long-term from&#xa0;two&#x2009;years after starting treatment. Regular injections appear crucial for preserving maximum vision. While our analysis did not identify an increased incidence of serious ocular adverse events, the long-term impact of anti-VEGF therapy on geographic atrophy remains unclear and warrants further investigation.}, }
@article {pmid40411685, year = {2025}, author = {Peng, M and Zeng, Q and Zheng, W and Xia, X}, title = {Peripheral Choroid/RPE/Sclera as a Shared Pathogenic Hub: Multi-Tissue Transcriptomic Profiling Identifies Common Differentially Expressed Genes in Age-Related Macular Degeneration and Alzheimer's Disease.}, journal = {Molecular neurobiology}, volume = {62}, number = {10}, pages = {12426-12444}, pmid = {40411685}, issn = {1559-1182}, support = {20200757//Research Program of Hunan Provincial Health Commission, China/ ; 2021JJ30397//the Hunan Natural Science Foundation Project, China/ ; 2020SK2119//the Hunan Provincial Science and Technology Department Focuses on Research and Development, China/ ; 81974134//National Natural Science Foundation of China/ ; 2020YFC2008205//National Key Research and Development Program of China/ ; }, mesh = {*Alzheimer Disease/genetics/pathology ; *Macular Degeneration/genetics/pathology ; *Gene Expression Profiling/methods ; Animals ; *Choroid/metabolism/pathology ; *Retinal Pigment Epithelium/metabolism/pathology ; Mice ; Protein Interaction Maps/genetics ; Humans ; *Transcriptome/genetics ; Gene Regulatory Networks ; Gene Expression Regulation ; Gene Ontology ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) and Alzheimer's disease (AD), two prevalent neurodegenerative disorders, share overlapping pathophysiological features yet lack cross-disease therapeutic strategies. This study systematically investigates their parallel genes and shared molecular mechanisms to identify potential therapeutic targets for dry AMD, a condition with limited treatment options.<br><br>METHODS: Transcriptomic datasets for AMD (GSE155154) and AD (GSE95587) were retrieved from the GEO database. AMD tissues were stratified into four subgroups: macular retina (MR), macular choroid/RPE/sclera (MCRS), peripheral retina (PR), and peripheral choroid/RPE/sclera (PCRS). Common differentially expressed genes (DEGs) were identified and analyzed via functional enrichment (GO, KEGG), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) networks. Drug-gene interactions and competing endogenous RNA (ceRNA) networks were constructed to prioritize therapeutic targets. Key hub genes were experimentally validated in a sodium iodate-induced AMD murine model using RT-qPCR.<br><br>RESULTS: Comparative analysis revealed 89, 56, 4, and 130 common DEGs between AD and MR, MCRS, PR, and PCRS subgroups, respectively. Neuroactive ligand-receptor interactions were prioritized in MR/MCRS-AD analyses, while extracellular matrix organization emerged as the dominant pathway in PCRS-AD comparisons. GSEA identified conserved the TNF&#x3b1; signaling pathway via NF-&#x3ba;B across both diseases. PCRS exhibited consistent expression trends for shared genes and pathways with AD. Computational screening prioritized seven druggable targets (COL1A1, COL1A2, COL3A1, MMP2, MMP9, VCAN, ITGA5) with dual therapeutic potential, along with a reconstructed circRNA (circRNA_002179)-miRNA (miR-124)-mRNA (VCAN) regulatory axis. Experimental validation in a sodium iodate-induced AMD murine model confirmed region-specific dysregulation: hub genes were significantly downregulated in MCRS but upregulated in PCRS.<br><br>CONCLUSIONS: Our study delineates both convergent and divergent molecular landscapes of AMD and AD, with PCRS emerging as a critical locus for shared pathophysiology. These findings bridge a critical gap in understanding AMD-AD comorbidity, offering actionable strategies for targeted drug development.}, }
@article {pmid40412129, year = {2025}, author = {Zhu, M and Wu, M and Yang, A and Tu, Y and Sun, C and Na, Y and Zhang, Y and Wang, Y and Su, H and Liu, X}, title = {(+)-a-Longipinene alleviates murine laser-induced choroidal neovascularization: Evidence from in vivo and in vitro experiments.}, journal = {International immunopharmacology}, volume = {159}, number = {}, pages = {114913}, doi = {10.1016/j.intimp.2025.114913}, pmid = {40412129}, issn = {1878-1705}, mesh = {Animals ; *Choroidal Neovascularization/drug therapy/etiology/pathology ; Humans ; Mice ; *Endothelial Cells/drug effects ; Lasers/adverse effects ; Mice, Inbred C57BL ; Fibroblast Growth Factor 2/metabolism ; Male ; Cells, Cultured ; Disease Models, Animal ; Signal Transduction/drug effects ; *Angiogenesis Inhibitors/therapeutic use/pharmacology ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Cell Proliferation/drug effects ; Cell Movement/drug effects ; Choroid/pathology/drug effects ; }, abstract = {Choroidal neovascularization (CNV) is a progressive, degenerative pathological change. CNV can lead to severe vision loss, even blindness. (+)-a-Longipinene (LON) is an essential oil isolated from Pinus koraiensis and Hypericum. It plays anti-inflammatory and anti-angiogenic roles. Here, we attempted to identify the role and mechanism of action of (+)-a-LON in a murine model of laser-induced CNV as well as in vitro in hypoxic human choroidal endothelial cells (HCECs). (+)-a-LON alleviated the formation of laser-induced CNV in mice without causing ocular and systemic toxicity. Moreover, (+)-a-LON inhibited the production of fibroblast growth factor 2 (FGF2) in hypoxic human HCECs by downregulating the M3 muscarinic acetylcholine receptor (M3 mAchR)/diacylglycerol (DAG)/protein kinase C alpha (PKCα)/E1A-binding protein P300 (EP300) pathway. Notably, (+)-a-LON inhibited the hypoxia-induced proliferation, migration, and tube formation of HCECs and also suppressed inflammatory responses in the cells by downregulating the M3 mAchR/DAG/PKCα/EP300/FGF2 pathway. Briefly, (+)-a-LON attenuated the symptoms of CNV possibly by blocking the M3 mAchR/DAG/PKCα/EP300/FGF2 pathway in CECs.}, }
@article {pmid40414338, year = {2025}, author = {Hussain, W and Jiang, ZL and Liu, Y and Wang, JY and Yasoob, TB and Hussain, SA and Laila, UE and Wu, DD and Ji, XY and Dang, YL}, title = {PEST-containing nuclear protein in eye health and disease: A review.}, journal = {Experimental eye research}, volume = {258}, number = {}, pages = {110451}, doi = {10.1016/j.exer.2025.110451}, pmid = {40414338}, issn = {1096-0007}, mesh = {Humans ; *Eye Diseases/metabolism/genetics ; *Nuclear Proteins/physiology/metabolism ; Animals ; }, abstract = {The human visual system plays a crucial role in how we perceive the world. However, it is susceptible to ocular conditions that can result in visual impairments. Globally, over 2.2 billion people suffer from vision impairments, including macular degeneration, refractive errors, cataracts, and glaucoma. In the field of iridology and ocular biology, essential proteins governing ocular homeostasis are frequently mutated or dysregulated. Clear vision is essential for people, and mutations related to these proteins can significantly impact the prevalence and progression of eye disorders. This review discusses proteins linked to ocular disorders, including the nuclear protein Ras, the human ER1 protein, and the PEST-containing nuclear protein (PCNP). Identifying and studying potential therapeutic targets and strategies to regulate these proteins is crucial for minimizing the burden of eye disorders. PCNP has been specifically linked to the development of several eye disorders. An understanding of these molecular processes will facilitate the development of clinical strategies to treat ocular disorders effectively. The main focus of this review is PCNP because of its significant role in the pathophysiology of eye disorders. Dysregulation of this protein has been linked to several ocular diseases, highlighting the need to clarify its functions. A comprehensive understanding of these essential proteins is vital for developing effective treatments and preventive measures against ocular pathologies. This review aims to advance global research, treatment, and management of preventable blindness and vision impairment by exploring strategies to target and regulate these potential therapeutic candidates.}, }
@article {pmid40417242, year = {2025}, author = {Arunachalam, T and Abraham, M and Orndahl, C and Menezes, S and Mukherjee, S and Duic, C and Prasad, M and Siddig, F and Bellur, S and Thavikulwat, AT and Bailey, C and Sadda, SR and Wong, WT and Chew, EY and Jeffrey, BG and Keenan, TDL}, title = {Longitudinal Analysis of Mesopic Microperimetry in a Phase II Trial Evaluating Minocycline for Geographic Atrophy.}, journal = {Ophthalmology science}, volume = {5}, number = {5}, pages = {100783}, pmid = {40417242}, issn = {2666-9145}, abstract = {PURPOSE: To analyze mesopic microperimetry data from a recent phase II trial of minocycline for geographic atrophy (GA) for possible efficacy on the change in visual function and, in the absence of efficacy, to perform longitudinal analyses as a natural history study.<br><br>DESIGN: Phase II, prospective, single-arm, nonrandomized trial. After a 9-month run-in phase, participants began oral minocycline 100&#xa0;mg twice daily for 3&#xa0;years.<br><br>PARTICIPANTS: Individuals with GA in &#x2265;1 eye.<br><br>METHODS: Participants underwent mesopic microperimetry at baseline, month 3, and every 6&#xa0;months thereafter, using a custom T-shaped test pattern. Rates of change in microperimetry parameters were compared between the 24-month treatment phase and 9-month run-in phase by linear spline regression.<br><br>MAIN OUTCOME MEASURES: The mean macular and responding sensitivity; the mean perilesional and extralesional sensitivity; number of absolute and relative scotomatous loci.<br><br>RESULTS: Thirty study eyes from 30 participants (mean age 74.1 years) underwent microperimetry (mean follow-up 27.4 months). For 5 of the 6 microperimetry parameters, no significant difference in the rate of change between the treatment and run-in phases was observed. The difference between the 2 phases was&#xa0;-0.74&#xa0;decibels (dB)/year (standard error [SE] 0.85; P&#xa0;=&#xa0;0.39) for mean macular sensitivity,&#xa0;-0.30&#xa0;dB/year (SE 0.85; P&#xa0;=&#xa0;0.72) for mean responding sensitivity, 1.23&#xa0;dB/year (SE 1.01; P&#xa0;=&#xa0;0.22) for mean perilesional sensitivity, and&#xa0;-0.02 (SE 0.01; P&#xa0;=&#xa0;0.31) for transformed mean extralesional sensitivity. The difference in incidence rate ratios between the 2 phases was 1.17 (SE 0.11; P&#xa0;=&#xa0;0.14) for absolute scotomatous loci and 0.73 (SE 0.11; P&#xa0;=&#xa0;0.004) for relative scotomatous loci.<br><br>CONCLUSIONS: The results do not appear consistent with a clinically meaningful effect of minocycline on the rate of visual function decline from GA progression. This is consistent with previous analyses of the corresponding structural data. The findings demonstrate the advantages and disadvantages of different microperimetry parameters. The optimal testing patterns and parameters represent a trade-off between greater sensitivity vs. greater risk of floor/ceiling effects, with regional averages providing a useful compromise. The results may provide insights to guide the development of microperimetry end points for clinical trials.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40417263, year = {2025}, author = {Marks, E and Anugu, A and Bisiani, J and Pentyala, S}, title = {Stem cell therapy as treatment for Stargardt disease.}, journal = {Therapeutic advances in ophthalmology}, volume = {17}, number = {}, pages = {25158414251320592}, pmid = {40417263}, issn = {2515-8414}, abstract = {Stargardt disease or Juvenile Macular Degeneration is a rare genetic disorder caused by a mutation in the ABCA4 gene that results in degeneration of the macula and loss of central vision. The mutation in the ABCA4 gene causes a build-up of lipofuscin, which is a substance that is left over from the breakdown and absorption of damaged blood cells. This build-up of lipofuscin causes the death of photoreceptor cells and the subsequent degeneration of the macula. Due to the nature of Stargardt's disease, there are currently no cures or treatment options. However, in recent years, there has been an increase in research and exploration of utilizing stem cell therapy as a potential cure and treatment for Stargardt disease. Growing research in the field of ophthalmology has found that the use of stem cells can potentially replace the loss of photoreceptor cells, slow the progression of the degeneration of vision, and be a potential new treatment option for Stargardt disease.}, }
@article {pmid40417310, year = {2025}, author = {Shi, D and Ning, Z and Zhang, Y and Guo, X and Wei, Y and Liu, M}, title = {Research Trends in Vascular Aging in the Last Decade: A Comprehensive Bibliometric Analysis.}, journal = {Vascular health and risk management}, volume = {21}, number = {}, pages = {411-423}, pmid = {40417310}, issn = {1178-2048}, mesh = {Humans ; Bibliometrics ; *Biomedical Research/trends ; *Aging/pathology/metabolism ; Time Factors ; Periodicals as Topic/trends ; Age Factors ; Animals ; *Blood Vessels/pathology/physiopathology/metabolism ; *Vascular Diseases/physiopathology/metabolism/pathology ; }, abstract = {BACKGROUND: In recent years, vascular aging has emerged as a hot topic in become an important direction of aging research, but a comprehensive bibliometric analysis has not been conducted.<br><br>METHODS: The Web of Science database was searched for articles and reviews on vascular aging from January 1, 2014, to August 20, 2024, and the literature was analyzed and knowledge maps were constructed using CiteSpace, VOSviewer, pajek and Scimago Graphica software for econometric analysis and knowledge graph construction of the literature.<br><br>RESULTS: A total of 38,910 authors from 7622 institutions in 111 countries published 7277 papers in 1344 academic journals, with a significant increase in publication volume. The United States is the country with the highest productivity and citation rates, and Mayo Clinic is the most active institution. Tarantini S published the most papers, while Csiszar A received the most citations. Retina-The Journal of Retinal and Vitreous Diseases journal published the most papers, and Circulation journal received the most citations. The main research aspects include age-related macular degeneration, arteriosclerosis, and oxidative stress, which are the main keywords in this field. In the last decade, the term c reactive protein has attracted great attention with its strongest citation explosion.<br><br>CONCLUSION: In the past decade, the research focus on vascular aging has been increasing year by year. Age-related macular degeneration, arteriosclerosis, oxidative stress and vascular endothelial cells are the emerging research directions in this field.}, }
@article {pmid40419209, year = {2025}, author = {Jones, A and Sun, A and Yang, H and Latuszek, A and Negron, N and Shi, P and Fury, W and Lehmann, GL and Hu, Y and Sagdullaev, B}, title = {Differential analysis of core complement components expression and localization across rodent, non-human primate, and human ocular tissues.}, journal = {Experimental eye research}, volume = {258}, number = {}, pages = {110433}, doi = {10.1016/j.exer.2025.110433}, pmid = {40419209}, issn = {1096-0007}, mesh = {Animals ; Humans ; *Complement C3/genetics/metabolism ; *Complement Factor H/metabolism/genetics ; *Choroid/metabolism ; *Retinal Pigment Epithelium/metabolism ; Disease Models, Animal ; Rats ; *Macular Degeneration/metabolism/genetics ; Mice ; Immunohistochemistry ; *Complement C5/genetics/metabolism ; *Complement System Proteins/genetics/metabolism ; Primates ; Macaca fascicularis ; *Gene Expression Regulation/physiology ; Macaca mulatta ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness. Genetic and pathophysiological studies have implicated that complement pathway dysfunction is a key contributor to progressive vision loss in AMD. Though the association between complement and AMD is recognized, numerous anti-complement therapeutics that had been tested in rodent model systems had limited success in clinical trials. Understanding complement factor production and site of action in ocular pathophysiology is critical for the development of efficacious therapeutics. However, our limited understanding of how these aspects of complement biology vary across species restricts our ability to predict clinical outcomes from studies using animal models. Here, we integrated transcriptomic and immunohistochemical assays to understand the expression and localization of core complement components (complement factor H (FH), complement 3 (C3), and complement 5 (C5)) between ocular tissues of rodent, non-human primate, and human species. We found that complement distribution varied significantly across the studied species, with the most striking differences observed in the FH. While rodents expressed Cfh, an alternative pathway inhibitor, mainly in the RPE, CFH expression in primate eyes was primarily confined to the choroid. These differences were consistent at the protein level, with rodent FH localized in the RPE and primate FH within the choriocapillaris, choroid and sclera. Regarding C5, a terminal complement pathway component, we observed minimal ocular mRNA levels in all three species. However, we observed detectable protein levels in the RPE in rodents and the choroid in humans. Next, C3 mRNA transcripts and C3 protein exhibited similar distribution in the choroid in both rodent and primate eyes. Together, our findings highlight key differences and similarities between rodent and primate complement biology that may offer insights into the translatability of animal models and inform the design of effective therapeutics.}, }
@article {pmid40419664, year = {2025}, author = {Vats, A and Xi, Y and Wolf-Johnston, AS and Clinger, OD and Arbuckle, RK and Sheng, L and Jiang, X and Dermond, CD and Li, J and Stolz, DB and St Leger, AJ and Sahel, JA and Jackson, EK and Birder, LA and Chen, Y}, title = {Oral 8-aminoguanine against age-related retinal degeneration.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {812}, pmid = {40419664}, issn = {2399-3642}, support = {R01 AG056944/AG/NIA NIH HHS/United States ; R01 EY033049/EY/NEI NIH HHS/United States ; R01DK135076//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; R01 EY026891/EY/NEI NIH HHS/United States ; R01 DK135076/DK/NIDDK NIH HHS/United States ; R01 EY030991/EY/NEI NIH HHS/United States ; R01EY026891//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01 EY032482/EY/NEI NIH HHS/United States ; R01EY032482//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01AG056944//U.S. Department of Health &amp; Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; Unrestricted grant//Research to Prevent Blindness (RPB)/ ; U01 EY034711/EY/NEI NIH HHS/United States ; R01EY030991//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; S10 RR019003/RR/NCRR NIH HHS/United States ; R01EY033049//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01HL109002//U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01EY034711//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01 CA256068/CA/NCI NIH HHS/United States ; P30EY08098//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; 1S10RR019003//U.S. Department of Health &amp; Human Services | NIH | National Center for Research Resources (NCRR)/ ; R01 HL109002/HL/NHLBI NIH HHS/United States ; Medical Student Eye Research Fellowship//Research to Prevent Blindness (RPB)/ ; P30 EY008098/EY/NEI NIH HHS/United States ; R01CA256068//U.S. Department of Health &amp; Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics)/ ; }, mesh = {Animals ; Rats, Inbred F344 ; Administration, Oral ; *Guanine/analogs &amp; derivatives/administration &amp; dosage/pharmacology ; Rats ; *Retinal Degeneration/drug therapy/pathology ; Retina/drug effects/pathology ; *Aging/drug effects ; Male ; Disease Models, Animal ; Apoptosis/drug effects ; Oxidative Stress/drug effects ; }, abstract = {Vision decline in the elderly, often due to retinal aging, predisposes individuals to pathologies like age-related macular degeneration. Currently, there are few effective oral treatments for this condition. Our study introduces an oral agent, 8-aminoguanine (8-AG), which targets age-related retinal degeneration using an aged Fischer 344 rat model. When administered in drinking water at a low dose for 8 weeks starting at 22 months of age, 8-AG significantly preserves retinal structure and function, as evidenced by increased retinal thickness, enhanced photoreceptor integrity, and improved electroretinogram responses. 8-AG reduces apoptosis, oxidative damage, and microglial/macrophage activation in aging retinae. 8-AG also mitigates retinal inflammation at transcriptional and cytokine levels. Extending treatment to 17 weeks further amplifies these protective effects. Given its efficacy in various disease models, 8-AG shows great promise as an anti-aging compound with the potential to mitigate common hallmarks of aging.}, }
@article {pmid40419840, year = {2025}, author = {Hu, W and Tu, Y and Tan, J and Lin, Y and Wang, Y and Zhou, Q}, title = {Global research trends on endoplasmic reticulum stress in retinal diseases from 2000 to 2024.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {210}, pmid = {40419840}, issn = {1573-2630}, support = {82260211 and 81460092//National Natural Science Foundation of China/ ; 20211ZDG02003//Central Government Guides Local Science and Technology Development Foundation/ ; 20203BBG73058 and 20192BBGL70033//Key research and development project in Jiangxi Province/ ; 2020A0166//Chinese medicine science and technology project in Jiangxi province/ ; }, mesh = {Humans ; *Retinal Diseases/metabolism ; *Endoplasmic Reticulum Stress/physiology ; *Biomedical Research/trends ; Bibliometrics ; }, abstract = {PURPOSE: To comprehensively explore global research trends on endoplasmic reticulum stress (ERS) in retinal diseases over the past 24 years.<br><br>METHODS: An analysis of 917 publications from the Web of Science Core Collection, spanning from 1 January 2000 to 15 April 2024, was conducted to explore ERS research in retinal diseases. Bibliometric and visualisation software was employed to identify key contributors and research trends.<br><br>RESULTS: Hideaki Hara and Sarah X. Zhang were identified as the most published and most cited authors, respectively. The United States led in both publications and citations. Sun Yat-sen University ranked highest in publications, while the University of Oklahoma received the most citations. Investigative Ophthalmology &amp; Visual Science was the leading journal in both publications and citations. A total of 108 of the 1385 author keywords, each occurring five or more times, clustered into four major themes: retinal photoreceptor degeneration, glaucoma and optic nerve damage, diabetic retinopathy and age-related macular degeneration. Keywords such as "in vivo", "dominant retinitis pigmentosa", "endothelial growth factor", "molecular", and "quality control" displayed the strongest citation bursts. ERS research (2000&#x2009;~&#x2009;2024) has evolved from retinal neuroprotection to include specific cell types and diseases, explored signalling pathways and therapeutic mechanisms, and more recently has focused on molecular insights and gene therapy applications.<br><br>CONCLUSION: This bibliometric analysis highlighted significant growth in publications on ERS in retinal diseases, reflecting an increasing scholarly focus. ERS represents a potential target for exploring pathological changes in retinal neuro-microvascular and related disorders, warranting further investigation.}, }
@article {pmid40423060, year = {2025}, author = {Löw, K and Sitnilska, V and Tang, Y and Lammert, JQ and Krohne, TU and Altay, L}, title = {Real-Life Treatment Intervals and Morphological Outcomes Following the Switch to Faricimab Therapy in Neovascular Age-Related Macular Degeneration.}, journal = {Journal of personalized medicine}, volume = {15}, number = {5}, pages = {}, pmid = {40423060}, issn = {2075-4426}, abstract = {Objectives: To evaluate the efficacy of faricimab in patients with neovascular age-related macular degeneration (nAMD) that did not respond to other VEGF inhibitors. Methods: This retrospective study included the eyes of patients diagnosed with nAMD who had been switched to faricimab treatment due to the persistence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), despite monthly anti-VEGF treatment with aflibercept, bevacizumab, or ranibizumab using the treat and extend regimen, and who had received at least three faricimab injections following the switch. Best-corrected visual acuity (BCVA) measurement and optical coherence tomography (OCT) analysis were performed at each visit, and the OCT results were graded by two independent readers. Results: We included 41 eyes of 39 patients (21 male, 18 female) with a mean age of 80.5 ± 8.1 years. The median duration of anti-VEGF treatment prior to the switch to faricimab was 5.0 years, with a median of 53 injections. Complete resolution of IRF and SRF was observed after the first dose of faricimab in 12 eyes (29.3%) and after the third dose in 15 eyes (36.6%). Twenty-eight eyes reached a follow-up time after a switch of at least 12 months, with a median of 10 faricimab injections. Of these 28 eyes, 10 eyes (35.7%) exhibited complete IRF/SRF resolution; treatment intervals were extended beyond 4 weeks in 21 eyes (80.7%), and 8 eyes (28.6%) presented complete IRF/SRF resolution under extended treatment intervals at month 12. Central retinal thickness after 12 months was reduced from a median of 368.0 µm to 297.5 µm (p < 0.001), and the BCVA remained stable (p = 0.057). No adverse events were reported throughout the entire treatment period. Conclusions: In nAMD patients with poor anti-VEGF treatment response, complete and fast fluid resolution and the extension of treatment intervals can be reached by switching to faricimab, even after years of prior unsuccessful therapy.}, }
@article {pmid40423616, year = {2025}, author = {Ollila, T and Joshi, A and Kulathinal, S and Immonen, I}, title = {Area Under the Curve Analysis in a Real-World Cohort of Finnish Patients Treated for Neovascular Age-Related Macular Degeneration.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {5}, pages = {23}, pmid = {40423616}, issn = {2164-2591}, mesh = {Humans ; Male ; Female ; Aged ; *Visual Acuity/physiology ; *Area Under Curve ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Finland ; Tomography, Optical Coherence ; *Wet Macular Degeneration/drug therapy/physiopathology ; Aged, 80 and over ; *Ranibizumab/therapeutic use/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Middle Aged ; Cohort Studies ; }, abstract = {PURPOSE: The purpose of this study was to explore the area under the curve (AUC) measures from visual acuity (VA) trajectories in describing outcomes for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: AUC analysis on 93 patients with nAMD was performed using VA trajectories up to 12&#xa0;months for the purpose of illustration. The broken stick model was first used to interpolate VA trajectories at prespecified times from uneven timepoints over the 4 year period. The AUC measures used were: general VA (AUCG; the area above 20 Early Treatment Diabetic Retinopathy Study [ETDRS] letters), change from baseline (AUCI), and adjusted AUC (Adj AUC) to adjust the change from baseline with respect to the ceiling (85 letters) and the ground (20 letters). We studied how AUC ranking of outcomes differed from VA change from baseline and how AUC-derived parameters correlated with known prognostic factors, such as baseline VA, and optical coherence tomography findings at baseline and during treatment.<br><br>RESULTS: Median AUCIs in ascending quartiles of baseline VA were 88, 116, 38, and 10, respectively. The corresponding Adj AUCs were 0.12, 0.28, 0.13 and 0.29 (scale -1 to +1), suggesting a compensation for the ceiling effect. Median AUCIs in patients with baseline intraretinal, intraretinal + subretinal, or subretinal fluid were 40, 50, or 59, respectively. The corresponding Adj AUCIs were 0.14, 0.19, and 0.23, both showing the expected response to baseline fluid status.<br><br>CONCLUSIONS: Using the measures described here, modifiers of VA change and different anti-vascular endothelial growth factor (VEGF) treatment protocols can be compared from only one to three of the AUC values even in materials with uneven evaluation points.<br><br>TRANSLATIONAL RELEVANCE: AUC-based analysis provides new tools to evaluate the effectiveness of nAMD treatment.}, }
@article {pmid40424622, year = {2025}, author = {Bedell, HE}, title = {Letter to the editor: The photochromatic interval in age-related macular degeneration.}, journal = {Optometry and vision science : official publication of the American Academy of Optometry}, volume = {102}, number = {7}, pages = {472-474}, doi = {10.1097/OPX.0000000000002266}, pmid = {40424622}, issn = {1538-9235}, support = {T35 EY07088/EY/NEI NIH HHS/United States ; P30 EY07551/EY/NEI NIH HHS/United States ; T35 EY07088/EY/NEI NIH HHS/United States ; P30 EY07551/EY/NEI NIH HHS/United States ; }, }
@article {pmid40425125, year = {2025}, author = {Kah, TA}, title = {A Bayesian approach to investigating presumed retinal micro(nano)plastics.}, journal = {Bio Systems}, volume = {253}, number = {}, pages = {105502}, doi = {10.1016/j.biosystems.2025.105502}, pmid = {40425125}, issn = {1872-8324}, mesh = {Bayes Theorem ; Humans ; *Retina/pathology/diagnostic imaging ; Tomography, Optical Coherence/methods ; Retinal Diseases ; }, abstract = {The human retina, a highly vascularized, metabolically active, and immunologically privileged neural tissue, stands in contrast to the ubiquity of micro(nano)plastics (MNPs), which have been reported in every other organ system. Despite this, the presence of MNPs in the retina remains undocumented, a critical gap given their potential to contribute to local inflammation, microvascular occlusion, or act as cofactors in diseases such as diabetic retinopathy, age-related macular degeneration, or uveitis. Furthermore, the diverse physicochemical properties of MNPs - including their varying sizes, shapes, colors, and optical characteristics - raise the intriguing possibility that their presence within the retina could mimic commonly observed ophthalmic features. I hypothesize that certain features-previously attributed to other causes-such as tiny discrete foci in fundus photography and hyperreflective retinal foci in optical coherence tomography, may actually contain MNPs. This hypothesis carries significant biological implications not only for ophthalmology but also for environmental toxicology and public health. To formally evaluate its plausibility, I constructed a Bayesian model incorporating initial skepticism and considering varying likelihoods of observed evidence under both null and alternative assumptions. The model demonstrates that even with an extremely low prior probability, the reproducibility and discernible patterns of certain imaging findings can justify a significantly increased posterior belief, thus warranting further scientific inquiry. This work offers a probabilistic framework to re-evaluate retinal anomalies and encourages empirical investigation in environmental ophthalmology, without definitively proving MNP presence. The development of retinal imaging techniques for the specific detection of MNPs could provide a valuable tool for environmental toxicology, preventive medicine, and public health by offering a non-invasive biomarker for systemic MNPs exposure.}, }
@article {pmid40426994, year = {2025}, author = {Arthur, P and Kandoi, S and Kalvala, A and Boirie, B and Nathani, A and Aare, M and Bhattacharya, S and Kulkarni, T and Sun, L and Lamba, DA and Li, Y and Singh, M}, title = {Cannabidiol-Loaded Retinal Organoid-Derived Extracellular Vesicles Protect Oxidatively Stressed ARPE-19 Cells.}, journal = {Biomedicines}, volume = {13}, number = {5}, pages = {}, pmid = {40426994}, issn = {2227-9059}, support = {R01 NS125016/NS/NINDS NIH HHS/United States ; U54 MD007582/MD/NIMHD NIH HHS/United States ; R16 GM149462/GM/NIGMS NIH HHS/United States ; 5R16GM149462-01//National Institute of Health/ ; G12 MD007582/MD/NIMHD NIH HHS/United States ; R01NS125016/NH/NIH HHS/United States ; }, abstract = {Background/Objectives: Age-related macular degeneration (AMD) is the third leading cause of irreversible blindness in elderly individuals aged over 50 years old. Oxidative stress plays a crucial role in the etiopathogenesis of multifactorial AMD disease. The phospholipid bilayer EVs derived from the culture-conditioned medium of human induced pluripotent stem cell (hiPSC) differentiated retinal organoids aid in cell-to-cell communication, signaling, and extracellular matrix remodeling. The goal of the current study is to establish and evaluate the encapsulation of a hydrophobic compound, cannabidiol (CBD), into retinal organoid-derived extracellular vesicles (EVs) for potential therapeutic use in AMD. Methods: hiPSC-derived retinal organoid EVs were encapsulated with CBD via sonication (CBD-EVs), and structural features were elucidated using atomic force microscopy, nanoparticle tracking analysis, and small/microRNA (miRNA) sequencing. ARPE-19 cells and oxidative-stressed (H2O2) ARPE-19 cells treated with CBD-EVs were assessed for cytotoxicity, apoptosis (MTT assay), reactive oxygen species (DCFDA), and antioxidant proteins (immunohistochemistry and Western blot). Results: Distinct miRNA cargo were identified in early and late retinal organoid-derived EVs, implicating their roles in retinal development, differentiation, and functionality. The therapeutic effects of CBD-loaded EVs on oxidative-stressed ARPE-19 cells showed greater viability, decreased ROS production, downregulated expression of inflammation- and apoptosis-related proteins, and upregulated expression of antioxidants by Western blot and immunocytochemistry. Conclusions: miRNAs are both prognostic and predictive biomarkers and can be a target for developing therapy since they regulate RPE physiology and diseases. Our findings indicate that CBD-EVs could potentially alleviate the course of AMD by activating the targeted proteins linked to the adenosine monophosphate kinase (AMPK) pathway. Implicating the use of CBD-EVs represents a novel frontline to promote long-term abstinence from drugs and pharmacotherapy development in treating AMD.}, }
@article {pmid40427443, year = {2025}, author = {Pu, N and Li, S and Wu, H and Zhao, N and Wang, K and Wei, D and Wang, J and Sha, L and Zhao, Y and Tao, Y and Song, Z}, title = {Beacon of Hope for Age-Related Retinopathy: Antioxidative Mechanisms and Pre-Clinical Trials of Quercetin Therapy.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {5}, pages = {}, pmid = {40427443}, issn = {2076-3921}, support = {221100310200//Science and Technology Major Project of Henan Province/ ; 224200510013//Zhongyuan Science and Technology Leading Talent Project/ ; }, abstract = {Age-related retinopathy is one of the leading causes of visual impairment and irreversible blindness, characterized by progressive neuronal and myelin loss. The damages caused by oxidation contributes to the hallmarks of aging and represents fundamental components in pathological pathways that are thought to drive multiple age-related retinopathies. Quercetin (Que), a natural polyphenol abundant in vegetables, herbs, and fruits, has been extensively studied for its long-term antioxidative effects mediated through diverse mechanisms. Additionally, Que and its derivatives exhibit a broad spectrum of pharmacological characteristics in the cellular responses of age-related retinopathy induced by oxidative stress, including anti-inflammatory, anti-neovascularization, regulatory, and neuroprotective effects in autophagy and apoptosis processes. This review mainly focuses on the antioxidative mechanisms and curative effects of Que treatment for various age-related retinopathies, such as retinitis pigmentosa, diabetic retinopathy, age-related macular degeneration, and glaucoma. Furthermore, we discuss emerging technologies and methods involving Que and its derivatives in the therapeutic strategies for age-related retinopathies, highlighting their promise for clinical translation.}, }
@article {pmid40427478, year = {2025}, author = {Falcão, AS and Pedro, ML and Tenreiro, S and Seabra, MC}, title = {Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {5}, pages = {}, pmid = {40427478}, issn = {2076-3921}, support = {NASCENT HR22-00569//CaixaBank/ ; Research Unit UID/04462 and Associated Laboratory LS4FUTURE (LA/P/0087/2020)//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss in the Western world, and it currently lacks effective therapy. It is believed that AMD initiates in the aged retinal pigment epithelium (RPE), which presents lysosomal dysfunction and oxidative stress (OxS) that ultimately leads to RPE damage and AMD progression. AMD is a complex pathology, so multitarget treatments are required to act on different pathways, presenting several challenges. In this review, we discuss the current knowledge on the pathogenesis of this disease, focusing mainly on lysosomal dysfunction and OxS. Because transcription factors regulate homeostasis, the transcription factor EB (TFEB), which controls lysosomal function and biogenesis, and the nuclear factor erythroid 2-related factor 2 (NRF2), which manages OxS, have been proposed as promising targets for disease intervention. Finally, we discuss the interplay of these pathways for a potential synergistic effect on AMD-targeted therapies, as they could change the course of today's available treatments for AMD.}, }
@article {pmid40428060, year = {2025}, author = {Devine, BC and Dogan, AB and Sobol, WM}, title = {Recent Optical Coherence Tomography (OCT) Innovations for Increased Accessibility and Remote Surveillance.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {40428060}, issn = {2306-5354}, abstract = {Optical Coherence Tomography (OCT) has revolutionized the diagnosis and management of retinal diseases, offering high-resolution, cross-sectional imaging that aids in early detection and continuous monitoring. However, traditional OCT devices are limited to clinical settings and require a technician to operate, which poses accessibility challenges such as a lack of appointment availability, patient and family burden of frequent transportation, and heightened healthcare costs, especially when treatable pathology is undetected. With the increasing global burden of retinal conditions such as age-related macular degeneration (AMD) and diabetic retinopathy, there is a critical need for improved accessibility in the detection of retinal diseases. Advances in biomedical engineering have led to innovations such as portable models, community-based systems, and artificial intelligence-enabled image analysis. The SightSync OCT is a community-based, technician-free device designed to enhance accessibility while ensuring secure data transfer and high-quality imaging (6 × 6 mm resolution, 80,000 A-scans/s). With its compact design and potential for remote interpretation, SightSync widens the possibility for community-based screening for vision-threatening retinal diseases. By integrating innovations in OCT imaging, the future of monitoring for retinal disease can be transformed to reduce barriers to care and improve patient outcomes. This article discusses the evolution of OCT technology, its role in the diagnosis and management of retinal diseases, and how novel engineering solutions like SightSync OCT are transforming accessibility in retinal imaging.}, }
@article {pmid40428094, year = {2025}, author = {Chatzara, A and Maliagkani, E and Mitsopoulou, D and Katsimpris, A and Apostolopoulos, ID and Papageorgiou, E and Georgalas, I}, title = {Artificial Intelligence Approaches for Geographic Atrophy Segmentation: A Systematic Review and Meta-Analysis.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {40428094}, issn = {2306-5354}, abstract = {Geographic atrophy (GA) is a progressive retinal disease associated with late-stage age-related macular degeneration (AMD), a significant cause of visual impairment in senior adults. GA lesion segmentation is important for disease monitoring in clinical trials and routine ophthalmic practice; however, its manual delineation is time-consuming, laborious, and subject to inter-grader variability. The use of artificial intelligence (AI) is rapidly expanding within the medical field and could potentially improve accuracy while reducing the workload by facilitating this task. This systematic review evaluates the performance of AI algorithms for GA segmentation and highlights their key limitations from the literature. Five databases and two registries were searched from inception until 23 March 2024, following the PRISMA methodology. Twenty-four studies met the prespecified eligibility criteria, and fifteen were included in this meta-analysis. The pooled Dice similarity coefficient (DSC) was 0.91 (95% CI 0.88-0.95), signifying a high agreement between the reference standards and model predictions. The risk of bias and reporting quality were assessed using QUADAS-2 and CLAIM tools. This review provides a comprehensive evaluation of AI applications for GA segmentation and identifies areas for improvement. The findings support the potential of AI to enhance clinical workflows and highlight pathways for improved future models that could bridge the gap between research settings and real-world clinical practice.}, }
@article {pmid40428167, year = {2025}, author = {Wang, MH}, title = {Integrating Artificial Intelligence and Precision Therapeutics for Advancing the Diagnosis and Treatment of Age-Related Macular Degeneration.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {40428167}, issn = {2306-5354}, support = {U22A2041, 62372047//National Natural Science Foundation of China/ ; ZDSYS20220422103800001//Shenzhen Key Laboratory of Intelligent Bioinformatics/ ; KQTD20200820113106007//Shenzhen Science and Technology Program/ ; 2024KTSCX226//Characteristic Innovation Project of Ordinary Universities in Guangdong Province/ ; }, abstract = {Age-related macular degeneration (AMD) is a multifactorial retinal disease influenced by complex molecular mechanisms, including genetic susceptibility, inflammation, oxidative stress, and metabolic dysregulation. While substantial progress has been made in understanding its pathogenesis, the full molecular underpinnings of AMD remain unclear, impeding the effectiveness of current therapeutic strategies. This study provides an in-depth exploration of the molecular interactions involved in AMD progression, particularly focusing on genetic predispositions (such as CFH, ARMS2/HTRA1, and APOE), inflammatory pathways (including complement system dysregulation and cytokine responses), lipid metabolism (e.g., cholesterol homeostasis and drusen formation), and angiogenesis (VEGF signaling). Through a systematic review and bibliometric analysis of literature published between 2015 and 2025, the study identifies emerging research trends, existing gaps, and promising future therapeutic directions. It further investigates innovative precision medicine approaches, including gene editing (CRISPR), RNA therapeutics (siRNA, antisense oligonucleotides), immunomodulatory therapies, and nanotechnology-based drug delivery systems. Additionally, the study examines the role of metabolic disorders such as diabetes and dyslipidemia in AMD progression, highlighting the influence of systemic health factors on disease onset. Finally, the potential of artificial intelligence (AI) in enhancing AMD management through biomarker-based risk stratification, predictive modeling, and personalized treatment optimization is assessed. By mapping the intricate molecular networks underlying AMD and evaluating novel therapeutic strategies, this research aims to contribute to the development of more effective, individualized treatment protocols for patients with AMD.}, }
@article {pmid40428724, year = {2025}, author = {Gong, CS}, title = {Advances in Electrode Design and Physiological Considerations for Retinal Implants.}, journal = {Micromachines}, volume = {16}, number = {5}, pages = {}, pmid = {40428724}, issn = {2072-666X}, support = {113-2221-E-008 -117 -MY3//National Science and Technology Council of Taiwan/ ; }, abstract = {Until now, the ultimate solution for blind people has not been achieved, because challenges still exist. Retinal implants have emerged as a promising solution for restoring vision in individuals suffering from retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. Central to the efficacy of these implants is the design and functionality of the electrode arrays responsible for stimulating retinal neurons. This review evaluates the evolution of retinal implants, with particular emphasis on electrode specifications, physiological considerations for electrical stimulation, and recent advancements in electrode design. A comprehensive analysis of state-of-the-art published studies provides a detailed cross-comparison of electrode characteristics, offering insights into current state-of-the-art technologies and future directions.}, }
@article {pmid40429443, year = {2025}, author = {Wolfrum, P and Böhm, EW and König, S and Lorenz, K and Stoffelns, B and Korb, CA}, title = {Safety and Long-Term Efficacy of Intravitreal rtPA, Bevacizumab and SF6 Injection in Patients with Submacular Hemorrhage Secondary to Age-Related Macular Degeneration.}, journal = {Journal of clinical medicine}, volume = {14}, number = {10}, pages = {}, pmid = {40429443}, issn = {2077-0383}, abstract = {Purpose: Acute submacular hemorrhage (SMH) is a vision-threatening complication common in patients affected by age-related macular degeneration (AMD). This study evaluates safety, long-term clinical outcomes and associated treatment factors following intravitreal triple injection of recombinant tissue plasminogen activator (rtPA), SF6 gas, and Bevacizumab due to acute SMH secondary to AMD. Methods: A retrospective analysis on patients who received treatment between January 2014 and December 2020 (n = 37) was conducted. Visual acuity (VA), central retinal thickness (CRT), central retinal volume (CRV), and axial pigment epithelial detachment height were analyzed at baseline (B), 4 weeks after triple injection (FU1), after the following anti-VEGF injection series (FU2), after 1 year (FU3), after 2 years (FU4), and at the final follow-up examination after 4.4 ± 1.6 years (FU5). Further, treatment courses and clinical outcomes were compared to a patient cohort treated for exudative AMD without prior SMH. Furthermore, an explorative data analysis on final VA was conducted, and adverse events following triple therapy were investigated. Results: Triple injection was performed on average 5.6 ± 5.7 days after onset of symptoms. Patients received 16 ± 3 additional intravitreal anti-VEGF injections due to persistent macular edema over the subsequent 2 years. Significant improvements were observed at FU1 in VA (p < 0.001), CRT (p = 0.005), and CRV (p = 0.007), as well as at FU2 in axial PED height (p < 0.001), with all improvements being stable until final follow-up examination. In the group comparison, patients with SMH demonstrated significantly worse functional and anatomical outcomes at 24 months except for the 24-month CRT, and patients on average received more intravitreal injections. Five of 37 patients (13.5%) experienced a retinal pigment epithelial tear following triple injection. Final VA correlated positively and significantly with FU1 VA, while no correlation was observed with baseline VA, the size or height of SMH, or the number of additional anti-VEGF injections. Conclusions: Triple injection constitutes a simple and effective therapy with long-term functional and anatomical improvements following treatment due to SMH, although patients have an increased risk for RPE tears. The 4-week postoperative VA following triple injection was predictive for long-term visual function.}, }
@article {pmid40429992, year = {2025}, author = {Heloterä, H and Kostanek, J and Liukkonen, M and Siintamo, L and Linna-Kuosmanen, S and Watala, C and Blasiak, J and Kaarniranta, K}, title = {Serum RNA Profile Reflects Fluid Status and Atrophic Retinal Changes in Neovascular Age-Related Macular Degeneration.}, journal = {International journal of molecular sciences}, volume = {26}, number = {10}, pages = {}, pmid = {40429992}, issn = {1422-0067}, support = {333302//Academy of Finland/ ; //Sigrid Juselius Foundation/ ; //Finnish Eye Foundation/ ; 5503770//Kuopio University VTR grant/ ; //Aarne Koskelo Foundation/ ; //Finnish Eye and Tissue Bank Foundation/ ; //Mary &amp; Georg C. Ehrnrooth Foundation/ ; }, mesh = {Humans ; Aged ; Female ; Male ; *Macular Degeneration/blood/pathology/genetics ; *Retina/pathology/metabolism ; *RNA/blood ; Tomography, Optical Coherence ; Aged, 80 and over ; Biomarkers/blood ; *Wet Macular Degeneration/blood/genetics/pathology ; }, abstract = {The increasing prevalence of age-related macular degeneration (AMD), a disease that can result in the loss of central vision, is an emerging problem worldwide due to aging societies. Growing patient numbers create a challenge for the healthcare system. Understanding the mechanisms of AMD pathogenesis will aid in early, personalized, and efficient intervention, helping to mitigate this issue. Current diagnostic methods rely on optical coherence tomography and angiography imaging, which identify existing damages, but do not provide information on the mechanisms behind them. In the present work, we demonstrate a difference in the serum RNA profile between neovascular AMD (nAMD) patients and controls. Moreover, the RNA profile of nAMD patients corresponded with anatomical changes in the retinal fluid compartments as well as atrophic changes of the retina. We followed two independent ways to control false positive leads, and when these approaches were combined, thioredoxin-related transmembrane protein 4 (TMX4) was observed to be differentially expressed by both approaches. This finding opens a new pathway in AMD studies, which are limited due to restricted access to live human target material and the limited value of animal models of human AMD.}, }
@article {pmid40430474, year = {2025}, author = {Vailoces, VAS and Tolentino, AJ and Arevalo, JF and Adelman, RA and Bhisitkul, R and Do, DV and Nguyen, QD and Tolentino, MJ and Tanito, M and Serizawa, H}, title = {Development of Rifampicin Eye Drops for the Treatment of Exudative Age-Related Macular Degeneration.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {5}, pages = {}, pmid = {40430474}, issn = {1424-8247}, support = {N/A//AMD Therapeutics LLC/ ; N/A//NeoVascularX, Inc/ ; }, abstract = {Background/Objectives: Exudative age-related macular degeneration (AMD) is a disease of choroidal neovascularization that causes blindness. Current treatments to preserve vision in this prevalent and blinding condition are repeat intraocular injections of anti-vascular endothelial growth factor medicines for a patient's lifetime to preserve and prevent vision loss leading to blindness. Rifampicin, a small-molecule antibiotic, has previously been reported to exhibit anti-angiogenic properties and a topical safety profile that is well-tolerated. Based on this evidence, we investigated the feasibility of formulating rifamycin as an ophthalmic drop capable of delivering therapeutic concentrations to the posterior segment of the eye. Methods: Inhibition of neovascularization by administration of rifampicin was analyzed in the rat oxygen-induced retinopathy (OIR) and mouse laser-induced choroidal neovascularization (CNV) models. Pharmacokinetic (PK) studies were conducted in mice, rats, and rabbits by dosing various formulations containing rifampicin, and the compound was quantified by LC/MS analysis. Results: Results from dose escalation studies in the mouse laser-induced CNV model suggested the minimum effective dose of rifampicin required for inhibiting neovascularization in subretinal tissues to be 0.7 mg/kg, which is substantially lower than the 20 mg/kg dosage approved for infectious disease treatments. The previous studies did not report the minimum effective dose in the anti-angiogenesis effects. The effective area under the concentration-time curve (AUC) in the sub-retina was evaluated as 0.27 h·ng/mg. In rabbits, rifampicin was delivered to the sub-retina by a single topical application of various formulations in a dose-dependent manner. The topical application of the formulations containing 1% rifampicin, which was well-tolerated in clinical trials previously reported for ocular trachoma, achieved subretinal delivery approximately 2-32 times greater than the effective AUC. Plasma exposure of the compound by the topical application was evaluated to range approximately 0.5-10 ng/mL. Conclusions: Rifampicin was delivered to the sub-retina in rabbits with an efficiency greater than the effective dose required for inhibiting neovascularization. Limited amounts of plasma exposure by the topical application were detected. These results suggested the therapeutic potential of the rifampicin formulations for the topical treatment of exudative macular degeneration.}, }
@article {pmid40431274, year = {2025}, author = {Schiavone, N and Isoldi, G and Calcagno, S and Rovida, E and Antiga, E and De Almeida, CV and Lulli, M}, title = {Exploring the Gut Microbiota-Retina Axis: Implications for Health and Disease.}, journal = {Microorganisms}, volume = {13}, number = {5}, pages = {}, pmid = {40431274}, issn = {2076-2607}, abstract = {The gut microbiota represents a rich and adaptive microbial network inhabiting the gastrointestinal tract, performing key functions in nutrient processing, immune response modulation, intestinal wall protection, and microbial defense. Its composition remains highly personalized and responsive to external influences, including lifestyle patterns, physical activity, body composition, and nutritional intake. The interactions of the gut microbiota with bodily systems are conventionally interpreted as broad systemic impacts on organ balance. Yet, emerging research-exemplified by the gut microbiota-brain axis-suggests the potential existence of more targeted and direct communication mechanisms. Dysbiosis, characterized by microbial ecosystem disturbance, generates multiple metabolic compounds capable of entering systemic circulation and reaching distant tissues, notably including ocular structures. This microbial imbalance has been associated with both systemic and localized conditions linked to eye disorders. Accumulating scientific evidence now supports the concept of a gut-retina axis, underscoring the significant role of microbiota disruption in generating various retinal pathologies. This review comprehensively investigates gut microbiota composition, functional dynamics, and dysbiosis-induced alterations, with specific focus on retinal interactions in age-related macular degeneration, diabetic retinopathy, glaucoma, and retinal artery occlusion. Moreover, the review explores microbiota-targeted therapeutic strategies, including precision nutritional interventions and microbial transplantation, as potential modulators of retinal disease progression.}, }
@article {pmid40433417, year = {2025}, author = {Gui, C and Gao, Y and Zhang, R and Zhou, G}, title = {Bioinformatics Analysis of Lactylation-related Biomarkers and Potential Pathogenesis Mechanisms in Age-related Macular Degeneration.}, journal = {Current genomics}, volume = {26}, number = {3}, pages = {191-209}, pmid = {40433417}, issn = {1389-2029}, abstract = {BACKGROUND: Lactylation is increasingly recognized to play a crucial role in human health and diseases. However, its involvement in age-related macular degeneration (AMD) remains largely unclear.<br><br>OBJECTIVES: The aim of this study was to identify and characterize the pivotal lactylation-related genes and explore their underlying mechanism in AMD.<br><br>METHODS: Gene expression profiles of AMD patients and control individuals were obtained and integrated from the GSE29801 and GSE50195 datasets. Differentially expressed genes (DEGs) were screened and intersected with lactylation-related genes for lactylation-related DEGs. Machine learning algorithms were used to identify hub genes associated with AMD. Subsequently, the selected hub genes were subject to correlation analysis, and reverse transcription quantitative real-time PCR (RT-qPCR) was used to detect the expression of hub genes in AMD patients and healthy control individuals.<br><br>RESULTS: A total of 68 lactylation-related DEGs in AMD were identified, and seven genes, including HMGN2, TOP2B, HNRNPH1, SF3A1, SRRM2, HIST1H1C, and HIST1H2BD were selected as key genes. RT-qPCR analysis validated that all 7 key genes were down-regulated in AMD patients.<br><br>CONCLUSION: We identified seven lactylation-related key genes potentially associated with the progression of AMD, which might deepen our understanding of the underlying mechanisms involved in AMD and provide clues for the targeted therapy.}, }
@article {pmid40434345, year = {2025}, author = {Gong, J and Chan, KS and Rajesh, A and Droho, S and Lavine, JA}, title = {Adrb2 Expression in Ocular-Infiltrating Macrophages Is Necessary for Interleukin-6 Expression and Choroidal Neovascularization.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {5}, pages = {43}, pmid = {40434345}, issn = {1552-5783}, support = {K08 EY030923/EY/NEI NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; R01 EY034486/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Choroidal Neovascularization/metabolism/genetics/pathology ; *Interleukin-6/biosynthesis/genetics/metabolism ; *Macrophages/metabolism ; Mice ; *Receptors, Adrenergic, beta-2/genetics/biosynthesis ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice, Knockout ; *Gene Expression Regulation/physiology ; }, abstract = {PURPOSE: Effective therapies for treatment resistant neovascular age-related macular degeneration (nAMD) remain an unmet need. Beta-adrenergic receptor (AR) blockers can decrease laser-induced choroidal neovascularization (CNV) size in mice. We have shown that monocyte-derived macrophages (MDMs) and interleukin-6 (IL-6) are necessary for beta-AR blockers to inhibit CNV. However, the specific beta-AR and the mechanism of this pathway are not fully elucidated. We hypothesized that beta2-AR (Adrb2) signaling on MDMs increases IL-6 production and stimulates CNV.<br><br>METHODS: Previously published single-cell RNA-sequencing data was reanalyzed to determine which mononuclear phagocytes express beta-ARs. Adrb2flox/flox: Cx3cr1CreER/+ mice (Adrb2&#x394;Macs) or Adrb2flox/flox (Adrb2flox) controls were given tamoxifen injections at either four weeks before or at the time of laser-induced CNV to knockout Adrb2 in tissue resident or all macrophages, respectively. Mice underwent laser induced-CNV, and eyes were collected for choroidal wholemount immunofluorescence imaging to measure CNV area, multiparameter flow cytometry to analyze macrophage heterogeneity, and ELISAs to quantitate IL-6 levels.<br><br>RESULTS: Adrb2 was the predominantly expressed beta-AR and was found on microglia, macrophages, and monocytes. Adrb2 deletion in tissue resident macrophages had no effect upon CNV area. Adrb2 deletion in all macrophages decreased CNV area by 1.4-fold. Adrb2&#x394;Macs posterior eye cups demonstrated similar levels of pro-angiogenic CD11c+ macrophages compared to Adrb2flox controls, but Ly6CnegCD11cneg macrophages were significantly increased. IL-6 levels increased with laser in Adrb2flox controls, but IL-6 levels in Adrb2&#x394;Macs posterior eye cups were unchanged.<br><br>CONCLUSIONS: Beta2-AR deletion in ocular-infiltrating macrophages decreases laser-induced CNV area. Beta2-AR expression regulates IL-6 expression in monocyte-derived macrophages.}, }
@article {pmid40434361, year = {2025}, author = {Pushin, DA and Garrad, DV and Kapahi, C and Silva, AE and Chahal, P and Cory, DG and Kulmaganbetov, M and Salehi, I and Mungalsingh, MA and Singh, T and Thompson, B and Yu, D and Sarenac, D}, title = {Characterizing the circularly oriented macular pigment using spatiotemporal sensitivity to structured light entoptic phenomena.}, journal = {Journal of vision}, volume = {25}, number = {6}, pages = {11}, pmid = {40434361}, issn = {1534-7362}, mesh = {Humans ; *Macular Pigment/physiology/metabolism ; Adult ; Photic Stimulation/methods ; Male ; Female ; Psychophysics/methods ; Sensory Thresholds/physiology ; *Light ; *Macula Lutea/physiology ; }, abstract = {To characterize the optical density of circularly oriented macular pigment (MP) in the human retina, as a quantification of macular health, Psychophysical discrimination tests were performed on human subjects using structured light-induced entoptic phenomena. Central exclusions were used to determine the visual extents of stimuli with varying spatiotemporal frequencies. A model was developed to describe the action of circularly oriented MP, and map stimuli to perceived sizes. The experimental results provided validation for the computational model, showing good agreement between measured data and predictions with a Pearson χ2 fit statistic of 0.06. This article contains a description of a new quantification of macular health and the necessary tools for clinical development. The integration of structured light into vision science has led to the development of more selective and versatile entoptic probes of eye health that provide interpretable thresholds of structured light perception. This work develops a model that maps perceptual thresholds of entoptic phenomena to the underlying MP structure that supports its perception. We selectively characterize the circularly oriented MP optical density, rather than the total MP optical density as typically measured. The presented techniques can be applied in novel early diagnostic tests for a variety of diseases related to macular degeneration such as age-related macular degeneration, macular telangiectasia, and pathological myopia. This work both provides insights into the microstructure of the human retina and uncovers a new quantification of macular health.}, }
@article {pmid40434460, year = {2025}, author = {Karabulut, S and Kaderli, ST and Karalezli, A}, title = {Long-term outcomes of drusenoid retinal pigment epithelium detachment in eyes with age-related macular degeneration.}, journal = {Indian journal of ophthalmology}, volume = {73}, number = {6}, pages = {843-846}, pmid = {40434460}, issn = {1998-3689}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnosis/etiology ; *Visual Acuity ; *Retinal Detachment/diagnosis/etiology ; *Retinal Pigment Epithelium/pathology ; Follow-Up Studies ; Aged ; *Fluorescein Angiography/methods ; Fundus Oculi ; *Macular Degeneration/complications/diagnosis ; Middle Aged ; Time Factors ; }, abstract = {PURPOSE: We aim to evaluate the changes in the size of drusens and drusenoid pigment epithelial detachments (PED) in patients with age-related macular degeneration.<br><br>DESIGN: This study was designed as an observational retrospective cohort study.<br><br>METHODS: We evaluated eyes with drusenoid PED tracked using spectral-domain and enhanced depth imaging optical coherence tomography. The cases were classified according to the follow-up visits and divided into two groups as eyes with collapsed PED and persisting PED. The best-corrected visual acuity (BCVA), size of drusens and PED, central macular thickness (CMT), and subfoveal choroidal thickness (SCT) were recorded.<br><br>RESULTS: We included 11 patients' 22 eyes with drusenoid PED. In the final comparison, the mean CMT, SCT, and BCVA were significantly lower in Group 1 compared to Group 2 (P = 0.05; P = 0.05; P = 0.002, respectively). The mean CMT, SCT, and BCVA were significantly decreased from baseline to the last visit in Group 1 (P = 0.013; P < 0.001; P = 0.001, respectively). No significant changes were observed regarding the mean CMT, SCT, and BCVA in Group 2 during the follow-up visits. (P = 0.317, P = 0.682, P = 0.056).<br><br>CONCLUSION: Spontaneous collapse of drusenoid PED is associated with poor visual outcome.}, }
@article {pmid40434532, year = {2025}, author = {Ohnaka, M and Sakurada, Y and Hayashi, A and Kadonosono, K and Ohno, H and Mori, R and Matsumoto, H and Nagamori, I and Murata, Y and Maio-Twofoot, T and Karcher, H and Takahashi, H}, title = {Real-World Outcomes of Brolucizumab Treatment in Japanese Patients with Neovascular Age-Related Macular Degeneration: A 12-Month, Multicenter Study.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {7}, pages = {1551-1565}, pmid = {40434532}, issn = {2193-8245}, abstract = {INTRODUCTION: The aim of this study was to evaluate the real-world outcomes of brolucizumab use in Japanese patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: PHEASANT was a retrospective, multicenter, single-arm cohort study. The study included 438 patients, of whom 123 were treatment-na&#xef;ve and 315 were pre-treated. The primary outcome was retinal fluid (subretinal fluid [SRF] and intraretinal fluid [IRF]) resolution at month 12, with change in visual and retinal anatomy parameters and safety assessed as key secondary outcomes.<br><br>RESULTS: At baseline in the treatment-na&#xef;ve cohort, 10.1% (n&#x2009;=&#x2009;7/69) of patients were free of retinal fluid, increasing to 62.3% (n&#x2009;=&#x2009;43/69) at month 12. In the pre-treated cohort, 14.9% (n&#x2009;=&#x2009;30/201) of patients were free of retinal fluid at baseline, increasing to 43.8% (n&#x2009;=&#x2009;88/201) at month 12. The median (interquartile range [IQR]) injection interval for pre-treated patients at month 12 was extended by 21 (7.0-35.0) days. The overall intraocular inflammation rate (including the rate of retinal vasculitis/retinal occlusive vasculitis of 0.46% [2/438]) was 8.4% (n&#x2009;=&#x2009;37/438).<br><br>CONCLUSION: In a real-world clinical setting, brolucizumab was effective at drying the retina in treatment-na&#xef;ve and pre-treated Japanese nAMD patients and therefore has the potential to reduce the treatment burden by prolonging injection intervals. Safety outcomes support the overall favorable benefit/risk profile of brolucizumab.<br><br>GOV IDENTIFIER: NCT06699914.}, }
@article {pmid40434533, year = {2025}, author = {Phillips, R}, title = {Diet, Mitochondrial Dysfunction, Vascular Endothelial Damage, and the Microbiome: Drivers of Ocular Degenerative and Inflammatory Diseases.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {7}, pages = {1429-1452}, pmid = {40434533}, issn = {2193-8245}, abstract = {There is abundant evidence in medical literature that Western diet and lifestyle drive the cellular and metabolic processes which underlie chronic non-communicable diseases. However, non-pharmaceutical interventions, which focus on nutrition, the microbiome and lifestyle, to prevent non-communicable diseases are not part of mainstream treatment, for a variety of reasons. Lack of progress in stemming the rise in chronic non-communicable diseases can be attributed to the current 'downstream' medical paradigm which is focused on treating disease and symptoms, rather than preventing disease via an 'upstream' approach, which looks at cause and process. Metabolic abnormalities and obesity have previously been noted as correlated with common chronic ophthalmic conditions such as age related macular degeneration (AMD), glaucoma, ocular inflammation, diabetic retinopathy and retinal vascular occlusive disease. These are ocular manifestations of an underlying common cause. The aim of this paper, using an ophthalmic context, is to provide an overview of the cellular pathophysiological mechanisms that underlie chronic non-communicable diseases, including ophthalmic diseases, and to draw the links between diet and lifestyle, the microbiome and chronic non-communicable diseases.}, }
@article {pmid40434931, year = {2025}, author = {Tóth, A and Jeney, V}, title = {Hypoxia-Induced Changes in Endothelial Cell Phenotype and Function.}, journal = {Antioxidants &amp; redox signaling}, volume = {43}, number = {16-18}, pages = {849-868}, doi = {10.1089/ars.2025.1022}, pmid = {40434931}, issn = {1557-7716}, mesh = {Humans ; *Endothelial Cells/metabolism/cytology/pathology ; Animals ; Phenotype ; Reactive Oxygen Species/metabolism ; *Hypoxia/metabolism ; Cell Hypoxia ; }, abstract = {Significance: Endothelial cells (ECs) are specialized cells lining the interior surface of blood vessels, playing a crucial role in vascular biology. They exhibit remarkable versatility, adapting to various tissue requirements. Their ability to respond to physiological and pathological stimuli ensures proper tissue function and homeostasis. Recent Advances: Hypoxia is when the oxygen level in a given organ, tissue, or cell type drops below the physiological level and is insufficient to maintain adequate homeostasis. ECs respond to hypoxia by activating various mechanisms. Hypoxia-induced changes in ECs can promote survival in low-oxygen environments by altering cellular metabolism and inducing neoangiogenesis. However, hypoxia-induced EC responses can also be detrimental, leading to increased production of reactive oxygen species, heightened inflammation, changes in vascular tone, increased permeability of the endothelial barrier, and a higher risk of coagulation. Critical Issues: Hypoxia-induced EC responses contribute to the pathogenesis of various diseases, including metabolic diseases (e.g., diabetes, chronic kidney disease), infectious diseases, chronic inflammation, neoplastic diseases, cardiovascular diseases (e.g., atherosclerosis, myocardial infarction, and stroke) lung diseases (e.g., chronic obstructive pulmonary disease and pulmonary hypertension), eye diseases (age-related macular degeneration and retinopathy), and neurodegenerative diseases (e.g., Alzheimer's disease and Parkinson's disease). Future Directions: Detailed, disease-specific investigations are essential to delineate how endothelial hypoxia responses contribute to various pathologies. Understanding these mechanisms could reveal whether targeting endothelial hypoxia holds therapeutic potential. Antioxid. Redox Signal. 43, 849-868.}, }
@article {pmid40436797, year = {2025}, author = {Inazu, A}, title = {Cholesteryl Ester Transfer Protein Deficiency and Hyperalphalipoproteinemia.}, journal = {Journal of atherosclerosis and thrombosis}, volume = {32}, number = {8}, pages = {911-923}, pmid = {40436797}, issn = {1880-3873}, mesh = {Humans ; *Cholesterol Ester Transfer Proteins/deficiency/antagonists &amp; inhibitors/genetics ; *Hyperlipoproteinemias/complications ; *Cholesterol Ester Storage Disease/complications/drug therapy ; *Atherosclerosis/etiology ; Cholesterol, HDL/blood ; Macular Degeneration/etiology ; Lipid Metabolism, Inborn Errors ; }, abstract = {Cholesteryl ester transfer protein (CETP) deficiency and lipoprotein phenotypes with CETP inhibitors were compared. The effects on atherosclerotic cardiovascular disease (ASCVD) and the recently suggested retinal disease of age-related macular degeneration (ARMD) were summarized and discussed in relation to CETP deficiency and extremely increased high-density lipoprotein (HDL) cholesterol levels (＞100 mg/dL). In CETP truncated variants leading to reduced low-density lipoprotein cholesterol levels, ASCVD risk was decreased in heterozygotes. ASCVD prevalence did not increase in homozygotes with CETP deficiency. However, the association between ASCVD and ARMD risks in cases of very high HDL cholesterol level found in multifactorial hyperalphalipoproteinemia needs to be clarified on an etiological basis. The hurdles facing the development of CETP inhibitors are summarized, including a new result for obicetrapib.}, }
@article {pmid40438521, year = {2025}, author = {Langlo, CS and Amin, A and Park, SS}, title = {Optical coherence tomography retinal imaging: narrative review of technological advancements and clinical applications.}, journal = {Annals of translational medicine}, volume = {13}, number = {2}, pages = {17}, pmid = {40438521}, issn = {2305-5839}, abstract = {BACKGROUND AND OBJECTIVE: Optical coherence tomography (OCT) is a non-invasive imaging tool that can provide rapid cross-sectional images of the retina, cornea, and optic nerve head in live patients. The objective of this review is to provide an overview of the technical advancements and current clinical applications of OCT for managing patients with retinal disorders.<br><br>METHODS: Narrative overview synthesizing the findings of literature retrieved from searches of computerized database, authoritative texts and authors' clinical experience and expertise.<br><br>KEY CONTENT AND FINDINGS: Unlike the first-generation time-domain OCT (TD-OCT) instruments, the newer spectral-domain OCT (SD-OCT) instruments use a broadband light source to increase axial image resolution. In addition, the decreased image acquisition time also increases the transverse image resolution, reduces motion artifacts, and allows serial cross-sectional images of the retina to be obtained rapidly. A three-dimensional (3D) image of the retina, reconstructed using serial two-dimensional (2D) OCT images, can be used to quantitate retinal thickness and volume and perform analysis of retinal topography. Currently, commercial SD-OCT instruments are used routinely in clinical practice to obtain morphologic information used to diagnose and manage patients with various retinal disorders including macular degeneration and diabetic retinopathy. Newer swept-source OCT technology with faster image acquisition, provides wider field imaging of the peripheral retina. SD-OCT instruments can be incorporated into surgical microscopes to allow imaging of the retina during retinal surgery so that morphologic changes in the retina from surgical maneuvers can be observed in real time. More recently, OCT angiography (OCTA) has been developed which allows rapid, non-invasive 3D imaging of retinal and choroidal vascular flow. This is achieved by processing rapid serial SD-OCT images to detect movement of blood cells within vessels. Research has been done to further improve image resolution of SD-OCT to a cellular level by adding adaptive optics (AO) technology. The latest in SD-OCT technology is optoretinography (ORG), a technique to derive functional information from OCT images of the retina.<br><br>CONCLUSIONS: Advancement in OCT technology has made it possible to obtain high resolution retinal images that can provide anatomic, physiologic and functional information of the retina in live patients.}, }
@article {pmid40441379, year = {2025}, author = {Berni, A and Foti, C and Bandello, F and Boscia, F and Breazzano, MP and Cicinelli, MV and Corradetti, G and Dolz-Marco, R and Feo, A and Gallego-Pinazo, R and Marolo, P and Russo, A and Sadda, SR and Sarraf, D and Soylu, C and Viggiano, P and Reibaldi, M and Borrelli, E}, title = {Predictors of Macular Atrophy after Serous Pigment Epithelial Detachment Collapse in Type 3 Macular Neovascularization and Age-Related Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {9}, number = {11}, pages = {1126-1130}, doi = {10.1016/j.oret.2025.05.028}, pmid = {40441379}, issn = {2468-6530}, }
@article {pmid40442413, year = {2025}, author = {Tang, F and Hogg, RE and Higgins, BE and Wright, DM and Smyth, L and Sivaprasad, S}, title = {Impact of Polygenic Risk Scores on Retinal Microstructures in Early and Intermediate Age-related Macular Degeneration: the Northern Ireland Sensory Aging Study.}, journal = {Eye (London, England)}, volume = {39}, number = {12}, pages = {2389-2397}, pmid = {40442413}, issn = {1476-5454}, mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; Northern Ireland/epidemiology ; *Macular Degeneration/genetics/pathology/diagnosis ; *Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence/methods ; Aged, 80 and over ; Polymorphism, Single Nucleotide ; Risk Factors ; *Multifactorial Inheritance ; Genetic Risk Score ; }, abstract = {BACKGROUND: Although polygenic risk scores (PRSs) have been developed for age-related macular degeneration (AMD), it is not known whether these scores are associated with changes of retinal microstructures in early AMD. We compared retinal microstructures due to age-related changes in eyes with healthy macula in people aged 55 years or above versus those with early AMD and then determined the associations of retinal microstructural changes with AMD PRS.<br><br>METHODS: Participants aged 55 years or above with healthy macula and a group of people with early or intermediate AMD from the Northern Ireland Sensory Ageing study were included. 45 SNPs were included for PRS calculation.<br><br>RESULTS: A total of 470 participants with healthy macula were included (Beckman stage 0 or 1). The comparator group consisted of participants with early AMD (n&#x2009;=&#x2009;87) or intermediate AMD (n&#x2009;=&#x2009;48). We found that photoreceptor layer thickness decreased with age in all participants, while retinal pigment epithelium (RPE) layer thickness decreased only in those with apparently healthy macula (P&#x2009;<&#x2009;0.05). Higher PRS was associated with thinner photoreceptor and RPE layer thickness, larger drusen size and presence of soft drusen.<br><br>CONCLUSIONS: We observed a significant association between higher PRS and decreased photoreceptor layer thickness, irrespective of the macular status. Our study provides additional evidence supporting the role of genetics on pathological processes of AMD.}, }
@article {pmid40443784, year = {2025}, author = {Arshad, MT and Maqsood, S and Ikram, A and Khan, AA and Raza, A and Ahmad, A and Gnedeka, KT}, title = {Encapsulation Techniques of Carotenoids and Their Multifunctional Applications in Food and Health: An Overview.}, journal = {Food science &amp; nutrition}, volume = {13}, number = {5}, pages = {e70310}, pmid = {40443784}, issn = {2048-7177}, abstract = {Carotenoids are a broad category of biologically active pigments in plants and animals with significant health associations, including immune-modulatory, anti-inflammatory, and antioxidant roles. They persuade prevention of illness through numerous mechanisms such as protection against oxidative stress, encouragement of cardiovascular and neuroprotective events, and reduction of diseases comprising cancer and macular degeneration. Carotenoids have several health benefits but are unstable, with low bioavailability, and easily degrade in environments containing light, heat, and oxygen. Since the encapsulation improves carotenoid solubility, stability, and controlled release, it has become a feasible strategy for overcoming these issues. This review considers a few encapsulation methods, including electrospinning, lipid-based delivery systems, spray drying, freeze drying, and supercritical fluid technology. Each of these methods is assessed in terms of their ability to retain carotenoids, improve bioavailability, and deliver targeted distribution. Evaluation of these methods has been made with the view of benefits, drawbacks, and suitability for industrial use. In conclusion, the analysis identifies current challenges in carotenoid encapsulation and potential future investigation and innovation directions in this area to exploit carotenoid-based functional foods, nutraceuticals, and medications.}, }
@article {pmid40443830, year = {2025}, author = {Cai, Y and Gu, Y and Zhang, J and Zhu, Y and Ma, Z and He, Q and Sun, Y and Yuan, M and Li, X and Zhu, K and Miao, B and Zhao, J and Liu, J and Tang, M and Tong, D and Feng, L and Ma, M and Zhong, G and Qiu, Z and Xue, T}, title = {An Engineered Intravitreal Injection Retinal-Pigment-Epithelium-Tropic Adeno-Associated Virus Vector Expressing a Bispecific Antibody Binding VEGF-A and ANG-2 Rescues Neovascular Age-Related Macular Degeneration in Animal Models and Patients.}, journal = {Research (Washington, D.C.)}, volume = {8}, number = {}, pages = {0717}, pmid = {40443830}, issn = {2639-5274}, abstract = {Antiangiogenesis gene therapy based on adeno-associated virus (AAV) vectors represents a promising advancement in the treatment of neovascular age-related macular degeneration (nAMD), providing an alternative to antibody-based therapies. However, the development of a safe and effective AAV vector capable of precisely targeting neovascularization and choroidal leakage remains a critical unmet need. In the present study, we engineered a novel intravitreally administered AAV vector with retinal-pigment-epithelium (RPE)-specific tropism. This vector demonstrated robust and localized gene expression in RPE cells while maintaining a favorable safety profile. The RPE-tropic AAV vector delivered a dual-acting antibody against vascular endothelial growth factor (VEGF) and angiopoietin-2 (ANG-2), exhibiting strong therapeutic efficacy and tolerability in both rodent and nonhuman primate choroidal neovascularization models. Based on the promising preclinical data, a single-center, single-arm, investigator-initiated trial (ChiCTR2400085329) was conducted to assess its safety and efficacy in patients with nAMD. The RPE-tropic AAV vector expressing anti-VEGF-A and anti-ANG-2 effectively alleviated disease progression and was well tolerated in the clinical setting. These findings highlight the potential of this engineered AAV-RPE capsid as a versatile platform for gene therapy, not only for nAMD but also for other ocular diseases involving RPE cells.}, }
@article {pmid40446575, year = {2025}, author = {Ganeshbabu, M and Manochkumar, J and Efferth, T and Ramamoorthy, S}, title = {Lutein: A natural defence combating age-related macular degeneration.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {143}, number = {}, pages = {156578}, doi = {10.1016/j.phymed.2025.156578}, pmid = {40446575}, issn = {1618-095X}, mesh = {*Lutein/therapeutic use/pharmacology ; Humans ; *Macular Degeneration/drug therapy/prevention &amp; control ; *Antioxidants/pharmacology/therapeutic use ; Dietary Supplements ; Microalgae/chemistry ; Animals ; NF-E2-Related Factor 2/metabolism ; }, abstract = {BACKGROUND: Recently, lutein has been gaining wide attention in the nutraceutical market due to its remarkable antioxidant and anti-inflammatory properties. Yet, about 200 million people across the globe are estimated to have age-related macular degeneration (AMD) that is highly correlated with lutein deficiency. Since lutein cannot be naturally synthesized in our body, it necessitates the intake of lutein through dietary supplements and diverse functional foods. With statistics supporting the fact that a massive group of the population is under the threat of AMD, it is the need of the hour to provide a palliative measure that is natural, effective, robust, and with minimal side effects. This review summarizes the potential of lutein as an effective measure that prevents the progression of AMD and emphasizes microalgae to be a reliable source for the commercialization of lutein.<br><br>HYPOTHESIS: Lutein is a natural curative to treat age-related macular degeneration.<br><br>RESULTS: Many epidemiological and clinical studies indicate the effective use of lutein to help prevent AMD. It is also inferred that several microalgae species are potent candidates compared to the other natural sources available for producing and commercializing lutein globally. Moreover, it has been figured out that lutein amplifies the translocation of Nrf2 into the nucleus and activates Nrf2 thereby supporting the hypothesized antioxidant pathway that takes place in the macular region of the eye.<br><br>CONCLUSION: Lutein, a carotenoid might considerably reduce the progression of AMD through its regular dietary consumption. Combinations of lutein along with zeaxanthin can be employed as supportive therapy as it may retard the advancement of AMD and other eye-related diseases. Though these facts might be convincing, the clarification regarding the exact mechanism of lutein in alleviating AMD needs to be further studied.}, }
@article {pmid40447166, year = {2025}, author = {Huang, KC and Chiang, YF and Wang, KL and Huang, YJ and Shieh, TM and Ali, M and Hsia, SM}, title = {Hinokitiol Protects RPE cells from Oxidative and Autophagic Dysfunction: Implications for AMD Therapy.}, journal = {Free radical biology &amp; medicine}, volume = {237}, number = {}, pages = {76-87}, doi = {10.1016/j.freeradbiomed.2025.05.424}, pmid = {40447166}, issn = {1873-4596}, mesh = {Humans ; *Macular Degeneration/drug therapy/pathology/metabolism ; *Oxidative Stress/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; *Autophagy/drug effects ; Hydrogen Peroxide/pharmacology/toxicity ; Reactive Oxygen Species/metabolism ; *Tropolone/analogs &amp; derivatives/pharmacology ; *Antioxidants/pharmacology ; *Monoterpenes/pharmacology ; Cell Survival/drug effects ; Membrane Potential, Mitochondrial/drug effects ; DNA Damage/drug effects ; Mitochondria/drug effects/metabolism ; Cell Line ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, driven by dysfunction of retinal pigment epithelial (RPE) cells. Oxidative stress-induced reactive oxygen species (ROS) play a critical role in AMD progression, although the underlying mechanisms remain unclear. Autophagy is essential for maintaining retinal homeostasis by clearing damaged organelles and misfolded proteins through lysosomal degradation. However, excessive ROS can disrupt autophagy balance, leading to the excessive degradation of cell components and ultimately triggering autophagy dysfunction-induced cell death. Hinokitiol, a natural compound derived from the heartwood of Cupressaceae plants, possesses potent antioxidant properties. This study aimed to investigate its roles against oxidative damage in RPE cells exposed to H2O2-induced ROS generation. Cell viability was assessed using MTT and crystal violet staining. ROS were measured using H2DCFDA and MitoSOX probes, while catalase activity was evaluated as indicator of antioxidant capacity. DNA damage was assessed by γ-H2AX immunocytochemistry and comet assay. Mitochondrial membrane potential (MMP) was analyzed using JC-1, and autophagy markers were examined by Western blotting. Hinokitiol significantly enhanced RPE cell viability, reduced ROS by increasing catalase activity, preserved mitochondrial function, and mitigated DNA damage. Furthermore, it restored autolysosome fusion impaired by H2O2, thereby maintaining cellular homeostasis. These findings suggest that hinokitiol may be a promising therapeutic candidate for AMD treatment.}, }
@article {pmid40448050, year = {2025}, author = {Lu, Y and Li, C and Liu, Y and Wu, T and Lu, P}, title = {Association between late age-related macular degeneration and dietary intake of copper, iron, zinc and selenium: a 2005-2008 NHANES cross-sectional observational study.}, journal = {BMC ophthalmology}, volume = {25}, number = {1}, pages = {327}, pmid = {40448050}, issn = {1471-2415}, support = {81671641//National Natural Science Foundation in China/ ; CXTDA2017039//Jiangsu Provincial Medical Innovation Team/ ; }, mesh = {Humans ; Cross-Sectional Studies ; Male ; Female ; *Macular Degeneration/epidemiology/prevention &amp; control ; *Selenium/administration &amp; dosage ; *Zinc/administration &amp; dosage ; *Copper/administration &amp; dosage ; Middle Aged ; Aged ; Nutrition Surveys ; *Diet ; Aged, 80 and over ; Adult ; United States/epidemiology ; Prevalence ; *Trace Elements/administration &amp; dosage ; Risk Factors ; *Iron, Dietary/administration &amp; dosage ; Odds Ratio ; *Iron/administration &amp; dosage ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a significant global cause of visual impairment. Our study seeks to explore the relationship between the intake of copper, iron, zinc, selenium in diet and late AMD.<br><br>METHOD: In this cross-sectional study, we utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted during 2005-2008. We employed three logistic regression models with or without adjustments to examine the association between dietary copper, iron, zinc, selenium and late AMD.<br><br>RESULT: Our study involved 4996 individuals aged 40 years and above with graded fundus pictures and dietary trace element intake data from a representative sample. The levels of copper intake were linked to a reduced risk of late AMD, resulting in odds ratios (OR) of 0.24 (95% confidence interval [CI]&#x2009;=&#x2009;0.13-0.46), 0.38 (95% CI&#x2009;=&#x2009;0.16-0.90), and 0.37 (95% CI&#x2009;=&#x2009;0.17-0.82) for crude model 1, adjusted model 2, and adjusted model 3 respectively. The intake levels of dietary iron, zinc and selenium showed an inverse correlation with the prevalence of late AMD in the crude model; ORs (95% CI) were as follows: Iron -&#x2009;0.92 (0.86, 0.97); Zinc- 0.88 (0.81, 0.96); Selenium- 0.98 (0.97, 0.99). However, in model 2 and 3, no significant association was observed between these three elements and late AMD. In subgroup analysis divided by age, there was only a significant inverse correlation observed between late AMD and copper intake in 70-85 years of age group.<br><br>CONCLUSION: Our findings suggest a higher dietary copper intake may be associated with a reduced risk of late AMD, with the protective effect remaining significant among individuals aged 70-85 years. While no significant association was identified between dietary intake of iron, zinc, selenium and AMD after adjusting for confounding factors. Further research is warranted to elucidate the mechanism underlying the relationship.}, }
@article {pmid40449644, year = {2025}, author = {Chiang, A and Davis, M and Stevens, W and Garg, S and Sheidow, T and Jones, DL and Intorcia, M and McKeown, A and Schmidt-Erfurth, UM and Sarda, SP and Baumal, CR}, title = {Visual Acuity and Quality of Life Outcomes With Pegcetacoplan Treatment: A Post Hoc Analysis From the OAKS and DERBY Trials.}, journal = {American journal of ophthalmology}, volume = {277}, number = {}, pages = {471-481}, doi = {10.1016/j.ajo.2025.05.023}, pmid = {40449644}, issn = {1879-1891}, mesh = {Humans ; *Visual Acuity/physiology ; *Quality of Life ; Male ; Female ; Double-Blind Method ; Aged ; *Geographic Atrophy/drug therapy/physiopathology/diagnosis/psychology ; Tomography, Optical Coherence ; Surveys and Questionnaires ; Intravitreal Injections ; Sickness Impact Profile ; Aged, 80 and over ; Treatment Outcome ; Middle Aged ; Follow-Up Studies ; }, abstract = {OBJECTIVE: To evaluate the effect of pegcetacoplan on visual function and patient quality of life (QoL) measures based on distance of geographic atrophy (GA) lesions from the center of the fovea.<br><br>DESIGN: Post hoc analysis from OAKS and DERBY, two global, 24-month, multicenter, randomized, double-masked, sham-controlled phase 3 studies evaluating pegcetacoplan treatment for GA in age-related macular degeneration (AMD).<br><br>PARTICIPANTS: 888 study patients with GA for whom all data necessary for the post hoc analysis to be performed had been collected were included.<br><br>METHODS: Best-corrected visual acuity (BCVA) and 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) were assessed at baseline and every 4 and 6 months, respectively, to completion at month 24 in both pegcetacoplan-treated eyes and sham (observed) eyes. Eyes were stratified based on optical coherence tomography&#x2012;derived GA lesion location &#x2265;250 &#xb5;m (n = 192) or <250 &#xb5;m (n = 696) from the foveal center.<br><br>MAIN OUTCOME MEASURES: Change from baseline in BCVA and NEI VFQ-25 was evaluated over 24 months in GA lesions based on distance (&#x2265;250 or <250 &#xb5;m) from the foveal center. Adjustment was conducted via propensity score weighting, where model specification and baseline covariate selection were done a priori based on clinical rationale.<br><br>RESULTS: Pegcetacoplan-treated eyes with GA lesion margins &#x2265;250 &#xb5;m from the foveal center demonstrated directionally slower decline in visual acuity (mean +5.6 [SE 3.2] [P = .0785]) and QoL (mean +4.0 [SE 2.4] [P = .0905]) from baseline at 24 months compared with sham. The change in visual acuity (BCVA, mean -1.6 [SE 1.1] [P = .1522]) and QoL (NEI VFQ-25, -2.3 [1.1] [P = .0284]) in pegcetacoplan-treated eyes with GA lesion margins <250 &#xb5;m from the foveal center were within the limits of variability compared with sham.<br><br>CONCLUSIONS: Pegcetacoplan treatment demonstrated a potentially meaningful slower decline in visual acuity and QoL for patients with GA lesions &#x2265;250 &#xb5;m from the foveal center. The change in visual acuity and QoL seen with pegcetacoplan treatment for patients with GA lesions <250 &#xb5;m from the foveal center were within the limits of variability.}, }
@article {pmid40449688, year = {2025}, author = {Eo, H and Park, J and Ju, IG and Oh, MS}, title = {6-shogaol, a bioactive component of ginger, alleviates aging-induced ocular inflammation and ER stress in the 25-month-old mice.}, journal = {The Journal of nutritional biochemistry}, volume = {144}, number = {}, pages = {109980}, doi = {10.1016/j.jnutbio.2025.109980}, pmid = {40449688}, issn = {1873-4847}, mesh = {Animals ; *Endoplasmic Reticulum Stress/drug effects ; Mice, Inbred C57BL ; *Zingiber officinale/chemistry ; *Catechols/pharmacology ; *Aging ; Male ; *Macular Degeneration/drug therapy/pathology ; Mice ; Retina/drug effects/pathology/metabolism ; Inflammation/drug therapy ; }, abstract = {In the elderly population, age-related macular degeneration (AMD) is a major cause of visual impairment, characterized by a thinner retinal pigment epithelium and loss of photoreceptors. 6-shogaol (6S), a component of dried Zingiber officinale Roscoe, has been studied for its multiple therapeutic effects. The current study aimed to investigate the effect of 6S supplementation on AMD. 25-month-old C57BL/6 mice were orally administered with 10 mg/kg of 6S for 28 consecutive days. The thickness of the retinal layer was measured by histological analysis. mRNA expression related to fibrosis, inflammation and endoplasmic reticulum stress was measured by real-time polymerase chain reaction. As a result, 6S increased the thickness of the retinal layer and promoted postsynaptic density protein-95 expression in the outer plexiform layer of the aged mice. Moreover, 6S suppressed ocular mRNA expression related to the fibrotic process, including transforming growth factor beta, collagen type 1 alpha 1, and alpha smooth muscle actin. Furthermore, 6S reduced pro-inflammatory cytokines including tumor necrosis factor alpha, interleukin 1 beta, cyclooxygenase-2, and inducible nitric oxide synthase in the eyeballs of aged mice. Lastly, 6S inhibited ocular endoplasmic reticulum stress measured by mRNA expression of C/EBP homologous protein and spliced X-box binding protein-1 in the aged mice. Taken together, these findings suggest that 6S and dried ginger could be a potential nutraceutical candidate for AMD or other age-related eye diseases.}, }
@article {pmid40450331, year = {2025}, author = {Huang, Z and Liu, S and Chen, C and Zhang, K and Du, Y and Zhu, X}, title = {Optimizing serum 25(OH)D levels to mitigate the risk of age-related ocular diseases: insights from a large-scale prospective cohort study.}, journal = {Nutrition journal}, volume = {24}, number = {1}, pages = {88}, pmid = {40450331}, issn = {1475-2891}, support = {82122017, 82271069, 81870642, 82371040, 81970780, 81470613, 81670835 and 82201161//the National Natural Science Foundation of China/ ; 23Y11909800 and 21S31904900//Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission/ ; SHDC12020111//Clinical Research Plan of Shanghai Shenkang Hospital Development Center/ ; shslczdzk01901//Shanghai Municipal Key Clinical Specialty Program/ ; }, mesh = {Humans ; *Vitamin D/blood/analogs &amp; derivatives ; Female ; Male ; Prospective Studies ; Aged ; Middle Aged ; *Eye Diseases/blood/epidemiology/prevention &amp; control ; Risk Factors ; Macular Degeneration/epidemiology/blood/prevention &amp; control ; Cataract/epidemiology/blood/prevention &amp; control ; United Kingdom/epidemiology ; Glaucoma, Open-Angle/epidemiology/blood/prevention &amp; control ; Proportional Hazards Models ; Diabetic Retinopathy/epidemiology/blood/prevention &amp; control ; Incidence ; }, abstract = {BACKGROUND: Investigations into the association between serum 25-hydroxyvitamin D (25(OH)D) levels and the risk of age-related ocular diseases have yielded inconsistent results. Thus, we aimed to provide robust longitudinal evidence, identify optimal serum thresholds, and explore the underlying mechanisms.<br><br>METHODS: We analyzed data of 322,953 participants from the UK Biobank. The serum 25(OH)D levels were assessed using chemiluminescent immunoassay. Outcomes were incidences of cataract, primary open-angle glaucoma (POAG), age-related macular degeneration (AMD), and diabetic retinopathy (DR). Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. Nonlinear relationships were explored using restricted cubic splines, and mediation analyses were performed to delineate potential mechanistic pathways.<br><br>RESULTS: Our findings revealed U-shaped associations for cataract and AMD, and L-shaped associations for DR (all P&#x2009;<&#x2009;0.05), with an optimal threshold of approximately 50 nmol/L, while no association with POAG was observed. Below this threshold, each 10 nmol/L increase in serum 25(OH)D concentration was linked to a 3.5%, 4.2%, and 6.0% reduction in the risk of cataract, AMD, and DR, respectively (HR 0.965 [95% CI 0.951-0.980]; HR 0.958 [95% CI 0.921-0.997]; HR 0.940 [95% CI 0.894-0.989], respectively), while above 50 nmol/L, no significant protective effects were observed. Mediation analyses revealed that the low-grade inflammation score and triglyceride-glucose index may mediate the effects of serum 25(OH)D on cataract and DR.<br><br>CONCLUSIONS: This study identified 50 nmol/L as the optimal serum 25(OH)D threshold for reducing risks of cataract, AMD and DR, with no benefits beyond this level. The protective effects may be mediated through modulation of inflammation and glucolipid metabolism pathways. The threshold effects highlight the importance of targeted vitamin D supplementation under careful monitoring of serum levels to optimize ocular health outcomes.}, }
@article {pmid40451257, year = {2025}, author = {Schweighofer, J and Birner, K and Mohamed, H and Schrittwieser, J and Bogunovic, H and Reiter, GS and Schmidt-Erfurth, U}, title = {Benchmarking test-retest variability in microperimetry for intermediate age-related macular degeneration using MP-3 and MAIA.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {60}, number = {6}, pages = {e879-e887}, doi = {10.1016/j.jcjo.2025.05.002}, pmid = {40451257}, issn = {1715-3360}, mesh = {Humans ; *Visual Field Tests/instrumentation/standards/methods ; Cross-Sectional Studies ; Prospective Studies ; Male ; Female ; Aged ; Tomography, Optical Coherence/methods ; Reproducibility of Results ; *Visual Fields/physiology ; *Visual Acuity ; *Benchmarking/methods ; *Macular Degeneration/diagnosis/physiopathology ; Aged, 80 and over ; Middle Aged ; }, abstract = {OBJECTIVE: Microperimetry (MP) has emerged as a clinical functional endpoint in nonexudative age-related macular degeneration (AMD). In this study, we aim to provide reference values for test-retest outcomes on two MP devices in intermediate AMD (iAMD).<br><br>DESIGN: Prospective, cross-sectional study.<br><br>PARTICIPANTS: 3 600 stimuli from 20 eyes in 20 subjects.<br><br>METHODS: Patients diagnosed with iAMD underwent consecutive testing on MP-3 (NIKED, Gamagori, Japan) and MAIA (CenterVue Icare, Padova, Italy). The obtained point-wise sensitivity (PWS) measurements were superimposed with optical coherence tomography (OCT) (Spectralis, Heildelberg Engineering) acquired. Hyperreflective foci (HRF), drusen volume, ellipsoid zone (EZ)-thickness and outer nuclear layer (ONL)-thickness were quantified with deep-learning algorithms. Subretinal drusenoid deposits (SDD) were manually annotated. We assessed test-retest repeatability at the location of these biomarkers using Bland-Altmann coefficients of repeatability. Furthermore, interdevice correlation, fixation stabilities, and examination durations were evaluated.<br><br>RESULTS: Comparable overall point-wise retest variances were detected for MP-3 (&#xb1;4.54 dB) and MAIA (&#xb1;5.24 dB). SDDs led to significantly worse repeatability in the MAIA device (p&#x202f;=&#x202f;0.03). Drusen, HRF, EZ-thickness, and ONL thickness had no significant impact on test-retest variance. A good intradevice correlation (MP-3: 0.869 [0.851 - 0.886] MAIA 0.848 [0.827 - 0.867]), and a good mean interdevice correlation (0.841 [0.819 - 0.861]) was observed.<br><br>CONCLUSIONS: Intradevice and interdevice repeatability for MP examinations with MP-3 and MAIA in patients with iAMD can be considered as good. Biomarkers except for SDD show no significant impact in repeatability in both devices. This supports MP as a reliable functional endpoint in clinical trials in iAMD.}, }
@article {pmid40451259, year = {2025}, author = {Starr, MR and Lovett, EA and Israilevich, R and Hsu, J and Hua, P and Huang, J and Maguire, MG and Martin, DF and Ying, GS and Kuriyan, AE}, title = {Association of changes in optical coherence tomography metrics with changes in refractive error in patients with neovascular age-related macular degeneration in the CATT.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {60}, number = {6}, pages = {e898-e905}, doi = {10.1016/j.jcjo.2025.05.016}, pmid = {40451259}, issn = {1715-3360}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology/complications ; Female ; Male ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged ; *Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; *Refraction, Ocular/physiology ; Follow-Up Studies ; *Refractive Errors/physiopathology/diagnosis ; Ranibizumab/administration &amp; dosage ; Bevacizumab/administration &amp; dosage ; Aged, 80 and over ; }, abstract = {OBJECTIVE: Assess the change in refractive error (RE) in patients receiving anti-vascular endothelial growth factor (VEGF) therapy for exudative age-related macular degeneration.<br><br>METHODS: Post hoc analysis of data from the Comparison of AMD Treatments Trials (CATT). Associations between spherical equivalent (SphE) change and optical coherence tomography (OCT) metrics were evaluated using correlation coefficients (r) and regression analyses stratified by baseline lens status.<br><br>RESULTS: Analysis included 1 171 patients with OCT fluid in the study eye at baseline. The mean (&#xb1; SD) of SphE shifted toward myopia in study eyes from 0.62 &#xb1; 1.63 diopters (D) at baseline to 0.50 &#xb1; 1.61 D at 2 years (p < 0.0001). Phakic study eyes had larger myopic shifts than pseudophakic eyes at 2 years (-0.19 &#xb1; 0.97 D vs -0.06 &#xb1; 0.90 D; p&#x202f;=&#x202f;0.03). In phakic study eyes, the RE change was significantly correlated with change in subretinal thickness (Spearman r&#x202f;=&#x202f;0.21; p < 0.0001), subretinal tissue complex (r&#x202f;=&#x202f;0.12; p&#x202f;=&#x202f;0.01), and total thickness (r&#x202f;=&#x202f;0.36; p < 0.0001). A myopic shift greater than 1.0 D occurred in 74 (7.0%) and 104 (10.2%) study eyes at years 1 and 2, respectively.<br><br>CONCLUSION: Among CATT participants, the RE of study eyes shifted toward myopia at 2 years with phakic eyes having larger shifts. OCT metric changes were weakly correlated with changes in RE, suggesting that drying of the macula with anti-VEGF therapy may have a minor impact on RE. Still, 10% of patients may develop a 1 D myopic shift at 2 years, typically in those with more baseline fluid. Patients with neovascular AMD may be able to update their spectacles, even if macular edema is present, as the change in RE is negligible when drying the macula.}, }
@article {pmid40451292, year = {2025}, author = {Hafner, M and Asani, B and Eckardt, F and Liesenhoff, C and Kufner, A and Siedlecki, J and Schworm, B and Priglinger, S and Schiefelbein, JB}, title = {Deep learning-assisted analysis of biomarker changes after increase of dosing from aflibercept 2 mg to 8 mg in therapy-resistant neovascular age-related macular degeneration.}, journal = {BMJ open ophthalmology}, volume = {10}, number = {1}, pages = {}, pmid = {40451292}, issn = {2397-3269}, mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage ; Female ; Male ; Aged ; Intravitreal Injections ; *Deep Learning ; Biomarkers/metabolism ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Visual Acuity ; Follow-Up Studies ; Dose-Response Relationship, Drug ; Treatment Outcome ; Fluorescein Angiography ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retrospective Studies ; Middle Aged ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) remains the leading cause of blindness in developed countries. There are many different intravitreal anti-vascular endothelial growth factor (VEGF) drugs available for the treatment of neovascular AMD (nAMD). Unfortunately, not all patients respond equally well to the drugs, and some show recurrences during treatment. Since 01/2024, aflibercept 8 mg represents an additional treatment option and contains a four times higher dosage than the already known aflibercept 2 mg.<br><br>METHODS: To evaluate the real-world efficacy of aflibercept 8&#x2009;mg in refractory nAMD patients, focusing on changes in key optical coherence tomography biomarkers over a follow-up period of the first four aflibercept 8&#x2009;mg injections using a deep learning-based semantic segmentation algorithm. Inclusion criteria were: switch to aflibercept 8&#x2009;mg after insufficient response to aflibercept 2&#x2009;mg, marked by persistent retinal fluid or inability to extend treatment beyond 6&#x2009;weeks; completion of at least 3&#x2009;months (90 days) follow-up under treat-and-extend treatment regime; and no confounding conditions like intraocular infection, uveitis or other retinal diseases.<br><br>RESULTS: 23 eyes of 21 patients with therapy-resistant nAMD were switched to aflibercept 8&#x2009;mg. All patients had previously received aflibercept 2&#x2009;mg, with an average of 30.7 previous anti-VEGF injections. Significant reductions in intraretinal fluid and fibrovascular pigment epithelial detachment at timepoint V3 were observed. The decrease in subretinal fluid and central retinal thickness at V3 was not significant. Treatment intervals extended significantly by 24%, from a baseline average of 34 days to 42 days. Best-corrected visual acuity remained stable throughout the study period.<br><br>CONCLUSIONS: Aflibercept 8&#x2009;mg demonstrated significant efficacy and durability in reducing nAMD biomarkers and extending intervals in a real-world setting. The use of deep learning for biomarker quantification highlighted its potential for enhancing treatment monitoring and decision-making. Future studies with a larger patient cohort and prospective study setting should explore long-term outcomes and integration of artificial intelligence-driven analysis.}, }
@article {pmid40451555, year = {2025}, author = {Liu, J and Hu, J and Li, Y and Hu, N and Wang, Y and Chang, B and Guo, Y and Li, X and Zhang, Q and Ming, Y and Lin, C and Ji, H and Yang, Z and Tang, J}, title = {Microneedle-mediated biomimetic nanoparticles for targeted antioxidant and anti-inflammatory therapy in age-related macular degeneration.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {384}, number = {}, pages = {113908}, doi = {10.1016/j.jconrel.2025.113908}, pmid = {40451555}, issn = {1873-4995}, mesh = {Animals ; Rabbits ; *Macular Degeneration/drug therapy/pathology ; *Antioxidants/administration &amp; dosage/therapeutic use ; *Nanoparticles/administration &amp; dosage/chemistry ; *Anti-Inflammatory Agents/administration &amp; dosage/therapeutic use ; Humans ; *Drug Delivery Systems ; *Resveratrol/administration &amp; dosage/therapeutic use ; Needles ; Retinal Pigment Epithelium/metabolism ; *Biomimetic Materials/administration &amp; dosage/chemistry ; Oxidative Stress/drug effects ; Iodates ; Biomimetics ; Retina/drug effects ; }, abstract = {Age-related macular degeneration (AMD) remains the leading cause of vision loss worldwide, with the lack of effective treatment for dry AMD posing a significant clinical challenge. Current therapies for wet AMD, while effective, are invasive, costly, and associated with notable side effects. Dry AMD, which is characterized by progressive retinal damage driven by oxidative stress and inflammation, lacks targeted therapeutic options, underscoring the critical need for innovative intervention strategies. Here, we present a dissolving microneedle-based delivery platform incorporating retinal pigment epithelial (RPE) cell membrane-cloaked biomimetic nanoparticles loaded with resveratrol. This system is designed for minimally invasive, targeted drug delivery to the retina. Upon administration, the microneedles rapidly dissolve, enabling localized release of the nanoparticles. The RPE membrane coating provides homologous targeting, enhancing cellular uptake while mitigating systemic exposure. In a rabbit model of NaIO3-induced dry AMD, this approach demonstrated significant preservation of retinal architecture, including significant mitigation of oxidative stress, inflammation, and retinal degeneration, alongside excellent safety and biocompatibility profiles. This innovative delivery strategy addresses the critical barriers in AMD treatment by offering a safe, efficient, and patient-friendly solution, paving the way for its broader application in posterior eye diseases.}, }
@article {pmid40451848, year = {2025}, author = {Hara, H}, title = {Research Progress in Drug Development Based on Functional Molecules Involved in Pathogenesis and Analysis of Their Mechanisms.}, journal = {Biological &amp; pharmaceutical bulletin}, volume = {48}, number = {6}, pages = {744-758}, doi = {10.1248/bpb.b25-00069}, pmid = {40451848}, issn = {1347-5215}, mesh = {Animals ; Humans ; *Drug Development ; *Glaucoma/drug therapy/pathology ; *Macular Degeneration/drug therapy ; Disease Models, Animal ; Mice ; Diabetic Retinopathy/drug therapy ; }, abstract = {Ocular diseases that result in blindness impair the QOL of patients as well as cause significant socioeconomic losses. Glaucoma is the leading cause of blindness, followed by retinitis pigmentosa, diabetic retinopathy, and age-related macular degeneration (AMD). Although the pathogeneses of these ocular diseases differ, they are all retinal diseases that lead to blindness owing to progressive retinal damage. However, the mechanisms underlying the pathogenesis and progression of these diseases have not yet been fully elucidated. In addition, treatment methods for these diseases have not yet been fully established, and their pathophysiology should be elucidated to establish novel treatment methods and drugs. Rodent pathological models, particularly mice and rats, have been established to elucidate the pathogenesis of these diseases. However, anatomical differences between the eyes of humans and rodents suggest that differences in pathogenic mechanisms may exist. In addition, species differences in drug responsiveness have become an issue in various respects, making it increasingly difficult to directly extrapolate the results obtained in rodents to humans. Therefore, evaluations using non-human primates, which are physiologically similar to humans, are required. This review outlines the basic research of AMD and glaucoma models using mice and non-human primates and their therapeutic strategies, focusing on the research findings.}, }
@article {pmid40453785, year = {2025}, author = {Kazemzadeh, K}, title = {Artificial intelligence in ophthalmology: opportunities, challenges, and ethical considerations.}, journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal}, volume = {14}, number = {1}, pages = {255-272}, pmid = {40453785}, issn = {2322-3219}, abstract = {BACKGROUND: By leveraging the imaging-rich nature of ophthalmology and optometry, artificial intelligence (AI) is rapidly transforming the vision sciences and addressing the global burden of ocular diseases. The ability of AI to analyze complex imaging and clinical data allows unprecedented improvements in diagnosis, management, and patient outcomes. In this narrative review, we explore the current and emerging opportunities of utilizing AI in the vision sciences, critically examine the associated challenges, and discuss the ethical implications of integrating AI into clinical practice.<br><br>METHODS: We searched PubMed/MEDLINE and Google Scholar for English-language articles published from January 1, 2005, to March 31, 2025. Studies on AI applications in ophthalmology and optometry, focusing on diagnostic performance, clinical integration, and ethical considerations, were included, irrespective of study design (clinical trials, observational studies, validation studies, systematic reviews, and meta-analyses). Articles not related to the use of AI in vision care were excluded.<br><br>RESULTS: AI has achieved high diagnostic accuracy across different ocular domains. In terms of the cornea and anterior segment, AI models have detected keratoconus with sensitivity and accuracy exceeding 98% and 99.6%, respectively, including in subclinical cases, by analyzing Scheimpflug tomography and corneal biomechanics. For cataract surgery, machine learning-based intraocular lens power calculation formulas, such as the Kane and ZEISS AI formulas, reduce refractive errors, achieving mean absolute errors below 0.30 diopters and performing particularly well in highly myopic eyes. AI-based retinal screening systems, such as the EyeArt and IDx-DR, can autonomously detect diabetic retinopathy with sensitivities above 95%, while deep learning models can predict age-related macular degeneration progression with an area under the receiver operating characteristic curve exceeding 0.90. In glaucoma detection, fundus and optical coherence tomography-based AI models have reached pooled sensitivity and specificity exceeding 90%, although performance varies with disease stage and population diversity. AI has also advanced strabismus detection, amblyopia risk prediction, and myopia progression forecasting by using facial analysis and biometric data. Currently, key challenges in implementing AI in ophthalmology include dataset bias, limited external validation, regulatory hurdles, and ethical issues, such as transparency and equitable access.<br><br>CONCLUSIONS: AI is rapidly transforming vision sciences by improving diagnostic accuracy, streamlining clinical workflow, and broadening access to quality eye care, particularly in underserved regions. Its integration into ophthalmology and optometry thus holds significant promise for enhancing patient outcomes and optimizing healthcare delivery. However, to harness the transformative potential of AI fully, sustained multidisciplinary collaboration, involving clinicians, data scientists, ethicists, and policymakers, is essential. Rigorous validation processes, transparency in algorithm development, and strong ethical oversight are equally important to mitigate risks such as bias, data misuse, and unequal access. Responsible implementation of AI in the vision sciences is essential to ensure that all populations are served equitably.}, }
@article {pmid40454673, year = {2025}, author = {Taylor, LJ and Josan, AS and MacLaren, RE}, title = {Exploring standard and low luminance visual acuity and the Moorfields Acuity Chart as outcome measures in inherited retinal disease.}, journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)}, volume = {45}, number = {5}, pages = {1158-1163}, pmid = {40454673}, issn = {1475-1313}, support = {NIHR202821//Research for Patient Benefit Programme/ ; //NIHR Oxford Biomedical Research Centre/ ; }, mesh = {Humans ; *Visual Acuity/physiology ; Male ; Female ; *Vision Tests/methods/instrumentation ; Middle Aged ; Adult ; Aged ; Reproducibility of Results ; *Retinal Diseases/physiopathology/diagnosis/genetics ; Young Adult ; }, abstract = {INTRODUCTION: Standard visual acuity (VA) is often insensitive to subtle changes in vision that result from inherited retinal disease. Low luminance VA (LLVA) has grown in popularity as an alternative acuity measure. A new test, the Moorfields Acuity Chart (MAC) has been designed as a more sensitive and repeatable test for use in patients with age-related macular degeneration. The study explores the utility and repeatability of standard VA, LLVA and the MAC in a mixed cohort of patients with inherited retinal disease.<br><br>METHODS: Participants were recruited as part of the visual function in retinal degeneration study (Ethics Reference 20/WM/0283). Standard VA was obtained using the Early Treatment of Diabetic Retinopathy study (ETDRS) chart placed at 4&#x2009;m. LLVA was obtained using the same ETDRS chart with the addition of a 2.0-log unit neutral density filter. MAC VA was obtained using standard clinic room lighting. All participants completed repeated testing.<br><br>RESULTS: Thirty-five patient participants and 36 healthy controls, with logMAR 1.00 (6/60) or better, completed testing. Both LLVA and MAC VA were reduced compared to standard VA in patient participants and healthy controls (linear mixed model: p&#x2009;<&#x2009;0.001). All three acuity tests show comparable sensitivity, specificity and repeatability. A subset of participants (patient participants n&#x2009;=&#x2009;34, healthy controls n&#x2009;=&#x2009;35) completed microperimetry. Post hoc analysis of microperimetry volume sensitivity correlated significantly with all of the acuity tests and showed no significant difference in the gradient of the slopes. This suggests that VA, LLVA and MAC VA decline at a consistent rate with disease progression.<br><br>CONCLUSION: All three acuity tests could be considered viable outcome measures for clinical trials. For patients with early to moderate inherited retinal disease (logMAR 1.00 (6/60) or better), no single acuity chart appeared significantly beneficial.}, }
@article {pmid40455036, year = {2025}, author = {Jayananthan, V and Taylor, TH and Greentree, DH and Collison, B and Kerur, N}, title = {AI Quantification of Vascular Lesions in Mouse Fundus Fluorescein Angiography.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {6}, pages = {4}, pmid = {40455036}, issn = {2164-2591}, support = {P30 EY032857/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Fluorescein Angiography/methods ; Mice ; *Artificial Intelligence ; Fundus Oculi ; Mice, Knockout ; *Choroidal Neovascularization/diagnostic imaging ; Disease Models, Animal ; *Retinal Vessels/pathology/diagnostic imaging ; *Retinal Neovascularization/diagnostic imaging ; Image Processing, Computer-Assisted/methods ; }, abstract = {PURPOSE: Quantifying vascular leakage in fundus fluorescein angiography (FFA) is a critical endpoint in preclinical models of diseases such as neovascular age-related macular degeneration, retinopathy of prematurity, and diabetic retinopathy. Traditional manual methods are labor intensive and prone to variability. We developed an artificial intelligence (AI)-assisted method to improve efficiency and accuracy in quantifying vascular lesions in FFA images.<br><br>METHODS: Nikon NIS-Elements software with AI functionality was used to create an automated FFA analysis method. FFA images were acquired using the Phoenix MICRON IV imaging system in two mouse models of ocular angiogenesis: (1) very low-density lipoprotein receptor (Vldlr) knockout mice exhibiting spontaneous pathological chorioretinal neovascularization, and (2) a laser-induced choroidal neovascularization model. The AI model was trained on manually segmented FFA images to delineate lesions and quantify lesion area and fluorescence intensity.<br><br>RESULTS: The AI model demonstrated high accuracy in quantifying vascular lesions in FFA images, achieving 99.7% agreement with manual counts. It attained a precision, recall, and F1 score of 0.94, with an intraclass correlation coefficient (ICC) of 0.991. The model showed strong spatial agreement with manual segmentations and consistent lesion area measurements. On validation images, it maintained expert-level performance (ICC = 0.998) with high sensitivity and precision. Additionally, it effectively captured temporal changes in vascular leakage by measuring lesion area and fluorescence intensity, demonstrating robustness in real-world experiments.<br><br>CONCLUSIONS: Our AI model quantifies vascular lesions in FFA images with high accuracy, outperforming manual analysis.<br><br>TRANSLATIONAL RELEVANCE: AI-based quantification provides a scalable, consistent alternative to manual methods, enhancing research efficiency.}, }
@article {pmid40455044, year = {2025}, author = {Klaassen, I and Vader, MJC and Aissa, K and Tanck, MWT and Schlingemann, RO and , }, title = {Several Common Genetic Variations Associate With Functional or Anatomic Effects of Anti-VEGF Treatment in Conditions With Macular Edema.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {6}, pages = {2}, pmid = {40455044}, issn = {1552-5783}, mesh = {Humans ; *Macular Edema/drug therapy/genetics/physiopathology ; *Angiogenesis Inhibitors/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Ranibizumab/therapeutic use ; Genome-Wide Association Study ; *Polymorphism, Single Nucleotide ; *Bevacizumab/therapeutic use ; Visual Acuity/physiology ; Intravitreal Injections ; Male ; Female ; Tomography, Optical Coherence ; Retinal Vein Occlusion/drug therapy/genetics ; Aged ; Diabetic Retinopathy/drug therapy/genetics ; }, abstract = {PURPOSE: This study aimed to identify genetic factors that may influence the effectiveness of anti-vascular endothelial growth factor (VEGF) treatment for macular edema (ME).<br><br>METHODS: We performed a genome-wide association study (GWAS) on 606 patients with macular edema that were treated with bevacizumab or ranibizumab from three randomized clinical trials, using a Infinium Global Screening Array. Well-characterized patient groups included diabetic macular edema (DME), retinal vein occlusion (RVO), and neovascular age-related macular degeneration (nAMD), with changes in best-corrected visual acuity (BCVA) and anatomical changes in central subfield thickness (CST) as outcomes. We conducted a meta-analysis on the combined patient groups, a targeted analysis on 28 previously reported genetic variants related to anti-VEGF response, and on variants of six genes involved in ME pathophysiology.<br><br>RESULTS: GWAS meta-analysis identified 12 SNPs (P < 1 &#xd7; 10-6), of which three SNPs reached genome-wide significance (P < 5 &#xd7; 10-8) and were linked to changes in CST after 6 months of anti-VEGF treatment. In addition, a genomic locus in the SGCZ gene was linked to changes in BCVA. Targeted GWAS revealed significant associations between changes in BCVA and variants in KDR, IL6, NRP1, and SPNS2, all known for their roles in VEGF signaling and retinal vascular permeability. Furthermore, changes in CST were associated with PLVAP, an important gene in vascular hyperpermeability in ME.<br><br>CONCLUSIONS: This GWAS meta-analysis uncovered genetic variants potentially linked to responses to anti-VEGF treatment in patients with retinal conditions featuring vascular leakage and/or ME. These findings could aid in identifying genetic markers for treatment response prediction or uncover new pathways relevant to retinal vascular leakage and ME.}, }
@article {pmid40455475, year = {2025}, author = {Zitser, M}, title = {Painting Through Macular Degeneration.}, journal = {AMA journal of ethics}, volume = {27}, number = {6}, pages = {E438-439}, doi = {10.1001/amajethics.2025.438}, pmid = {40455475}, issn = {2376-6980}, mesh = {Humans ; *Macular Degeneration/psychology ; *Narration ; *Paintings ; }, abstract = {This article investigates the importance of storytelling for human well-being. Special attention is given to the roles storytelling has played in human evolution, how sharing stories informs embodied experiences, and the role of storytelling within medicine to promote health.}, }
@article {pmid40456126, year = {2025}, author = {Lee, HJ and Lee, EK and Sagong, M and Woo, SJ and Park, KH and Park, UC}, title = {CLINICAL CHARACTERIZATION AND TREATMENT OUTCOMES OF MACULAR NEOVASCULARIZATION IN RETINITIS PIGMENTOSA.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {10}, pages = {1951-1958}, doi = {10.1097/IAE.0000000000004541}, pmid = {40456126}, issn = {1539-2864}, mesh = {Humans ; *Retinitis Pigmentosa/complications/drug therapy/diagnosis ; Middle Aged ; Male ; Retrospective Studies ; Aged ; Female ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Visual Acuity/physiology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence ; Fluorescein Angiography ; Treatment Outcome ; Ranibizumab/therapeutic use ; Electroretinography ; *Retinal Neovascularization/drug therapy/diagnosis/etiology/epidemiology ; Follow-Up Studies ; *Macula Lutea/pathology ; Republic of Korea/epidemiology ; Bevacizumab ; }, abstract = {PURPOSE: To investigate the clinical features, prevalence, and treatment outcomes of macular neovascularization (MNV) in patients with retinitis pigmentosa (RP).<br><br>METHODS: The authors retrospectively reviewed the medical records of patients diagnosed with RP at three tertiary hospitals in South Korea. The diagnosis of RP was based on symptoms, funduscopic findings, and electroretinography. All patients were treated with intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) injection.<br><br>RESULTS: Among the 2,730 patients with RP, MNV was identified in 7 patients (prevalence: 0.26%). The median age at MNV onset was 59 years (range: 52-75 years). The median number of anti-VEGF injections was 5 (range: 1-43). After treatment, visual and anatomical improvements were observed in all patients. In six patients, MNV stabilized without recurrence after one to six anti-VEGF injections, whereas one patient needed repeated treatment. The 5 patients with a follow-up period more than 3 years exhibited no signs of disease progression or further constriction of the visual field.<br><br>CONCLUSION: The MNV is a rare complication in patients with RP, occurring at a younger age than in those with age-related macular degeneration. Intravitreal anti-VEGF injections for the treatment of RP-related MNV were effective in preserving vision without accelerating the clinical course of RP.}, }
@article {pmid40456958, year = {2025}, author = {Veritti, D and Sarao, V and Lanzetta, P}, title = {Extended duration of VEGF inhibition with aflibercept 8 mg: the role of reduced ocular clearance.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {263}, number = {10}, pages = {2985-2987}, pmid = {40456958}, issn = {1435-702X}, }
@article {pmid40458667, year = {2025}, author = {Heier, JS and Holekamp, NM and Busquets, MA and Elman, MJ and Schechet, SA and Ladd, BS and Kapoor, KG and Schneider, EW and Leung, EH and Danis, RP and Nahen, K and Mohan, N and Benyamini, G}, title = {Pivotal Trial Validating Usability and Visualization Performance of Home OCT in Neovascular Age-Related Macular Degeneration: Report 1.}, journal = {Ophthalmology science}, volume = {5}, number = {5}, pages = {100772}, pmid = {40458667}, issn = {2666-9145}, abstract = {PURPOSE: To validate the usability and visualization performance of the index test of the home OCT system (HOCT) during a pivotal study toward de novo US Food and Drug Administration marketing authorization.<br><br>DESIGN: A prospective, 5-week longitudinal, at-home visualization multicenter study with preplanned office visits at week 1 and week 5 and as-needed interim visits.<br><br>PARTICIPANTS: The study enrolled adults aged &#x2265;55 years diagnosed with neovascular age-related macular degeneration (nAMD) on anti-VEGF therapy in at least 1 eligible eye and best-corrected visual acuity of 20/320 or better.<br><br>METHODS: Participants self-installed and imaged daily with the HOCT at home for 5 weeks with 2 or 3 interspersed office visits at 1 and 5 weeks with interim reading center (RC)-triggered visits including a comparator in-office OCT (IO-OCT). Scans with an acceptable quality signal index were independently graded by the RC in a masked manner.<br><br>MAIN OUTCOME MEASURES: Ability to self-image at home, positive and negative percent agreement (NPA) in visualization of total hyporeflective spaces (TRO) on HOCT and on IO-OCT.<br><br>RESULTS: At home, self-imaging success rate was 96.1% (95% confidence interval [CI]: 92.2%-98.4%). One hundred eighty participants self-imaged the primary and secondary eyes 5426 and 4012 times with a mean (standard deviation) manufacturer signal quality index of 4.40 (1.26) and 4.58 (1.28), respectively. Positive percent agreement was 86.6% (95% CI: 80.4%-92.8%) and NPA was 86.1% (95% CI: 80.4%-91.8%), with nearly all disagreements being minimal.<br><br>CONCLUSIONS: The target population successfully self-installed and self-imaged at home with image quality comparable to IO-OCT. The findings of the visualization study support the intended use of the system as a tool to monitor TRO at home between routine clinical visits during the management of nAMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40463243, year = {2025}, author = {Hulleman, JD and Jeon, S and Bali, S and DiCesare, SM and Abbas, A and Daniel, S and Ortega, AJ and Collier, GE and Yang, J and Bhattacharyaa, A and McCoy, MK and Joachimiak, LA and Posner, BA}, title = {Select azo compounds post-translationally modulate HTRA1 abundance and activity potentially through interactions at the trimer interface.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40463243}, issn = {2692-8205}, support = {P30 EY030413/EY/NEI NIH HHS/United States ; R21 EY032693/EY/NEI NIH HHS/United States ; RF1 AG076459/AG/NIA NIH HHS/United States ; T35 EY026510/EY/NEI NIH HHS/United States ; }, abstract = {High-temperature requirement protein A1 (HTRA1) is a secreted serine protease with diverse substrates, including extracellular matrix proteins, proteins involved in amyloid deposition, and growth factors. Accordingly, HTRA1 has been implicated in a variety of neurodegenerative diseases including a leading cause of blindness in the elderly, age-related macular degeneration (AMD). In fact, genome wide association studies have identified that the 10q26 locus which contains HTRA1 confers the strongest genetic risk factor for AMD. A recent study has suggested that AMD-associated risk alleles in HTRA1 correlate with a significant age-related defect in HTRA1 synthesis in the retinal pigmented epithelium (RPE) within the eye, possibly accounting for AMD susceptibility. Thus, we sought to identify small molecule enhancers of HTRA1 transcription and/or protein abundance using an unbiased high-throughput screening approach. To accomplish this goal, we used CRISPR/Sp.Cas9 engineering to introduce an 11 amino acid luminescent peptide tag (HiBiT) onto the C-terminus of HTRA1 in immortalized ARPE-19 cells. Editing was very efficient (~88%), verified by genomic DNA analysis, short interfering RNA (siRNA), and HiBiT blotting. Nineteen-hundred and twenty compounds from two libraries were screened. An azo compound with reported anti-amyloidogenic and cardioprotective activity, Chicago Sky Blue 6B (CSB), was identified as an enhancer of endogenous HTRA1 secretion (2.0 ± 0.3 fold) and intracellular levels (1.7 ± 0.2 fold). These results were counter-screened using HiBiT complement factor H (CFH) edited ARPE-19 cells, verified using HiBiT blotting, and were not due to HTRA1 transcriptional changes. Importantly, serine hydrolase activity-based protein profiling (SH-ABPP) demonstrated that CSB does not affect HTRA1's specific activity. However, interestingly, in follow-up studies, Congo Red, another azo compound structurally similar to CSB, also substantially increased intracellular HTRA1 levels (up to 3.6 ± 0.3 fold) but was found to significantly impair HTRA1 enzymatic reactivity (0.45 ± 0.07 fold). Computational modeling of potential azo dye interaction with HTRA1 suggests that CSB and Congo Red can bind to the non-catalytic face of the trimer interface but with different orientation tolerances and interaction energies. These studies identify select azo dyes as HTRA1 chemical probes which may serve as starting points for future HTRA1-centered small molecule therapeutics.}, }
@article {pmid40465138, year = {2025}, author = {Lai, YA and Tsui, MC and Cheng, SF and Hsieh, YT and Lai, TT and Hsia, Y and Wang, SW and Ma, IH and Hung, KC and Lin, CP and Yang, CH and Yang, CM and Ho, TC}, title = {Early Anatomical and Functional Outcomes of Faricimab in Recalcitrant Neovascular Age-Related Macular Degeneration: A Retrospective Real-World Study in an East-Asian Population.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {8}, pages = {1723-1737}, pmid = {40465138}, issn = {2193-8245}, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss, with some eyes showing recalcitrant disease despite standard anti-vascular endothelial growth factor (anti-VEGF) therapy. While clinical trials have demonstrated promising efficacy and safety of faricimab in treatment-naïve patients, only 9% of participants were Asian, and real-world data on its effectiveness in pretreated Asian populations remain limited. This study aims to evaluate the efficacy and longitudinal response of intravitreal faricimab in patients with recalcitrant nAMD in Taiwan by analyzing visual acuity, anatomical outcomes, and treatment interval extension over a 6-month period.<br><br>METHODS: This was a retrospective observational study at National Taiwan University Hospital. Patients switched to intravitreal faricimab (6&#xa0;mg/0.05&#xa0;mL; Vabysmo&#x2122;) from July 2023 to May 2024 with 6&#xa0;months follow-up identified via electronic medical records. Injections were administered without a loading phase. Retreatment was guided by the presence of retinal fluid on optical coherence tomography (OCT), with or without visual decline.<br><br>RESULTS: A total of 33 eyes from 28 patients were analyzed. Visual acuity remained stable over 6&#xa0;months (p&#x2009;=&#x2009;0.147). Central retinal thickness significantly improved from 267 to 235&#xa0;&#x3bc;m at 3&#xa0;months (p&#x2009;=&#x2009;0.002) and remained stable at 6&#xa0;months (p&#x2009;=&#x2009;0.003). Subretinal fluid resolved in 36.4% of eyes at 3&#xa0;months (p&#x2009;<&#x2009;0.001) and 48.5% at 6&#xa0;months (p&#x2009;=&#x2009;0.002), while changes in intraretinal fluid (IRF) and pigment epithelial detachment (PED) height were not significant. Treatment intervals were extended in 52% of eyes, with 56% reaching&#x2009;&#x2265;&#x2009;16 weeks (Q16W) intervals. No serious ocular or systemic adverse events were reported.<br><br>CONCLUSIONS: Intravitreal faricimab demonstrated improved anatomical outcomes with stable visual acuity and extended treatment intervals in patients with recalcitrant nAMD in Taiwan, addressing a key evidence gap. Future studies with longer follow-ups are needed to validate these findings.}, }
@article {pmid40466770, year = {2025}, author = {Regillo, C and Kaiser, PK and Kertes, PJ and Gillies, M and Maio-Twofoot, T and D'Souza, D and Guenther, S and Lawrence, D and Holz, FG}, title = {TALON Phase IIIb Study: 32-Week Primary Results of Brolucizumab Using Treat and Extend for Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {9}, number = {12}, pages = {1175-1186}, doi = {10.1016/j.oret.2025.05.030}, pmid = {40466770}, issn = {2468-6530}, mesh = {Humans ; Double-Blind Method ; *Recombinant Fusion Proteins/administration &amp; dosage ; Male ; *Visual Acuity ; Female ; Intravitreal Injections ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; Tomography, Optical Coherence/methods ; Aged ; Treatment Outcome ; Follow-Up Studies ; Fluorescein Angiography/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Time Factors ; Dose-Response Relationship, Drug ; Fundus Oculi ; Aged, 80 and over ; *Macula Lutea/pathology ; }, abstract = {OBJECTIVE: To compare the efficacy and safety of brolucizumab 6 mg and aflibercept 2 mg using an identical 4-week adjustment treat-and-extend regimen in patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Randomized, double-masked, multicenter, active-controlled, 2-arm, phase IIIb study.<br><br>PARTICIPANTS: Patients (N = 737) with untreated, active choroidal neovascularization secondary to nAMD.<br><br>METHODS: Patients were randomized 1:1 to either brolucizumab 6 mg or aflibercept 2 mg with injections at weeks 0, 4, 8, and 16 followed by 4-week interval adjustments depending on disease activity (DA) up to intervals of 16 weeks. After the introduction of the urgent safety measure, patients requiring a 4-week interval were discontinued from study treatment and moved to the standard of care.<br><br>MAIN OUTCOME MEASURES: Coprimary end points were the distribution of the last treatment interval with no DA at week 32 and the average change in best-corrected visual acuity (BCVA) from baseline to weeks 28 and 32. Key secondary end points included average change from baseline in central subfield thickness (CSFT), presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), and subretinal pigment epithelium fluid at weeks 28 and 32. Safety end points included the incidence of ocular and nonocular adverse events (AEs) and AEs of special interest (AESIs).<br><br>RESULTS: Brolucizumab achieved superiority to aflibercept in the distribution of last interval with no DA at week 32 (proportion of patients on 12-week treatment intervals: 38.5% vs. 19.8%; 8 weeks: 35.8% vs. 39.9%; 4 weeks: 25.7% vs. 40.2%, respectively; P < 0.0001) and noninferiority to aflibercept for least square mean difference in average change in BCVA from baseline at weeks 28 and 32 (+5.2 vs. +5.1; P < 0.0001). The least square mean difference in the average change in CSFT (&#x3bc;m) from baseline at weeks 28 and 32 (brolucizumab -172.8 vs. aflibercept -142.5) was -30.3 (P = 0.002). Fewer brolucizumab versus aflibercept patients had IRF and/or SRF and subretinal pigment epithelium fluid. Incidences of ocular AEs, serious ocular AEs, and AESIs in the brolucizumab versus aflibercept arms were 29.2% versus 26.1%, 2.5% versus 0.5%, and 5.5% versus 1.1%, respectively.<br><br>CONCLUSIONS: In TALON, more brolucizumab-treated patients achieved longer treatment intervals without DA than aflibercept with comparable visual gains. Brolucizumab showed improved anatomical outcomes and demonstrated an overall favorable benefit/risk profile.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40466854, year = {2025}, author = {You, Y and Liu, Y and Huang, L and Lu, WN and Zhang, Y and Nie, T and Jing, M and Hejtmancik, JF and Li, X and Hou, L and Ma, X}, title = {DAPL1 inhibits epithelial-mesenchymal transition of retinal pigment epithelial cells by regulating the TGF-β/MITF pathway.}, journal = {Experimental eye research}, volume = {258}, number = {}, pages = {110473}, pmid = {40466854}, issn = {1096-0007}, support = {Z01 EY000272/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/pathology ; *Epithelial-Mesenchymal Transition/physiology ; Mice ; Signal Transduction/physiology ; Mice, Knockout ; *Transforming Growth Factor beta/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; *Adaptor Proteins, Signal Transducing/physiology ; Humans ; Cells, Cultured ; *Gene Expression Regulation/physiology ; *Vitreoretinopathy, Proliferative/metabolism/pathology ; Blotting, Western ; }, abstract = {Epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is a critical factor in the development of retinopathies, including proliferative vitreoretinopathy (PVR) and age-related macular degeneration (AMD), which are the leading causes of blindness worldwide. Deficiency in DAPL1 can induce RPE-EMT in vivo, and Dapl1 knockout mice (Dapl1 -/-) are prone to PVR, while aged Dapl1 -/- mice display AMD-like pathological features. However, the molecular mechanisms through which DAPL1 regulates RPE-EMT remain largely unknown. Here, using Dapl1 -/- mice and DAPL1 knockdown or overexpression RPE cells, we show that DAPL1 inhibits RPE-EMT by regulating the TGF-β/MITF signaling pathway, a critical signaling pathway/transcription factor in RPE cells. Overexpression of DAPL1 inhibits TGF-β-induced RPE-EMT, while deletion of Dapl1 in mice activates TGF-β signaling, decreases MITF expression, and promotes RPE-EMT under physiological or PVR pathological conditions. Gene therapy demonstrates that transgenic overexpression of MITF in Dapl1 -/- mice inhibits RPE-EMT in vivo and prevents retinal detachment-induced PVR pathological progress, offering hope for future treatment. Similarly, pharmacological therapy with Isoviolanthin, a flavonoid glycoside isolated from traditional medicinal herbs, inhibits TGF-β signaling and increases MITF expression in RPE cells in Dapl1 -/- mice, which then effectively rescues experimental PVR in Dapl1 -/- mice. These results suggest that DAPL1 regulates RPE-EMT at least partial through the TGF-β/MITF pathway and that targeting the TGF-β/MITF pathway could be a potential therapeutic strategy to treat Dapl1 deficiency-induced RPE-EMT-related retinal diseases, instilling hope for the future of retinal disease treatment.}, }
@article {pmid40466938, year = {2025}, author = {McLellan, FC and Huang, K and Wong, E and Shu, DY}, title = {The Angiofibrotic Switch in Retinal and Choroidal Vascular Diseases: Mechanistic Drivers of Angiogenesis and Endothelial-Mesenchymal Transition.}, journal = {The American journal of pathology}, volume = {195}, number = {8}, pages = {1363-1375}, doi = {10.1016/j.ajpath.2025.05.004}, pmid = {40466938}, issn = {1525-2191}, mesh = {Humans ; *Neovascularization, Pathologic/pathology/metabolism ; Animals ; Fibrosis ; *Choroidal Neovascularization/pathology/metabolism ; *Epithelial-Mesenchymal Transition ; *Retinal Diseases/pathology/metabolism ; Endothelial-Mesenchymal Transition ; Angiogenesis ; }, abstract = {The angiofibrotic switch refers to the pathologic transition from active angiogenesis to fibrosis, a process that contributes to disease progression in retinal and choroidal neovascular diseases, such as age-related macular degeneration and proliferative diabetic retinopathy. This switch marks the replacement of newly formed, fragile blood vessels with fibrotic tissue, ultimately leading to scarring and permanent vision loss. Understanding this process is crucial, as fibrosis results in severe visual impairment and, currently, no anti-fibrotic therapies exist. Central to the angiofibrotic switch is endothelial-mesenchymal transition, a process where endothelial cells lose their vascular endothelial identity and acquire mesenchymal properties, contributing to extracellular matrix deposition and fibrosis. This review explores the cellular and molecular mechanisms underlying the angiofibrotic switch, emphasizing the interplay between angiogenesis, endothelial-mesenchymal transition, and metabolic dysregulation in driving fibrosis. Key mediators, such as transforming growth factor-β and vascular endothelial growth factor, are discussed in the context of their dual roles in promoting angiogenesis and fibrosis. This review underlines the need for early detection methods and targeted therapies to mitigate the angiofibrotic switch and improve outcomes in patients with neovascular retinal and choroidal diseases. By unraveling the complexities of this transition, this review aims to provide a framework for developing innovative diagnostic and therapeutic strategies to prevent fibrosis and mitigate vision loss in retinal and choroidal neovascular diseases.}, }
@article {pmid40467021, year = {2025}, author = {Berni, A and Cheng, Y and Shen, M and El-Mulki, OS and Herrera, G and Beqiri, S and Kastner, JD and Zhang, Q and Gregori, G and Wang, RK and Rosenfeld, PJ}, title = {Updated Guidelines for Imaging the Choriocapillaris in Eyes with Age-Related Macular Degeneration Using Swept-Source Optical Coherence Tomography Angiography.}, journal = {American journal of ophthalmology}, volume = {278}, number = {}, pages = {52-64}, doi = {10.1016/j.ajo.2025.05.021}, pmid = {40467021}, issn = {1879-1891}, mesh = {Humans ; *Tomography, Optical Coherence/methods/standards ; *Choroid/blood supply/diagnostic imaging ; *Fluorescein Angiography/methods ; *Macular Degeneration/physiopathology/diagnosis/diagnostic imaging ; Capillaries/diagnostic imaging/pathology ; *Practice Guidelines as Topic ; Regional Blood Flow/physiology ; Retinal Drusen ; *Retinal Vessels/diagnostic imaging/physiopathology ; }, abstract = {PURPOSE: To update the recommended guidelines when quantifying choriocapillaris (CC) flow deficits (FDs) in eyes with age-related macular degeneration (AMD) using swept-source optical coherence tomography angiography (SS-OCTA).<br><br>DESIGN: Evidence-based perspective.<br><br>METHODS: Review of literature and experience of authors.<br><br>RESULTS: A current challenge when quantifying CC FDs using SS-OCTA is the implementation of an objective compensation strategy to adjust for the signal attenuation arising under drusen in eyes with AMD. Our previous compensation strategy was used as a general approach to adjust for the OCTA signal attenuation associated with most drusen. However, the variability of the OCTA signal loss under drusen necessitated a more objective strategy that could be tailored to each case. We propose a compensation strategy using a parameter gamma (&#x3b3;) that allows for the selection of an appropriate compensation level. The optimal &#x3b3; value is identified as the one producing the most homogeneous OCT signal across the whole CC structural slab. This approach minimizes the possibility that areas of decreased flow in the compensated CC flow image might reflect drusen-related or compensation-related artifacts rather than true deficits. Additional lesions that present unique challenges when quantifying CC FDs include the presence of choroidal hypotransmission defects (hypoTDs) caused by calcified drusen and hyperreflective foci as well as choroidal hypertransmission defects (hyperTDs) caused by foci of atrophy. We recommend identifying and outlining these regions on an en face sub-retinal pigment epithelium (subRPE) slab with segmentation boundaries between 64 and 400 &#xb5;m beneath the Bruch membrane (BM). The hypoTDs should be excluded from CC quantification because of the lack of significant OCTA signal, whereas the hyperTDs should be excluded from being compensated because doing so can artifactually increase the percentage of CC FDs.<br><br>CONCLUSIONS: The analysis of CC FDs in AMD requires special attention to drusen, hypoTDs, and hyperTDs to avoid introducing artifacts. By properly adjusting the compensation levels under drusen and adjusting the quantification of CC FDs by accounting for hyperTDs and hypoTDs, researchers interested in measuring CC FDs in AMD can have greater confidence in their measurements, particularly when investigating the role of CC flow impairment in AMD progression.}, }
@article {pmid40467303, year = {2025}, author = {Michaud, C and Guénot, J and Faurite, C and Gallice, M and Chiquet, C and Vayssière, N and Berry, I and Trotter, Y and Soler, V and Peyrin, C and Cottereau, BR}, title = {Motion Processing in Visual Cortex of Maculopathy Patients.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {45}, number = {30}, pages = {}, pmid = {40467303}, issn = {1529-2401}, mesh = {Humans ; Female ; *Motion Perception/physiology ; *Visual Cortex/physiopathology/blood supply ; Male ; Middle Aged ; *Macular Degeneration/physiopathology/pathology ; Photic Stimulation/methods ; Magnetic Resonance Imaging ; Aged ; Visual Fields/physiology ; Adult ; Scotoma/physiopathology ; Stargardt Disease ; Brain Mapping ; }, abstract = {Previous studies on animal models suggested that visual areas involved in motion processing could undergo important cortical reorganizations following retinal damages. This could have major implications for patients suffering from macular degeneration (MD), one leading cause of vision loss. Here, we performed fMRI recordings in a group of maculopathy patients (N = 7, 3 women, including individuals suffering from age-related macular degeneration or from Stargardt's disease) and a control group to characterize the motion processing cortical network in MD patients and determine whether this network is modified following the onset of the scotoma. We used an experimental protocol based on random-dot kinematograms classically employed to characterize motion-selective areas in the brain. To ensure that the visual information processed by the two groups was equivalent, the visual field in each control participant was masked using an artificial scotoma directly derived from clinical measurements in their paired patient. We found that in MD patients, translational motion elicited significant and robust activations in a restricted cortical network which included the human V5/MT+ complex (hMT+), areas V3A and V6, and a portion of primary visual areas (V1, V2, and V3) connected to peripheral vision. Importantly, the same patterns of responses were also observed in control participants. Moreover, the extent and strength of activation within these motion-selective areas did not differ significantly between the two groups. Altogether, these results suggest that in humans, the motion-selective network does not undergo significant large-scale cortical reorganizations following the onset of MD.}, }
@article {pmid40467849, year = {2025}, author = {Arend, N}, title = {[Nutritional therapy in ophthalmology-patients' interest and motivation].}, journal = {Die Ophthalmologie}, volume = {122}, number = {9}, pages = {700-707}, pmid = {40467849}, issn = {2731-7218}, mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; *Motivation ; *Eye Diseases/diet therapy/epidemiology/psychology ; Aged, 80 and over ; Adult ; *Nutrition Therapy/statistics &amp; numerical data/psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Several therapeutic diets are known for ophthalmologic diseases. Therefore, the present study evaluates the interest of our patients in healthy and therapeutic nutrition.<br><br>METHODS: In all, 100 representative patients answered a&#xa0;structured interview questionnaire about their nutrition behavior and interest in therapeutic diet for their ophthalmologic diseases. Data from our patient files were correlated with their answers.<br><br>RESULTS: Over 70% of the patient were interested in and followed a&#xa0;healthy diet and ate fruits and vegetables daily. Only one third had fish weekly. Two thirds showed high interest in therapeutic diet, especially patients of higher age and with the diagnoses sicca, age related macular degeneration (AMD) and glaucoma. There was no correlation of nutrition interest with the patient sex, disease stage, presence of diabetes or need for intravitreal drug administration. In all, 60% agreed to pay for the consultation, albeit rather low amounts. Greater interest and adherence to a&#xa0;healthy diet but not sex, higher age or stages of disease correlated with the willingness pay.<br><br>CONCLUSION: Our patients who were surveyed had high interest in nutritional therapy for ophthalmologic diseases, and were also theoretically motivated to implement it. Patients with sicca, glaucoma and AMD were more motivated; however this was not related to the stage of their disease. Most patients are willing to only pay small amounts for the consultation.}, }
@article {pmid40468952, year = {2025}, author = {Lu, Y and Tan, Y and Jin, K and Xiong, W}, title = {Assessing the relationship between different sleep traits and retinal neurodegenerative diseases: A bidirectional Mendelian randomization study.}, journal = {Chronobiology international}, volume = {42}, number = {6}, pages = {784-794}, doi = {10.1080/07420528.2025.2509631}, pmid = {40468952}, issn = {1525-6073}, mesh = {Humans ; Mendelian Randomization Analysis ; *Sleep/genetics/physiology ; Genome-Wide Association Study ; *Neurodegenerative Diseases/genetics/physiopathology ; Risk Factors ; *Circadian Rhythm/genetics/physiology ; Macular Degeneration/genetics/physiopathology ; Male ; Female ; *Diabetic Retinopathy/genetics/physiopathology ; Polymorphism, Single Nucleotide ; Middle Aged ; Aged ; Glaucoma, Open-Angle/genetics/physiopathology ; }, abstract = {his bidirectional Mendelian randomization (MR) study assessed causal relationships between sleep traits (chronotype, sleep duration, insomnia) and retinal neurodegenerative diseases (RNDs), including open-angle glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). Using genome-wide association study data and inverse variance weighting, we found chronotype significantly increased DR risk (OR: 1.60, p = 0.023). Reverse MR showed AMD was inversely associated with short sleep duration and chronotype. Sensitivity analyses supported result robustness. Mediation analysis identified six traits potentially linking chronotype to DR. These findings suggest sleep-related traits may be modifiable risk factors in RNDs, offering insights for early prevention and intervention.}, }
@article {pmid40469898, year = {2025}, author = {Wu, Z and Sadda, SR and Ach, T and Blodi, BA and Bottoni, F and Chakravarthy, U and Chew, EY and Curcio, CA and Ferris, FL and Fleckenstein, M and Freund, KB and Grunwald, JE and Holz, FG and Jaffe, GJ and Liakopoulos, S and Lim, TH and Monés, JM and Pagliarini, S and Pauleikhoff, D and Pfau, M and Rosenfeld, PJ and Sarraf, D and Schmitz-Valckenberg, S and Spaide, RF and Sparrow, JR and Staurenghi, G and Tufail, A and Viola, F and Guymer, RH}, title = {Onset of End-Stage Atrophic Age-Related Macular Degeneration as an End Point-A Delphi Study: Classification of Atrophy Meetings Report 7.}, journal = {Ophthalmology science}, volume = {5}, number = {5}, pages = {100777}, pmid = {40469898}, issn = {2666-9145}, abstract = {PURPOSE: To investigate whether consensus can be reached on the acceptability of end-stage atrophy onset as a clinical end point in early intervention trials of age-related macular degeneration (AMD), and the criteria for defining such an end point.<br><br>DESIGN: A modified Delphi study.<br><br>PARTICIPANTS: International panel of experts in AMD, retinal imaging, and histopathology that are part of the Classification of Atrophy Meetings group.<br><br>METHODS: A modified Delphi study was undertaken to determine if there is consensus on the acceptability of the onset of end-stage atrophic AMD as a clinical end point to evaluate early interventions and the criteria for defining such an end point. Two initial rounds of online surveys were conducted. Aggregate results and anonymized comments were provided after each round, followed by a face-to-face meeting before a final survey round was completed.<br><br>MAIN OUTCOME MEASURES: Statements where consensus was reached, defined as &#x2265;80% of responses within the 3-point bracket for agreement or disagreement based on a 9-point Likert rating scale, from a total of 33 statements included in the final round of the survey.<br><br>RESULTS: Consensus was reached for the statement that the onset of end-stage atrophic AMD was an appropriate clinical end point to evaluate early interventions (82% responses in agreement). Consensus was also reached for the statement that such an end point should be defined based on anatomical changes that have been previously shown in clinical studies to be associated with marked, but not necessarily complete, functional loss (95% responses in agreement). Consensus was nearly reached for the specific criterion that &#x2265;90% of such atrophic AMD lesions should have &#x2265;1 test location that was &#x2264;10&#xa0;decibels on 2 microperimetry tests (77% responses in agreement).<br><br>CONCLUSIONS: There was expert group consensus that the onset of end-stage atrophy is an appropriate clinical end point to evaluate early interventions in AMD, and that such an end point should show evidence of marked functional loss in prior clinical studies. We believe these findings will help to define incident clinical end points that are acceptable to regulatory authorities.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40469929, year = {2025}, author = {Kawasaki, A and Yuki, M and Nakagawa, S and Iwasaki, K and Ochi, H and Sugitani, Y}, title = {Patient Preference on Age-Related Macular Degeneration Treatment: A Systematic Review.}, journal = {Patient preference and adherence}, volume = {19}, number = {}, pages = {1639-1652}, pmid = {40469929}, issn = {1177-889X}, abstract = {PURPOSE: Patient preference is important in decision-making processes, such as drug approval and price determination. We conducted a systematic review regarding the preference of age-related macular degeneration (AMD) treatment.<br><br>PATIENTS AND METHODS: We searched for articles on patient preferences for AMD treatment published between January 1, 2000 and December 31, 2023 using EMBASE, Google scholar, MEDLINE, and PLOS.<br><br>RESULTS: Seven studies were included in this systematic review. Conjoint analysis was used in all seven trials, of which six were Discrete Choice Experiments and one was a ranking. These studies were conducted in Germany, United States, United Kingdom, Japan, Spain, and Singapore. Six studies focused on patients with neovascular AMD (nAMD, also called wet AMD, ie, wAMD), and one focused on patients with nAMD or diabetic macular edema. The attributes of the treatments used in these seven studies were efficacy, safety, convenience, and cost. Overall, the relative importance of attributes related to efficacy and safety were the highest, followed by those related to convenience and costs. The convenience and cost attributes were almost equal.<br><br>CONCLUSION: Although the definitions of treatment attributes differed among the studies, patients with nAMD considered efficacy and safety to be the most important. The results of several studies suggest that patient preferences may be affected by patient demographics, such as sex. Although there are currently only a few preference studies on patients with AMD, it is necessary to continue conducting studies to understand the trends in patient preferences according to patient demographics.}, }
@article {pmid40470323, year = {2025}, author = {Zhang, G and Qu, Y and Wan, X and Fang, X and Wu, Y and Li, T and Sun, J and Liu, X and Xu, Y and Luo, H and Meng, X and Hu, W and Chen, R and Wu, Z and Jia, H and Sun, X}, title = {Ozone exposure and increased risk of age-related macular degeneration: Evidence from nationwide cohort and toxicological studies.}, journal = {Innovation (Cambridge (Mass.))}, volume = {6}, number = {4}, pages = {100808}, pmid = {40470323}, issn = {2666-6758}, abstract = {Evidence regarding the impact of ozone on age-related macular degeneration (AMD) remains limited. We conducted a nationwide cohort analysis of 27,923 participants in China, along with a random control animal toxicological study, to elucidate the temporal relationship between ozone exposure and AMD as well as the underlying biological explanation. In the population study, 5,149 participants were diagnosed with incident AMD during a 348,701 person-month follow-up. The participants were divided into low-, medium-, and high-exposure groups. Fully adjusted Cox regression models showed that the risk of AMD increased by 28% for the medium- and 101% for the high-exposure groups relative to the low-exposure group (p for trend < 0.001). The exposure-response curves exhibited a J-shaped trend. Sensitivity analyses confirmed these results, revealing stronger associations among participants older than 65 years old and those living in rural or northern China. In the toxicological study, the mice were randomized to inhale ozone or filtered air, and those exposed to ozone had photoreceptor damage and vision impairment, which are hallmarks of AMD. We further clarified that ozone exposure contributes to AMD by activating systemic inflammation and detailing how external air-pollutant-induced inflammation factors reach the retina, which is the innermost layer of the eye, and cause retinal disease. Our comprehensive studies provide key evidence on the temporal relationship between ozone exposure and increased AMD risk, suggesting the visual health benefits of collaboratively enforcing necessary ozone pollution control policies, especially in regions with high ozone concentrations, within the context of a globally aging population.}, }
@article {pmid40471562, year = {2025}, author = {Shor, R and Mihalache, A and Noori, A and Shor, R and Kohly, RP and Popovic, MM and Muni, RH}, title = {Glucagon-Like Peptide-1 Receptor Agonists and Risk of Neovascular Age-Related Macular Degeneration.}, journal = {JAMA ophthalmology}, volume = {143}, number = {7}, pages = {587-594}, pmid = {40471562}, issn = {2168-6173}, mesh = {Humans ; Female ; Retrospective Studies ; Aged ; Male ; *Glucagon-Like Peptide-1 Receptor Agonists ; *Hypoglycemic Agents/adverse effects/therapeutic use ; Ontario/epidemiology ; *Wet Macular Degeneration/epidemiology/chemically induced/diagnosis ; Follow-Up Studies ; Incidence ; Risk Factors ; Aged, 80 and over ; Diabetes Mellitus, Type 2/drug therapy ; }, abstract = {IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are extensively used in treating diabetes and obesity, yet little is known about the long-term ocular effects of systemic prolonged exposure.<br><br>OBJECTIVE: To evaluate the risk of developing neovascular age-related macular degeneration (nAMD) associated with the use of GLP-1 RAs in patients with diabetes.<br><br>This population-based, retrospective cohort study was conducted from January 2020 to November 2023, with a follow-up period of 3 years. Data analysis was performed from August 2024 to October 2024. The investigators used comprehensive administrative health and demographic data from patients in Ontario, Canada, which were collected by the Institute for Clinical Evaluative Sciences in the context of a universal public health care system. Inclusion criteria were patients aged 66 years or older with a diagnosis of diabetes and a minimum follow-up period of 12 months following initial diabetes diagnosis. Patients with incomplete Ontario Health Insurance Plan or Ontario Drug Benefit data or patients exposed to GLP-1 RA for less than 6 months were excluded. Of 1&#x202f;119&#x202f;517 eligible patients, a 1:2 matched cohort of 139&#x202f;002 patients was created, including 46&#x202f;334 patients who were exposed to GLP-1 RAs and 92&#x202f;668 unexposed matched patients. Systemic comorbidities that were associated with any kind of AMD and socioeconomic status were used to calculate propensity scores.<br><br>EXPOSURE: GLP-1 RA use for 6 months or longer.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence and time to event of nAMD during the follow-up period.<br><br>RESULTS: Among 139&#x202f;002 matched patients, mean (SD) patient age was 66.2 (7.5) years, and 64&#x202f;775 patients (46.6%) were women. The incidence of nAMD was higher among the exposed cohort than among the unexposed cohort. Cox proportional hazard models, both unadjusted (crude) and adjusted, estimated hazard ratios for nAMD development of greater than 2.0 among patients exposed to GLP-1 RAs (exposed, 0.2% vs unexposed, 0.1%; difference, 0.1%; crude: HR, 2.11; 95% CI, 1.58-2.82; adjusted: HR, 2.21; 95% CI, 1.65-2.96).<br><br>CONCLUSIONS AND RELEVANCE: In this cohort study, the use of GLP-1 RAs among patients with diabetes was associated with a 2-fold higher risk of incident nAMD development than among similar patients with diabetes who did not receive a GLP-1 RA. Further research is needed to elucidate the exact pathophysiological mechanisms involved and to understand the trade-offs between the benefits and risks of GLP-1 RAs.}, }
@article {pmid40471752, year = {2025}, author = {Tan, NRX and Chan, KE and Lim, BXH and Giannaccare, G and Najjar, RP and Lim, CHL}, title = {Photobiomodulation: evidence and applications in ophthalmology.}, journal = {Current opinion in ophthalmology}, volume = {36}, number = {5}, pages = {345-381}, doi = {10.1097/ICU.0000000000001154}, pmid = {40471752}, issn = {1531-7021}, mesh = {Humans ; *Low-Level Light Therapy/methods ; *Ophthalmology/methods ; *Eye Diseases/radiotherapy ; }, abstract = {PURPOSE OF REVIEW: Photobiomodulation (PBM) is a noninvasive therapy utilising low-level light energy to stimulate cellular processes, modulate inflammatory pathways, enhance mitochondrial activity, promote tissue regeneration. With growing interest in PBM as a potential treatment modality, this review synthesises current evidence and highlights challenges of implementing PBM across various ophthalmic conditions.<br><br>RECENT FINDINGS: Current ophthalmic applications of PBM can be categorised into established and exploratory therapies, differentiated primarily by the attainment of regulatory approval. Established applications of PBM include the treatment of dry eye disease and nonexudative age-related macular degeneration, while the use of PBM is still largely exploratory in conditions such as diabetic macular oedema and retinopathy of prematurity. Regardless of the level of regulatory authorisation, the application of PBM in each ophthalmic condition presents with distinct challenges requiring further research for comprehensive validation.<br><br>SUMMARY: While PBM holds promise as a novel therapeutic option, its long-term efficacy and safety remains to be fully established. Standardised treatment guidelines and larger randomised controlled trials are essential to optimise its use in future clinical practice.}, }
@article {pmid40473035, year = {2025}, author = {Hyttinen, JMT and Niittykoski, M and Kaarniranta, K}, title = {The role of secretory autophagy and exosomes in the accumulation of drusen during the development of age-related macular degeneration (AMD).}, journal = {Ageing research reviews}, volume = {110}, number = {}, pages = {102796}, doi = {10.1016/j.arr.2025.102796}, pmid = {40473035}, issn = {1872-9649}, mesh = {Humans ; *Autophagy/physiology ; *Exosomes/metabolism ; *Macular Degeneration/pathology/metabolism ; *Retinal Drusen/pathology/metabolism ; Retinal Pigment Epithelium/metabolism/pathology ; Animals ; }, abstract = {Age-related macular degeneration (AMD) is the most common disease of the elderly that leads to the loss of sight. So far, no satisfactory therapy exists for this complex eye disease. The appearance of extracellular deposits, called drusen, on the outside of the retinal pigment epithelium (RPE) is considered to be the main clinical hallmark of AMD. Whilst the mechanisms of drusen formation are not well known, secreted material from the RPE, during its degeneration, is thought to contribute to the development of AMD. Various unconventional protein secretion (UPS) pathways are considered to be routes for the delivery of material which form the drusen. The two main forms of UPS are secretory autophagy, which is responsible for the cleansing of cellular debris from the RPE cells and endosomal secretion which carries material outside of the cell via exosomes. These pathways are unconventional in the sense that they comprise the delivery of material to the exterior of cells by bypassing the Golgi apparatus. Although secretory autophagy and exosome release are regarded as different routes by which cells exude material, they share similarities, such as common molecular participants and that their routes converge. Therefore, manipulation of these two processes might be useful in a therapy against AMD by diminishing the destructive drusen progression in the vicinity of the RPE.}, }
@article {pmid40473146, year = {2025}, author = {Qi, CC and Wang, XS and Zhang, Z and Chen, L and Song, WC and Wang, JH and Zhu, Y and Guo, S and Su, SL and Duan, JA}, title = {JuJing formula protects retinal by regulating Nrf2/HO-1 pathways and sphingolipid rheostat and its key protein levels on liver-kidney Yin deficient retinal damage mice.}, journal = {Journal of ethnopharmacology}, volume = {351}, number = {}, pages = {120085}, doi = {10.1016/j.jep.2025.120085}, pmid = {40473146}, issn = {1872-7573}, mesh = {Animals ; Mice ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *NF-E2-Related Factor 2/metabolism ; *Retina/drug effects/pathology/metabolism ; Male ; Liver/drug effects/metabolism/pathology ; Disease Models, Animal ; Oxidative Stress/drug effects ; *Sphingolipids/metabolism ; Signal Transduction/drug effects ; *Yin Deficiency/drug therapy/metabolism ; Mice, Inbred C57BL ; Kidney/drug effects/metabolism/pathology ; Heme Oxygenase-1/metabolism ; Membrane Proteins/metabolism ; }, abstract = {Dry age-related macular degeneration (AMD) has a high rate of blindness, which still lacks effective treatment. JuJing Formula (JJF) is a traditional herbal prescription known for its hepatorenal tonic effects and therapeutic applications in ocular disorders. Previous investigations have demonstrated its efficacy in the management of dry AMD. However, the underlying mechanisms of JJF against dry AMD have not been fully characterized.<br><br>AIM OF THE STUDY: The protective effect and mechanism of JJF on dry AMD were investigated in the liver-kidney Yin deficient retinal damage (LKYD-RD) model of mice.<br><br>MATERIALS AND METHODS: Initially, a LKYD-RD mouse model was established through a combination of thyroxine administration, tail clamping, and sodium iodate injection. Secondly, the amelioration of Yin deficiency symptoms was examined by detecting biochemical indices and histopathologic changes. Meanwhile, the therapeutic efficacy on retinal damage was evaluated using optical coherence tomography (OCT), hematoxylin and eosin (H&amp;E) staining, terminal deoxynucleotidyl (TUNEL) staining, and levels of oxidative stress markers (SOD, MDA, and GSH) and inflammatory factors (IL-1&#x3b2;, IL-6, and TNF-&#x3b1;). Furthermore, serum metabolomics studies were performed to predict the mechanisms of JJF on LKYD-RD mice. Eventually, ELISA, immunofluorescence analysis, RT-qPCR, and Western blotting assays were conducted to verify the mechanisms.<br><br>RESULTS: JJF not only significantly ameliorated LKYD syndrome but also restored the retinal structure and function in LKYD-RD mice. Furthermore, JJF inhibited the inflammatory response and suppressed oxidative stress through the Nrf2/HO-1 signaling pathway. Metabolomic profiling revealed sphingolipid signaling as the predominant regulatory pathway mediating JJF's therapeutic effects on LKYD-RD. Specifically, JJF treatment normalized sphingolipid metabolism by reducing elevated ocular levels of ceramide and sphingosine while increasing sphingosine-1-phosphate concentrations. At the molecular level, JJF upregulated the expression of p-Sphk1/Sphk1, Asah1, and Bcl2, while downregulating Cers2, Cers6, Bax, cleaved-Caspase 3, and Sgpp1. The findings suggested that regulation of the sphingolipid rheostat and its critical proteins is a potential mechanism of JJF resistance to dry AMD.<br><br>CONCLUSIONS: In summary, the current study demonstrates that JJF exerts significant therapeutic effects in the LKYD-RD murine model, primarily through the modulation of sphingolipid metabolic signaling pathways. This research provides a reference for the clinical management of dry AMD.}, }
@article {pmid40473932, year = {2025}, author = {Zarranz-Ventura, J and Marías-Pérez, S and Martin-Pinardel, R and Fernandez-Bonet, M and Pina-Marin, B and Cobos, E and Rodríguez-Fernandez, CA and Parrado-Carrillo, A and Alarcón-Valero, I and Barnes, C and Cilveti, E and Aramburu-Claveria, J and Ascaso-Puyuelo, FJ and Calvo, P and Ruiz-Del-Tiempo, MP and Susanna-González, G and Figueras-Roca, M and Casaroli-Marano, RP and Bernal-Morales, C and , }, title = {Brolucizumab clinical and safety outcomes in a neovascular age-related macular degeneration national database: Fight Retinal Blindness Spain (FRB Spain).}, journal = {Eye (London, England)}, volume = {39}, number = {12}, pages = {2407-2414}, pmid = {40473932}, issn = {1476-5454}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Angiogenesis Inhibitors/therapeutic use ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Databases, Factual ; Follow-Up Studies ; Intravitreal Injections ; Spain/epidemiology ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity/physiology ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; }, abstract = {AIM: To evaluate clinical outcomes, treatment intervals, and safety outcomes of brolucizumab (BRO) treatment in a national neovascular age-related macular degeneration (nAMD) database.<br><br>METHODS: Multicentre, national, routine clinical care database study of nAMD eyes receiving &#x2265;1 BRO injection. Demographics, visual acuity (VA) measured in logMAR letters, macular neovascularization (MNV) activity, number of injections, visit data and information on any adverse events were collected at baseline and at 3, 6, 9 and 12 months after BRO initiation for each patient/eye.<br><br>RESULTS: A total of 305 eyes received &#x2265; 1 BRO injection and 214 eyes (14% na&#xef;ve, 86% switchers) completed &#x2265; 3 months follow-up. In switchers, the percentage of eyes extended to &#x2265;8 week intervals at 3/6/9 months was 43.2%/45.7%/54.5% and to &#x2265;10 week intervals was 12.9%/18.5%/13.6%, respectively. Eyes with VA&#x2009;&#x2265;&#x2009;70 increased from 36% at baseline to 48% at 3 months and 50% at 9 months. MNV lesion activity status decreased from 94% (active/active-only SRF, 46/48%) at baseline to 56% (21/35%), 61% (23/38%), 76% (27/49%) and 65% (24/41%) at months 3/6/9 and 12, respectively. Adverse effects were observed in 6.5% of the treated eyes, being the most prevalent anterior uveitis (3.2%), vitritis (4.5%) and vasculitis (2.2%).<br><br>CONCLUSION: In this series BRO achieves an extension in the treatment intervals in half of the patients which require frequent reinjections (<8 weekly), reducing MNV activity in a third of this specific difficult-to-treat subgroup. The adverse event rates described are consistent with other cohorts and need to be considered to inform treatment decisions in case-by-case discussions.}, }
@article {pmid40474962, year = {2025}, author = {Mat Nor, MN and Green, CR and Squirrell, D and Acosta, ML}, title = {Retinal Hyperreflective Foci Are Biomarkers of Ocular Disease: A Scoping Review With Evidence From Humans and Insights From Animal Models.}, journal = {Journal of ophthalmology}, volume = {2025}, number = {}, pages = {9573587}, pmid = {40474962}, issn = {2090-004X}, abstract = {Background: Abnormalities in the retina have a profound impact on vision, and accurate diagnosis and monitoring are essential for effective clinical management. Retinal hyperreflective foci (HRF), lesions, or dots, identified using optical coherence tomography (OCT), are observed in both animals and humans and have been associated with several ocular conditions, including diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vascular diseases. Methods: To evaluate the relevance of retinal HRF, we conducted a comprehensive scoping review of the literature published up to July 2024 including in the discussion key papers that emerged in 2025. Our search spanned electronic databases utilizing carefully identified search terms related to HRF and OCT within the last six years. We excluded publications on HRF outside the retina, treatments, non-peer-reviewed content, duplicates, studies older than 6 years, and those not focused on AMD, DR, or glaucoma. Results: A total of 141,085 records were initially identified from various databases and further refined based on keywords and content relevance. Finally, 42 reports meeting the criteria were retained for in-depth analysis. HRF were observed mainly in OCT scans of the AMD retina, as well as in DR and, to a lesser extent, in other retinopathies and interestingly in glaucoma. In AMD, HRF are described as a marker for disease progression, often associated with a compromised photoreceptor structure. In DR, HRF indicated issues such as abnormal blood vessels and cellular changes linked to microglia activation. In glaucoma, HRF may reflect microglia and macrophage activation. Most publications concur that the presence of HRF correlates with inflammatory processes and aging in the retina, with early appearance of small HRF serving as a biomarker for ocular disease. The size of HRF and their location were consistent with disease presentation. Conclusion: There is an agreement that HRF of less than 30 μm are biomarkers of inflammation in the retina despite having variable intraretinal locations. HRF resulting from the effect of aging can be discerned from AMD based on their quantity and appearance. The results show the importance of HRF as a biomarker of ocular disease and confirm that HRF are indicative of an inflammatory eye disorder.}, }
@article {pmid40478389, year = {2025}, author = {Banerjee, M and Moharana, S and Padhy, SK}, title = {Systemic Effects of Intravitreal Anti-VEGF Therapy: A Review of Safety across Organ Systems.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {8}, pages = {1661-1684}, pmid = {40478389}, issn = {2193-8245}, support = {Intramural Grant//Hyderabad Eye Research Foundation/ ; }, abstract = {Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies have transformed the management of retinal diseases such as diabetic macular edema and neovascular age-related macular degeneration. However, concerns about their systemic absorption and potential adverse effects on overall health remain. In this review, we systematically aggregate existing literature on the systemic impact of anti-VEGF therapy, with a detailed analysis of the pharmacodynamics and pharmacokinetics of individual drugs. By examining their metabolism, clearance, and systemic exposure, we aim to clarify the extent of their effects beyond the eye. We further explore their influence on renal and cardiovascular health, with evidence suggesting a generally safe profile in the short term but potential risks in high-risk patients, particularly those with preexisting kidney or heart conditions. Additionally, this review addresses the critical concerns surrounding anti-VEGF use in special populations, including pregnant and lactating women and neonates with retinopathy of prematurity (ROP). We discuss the potential risks, the safest options available, and precautionary measures that should be taken when administering these therapies in these groups. While anti-VEGFs remain an essential tool in ophthalmology, careful patient selection, monitoring, and individualized treatment approaches are necessary to mitigate potential systemic risks. Further research is needed to refine our understanding of long-term safety.}, }
@article {pmid40478589, year = {2025}, author = {Won, J and Yaghy, A and Ploner, SB and Kaiser, S and Girgis, JM and Hwang, Y and Jamil, MU and Maier, A and Waheed, NK and Fujimoto, JG}, title = {High-Resolution, Motion-Corrected, Volume-Fused OCT for Investigating Longitudinal Changes in Subretinal Drusenoid Deposits in Intermediate AMD.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {6}, pages = {15}, pmid = {40478589}, issn = {2164-2591}, support = {R01 EY011289/EY/NEI NIH HHS/United States ; R01 EY034080/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnostic imaging ; *Macular Degeneration/diagnostic imaging ; Aged ; Male ; Female ; Motion ; Middle Aged ; Aged, 80 and over ; }, abstract = {PURPOSE: To demonstrate high-resolution, motion-corrected, volume-fused optical coherence tomography (OCT) for assessing longitudinal changes in macular dot form subretinal drusenoid deposits (SDDs).<br><br>METHODS: Six consecutive isotropic volume raster scans over 6 &#xd7; 6&#xa0;mm (500 &#xd7; 500 A-scans) were acquired using a high-resolution (2.7 &#xb5;m axial resolution) spectral domain OCT prototype instrument. OCT volumes were computationally motion-corrected and fused. The distribution and longitudinal changes in dot SDDs were evaluated using en face OCT in a 50-&#xb5;m-thick slab, from 27 &#xb5;m above Bruch's membrane.<br><br>RESULTS: Computational motion correction and volume fusion methods improve visibility of small en face features and compensate for motion artifacts to facilitate longitudinal assessment. In total, 326 SDDs were identified in a representative series of four eyes from four patients with intermediate age-related macular degeneration (AMD) and assessed with a 3- to 12-month follow-up. Of the SDDs, 85.3% remained stable over the follow-up, while 9.8% regressed, 3.4% fused, and 1.5% new SDDs appeared.<br><br>CONCLUSIONS: Computational motion correction and volume fusion combined with high-resolution OCT B-scans and en face slabs facilitate visualization and longitudinal tracking of focal pathologies, such as SDDs.<br><br>TRANSLATIONAL RELEVANCE: The methods presented have the potential to improve OCT analysis of focal features, such as quantification of SDDs and other AMD biomarkers.}, }
@article {pmid40479828, year = {2025}, author = {Sansare, Y and Kejamurthy, P and Singh, S and Ayush, A and Khani, K and Ramya Devi, KT}, title = {Aptamers as therapeutic targets: prospects and progress in the treatment of cancers.}, journal = {Nucleosides, nucleotides &amp; nucleic acids}, volume = {}, number = {}, pages = {1-39}, doi = {10.1080/15257770.2025.2512853}, pmid = {40479828}, issn = {1532-2335}, abstract = {Contemporary cancer treatments encompass diverse strategies like surgery, chemotherapy, radiation, immunotherapy, and targeted therapies, aiming for effective cancer cell control with minimal impact on healthy tissues. Aptamers are short nucleotide sequences typically containing 25-80 bases and can attach to specific target molecules as effectively as monoclonal antibodies. While the FDA has yet to approve any aptamers for oncology applications, a few, such as Pegaptanib (Macugen), have been approved for ophthalmologic conditions like age-related macular degeneration. Pegaptanib and Izervay are the approved aptamers against age-related macular degeneration (AMD) that target vascular endothelial growth factor (VEGF) and block complement component protein C5, respectively. A new type of highly sensitive and specific biosensor has recently been created to detect leukaemia cancer cells. Aptamosomes, encapsulating drugs like doxorubicin, effectively reduce tumour size and are highly advantageous over targeted drug delivery. Many aptamers have been generated against ERα, Epithelial cell adhesion molecule, EGFR, B subunit of platelet-derived growth factor, Vimentin, Osteopontin, Type II membrane protein PSMA, MUC-1, AXL receptor tyrosine kinase, CD28 agonistic aptamer, as well as for the B7-CD28 interaction, etc. This review suggests the pros and cons of aptamer usage and its advantages over antibody treatment. It also outlines the roles of aptamers and connects their modes of action with specific cancer types. The content is highly detailed, providing a comprehensive understanding of aptamer therapy and its applications.}, }
@article {pmid40481786, year = {2026}, author = {Falemban, AH and Söderberg-Löfdal, K and Jonsson, F and Almlöf-Sarman, S and von Euler, M and Westborg, I}, title = {Intravitreal anti-vascular endothelial growth factor injections and risks of stroke in patients with neovascular age-related macular degeneration-A registry-based cohort study.}, journal = {Acta ophthalmologica}, volume = {104}, number = {1}, pages = {98-105}, pmid = {40481786}, issn = {1755-3768}, support = {//Region Stockholm/ ; }, mesh = {Humans ; Intravitreal Injections ; Male ; Female ; *Registries ; Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; *Stroke/epidemiology/chemically induced/etiology ; *Ranibizumab/administration &amp; dosage/adverse effects ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; Aged ; *Bevacizumab/administration &amp; dosage/adverse effects ; Sweden/epidemiology ; Recombinant Fusion Proteins/administration &amp; dosage/adverse effects ; Risk Factors ; Aged, 80 and over ; Incidence ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Follow-Up Studies ; Case-Control Studies ; Retrospective Studies ; Risk Assessment/methods ; }, abstract = {BACKGROUND: Intravitreal Anti-Vascular Endothelial Growth Factor (VEGF) rescues retinal vasculatures and prevents disease progression in patients with neovascular Age-Related Macular Degeneration (nAMD). However, systemic anti-VEGF may increase the risk of thromboembolic related complications including stroke and TIA. This study aims to explore the association between stroke and intravitreal anti-VEGF agents; ranibizumab, aflibercept and bevacizumab.<br><br>METHODS: This nationwide, population- registry-based case-control study used registered data 2007-2019. Data from the Swedish Stroke Registry (Riksstroke) and the Swedish Macula Register (SMR) were cross-linked to identify nAMD patients who developed stroke/TIA within 90&#x2009;days after intravitreal anti-VEGF injection. Each stroke case was matched with three controls from Riksstroke with stroke/TIA but no anti-VEGF treatment.<br><br>RESULTS: A total of 33&#x2009;585 patients with nAMD underwent intravitreal anti-VEGF agent injections. A stroke occurred in 1693 patients of this group, and 936 of them within 90&#x2009;days of treatment. Compared with nonuse, intravitreal anti-VEGF agent use was associated with an increased risk of stroke within 90&#x2009;days of anti-VEGF treatment in 2.9% of the nAMD-patients [Risk Ratio (RR) 1.27, 95% confidence interval (CI) 1.22; 1.33] compared to non-users. The RR within 30, 31-60 and 61-90&#x2009;days were 1.36 (1.15; 1.66), 1.40 (1.09; 1.79) and 0.58 (0.52; 0.65), respectively.<br><br>CONCLUSIONS: Even though the risk is small, intravitreal injections with anti-VEGF agents for the treatment of nAMD are associated with an increased risk of stroke/TIA. The risk seems to be higher within 60&#x2009;days of last injection. An assessment of high-risk populations and risk-benefit weighting is necessary before intravitreal anti-VEGF injections are considered.}, }
@article {pmid40484298, year = {2025}, author = {Berni, A and Foti, C and Ulla, L and Vyas, C and Chhablani, J and Chaudhary, V and Subhi, Y and Gregori, G and Wang, RK and Rosenfeld, PJ and Sadda, SR and Bandello, F and Reibaldi, M and Borrelli, E}, title = {Choriocapillaris in Age-Related Macular Degeneration: A Systematic Review of Optical Coherence Tomography Angiography-Based Assessments and Challenges in Standardization.}, journal = {American journal of ophthalmology}, volume = {277}, number = {}, pages = {482-496}, doi = {10.1016/j.ajo.2025.05.051}, pmid = {40484298}, issn = {1879-1891}, mesh = {Humans ; *Tomography, Optical Coherence/methods/standards ; *Choroid/blood supply/diagnostic imaging ; *Fluorescein Angiography/methods/standards ; *Macular Degeneration/diagnostic imaging/physiopathology/diagnosis ; *Capillaries/diagnostic imaging/pathology ; *Retinal Vessels/diagnostic imaging ; }, abstract = {TOPIC: This systematic review evaluates the methodologies used for assessing the choriocapillaris (CC) in age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA). It focuses on identifying methodological heterogeneity in imaging and analysis protocols and its implications for clinical and research applications.<br><br>CLINICAL RELEVANCE: AMD is a leading cause of vision loss, and assessing CC perfusion provides critical insights into its pathophysiology. OCTA has emerged as a noninvasive imaging technique offering high-resolution visualization of the CC. However, variability in methodologies has hindered the standardization of CC assessments. Establishing consistent practices is essential for improving clinical and research outcomes in AMD management.<br><br>DESIGN: Systematic review.<br><br>METHODS: Studies included in this review were selected on the basis of eligibility criteria defined by the Population, Intervention, Comparator, Outcome, Study design framework. Participants included patients with early, intermediate, and late AMD. Interventions involved the use of OCTA for CC assessment, with no restrictions on device type or scan parameters. Comprehensive searches of MEDLINE, Web of Science Core Collection, and the Cochrane Library were conducted up to November 30, 2024. Data extractions and narrative synthesis focused on device types, scan protocols, segmentation techniques, compensation strategies, and quantitative metrics.<br><br>RESULTS: A total of 102 studies, encompassing 4047 patients with AMD and 4415 eyes, were analyzed. Fifty-two studies used spectral-domain OCTA, and 49 studies used swept-source OCTA, with significant heterogeneity in segmentation boundaries and slab thickness (4.4-30 &#xb5;m). Only 32 studies used compensation strategies to address signal attenuation under drusen. Quantitative metrics varied widely, with CC flow deficit percentage being the most common. However, inconsistencies in thresholding methods and lack of standardized Phansalkar radius reporting limited comparability. The review highlights gaps in reporting segmentation boundaries and compensation techniques, which impact the ability to assess the reliability of findings.<br><br>CONCLUSIONS: This review underscores substantial variability in methodologies for CC assessment in AMD, highlighting the urgent need for standardized imaging protocols and analytical approaches. Despite advances in OCTA technology, inconsistencies in segmentation, thresholding, and compensation strategies challenge data reliability and reproducibility. Future research should prioritize methodological standardization to enhance comparability and clinical applicability.}, }
@article {pmid40484678, year = {2025}, author = {Obayashi, M and Otsu, W and Yamazaki, K and Nakamura, S and Ishikawa, H and Sakata, Y and Tsuboi, M and Tsusaki, H and Shimazawa, M}, title = {Pentadecyl, an Active Component of Microalgae, Ameliorates Endoplasmic Reticulum Stress and Blue Light-Induced Cell Death in Mouse Retina-Derived 661W Cells.}, journal = {Biological &amp; pharmaceutical bulletin}, volume = {48}, number = {6}, pages = {791-800}, doi = {10.1248/bpb.b24-00889}, pmid = {40484678}, issn = {1347-5215}, mesh = {*Endoplasmic Reticulum Stress/drug effects/radiation effects ; Animals ; *Light/adverse effects ; Mice ; Activating Transcription Factor 4/metabolism/genetics ; Cell Death/drug effects/radiation effects ; Cell Line ; *Microalgae/chemistry ; *Retina/drug effects/cytology/radiation effects ; Oxidative Stress/drug effects ; Tunicamycin/pharmacology ; Unfolded Protein Response/drug effects ; Hydrogen Peroxide ; Blue Light ; }, abstract = {Light stress is a risk factor leading to retinal diseases such as age-related macular degeneration. However, the mechanism underlying the stress response to light in the retina has yet to be elucidated. We have reported that exposure to blue light-emitting diode light induces excessive production of reactive oxygen species and activates the unfolded protein response, robustly increasing activating transcription factor 4 (ATF4) expression. These processes result in photoreceptor cell death. This study investigates the effects of Pentadecyl, a bioactive product obtained from Aurantiochytrium limacinum, on either chemical-induced or blue light-induced endoplasmic reticulum (ER) stress. Pentadecyl suppressed cell death induced by either thapsigargin or tunicamycin in a concentration-dependent manner. Pentadecyl also suppressed the expression of unfolded protein response target genes, including Atf4 and ER chaperones. Consistently, immunoblotting revealed that Pentadecyl suppressed the increased expression of ATF4 at the protein level. Pentadecyl also protected 661W cells from blue light-induced damage but did not protect against hydrogen peroxide (H2O2)-induced oxidative stress. These results indicated that Pentadecyl has a novel function that protects against ER stress induced by photodamage.}, }
@article {pmid40484741, year = {2025}, author = {Ma, Y and Lin, Q and He, HL and Liu, YX and Li, M and Zhang, XH and Jin, ZB}, title = {Juvenile macular degeneration in nonhuman primates generated by germline knockout of ABCA4 gene.}, journal = {Science bulletin}, volume = {70}, number = {14}, pages = {2237-2240}, doi = {10.1016/j.scib.2025.04.077}, pmid = {40484741}, issn = {2095-9281}, }
@article {pmid40487113, year = {2025}, author = {Patel, HP and Robbins, CB and Karl, JJ and Weng, P and Vajzovic, L and Fekrat, S}, title = {Oral Antithrombotic Medication Is Associated with Improved Visual Outcomes in Eyes with Submacular Hemorrhage from Wet Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {5}, number = {5}, pages = {100796}, pmid = {40487113}, issn = {2666-9145}, abstract = {PURPOSE: To determine differences in visual acuity (VA) outcomes in eyes of patients on antithrombotics (antiplatelet agents and anticoagulants) that develop submacular hemorrhage (SMH) compared with eyes of patients who are not on antithrombotics and develop SMH.<br><br>DESIGN: A retrospective study of patients presenting with fovea-involving SMH due to wet age-related macular degeneration over an 8-year period who had &#x2265;6 months of follow-up.<br><br>SUBJECTS: Demographics, VA at presentation and final follow-up after SMH management, and history of any antithrombotic therapy were collected. Patients were grouped based on whether they were on anticoagulants (direct oral anticoagulants or warfarin), antiplatelet agents (P2Y12 inhibitors, aspirin, or both), or neither.<br><br>METHODS: Multivariate generalized estimating equations were used for statistical analysis.<br><br>MAIN OUTCOME MEASURES: The difference between VA at presentation with SMH and VA at final follow-up was compared between patients taking oral anticoagulants or antiplatelet agents and those not on any antithrombotic agent.<br><br>RESULTS: Seventy-seven eyes of 74 patients were included. Twenty were on oral anticoagulants, 38 were on antiplatelet agents, and 22 were on neither. After controlling for age, sex, post-SMH cataract surgery, time to presentation, treatments received, initial VA, and follow-up duration, patients taking oral anticoagulants had greater improvement in VA at final follow-up compared with patients who were not taking a concurrent antithrombotic agent (P = 0.001); however, patients on oral antiplatelets did not (P = 0.09). After additionally controlling for the initial size and thickness of SMH, patients taking oral anticoagulants and patients taking oral antiplatelets had greater improvement in VA at final follow-up compared with patients who were not taking an antithrombotic (P = 0.002 and P < 0.001, respectively).<br><br>CONCLUSIONS: Patients taking oral anticoagulants who then develop an SMH may have better long-term VA outcomes than those who were not. However, this effect was not seen in patients taking oral antiplatelet medications. This suggests that baseline anticoagulants may be associated with improved VA outcomes in eyes that develop an SMH. When controlling for size and thickness of SMH, patients taking oral anticoagulants and those taking oral antiplatelets had better long-term VA outcomes than those who were not, suggesting a potential mitigating effect of oral antithrombotics.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40488118, year = {2025}, author = {Alemu, DS and Munaw, MB and Bekele, MM and Asmare Kindie, C and Ayele, FA and Limenih, MA}, title = {Determinants of Healthcare Professionals' Knowledge on Age-Related Macular Degeneration Risk Factors in Ethiopia.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {1771-1785}, pmid = {40488118}, issn = {1177-5467}, abstract = {PURPOSE: The aim of this study was to assess knowledge of healthcare professionals on risk factors of age-related macular degeneration and to identify factors that affect their level of knowledge.<br><br>PATIENTS AND METHODS: A cross-sectional study design was employed to collect data from 607&#xa0;healthcare professionals in Gondar City from August 1 to 30, 2024. Systematic random sampling was used to select study participant. Interviewer administered questionnaire was used to collect data. Bi-variable and multivariable logistic regression analyses were conducted using R statistical software to identify determinants affecting knowledge on age-related macular degeneration risk factors. The strength and precision of relationships between the outcome and the factors were quantified using adjusted odds ratios with 95% confidence intervals. P - value below 5% was used to declare statistically significance associations.<br><br>RESULTS: Six hundred seven healthcare professionals took part in this study. Less than one-third of the participants (29.7%; 95% CI: 25.0%, 34.8%) showed adequate knowledge of risk factors of age-related macular degeneration. Male sex (AOR: 1.68; 95% CI: 1.16, 2.43), healthcare service experience less than five years (AOR: 1.86; 95% CI: 1.23, 2.88), ten years of experience in healthcare (AOR: 0.57; 95% CI: 0.34, 0.95), eye health-related training (AOR: 1.91; 95% CI: 1.23, 2.83), hypertension history (AOR: 2.28; 95% CI: 1.52, 3.44) and diabetes mellitus (AOR: 2.48; 95% CI: 1.02, 6.27) determine healthcare professionals' knowledge of age-related macular degeneration risk factors.<br><br>CONCLUSION: The study highlights a significant knowledge gap among healthcare professionals regarding age-related macular degeneration risk factors. Gender, years of experience in healthcare, and receiving eye health-related training are key determinates of knowledge on age-related macular degeneration risk factors, underscoring the importance of directed educational and trainings to improve healthcare professionals' knowledge on age-related macular degeneration risk factors.}, }
@article {pmid40488699, year = {2025}, author = {Adeyoju, DAO and Josan, AS and Taylor, LJ and MacLaren, RE}, title = {An Analysis of Scotopic Microperimetry in Healthy Adults.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {6}, pages = {18}, pmid = {40488699}, issn = {2164-2591}, mesh = {Humans ; Male ; Female ; *Visual Field Tests/methods ; Reproducibility of Results ; Adult ; *Visual Fields/physiology ; Young Adult ; *Night Vision/physiology ; Dark Adaptation/physiology ; Healthy Volunteers ; Visual Acuity/physiology ; *Retina/physiology ; }, abstract = {PURPOSE: Scotopic microperimetry measures retinal sensitivity under very low light and may be useful in conditions characterized by nyctalopia, such as retinitis pigmentosa and age-related macular degeneration. The Scotopic Macular Integrity Assessment device enables two-color perimetry to isolate rod and cone responses. This study assesses the reliability, test-retest repeatability, and sensitivity in healthy participants aiming to establish normative values.<br><br>METHODS: Scotopic microperimetry was performed using cyan and red stimuli on a 37-point radial grid after dark adaptation on control participants with no history of eye disease and visual acuity of 0.1 logarithm of the minimum angle of resolution or better. Fixation stability, fixation losses, and identification of the rod-free zone were used as reliability metrics. A subset underwent repeat testing within 4 weeks.<br><br>RESULTS: Thirty-nine participants (19 male and 20 female), median age 24&#xa0;years (interquartile range, 9.5&#xa0;years) and 23 years (interquartile range, 9&#xa0;years) for the right and left eyes, respectively, completed testing. Overall 77 eyes underwent scotopic testing, with 82% meeting reliability criteria. Mean cyan and red sensitivities were 19.9 &#xb1; 1.1&#xa0;dB and 20.9 &#xb1; 1.2&#xa0;dB in right eyes, and 20.1 &#xb1; 1.4&#xa0;dB and 21.3 &#xb1; 1.4 dB in left eyes, respectively. Volumetric cyan and red sensitivities were 2868 &#xb1; 157&#xa0;dB.deg2 and 3077 &#xb1; 176&#xa0;dB.deg2 in the right eyes, respectively, and 2892 &#xb1; 205&#xa0;dB.deg2 and 3126 &#xb1; 207&#xa0;dB.deg2 in the left eyes, respectively. Mean sensitivity coefficients of repeatability (CoR) were &#xb1; 1.4 dB (cyan) and &#xb1; 2.1 dB (red) while pointwise coefficients of repeatability were &#xb1; 7.2 dB (95% confidence interval, 6.5-7.6&#xa0;dB) for cyan and &#xb1; 7.9 dB (95% confidence interval, 7.3-8.4&#xa0;dB) for red, with no significant differences between eyes or genders. Fixation stability assessed using the 95% bivariate contour ellipse area for cyan was 2.9 &#xb1; 5.9 deg2 and 2.3 &#xb1; 2.2 deg2 for the right and left eyes, respectively, and for red were 0.7 &#xb1; 0.6 deg2 and 0.9 &#xb1; 0.8 deg2 for the right and left eyes, respectively. Again, there were no significant differences between cyan and red tests (Friedman test, bivariate contour ellipse area 63%, P = 0.455; bivariate contour ellipse area 95%, P = 0.432).<br><br>CONCLUSIONS: Scotopic microperimetry using the Scotopic Macular Integrity Assessment device was feasible and well-tolerated. Repeatability metrics demonstrated limitations in fine spatial mapping of scotopic retinal sensitivity.<br><br>TRANSLATIONAL RELEVANCE: This study highlights potential areas for future improvements in scotopic microperimetry before its use as an outcome measure in clinical trials for retinal disease.}, }
@article {pmid40488701, year = {2025}, author = {Arora, S and Singh, SR and Vupparaboina, SC and Rosario, B and Ibrahim, MN and Selvam, A and Zarnegar, A and Harihar, S and Sant, V and Sahel, JA and Vupparaboina, KK and Chhablani, J}, title = {Three-Dimensional Choroidal Contour Mapping in Healthy and Diseased Eyes.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {6}, pages = {16}, pmid = {40488701}, issn = {2164-2591}, support = {P30 EY008098/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Choroid/diagnostic imaging/pathology ; Retrospective Studies ; Female ; Male ; Middle Aged ; *Tomography, Optical Coherence/methods ; *Imaging, Three-Dimensional/methods ; *Central Serous Chorioretinopathy/diagnostic imaging/pathology ; Aged ; *Macular Degeneration/diagnostic imaging ; Adult ; *Geographic Atrophy/diagnostic imaging ; Fluorescein Angiography/methods ; }, abstract = {PURPOSE: Quantitative evaluation of choroidal curvature including choroidal inner boundary (CIB) and choroidal outer boundary (COB) and report a comparison between healthy and diseased eyes.<br><br>METHODS: This retrospective study was conducted on 97 eyes of 97 patients. Eyes were divided into three groups: central serous chorioretinopathy (CSCR), dry age-related macular degeneration (AMD), and healthy eyes. Delineation of CIB and COB was performed using a hybrid method based on our previously validated deep learning and three-dimensional (3D) smoothing methods for choroidal layer segmentation. Quantitative analysis of the surfaces was based on best-fit spherical radius (R). R for overall surface, as well as for each region (central/nasal/temporal/superior/inferior region), was estimated. Statistical analysis was done using SPSS software.<br><br>RESULTS: There were 35 healthy eyes, 32 eyes with CSCR, and 30 eyes with dry AMD. At CIB and COB; RCSCR > Rhealthy > RAMD (P &#x2264; 0.001). The central region had the lowest R among all the regions within a group at CIB and COB (P&#xa0;<&#xa0;0.001) in healthy, CSCR, and AMD eyes. There was moderate positive correlation of R of CIB and COB with subfoveal choroidal thickness in healthy eyes and a negligible/weak correlation in CSCR and AMD eyes.<br><br>CONCLUSIONS: Contour of choroid at CIB and COB was the flattest in CSCR and steepest in AMD. Central region was the steepest among all sectors in both healthy and diseased eyes.<br><br>TRANSLATIONAL RELEVANCE: Quantitative study of surface at CIB and COB in diseases helps in understanding the pathophysiological changes and provides a clinical biomarker in disease monitoring and treatment as well.}, }
@article {pmid40488713, year = {2025}, author = {Sreekumar, PG and Nam, MH and Hong, E and Kannan, R and Nagaraj, RH}, title = {RAGE Is Essential for Subretinal Fibrosis in Laser-Induced Choroidal Neovascularization: Therapeutic Implications.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {6}, pages = {30}, pmid = {40488713}, issn = {1552-5783}, support = {R01 EY030141/EY/NEI NIH HHS/United States ; R01 EY033915/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Choroidal Neovascularization/metabolism/etiology/pathology ; Fibrosis/metabolism ; Mice ; *Receptor for Advanced Glycation End Products/antagonists &amp; inhibitors/physiology ; Male ; Retinal Pigment Epithelium/pathology/metabolism/drug effects ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Epithelial-Mesenchymal Transition ; Tomography, Optical Coherence ; Mice, Knockout ; Laser Coagulation/adverse effects ; Cells, Cultured ; Signal Transduction ; Transforming Growth Factor beta2/pharmacology ; Benzamides ; }, abstract = {PURPOSE: Subretinal fibrosis, a complication of neovascular age-related macular degeneration (nAMD), involves the epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells as a contributing mechanism. The receptor for advanced glycation end products (RAGE) is a multiligand receptor implicated in fibrotic diseases, but its role in subretinal fibrosis has not been studied. This study investigated the role of RAGE in subretinal fibrosis.<br><br>METHODS: Subretinal fibrosis was induced in male RAGE-/- and wild-type (WT) mice via laser photocoagulation, and fibrosis lesion volume was assessed on day 35 using optical coherence tomography and immunostaining. In vitro, EMT was induced in primary human RPE cells with transforming growth factor-beta 2 (TGF-&#x3b2;2). The role of RAGE in EMT was studied in cells pretreated with RAGE antagonists (FPS-ZM1 or azeliragon), followed by cotreatment with TGF-&#x3b2;2 for 48&#xa0;hours. Signaling studies were conducted by pretreatment with FPS-ZM1 for 2&#xa0;hours, cotreatment with TGF-&#x3b2;2 for 60&#xa0;minutes, and subsequent immunoblot analysis.<br><br>RESULTS: In RAGE-/- mice, subretinal fibrosis after laser-induced choroidal neovascularization was significantly reduced, with a smaller fibrosis volume, less inflammation, decreased activation of pSmad2, and reduced deposition of fibrotic markers (&#x3b1;SMA, collagen I) compared to WT mice. In vitro treatment with TGF-&#x3b2;2 in human RPE cells increased mitochondrial reactive oxygen species and upregulated EMT markers (&#x3b1;SMA, collagen I, and fibronectin), which were inhibited by cotreatment with FPS-ZM1 or azeliragon. FPS-ZM1 blocked TGF-&#x3b2;2-induced Smad2-dependent signaling and EMT without affecting the extracellular signal-regulated kinase (ERK) pathway.<br><br>CONCLUSIONS: Our findings indicate that RAGE plays a role in RPE cell EMT in subretinal fibrosis and that RAGE antagonists attenuate this process, making RAGE a promising therapeutic target for subretinal fibrosis in nAMD.}, }
@article {pmid40489855, year = {2025}, author = {Jezani, SN and Bastion, MC}, title = {Usage of brolucizumab as treatment for wet age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV): A narrative review.}, journal = {Medicine}, volume = {104}, number = {23}, pages = {e42666}, pmid = {40489855}, issn = {1536-5964}, mesh = {Humans ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy ; Intravitreal Injections ; *Choroidal Neovascularization/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Polypoidal Choroidal Vasculopathy ; }, abstract = {Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is the gold standard treatment for neovascular age-related macular degeneration (nAMD) which is responsible for central vision loss. This results in loss of quality of life, comparably severe to having coronary artery disease or cancer. New anti-VEGF agents need to address issues of potency and durability as existing agents tend to lose their effect after 1 month thus, requiring multiple injections at close intervals. Brolucizumab is one of the latest anti-VEGF agents clinically proven to treat nAMD after on-label agents namely, ranibizumab and aflibercept. Several clinical trials were conducted on Brolucizumab to ensure its safety and efficiency before it is approved to be used as treatment. Brolucizumab maintains and improves retinal edema in nAMD leading to improved vision with longer intervals possible between injections. However, it also has a risk of intraocular inflammation. This review summarizes the evidence for brolucizumab in the treatment of nAMD.}, }
@article {pmid40490296, year = {2025}, author = {Merle, DA and Guymer, RH and Chia, MA and Chopra, R and Williamson, DJ and Struyven, RR and Jannaud, M and Hadoux, X and van Wijngaarden, P and Keane, PA and Wu, Z}, title = {Mapping the impact: AI-driven quantification of geographic atrophy on OCT scans and its association with visual sensitivity loss.}, journal = {The British journal of ophthalmology}, volume = {109}, number = {10}, pages = {1187-1193}, doi = {10.1136/bjo-2024-326603}, pmid = {40490296}, issn = {1468-2079}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Geographic Atrophy/physiopathology/diagnosis/etiology ; Male ; Aged ; Female ; Visual Field Tests ; *Visual Fields/physiology ; *Artificial Intelligence ; *Visual Acuity/physiology ; Aged, 80 and over ; Middle Aged ; Macular Degeneration/complications ; Fluorescein Angiography ; }, abstract = {BACKGROUND/AIMS: To examine the association between artificial intelligence (AI)-driven segmentation of geographic atrophy (GA) on optical coherence tomography (OCT) and visual sensitivity loss quantified by defect-mapping microperimetry, a testing strategy optimised to quantify the spatial extent of deep visual sensitivity losses.<br><br>METHODS: 50 individuals with GA secondary to age-related macular degeneration underwent defect-mapping microperimetry testing within the central 8&#xb0; radius region in one eye. GA on OCT was automatically segmented with an AI-based multiclass classification and segmentation model, and GA on fundus autofluorescence (FAF) images was manually annotated. Their extent in the topographically corresponding region sampled on microperimetry was derived, and structure-function relationships were examined based on Spearman correlation coefficients (&#x3c1;). The distance of each test location from the OCT-defined and FAF-defined GA margin was also derived and used in prediction models of non-response on defect-mapping microperimetry.<br><br>RESULTS: There was a strong correlation between the proportion of locations missed on defect-mapping microperimetry and the corresponding percentage of the central 8&#xb0; radius region with GA on OCT (&#x3c1;=0.85) and FAF (&#x3c1;=0.89). Prediction models for non-response at individual test locations using GA derived from OCT and FAF imaging had a sensitivity of 59% and 62% (p=0.310), respectively, at 95% specificity.<br><br>CONCLUSIONS: AI-driven, automated quantification of GA on OCT showed a strong correlation with the global extent of visual sensitivity loss, comparable with those based on manual annotations on FAF imaging. These findings affirm the expected functional relevance of OCT-derived GA measurements and their clinical utility for monitoring disease progression in those with GA.}, }
@article {pmid40491424, year = {2025}, author = {Xie, X and Lian, S and Yang, W and He, S and He, J and Wang, Y and Zeng, Y and Lu, F and Jiang, J}, title = {Natural products for the treatment of age-related macular degeneration: New insights focusing on mitochondrial quality control and cGAS/STING pathway.}, journal = {Journal of pharmaceutical analysis}, volume = {15}, number = {5}, pages = {101145}, pmid = {40491424}, issn = {2214-0883}, abstract = {Age-related macular degeneration (AMD) is a disease that affects the vision of elderly individuals worldwide. Although current therapeutics have shown effectiveness against AMD, some patients may remain unresponsive and continue to experience disease progression. Therefore, in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment. Recently, studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species (ROS) and activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) innate immunity pathways, ultimately resulting in sterile inflammation and cell death in various cells, such as cardiomyocytes and macrophages. Therefore, combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management. Notably, emerging evidence indicates that natural products targeting mitochondrial quality control (MQC) and the cGAS/STING innate immunity pathways exhibit promise in treating AMD. Here, we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways, as well as their interconnected mediators, which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses, thereby hoping to offer new insights into therapeutic interventions for AMD treatment.}, }
@article {pmid40491639, year = {2025}, author = {Yasuda, S and Tsujinaka, H and Nishiyama, T and Mizusawa, Y and Ueda, T}, title = {Intraocular Inflammation Following Faricimab Intravitreal Injection Treated With Sub-tenon Triamcinolone Acetonide Injection.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e83764}, pmid = {40491639}, issn = {2168-8184}, abstract = {We report the management of intraocular inflammation (IOI) following faricimab intravitreal injection. Severe IOI was observed in three eyes (one eye with age-related macular degeneration (AMD) and two eyes in the same patient with diabetic macular edema (DME)). These three eyes had fine keratic precipitates, inflammatory cells in the anterior chamber, and vitreous opacity, with decreased best-corrected visual acuity (BCVA) in all patients. Blood tests did not reveal any abnormalities, and anterior chamber multiplex polymerase chain reaction and bacterial cultures were negative. Sub-tenon triamcinolone acetonide (STTA) injections improved anterior inflammation, vitreous opacity, and BCVA, although posterior iris synechia caused by inflammation persisted in one patient. Faricimab injection can induce IOI. In this study, IOI was managed with a STTA injection during the early stage of uveitis. Severe inflammation can lead to complications such as posterior iris synechia.}, }
@article {pmid40492092, year = {2025}, author = {Siraz, S and Kamanda, H and Gholami, S and Nabil, AS and Yee Ong, SS and Alam, MN}, title = {Multi-class classification of central and non-central geographic atrophy using Optical Coherence Tomography.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.05.27.25328446}, pmid = {40492092}, support = {R15 EY035804/EY/NEI NIH HHS/United States ; R21 EY035271/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE: To develop and validate deep learning (DL)-based models for classifying geographic atrophy (GA) subtypes using Optical Coherence Tomography (OCT) scans across four clinical classification tasks.<br><br>DESIGN: Retrospective comparative study evaluating three DL architectures on OCT data with two experimental approaches.<br><br>SUBJECTS: 455 OCT volumes (258 Central GA [CGA], 74 Non-Central GA [NCGA], 123 no GA [NGA]) from 104 patients at Atrium Health Wake Forest Baptist. For GA versus age-related macular degeneration (AMD) classification, we supplemented our dataset with AMD cases from four public repositories.<br><br>METHODS: We implemented ResNet50, MobileNetV2, and Vision Transformer (ViT-B/16) architectures using two approaches: (1) utilizing all B-scans within each OCT volume and (2) selectively using B-scans containing foveal regions. Models were trained using transfer learning, standardized data augmentation, and patient-level data splitting (70:15:15 ratio) for training, validation, and testing.<br><br>MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC-ROC), F1 score, and accuracy for each classification task (CGA vs. NCGA, CGA vs. NCGA vs. NGA, GA vs. NGA, and GA vs. other forms of AMD).<br><br>RESULTS: ViT-B/16 consistently outperformed other architectures across all classification tasks. For CGA versus NCGA classification, ViT-B/16 achieved an AUC-ROC of 0.728&#xb1;0.083 and accuracy of 0.831&#xb1;0.006 using selective B-scans. In GA versus NGA classification, ViT-B/16 attained an AUC-ROC of 0.950&#xb1;0.002 and accuracy of 0.873&#xb1;0.012 with selective B-scans. All models demonstrated exceptional performance in distinguishing GA from other AMD forms (AUC-ROC>0.998). For multi-class classification, ViT-B/16 achieved an AUC-ROC of 0.873&#xb1;0.003 and accuracy of 0.751&#xb1;0.002 using selective B-scans.<br><br>CONCLUSIONS: Our DL approach successfully classifies GA subtypes with clinically relevant accuracy. ViT-B/16 demonstrates superior performance due to its ability to capture spatial relationships between atrophic regions and the foveal center. Focusing on B-scans containing foveal regions improved diagnostic accuracy while reducing computational requirements, better aligning with clinical practice workflows.}, }
@article {pmid40492668, year = {2025}, author = {Kopecny, LR and Agar, A and Wong, SW}, title = {Vision &amp; the Ageing Surgeon: A Review.}, journal = {ANZ journal of surgery}, volume = {95}, number = {7-8}, pages = {1312-1319}, doi = {10.1111/ans.70213}, pmid = {40492668}, issn = {1445-2197}, mesh = {Humans ; *Aging/physiology ; *Surgeons ; *Vision, Ocular/physiology ; Aged ; }, abstract = {Populations in the developed world are ageing and their surgeons are no exception. Accurate vision is essential for the surgeon to operate effectively, yet optimal vision has an expiry date in advancing age. This review examines the effects of ageing on the eye with particular focus on the visual changes of significance to senior surgeons who currently account for 20%-25% of the surgeon workforce. The major age-related diseases of the eye, which include cataracts, glaucoma, age-related macular degeneration and diabetic retinopathy, are surmised; together with physiologic ocular changes that accompany normal ageing, including loss of accommodation (presbyopia), reduced pupil size (senile miosis), reduced contrast sensitivity, and impaired binocular vision, amongst others. The aforementioned conditions may impair operative visualisation in the elderly surgeon and potentially impact surgical performance. Strategies and available technologies that support operative visualisation-particularly magnification aids, illumination systems and fluorescent dyes in surgery-are appraised with consideration to the senior surgeon who may be affected by the aforementioned visual changes associated with ageing. To inform minimum standards of visual function for safe surgical practice, future prospective studies are needed which report on individual surgeon-related measures of visual function together with postoperative outcomes. This vein of future research will allow for an evidence-based evaluation of proposed safety measures for which the data are currently lacking, thereby providing clarity regarding whether requisite age-based visual assessments improve surgical outcomes, and if so, at what age and frequency should such evaluations take place.}, }
@article {pmid40492987, year = {2025}, author = {Sasaki, M and Cheong, KX and Chong, CCY and Yu, M and Hanyuda, A and Yuki, K and Negishi, K and Hashimoto, S and Fujiwara, K and Sonoda, K and Wang, YX and Gao, F and Amornpetchsathaporn, A and Chainakul, M and Srinivasan, R and Khan, R and Raman, R and Ruamviboonsuk, P and Kim, SH and Song, SJ and Emamian, MH and Hashemi, H and Fotouhi, A and Liu, J and Li, X and Jonas, JB and Cheung, CMG and Wong, TY and Cheng, CY and Tham, YC and Yanagi, Y and Tan, ACS}, title = {Relationship of Choroidal Thickness With Age-Related Macular Degeneration in Asians: An Asian Eye Epidemiology Consortium Meta-Analysis.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {6}, pages = {36}, pmid = {40492987}, issn = {1552-5783}, mesh = {Humans ; *Choroid/pathology ; Tomography, Optical Coherence/methods ; Male ; *Asian People/ethnology ; Female ; Middle Aged ; *Macular Degeneration/epidemiology/ethnology/diagnosis/pathology ; Aged ; Asia/epidemiology ; Singapore/epidemiology ; }, abstract = {PURPOSE: To compare the choroidal thickness (CT) of participants with various stages of age-related macular degeneration vs. normal controls through a meta-analysis of studies conducted within the Asian Eye Epidemiology Consortium.<br><br>METHODS: Eight population-based studies from China, Iran, Japan, and Singapore were included. Axial length and spherical equivalent measurements and imaging with color fundus photography and spectral-domain optical coherence tomography were performed. Random-effects meta-analysis was performed to examine the association between AMD and its stages (early AMD, intermediate AMD [iAMD], neovascular AMD [nAMD], and geographic atrophy [GA]) with CT, while adjusting for age, sex, current smoking status, and axial length/spherical equivalent.<br><br>RESULTS: Of 17,916 participants, 13,116 participants (mean age, 62.15 &#xb1; 9.66&#xa0;years) were included into the study. The mean unadjusted CT was 245.01 &#xb1; 84.04&#xa0;&#xb5;m (mean CT, 255.4&#xa0;&#xb5;m [no AMD], 263.59&#xa0;&#xb5;m [early AMD], 270.64&#xa0;&#xb5;m [iAMD], 273.32&#xa0;&#xb5;m [nAMD], and 156.50&#xa0;&#xb5;m [GA]). The presence of AMD was associated with a thicker choroid (&#x3b2; = 11.51; 95% confidence interval [CI], 4.10-18.92). AMD severity was also positively associated with CT. Early AMD (&#x3b2; = 8.75; 95% CI, 0.03-17.47), iAMD (&#x3b2; = 19.68; 95% CI, 13.20-26.16), and nAMD (&#x3b2; = 34.15; 95% CI, 6.84-61.46) were each positively associated with a thicker CT after adjusting for age, sex, smoking, and spherical equivalent. GA was not significantly associated with CT.<br><br>CONCLUSIONS: In a large Asian cohort, AMD is associated with a thicker choroid in early AMD, iAMD, and nAMD, but not in GA. Studying the CT will help to better characterize Asian AMD phenotypes, which may show differences compared with AMD phenotypes in Western populations.}, }
@article {pmid40493193, year = {2025}, author = {Wang, Y and Zhang, YC and Ding, ZQ and Xu, SY and Zhang, YR and Zhu, HJ and Huang, C and Wang, JN and Zhu, M and Ji, JD and Yan, B and Liu, QH and Chen, X}, title = {Feedback regulation between histone lactylation and ALKBH3-mediated glycolysis regulates age-related macular degeneration pathology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {24}, pages = {e2416046122}, pmid = {40493193}, issn = {1091-6490}, support = {82471105//MOST | National Natural Science Foundation of China (NSFC)/ ; 82070974//MOST | National Natural Science Foundation of China (NSFC)/ ; 82471096//MOST | National Natural Science Foundation of China (NSFC)/ ; 82271100//MOST | National Natural Science Foundation of China (NSFC)/ ; BK20231371//JST | Natural Science Foundation of Jiangsu Province (Jiangsu Natural Science Foundation)/ ; NA//"333 Project" of Jiangsu Province ("333" Project of Jiangsu Province)/ ; BE2022805//Social Development Program of Jiangsu Province/ ; CZ0121002010037//Jiangsu Province Hospital High-level Talent Cultivation Program (Phase I)/ ; NM202409//The Joint Open Research Fund of Suzhou Institute of Nanotechnology and Nano-bionics &amp; Jiangsu Province Hospital and the Medical Engineering Translational Fund of Jiangsu Province Hospital/ ; }, mesh = {*Macular Degeneration/metabolism/pathology/genetics ; Animals ; Mice ; Humans ; Retinal Pigment Epithelium/metabolism/pathology ; *Glycolysis ; *Histones/metabolism ; Mice, Knockout ; *AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase/metabolism/genetics ; Vascular Endothelial Growth Factor A/metabolism/genetics ; Feedback, Physiological ; Choroidal Neovascularization/metabolism/pathology/genetics ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly. It is characterized by degeneration of the retinal pigment epithelium (RPE), which can develop into choroidal neovascularization (CNV) to cause severe and rapid vision loss. Preventing this progression might help save vision, but the exact mechanisms remain unclear. In this study, using clinical AMD samples and the gene knockout mice, we reported that the m[1]A eraser ALKBH3 reshaped retinal metabolism to promote this progression. In RPE, the dm[1]ACRISPR system demonstrated that ALKBH3 demethylated the rate-limiting glycolytic enzyme HK2 to activate glycolysis, resulting in excess lactate production. This lactate promoted histone lactylation at H3K18, which in turn bound to ALKBH3 to amplify its transcription, establishing a positive feedback loop. The ALKBH3 inhibitor HUHS015 disrupted this loop, effectively mitigating RPE degeneration. Furthermore, ALKBH3 directly targeted the proangiogenic factor VEGFA to modulate the metabolic cross-talk between RPE and choroidal capillaries, thus promoting CNV. HUHS015 inhibited CNV synergistically with the anti-VEGF drug Aflibercept. Overall, our study provides critical insights into the molecular mechanisms and metabolic events that facilitates the progression from RPE degeneration to CNV in AMD, laying the groundwork for new treatments of age-related retinal disorders.}, }
@article {pmid40493982, year = {2025}, author = {Yang, B and Yang, K and Xi, R and Li, S and Chen, J and Wu, Y}, title = {Long-term senolytic therapy with Dasatinib and Quercetin alleviates lipofuscin-dependent retinal degeneration in mice.}, journal = {Redox biology}, volume = {85}, number = {}, pages = {103716}, pmid = {40493982}, issn = {2213-2317}, mesh = {Animals ; Mice ; *Lipofuscin/metabolism ; *Dasatinib/pharmacology/therapeutic use/administration &amp; dosage ; *Quercetin/pharmacology/therapeutic use/administration &amp; dosage ; Disease Models, Animal ; *Retinal Degeneration/drug therapy/metabolism/pathology/etiology ; Mice, Knockout ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Oxidative Stress/drug effects ; *Senotherapeutics/pharmacology ; Macular Degeneration/drug therapy/metabolism/pathology ; ATP-Binding Cassette Transporters/genetics ; Alcohol Oxidoreductases/genetics ; }, abstract = {Dry age-related macular degeneration (AMD) is one of the common blinding eye diseases, with pathological hallmarks of lipofuscin accumulation, neuroretina atrophy and retinal pigment epithelium (RPE) degeneration. Currently, there are no effective interventions for dry AMD. Although there is already evidence suggesting a link between cellular senescence and age-related diseases, it is still unclear whether long-term senolytic therapy with Dasatinib and Quercetin (D + Q) can slow the progression of dry AMD and ultimately prevent retinal structural damage and function loss. Mice lacking the Abca4 and Rdh8 genes (Abca4[-/-]Rdh8[-/-] mice) are a preclinical model of dry AMD. In this study, we performed a 4-month senolytic therapy with D + Q on 4-month-old Abca4[-/-]Rdh8[-/-] mice. Abca4[-/-]Rdh8[-/-] mice at the age of 8 months showed obvious retinal degeneration, along with RPE senescence, lysosomal alkalinization, lipofuscin accumulation and oxidative stress. Importantly, the long-term D + Q regimen significantly alleviated the degeneration of retinal structures and function in 8-month-old Abca4[-/-]Rdh8[-/-] mice, and it effectively repressed cellular senescence, lysosomal alkalinization, lipofuscin accumulation and oxidative stress in the RPE. This study is the first to demonstrate the effect of long-term intervention with senolytics D + Q on dry AMD. Overall, these findings highlight the potential of long-term senolytic treatment as an intervention for dry AMD.}, }
@article {pmid40494650, year = {2025}, author = {Chen, PJ and Lee, JL and Wan, L and Lin, HJ and Chen, WL and Chen, SN and Lin, CJ and Lin, JM and Lai, CT and Hsia, NY and Huang, YT and Tsai, YY and Lin, HJ and Hsieh, YW and Cheng, YD and Tsai, FJ and Chou, CC and Tien, PT}, title = {Impact of long-term statin therapy on age-related macular degeneration: A nationwide population-based study.}, journal = {British journal of clinical pharmacology}, volume = {91}, number = {10}, pages = {2946-2956}, doi = {10.1002/bcp.70128}, pmid = {40494650}, issn = {1365-2125}, support = {DMR-112-102; DMR-113-121; DMR-113-205; DMR-113-084//China Medical University Hospital/ ; DMR-112-102//China Medical University Hospital/ ; DMR-113-121//China Medical University Hospital/ ; DMR-113-205//China Medical University Hospital/ ; DMR-113-084//China Medical University Hospital/ ; MOHW113-TDU-B-212-114009//Taiwan Ministry of Health and Welfare Clinical Trial Center/ ; }, mesh = {Humans ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration &amp; dosage/therapeutic use ; Male ; Female ; Taiwan/epidemiology ; Aged ; *Macular Degeneration/epidemiology/prevention &amp; control ; Incidence ; Middle Aged ; Databases, Factual ; Aged, 80 and over ; Time Factors ; Risk Factors ; Kaplan-Meier Estimate ; Proportional Hazards Models ; }, abstract = {AIMS: Age-related macular degeneration (AMD) is a leading cause of vision loss worldwide among older adults. Although some studies propose that statins could reduce AMD risk and progression, others report conflicting findings. This study aimed to evaluate the impact of statin use on the incidence of AMD.<br><br>METHODS: This study used Taiwan's National Health Insurance Research Database (2000-2021) with the LGTD2000 cohort. Participants were categorized into statin users (&#x2265;6&#x2009;months, 2001-2020) and nonusers. AMD incidence was analysed using Cox regression and Kaplan-Meier methods, with propensity score matching applied to report adjusted hazard ratios (AHRs) and confidence intervals (CIs).<br><br>RESULTS: After adjusting for confounding factors, statin use for over 2&#xa0;years was associated with a significantly lower risk of AMD compared to nonstatin users (AHR&#x2009;=&#xa0;0.79, 95% CI: 0.69-0.91). Subgroup analyses demonstrated that long-term statin use (&#x2265;730&#x2009;days) showed protective associations across most sex and age groups. Specifically, risk reduction was observed for both non-neovascular AMD (AHR&#x2009;=&#xa0;0.84, 95% CI: 0.70-1.02) and neovascular AMD (AHR&#x2009;=&#xa0;0.72, 95% CI: 0.59-0.88). Furthermore, dose-response analysis revealed that higher cumulative statin exposure was associated with a decreased AMD risk, while lower cumulative exposure was associated with an increased risk.<br><br>CONCLUSION: This study indicated that prolonged statin use exceeding 2 years was associated with a significantly decreased risk of developing both non-neovascular and neovascular AMD.}, }
@article {pmid40496216, year = {2025}, author = {Sideri, O and Correa, V and Ziakas, N and Tsinopoulos, I and Miller, JW and Vavvas, DG}, title = {Systematic Review of Proteomics in Age-Related Macular Degeneration and Pathway Analysis of Significant Protein Changes.}, journal = {Ophthalmology science}, volume = {5}, number = {5}, pages = {100793}, pmid = {40496216}, issn = {2666-9145}, support = {R01 EY030088/EY/NEI NIH HHS/United States ; }, abstract = {TOPIC: Proteomics in age-related macular degeneration (AMD) research.<br><br>CLINICAL RELEVANCE: AMD is the leading cause of blindness in industrialized countries, with a poorly understood pathogenesis. Proteomics can identify significantly altered proteins in AMD patients, aiding in understanding the disease's pathophysiology and potentially improving diagnosis or treatment strategies.<br><br>METHODS: A systematic review of proteomic studies in AMD was conducted. Proteins significantly altered in dry and wet AMD and those tested as biomarkers were presented according to sample type (aqueous humor, plasma, urine, vitreous, retinal pigment epithelium/choroid, and tear film) and type of assay (mass spectrometry or aptamers) used in the individual studies. Proteins that exhibited at least a 2&#xd7; fold change (FC) were further analyzed through functional enrichment analysis and protein-protein interaction networks (STRING database).<br><br>RESULTS: Twenty-two studies (case-control and cohorts) with a total of 6932 participants were included. The included studies showed significant heterogeneity, and most of them lacked sufficient power. Results suggested that various proteins and pathways are implicated in AMD, and there were differences when comparing results from the individual studies and unbiased results. Although many proteins differed significantly between AMD and control groups, most exhibited less than a 2-FC. Functional analysis of proteins with &#x2265;|2|-FCs (identified by unbiased proteomics in multiple biofluids) highlighted lipid metabolism and protease regulation pathways as central to both dry and wet AMD. Complement and coagulation cascades, chaperones, and glycolysis pathways were significant in wet AMD, whereas matrix remodeling pathways were enriched mostly in dry AMD.<br><br>CONCLUSION: Combining proteomics from various studies could reveal new protein-protein interaction networks and associated functional pathways that may suggest novel potential therapeutic targets for AMD. However, there is a scarcity of data available for early AMD from ocular biofluids, and it should be the aim of future proteomics studies.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40496348, year = {2025}, author = {Jeong, HC and Cho, CS and Kim, JH and Chang, I and Kim, JH}, title = {Evaluating the Therapeutic Potential of Superoxide Dismutase in a Rat Model of Wet Age-Related Macular Degeneration.}, journal = {FASEB bioAdvances}, volume = {7}, number = {6}, pages = {e70015}, pmid = {40496348}, issn = {2573-9832}, abstract = {Age-related macular degeneration (AMD) is a major cause of vision loss in the elderly, with limited oral treatment options for the wet form characterized by choroidal neovascularization (CNV). This study evaluated GF103, a mutant superoxide dismutase (SOD) from Bacillus amyloliquefaciens, for its potential as an oral therapy in a laser-induced CNV rat model. GF103 was orally administered at varying doses, and outcomes included CNV area, retinal leakage, and VEGF/HIF-1α expression. GF103 was well tolerated and significantly reduced CNV area and retinal VEGF expression at higher doses (≥ 25 mg/kg for retinal VEGF expression; ≥ 50 mg/kg for CNV area). While reductions in fluorescein leakage and HIF-1α levels were not statistically significant, trends suggested modulation of oxidative and hypoxia-related pathways. These results support the potential of GF103 as a safe oral adjunct to existing therapies for wet AMD, meriting further investigation.}, }
@article {pmid40497378, year = {2025}, author = {Anisetti, B and Stewart, MW and Markovic, D and Eggenberger, ER and Ertekin-Taner, N and Meschia, JF and Lin, MP}, title = {Age-related macular degeneration and risk of stroke and all-cause mortality.}, journal = {Neurologia i neurochirurgia polska}, volume = {59}, number = {4}, pages = {413-419}, doi = {10.5603/pjnns.98951}, pmid = {40497378}, issn = {0028-3843}, mesh = {Humans ; Female ; Male ; *Macular Degeneration/mortality/epidemiology/complications ; Middle Aged ; Aged ; *Stroke/mortality/epidemiology ; Risk Factors ; United States/epidemiology ; Adult ; Nutrition Surveys ; Aged, 80 and over ; }, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is the most common degenerative disorder of the retina and choroid. Retinal vascular diseases have been associated with adverse cardiovascular outcomes, but an association between AMD and stroke has not been well established. We aimed to test the relationship between AMD, stroke, and age-adjusted mortality.<br><br>MATERIAL AND METHODS: Data was obtained from the US National Health and Nutrition Examination Surveys 2005 to 2008, with linked mortality through to 2015. Participants aged 40 or older with gradable AMD on fundus photographs were included. AMD was classified as either early or late. Independent relationships between AMD and stroke were assessed using multivariable logistic regression models. Risk of all-cause mortality was assessed using Cox regression models, before and after adjusting for covariates.<br><br>RESULTS: Of the 5,481 participants included, 49.8% were women, 56.5% white, 20.3% black, and 15.5% Hispanic. 425 (7.8%) had AMD. After adjusting for vascular risk factors, we found that AMD was associated with an increased risk of stroke (aOR 1.87, 95% CI 1.25-2.79, p = 0.002). There was a relationship between AMD and stroke depending on whether participants had early AMD (aOR 1.66, 95% CI 1.09-2.51) or late AMD (aOR 3.32, 95% CI 1.36-8.12). All-cause mortality was higher in those with AMD (HR 1.35, 95% CI 1.06-1.72) and late AMD (HR 2.18, 95% CI 1.33-3.58).<br><br>CONCLUSIONS: Age-related macular degeneration is associated with stroke and all-cause mortality, independent of age and vascular risk factors. Our findings suggest potential non-vascular mechanisms related to the aetiology of AMD may increase the risk of stroke.}, }
@article {pmid40498279, year = {2025}, author = {Faia, LJ and Ackert, J and Rodriguez, R and Abdul Sultan, A and Garey, C and Teneralli, RE and Ong, R}, title = {Comorbid Depression and Anxiety Risk in Older Individuals with Geographic Atrophy: A US Claims Data Analysis.}, journal = {Advances in therapy}, volume = {42}, number = {8}, pages = {3826-3838}, pmid = {40498279}, issn = {1865-8652}, mesh = {Humans ; Female ; Aged ; Male ; Retrospective Studies ; United States/epidemiology ; Comorbidity ; *Anxiety/epidemiology ; Middle Aged ; *Depression/epidemiology ; *Geographic Atrophy/psychology/epidemiology ; Aged, 80 and over ; Databases, Factual ; }, abstract = {INTRODUCTION: Geographic atrophy (GA), an advanced stage of nonexudative age-related macular degeneration (AMD), is associated with progressive central vision loss and blindness. While the association between GA and impaired vision-related quality of life has been established, understanding of the co-occurrence of anxiety and depression in individuals with GA is limited.<br><br>METHODS: We conducted a retrospective, noninterventional, cohort study analyzing data from three large US databases (Optum's de-identified Clinformatics[&#xae;] Data Mart Database [Clinformatics[&#xae;]], Merative&#x2122; MarketScan[&#xae;] Commercial and Medicare Databases [MarketScan], and IQVIA US PharMetrics[&#xae;] [PharMetrics]), employing a common data model. Patients aged&#x2009;&#x2265;&#x2009;50&#xa0;years with a diagnosis of GA were included and were matched to patients without GA in a 1:2 ratio using propensity score matching to create a non-GA/AMD control population. Outcomes included time from GA diagnosis to first interaction with a health care provider for depression or anxiety and health care resource utilization (HCRU). Relative risks (RRs) and 95% confidence intervals (CIs) were calculated between GA and control cohorts with stratification by eye and subfoveal involvement.<br><br>RESULTS: The Clinformatics[&#xae;], MarketScan, and PharMetrics datasets included 44,595, 9468, and 27,427 patients with GA, respectively. Across databases, mean (SD) age ranged from 75.7 (8.3) to 80.5 (7.2) years, and 61% to 64% were female. Comorbid depression and anxiety risk were higher in patients with GA versus controls across datasets (depression RR [95%&#xa0;CI] 1.24 [1.13-1.35] to 1.36 [1.31-1.41]; anxiety RR [95%&#xa0;CI] 1.17 [1.06-1.30] to 1.33 [1.27-1.39]), with the greatest risk seen in those with bilateral GA with subfoveal involvement. HCRU was also significantly higher in patients with GA versus controls.<br><br>CONCLUSION: This study found a higher risk for comorbid depression or anxiety in patients with GA versus propensity score-matched controls. Risk was greatest among those with bilateral GA with subfoveal involvement. These findings highlight the important mental health burden experienced by patients with GA.}, }
@article {pmid40498743, year = {2025}, author = {Sugisawa, T and Gomi, F and Harada, Y and Imaizumi, H and Aoki, S and Miki, A and Kishi, M and Yamauchi, T and Nagasato, D and Ozawa, Y and Haruta, M and Kato, N and Matsubara, H and Yasukawa, T and Kato, A and Terasaki, H and Hirano, T and Iesato, Y and Tsujinaka, H and Murakami, T and Mitamura, Y and Wakuta, M and Kimura, K and Shimura, M and , }, title = {Factors that contribute to loss to follow-up in the medium term after initiation of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration in Japanese patients.}, journal = {PloS one}, volume = {20}, number = {6}, pages = {e0325963}, pmid = {40498743}, issn = {1932-6203}, mesh = {Humans ; Female ; Male ; Aged ; Retrospective Studies ; Japan/epidemiology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Case-Control Studies ; *Angiogenesis Inhibitors/therapeutic use ; *Macular Degeneration/drug therapy ; *Lost to Follow-Up ; Visual Acuity ; Follow-Up Studies ; Middle Aged ; East Asian People ; }, abstract = {PURPOSE: To identify time-specific factors associated with loss to follow-up (LTFU) in the early to medium term after initiating anti-vascular endothelial growth factor (VEGF) treatment in patients with neovascular age-related macular degeneration (nAMD) in Japan.<br><br>METHODS: The study had a retrospective multicenter case-control design and was performed across 16 specialist retinal facilities in Japan. Patients diagnosed with nAMD at their initial visit who initiated treatment between January 2017 and December 2020 were included. Patient characteristics were analyzed to identify factors associated with LTFU within 3 months (very early), 3 months to 1 year (early), and 1 year to 2 years (medium term) after starting treatment.<br><br>RESULTS: Data for 2389 patients with nAMD were analyzed. The very early, early, and medium-term LTFU rates were 6.8%, 13.8%, and 21.2%, respectively. Stepwise regression analysis identified factors that were significantly associated with LTFU at a very early stage to be greater central retinal thickness at baseline and a prior treatment history, those associated with early LTFU to be worse baseline best-corrected visual acuity (BCVA), anti-VEGF treatment combined with photodynamic therapy, and a follow-up period that overlapped with the COVID-19 pandemic, and that associated with medium-term LTFU to be worse BCVA at 3 months. LTFU in any period within 3 months to 2 years was more likely in patients aged >80 years, and LTFU very early within 3 months was more likely in those aged <60 years. A poor baseline BCVA (logMAR) of >1 was a risk factor for LTFU within 3 months and 1 year, whereas LTFU was significantly less likely in patients with good baseline BCVA (<0.1).<br><br>CONCLUSION: The LTFU rate in patients with nAMD increased over time. Factors contributing to LTFU vary depending on the time since initiation of treatment.}, }
@article {pmid40499235, year = {2025}, author = {Tabilo, C and Squella, V and Illesca, P and Muñoz, Y and Farías, C and Valenzuela, R}, title = {Impact of n-3 polyunsaturate fatty acids supplementation on visual health throughout the life cycle: A systematic review.}, journal = {Prostaglandins, leukotrienes, and essential fatty acids}, volume = {206}, number = {}, pages = {102686}, doi = {10.1016/j.plefa.2025.102686}, pmid = {40499235}, issn = {1532-2823}, mesh = {Humans ; *Fatty Acids, Omega-3/administration &amp; dosage/pharmacology ; *Dietary Supplements ; Female ; *Vision, Ocular/drug effects ; Pregnancy ; Adult ; Male ; Child ; Randomized Controlled Trials as Topic ; Infant ; Child, Preschool ; Adolescent ; Attention Deficit Disorder with Hyperactivity ; }, abstract = {INTRODUCTION: N-3 polyunsaturated fatty acids (n-3 PUFA) are important for mammals and have relevant functions in the body. These fatty acids play an important role in brain development, in the protection of the retina, and in the prevention of macular degeneration. Currently, clinical trials do not yet confirm a clear benefit of n-3 PUFA supplementation on vision throughout the life cycle. Therefore, the aim of this study is to systematically evaluate the available scientific evidence to determine the effects of n-3 PUFA supplementation on visual health throughout the life cycle.<br><br>MATERIAL AND METHODS: A search of scientific literature was performed, based on randomized, controlled clinical studies, published in PubMed, using keywords. We included people of both sexes throughout the life cycle that evaluated the impact of n-3 PUFA supplementation on visual health.<br><br>RESULTS: Of the 87 articles included in this review, there are important contradictions in the literature regarding the effects of supplementation in pregnant women, infants and older adults. While some studies highlight beneficial effects, an equal number of studies report no impact. In the case of preschoolers and schoolchildren, predominantly positive effects were identified, especially in children with Attention Deficit Hyperactivity Disorder (ADHD). For youth and adults, the impact of supplementation varied according to the health condition assessed, mostly supporting significant benefits in individuals with dry eye symptoms.<br><br>CONCLUSION: Evidence supports supplementation with n-3 PUFA, especially docosahexaenoic acid (DHA), to improve visual development in infants, schoolchildren, especially those with ADHD. Despite variability in visual outcomes, these findings suggest a crucial role of n-3 PUFA supplementation in visual health in the first steps of life, but in adults and older adults remain uncertain or null. Therefore, it is critical to investigate optimal dosing, duration of the intervention as the age of the participants in future research.}, }
@article {pmid40499265, year = {2025}, author = {Zhang, T and Jin, K and Zeng, S and Yang, P and Zhu, M and Zhang, J and Chen, Y and Lee, S and Yam, M and Zeng, Y and Lu, X and Loo, L and Neely, GG and Chang, A and Zhou, F and Du, J and Fan, X and Zhu, L and Gillies, MC}, title = {Divergent redox responses of macular and peripheral Müller Glia: Implications for retinal vulnerability.}, journal = {Redox biology}, volume = {85}, number = {}, pages = {103691}, pmid = {40499265}, issn = {2213-2317}, mesh = {*Ependymoglial Cells/metabolism/pathology ; Oxidation-Reduction ; Humans ; Oxidative Stress ; *Macula Lutea/metabolism/pathology ; *Retina/metabolism/pathology ; Animals ; Gene Expression Regulation ; Macular Degeneration/metabolism/genetics/pathology ; }, abstract = {The macula is preferentially affected in some common retinal diseases (such as age-related macular degeneration, diabetic retinopathy and macular telangiectasia type 2), whereas most inherited retinal degenerations (e.g., retinitis pigmentosa) tend to initially affect the peripheral retina. This pattern suggests the macula may have intrinsic vulnerabilities in its oxidative stress defences, compared to the periphery. Profiling of single-cell level transcriptional changes found that the peripheral retina exhibited greater transcriptional alterations than the macula in response to stress. One pronounced change was in a subgroup of Müller glia (MG) that was dominant in the peripheral retina. Genes more abundantly expressed in peripheral MG were mainly associated with redox regulation, oxidative stress responses and cellular detoxification and were more influenced by oxidative insults, such as light-induced stress. In contrast, genes highly expressed in macular MG were primarily involved in cellular homeostasis and neuroprotection, showing less responsiveness to oxidative challenges. Notably, Metallothionein 1 (MT1), A-Kinase Anchor Protein 12 (AKAP12) and MAF BZIP Transcription Factor F (MAFF) were significantly more expressed in peripheral MG than in macular MG, indicating a region-specific redox regulatory mechanism. Knockdown of these genes in primary MG led to decreased viability under oxidative stress, suggesting their role in antioxidant defence. Our findings indicate that macular MG prioritise retinal function over redox adaptation, which may contribute to their vulnerability to degenerative diseases associated with oxidative damage. These insights underscore the importance of region-specific redox homeostasis in retinal health and disease.}, }
@article {pmid40499495, year = {2025}, author = {Qin, S and Zhu, Y and Liu, Y and Xie, H and Zhang, J and Zhang, C and Xu, G}, title = {Nintedanib inhibits neovascularization and subretinal fibrosis in a laser-induced choroidal neovascularization mouse model.}, journal = {Biochemical and biophysical research communications}, volume = {775}, number = {}, pages = {152169}, doi = {10.1016/j.bbrc.2025.152169}, pmid = {40499495}, issn = {1090-2104}, mesh = {Animals ; *Choroidal Neovascularization/drug therapy/pathology/etiology/metabolism ; Fibrosis/drug therapy ; *Indoles/administration &amp; dosage/pharmacology/therapeutic use ; Disease Models, Animal ; Mice ; Epithelial-Mesenchymal Transition/drug effects ; Mice, Inbred C57BL ; Cell Line ; Humans ; Lasers/adverse effects ; *Retina/pathology/drug effects ; Intravitreal Injections ; Cell Movement/drug effects ; Male ; Retinal Pigment Epithelium/drug effects/pathology ; }, abstract = {BACKGROUND: Subretinal fibrosis is a pivotal pathological factor contributing to vision loss in the elderly with neovascular age-related macular degeneration (nAMD), which is lack of effective treatment currently. The aim of this study was to assess the effects of nintedanib on subretinal fibrosis in a laser-induced choroidal neovascularization (CNV) mouse model and elucidate the molecular mechanisms of its action.<br><br>METHODS: The CNV mouse model was established by laser photocoagulation, and nintedanib was administered intravitreally 1 day after laser induction to verify the therapeutic efficacy of nintedanib on mice. TGF-&#x3b2;1 was employed to induce epithelial-mesenchymal transition (EMT) in ARPE-19&#xa0;cells. Subsequently, immunofluorescence, transwell migration, scratch assay and Western blot were employed to assess the effect of nintedanib on subretinal fibrosis, EMT and EMT-associated cell function.<br><br>RESULTS: The neovascular and fibrotic lesions exhibited a significant reduction in laser-induced CNV mice on days 7 and 14 after intravitreal injection of various concentrations of nintedanib. Compared to normal control mice, the expression of fibrosis markers (collagen-1, &#x3b1;-SMA and fibronectin) was significantly upregulated in the RPE-choroid-sclera complexes of CNV mice, which was effectively attenuated by nintedanib. Furthermore, following nintedanib treatment, the TGF-&#x3b2;1-induced EMT of the ARPE-19&#xa0;cells was significantly inhibited, as evidenced by a reduction in the levels of collagen-1, &#x3b1;-SMA, fibronectin, Vimentin and N-cadherin, along with a diminished capacity for cell migration. Mechanistically, nintedanib effectively blocked the activation of Smad 2/3, ERK 1/2, p38 and Akt signaling pathways in ARPE-19&#xa0;cells induced by TGF-&#x3b2;1.<br><br>CONCLUSION: The inhibition of subretinal fibrosis by nintedanib might be attributed to its suppression of EMT via inactivation of the Smad 2/3, ERK 1/2, p38 and Akt signaling pathways, thereby providing a potential molecule for the treatment of subretinal fibrosis.}, }
@article {pmid40499938, year = {2025}, author = {Faranoush, M and Khesali, F and Faranoush, P and Foroughi-Gilvaee, MR and Shams, P and Sadighnia, N and Ahmadi, SAY and Fallah Azad, D and Nekouian, R}, title = {Insights into retinoblastoma pathogenesis: unraveling RB1, N-MYC and miRNA profiles.}, journal = {BMJ open ophthalmology}, volume = {10}, number = {1}, pages = {}, pmid = {40499938}, issn = {2397-3269}, mesh = {Humans ; *Retinoblastoma/genetics/diagnosis/metabolism ; Male ; *MicroRNAs/genetics/biosynthesis ; Female ; Child, Preschool ; *Retinal Neoplasms/genetics/metabolism/diagnosis ; Child ; *Retinoblastoma Binding Proteins/genetics/biosynthesis ; *Ubiquitin-Protein Ligases/genetics/biosynthesis ; *Gene Expression Regulation, Neoplastic ; *N-Myc Proto-Oncogene Protein/genetics/biosynthesis ; Real-Time Polymerase Chain Reaction ; Biomarkers, Tumor/genetics ; }, abstract = {OBJECTIVE: Retinoblastoma is the most common paediatric intraocular malignancy, originating in neural retina germ cells. Early diagnosis is crucial for survival and eye preservation. This study analyses gene expression and specific microRNAs (miRNAs) in patients with retinoblastoma to enhance early diagnosis, prognosis and treatment strategies.<br><br>METHODS: This study examined gene and miRNA expression in 18 patients with retinoblastoma and 10 healthy individuals. Peripheral blood samples were collected from all participants, and patient demographics were recorded. The analysis was performed using real-time PCR targeting the RB1 and N-MYC genes, along with the miRNAs miR-125-5p, miR-221-3p and miR-519-3p.<br><br>RESULTS: The patient group consisted of 18 participants (9 males, 9 females), aged between 2 and 6 years (mean&#xb1;SD: 4.8&#xb1;1.33 years), with a mean diagnosis age of 3.01&#xb1;1.37 years. All participants were followed for 3 years, with no fatalities. The control group comprised 10 participants (4 males, 6 females), aged 2-8 years (mean&#xb1;SD: 5.01&#xb1;1.77 years). 11 patients underwent enucleation due to tumour progression: 3 right eyes and 8 left eyes. Gene expression analysis showed significant downregulation of miR-125-5p, miR-519-3p and NMYC in the retinoblastoma group. RB1 downregulation and miR-221-3p upregulation were noted in most patients, but without significant associations.<br><br>CONCLUSION: miRNAs, along with RB1 and N-MYC genes, may serve as predictive and prognostic biomarkers in retinoblastoma. While previous studies have highlighted the impact of certain miRNAs on survival and clinical outcomes, our study is limited by a small sample size and lack of strong statistical correlations. Large-scale studies are needed to validate these preliminary findings and clarify their clinical significance. Understanding the role of miRNAs in cancer biology could improve retinoblastoma mechanism insights and patient care.}, }
@article {pmid40500585, year = {2025}, author = {Ota, H and Takeuchi, J and Nonogaki, R and Tamura, K and Kaneko, H and Nishiguchi, KM}, title = {Efficacy of switching from existing anti-vascular endothelial growth factor drugs to ranibizumab biosimilar in neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {69}, number = {6}, pages = {886-893}, pmid = {40500585}, issn = {1613-2246}, support = {7122Jr-09c//Senju/ ; }, mesh = {Humans ; *Ranibizumab/administration &amp; dosage ; Prospective Studies ; Female ; Male ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Intravitreal Injections ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Wet Macular Degeneration/drug therapy/diagnosis/metabolism ; *Drug Substitution ; *Biosimilar Pharmaceuticals/administration &amp; dosage ; Treatment Outcome ; Aqueous Humor/metabolism ; Tomography, Optical Coherence ; Aged, 80 and over ; Follow-Up Studies ; Fluorescein Angiography ; Fundus Oculi ; }, abstract = {PURPOSE: This study evaluated the clinical outcomes and aqueous humor cytokine levels in eyes with neovascular age-related macular degeneration (nAMD) switched from intravitreal aflibercept to ranibizumab biosimilar (BS).<br><br>STUDY DESIGN: Prospective observational study.<br><br>METHODS: Thirty-eight eyes of 38 patients with nAMD who received aflibercept under a treat-and-extend (TAE) regimen were prospectively switched to ranibizumab BS. Eight eyes with cataracts undergoing surgery served as controls for aqueous humor cytokine analysis. Best-corrected visual acuity (BCVA) and anatomical outcomes were assessed over one year. The aqueous humor levels of vascular endothelial growth factor (VEGF)-A, angiopoietin-2 (Ang-2), and placental growth factor (PlGF) were measured before and after switching in eyes with nAMD and at surgery in controls.<br><br>RESULTS: Disease activity remained controlled in 94.3% of patients with nAMD for over one year. No significant changes were observed in the BCVA (P=0.65) after one year. Ang-2 levels remained unchanged (P=0.66) and were not significantly different between eyes with nAMD and controls both before (P=0.64) and after switching (P=0.30). PlGF levels also remained stable (P=0.12) but were significantly higher in eyes with nAMD than in controls both before (P<0.01) and after switching (P=0.03). VEGF-A levels significantly increased after switching (P<0.01) but remained lower than in the controls both before (P<0.01) and after switching (P=0.02).<br><br>CONCLUSION: Switching from aflibercept to ranibizumab BS effectively maintained disease stability and cytokine balance in eyes with nAMD. These findings support ranibizumab BS as a viable and cost-effective alternative for long-term treatment.}, }
@article {pmid40500586, year = {2025}, author = {Wada, I and Nakao, S and Shiose, S and Kaizu, Y and Yamaguchi, M and Ishikawa, K and Kiyohara, K and Ishibashi, T and Sonoda, KH}, title = {En-face quantitative evaluation using ultra-high-resolution OCT of hyperreflective foci in neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {69}, number = {5}, pages = {738-744}, pmid = {40500586}, issn = {1613-2246}, support = {20K09829//JSPS KAKENHI/ ; }, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; Intravitreal Injections ; *Visual Acuity ; Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis ; Aged ; Fluorescein Angiography/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Follow-Up Studies ; Fundus Oculi ; Ranibizumab/administration &amp; dosage ; *Macula Lutea/pathology ; Bevacizumab/administration &amp; dosage ; }, abstract = {PURPOSE: This study quantifies hyperreflective foci (HRFs) in neovascular age-related macular degeneration (nAMD) before and after anti-VEGF therapy in the initial loading phase using en-face ultra-high-resolution spectral domain OCT (UHR-SD-OCT), investigating their correlation with clinical findings.<br><br>STUDY DESIGN: Retrospective observational study METHODS: This retrospective study included 30 eyes from 30 patients with treatment-na&#xef;ve nAMD. The patients received monthly intravitreal injections of anti-VEGF therapy for three months as the initial loading phase. At each visit, comprehensive ophthalmic examinations were conducted. HRFs were quantified using our custom-developed&#xa0;software from an en-face UHR-SD-OCT. The number of HRFs was compared before and after the loading phase and investigated the relationship with best-corrected visual acuity (BCVA), greatest linear dimension (GLD), macular neovascularization (MNV) size and incidence of macular atrophy (MA).<br><br>RESULTS: This evaluation system showed a significant reduction in the number of HRFs after anti-VEGF therapy compared to before the loading phase (p < 0.0001). The number of pre-treatment HRFs significantly correlated with pre-treatment BCVA, GLD, and MNV size. The number of post-treatment HRFs significantly correlated with pre-treatment GLD and pre-treatment MNV size. Additionally, patients who developed MA two years after treatment initiation exhibited significantly higher counts of pre-treatment HRFs compared to those without the MA development (465.7 &#xb1; 187.0 vs. 212.9 &#xb1; 93.8, p < 0.05).<br><br>CONCLUSIONS: Quantification of HRF using en-face UHR-SD-OCT may be a useful clinical biomarker during anti-VEGF therapy in nAMD.}, }
@article {pmid40502292, year = {2025}, author = {Terao, R and Aoki, S and Kitamoto, K and Totani, K and Yamanari, M and Sugiyama, S and Inoue, T and Obata, R and Azuma, K}, title = {Quantification of Hyperreflective Foci in Age-related Macular Degeneration by Polarization-Sensitive OCT.}, journal = {Ophthalmology science}, volume = {5}, number = {5}, pages = {100792}, pmid = {40502292}, issn = {2666-9145}, abstract = {PURPOSE: To quantify hyperreflective foci (HRF) using polarization-sensitive OCT (PS-OCT) and evaluate the effect of anti-VEGF therapy on HRF reduction.<br><br>DESIGN: Retrospective study.<br><br>SUBJECTS: Twelve eyes from 12 patients with neovascular age-related macular degeneration (nAMD) who underwent PS-OCT imaging before and after 4 intravitreal injections of faricimab, administered every 4 weeks.<br><br>METHODS: Retinal layers between the inner border of the inner nuclear layer and the outer border of the outer segment of photoreceptors were analyzed. Regions with entropy values exceeding the mean + 2 standard deviations from healthy controls (entropy: 0.0896 &#xb1; 0.0270) were isolated to quantify hyperentropic foci (HEF), representing HRF.<br><br>MAIN OUTCOME MEASURES: The sum and area of HEF were calculated as total HEF and area aggregate to compare before and after the treatment.<br><br>RESULTS: The mean patient age was 77.4 &#xb1; 8.6 years, with an equal distribution of males and females (6 each). Total HEF was significantly associated with worse baseline visual acuity (coefficient: 0.0015297, P = 0.0004). Faricimab treatment significantly reduced both total HEF (P = 0.0049) and area aggregate (P = 0.0068). However, conventional OCT did not detect significant improvements in total reflectivity nor area aggregate.<br><br>CONCLUSIONS: Polarization-sensitive OCT is a valuable imaging modality for extracting and quantifying HRF in the neurosensory retina. Faricimab significantly reduces HEF in nAMD eyes, highlighting its potential therapeutic effect beyond conventional OCT-detected changes.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosures may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40502295, year = {2025}, author = {Liu, TYA and Liu, Y and Gastonguay, MS and Midgett, D and Kuo, N and Zhao, Y and Ullah, K and Alexander, G and Hartman, T and Koseoglu, ND and Jones, C}, title = {Predicting Imminent Conversion to Exudative Age-Related Macular Degeneration Using Multimodal Data and Ensemble Machine Learning.}, journal = {Ophthalmology science}, volume = {5}, number = {5}, pages = {100785}, pmid = {40502295}, issn = {2666-9145}, abstract = {OBJECTIVE: Exudative age-related macular degeneration (eAMD) is a major cause of central vision loss. Identifying patients at high risk of imminent eAMD could enable timely treatment and improve outcomes. Our goal was to develop and compare classical machine learning (ML) and deep learning (DL) models to predict imminent eAMD conversion within 6 months and integrate OCT with clinical data into a single predictive model.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Patients seen at the Wilmer Eye Institute between 2013 and 2021 with eAMD in &#x2265;1 eye.<br><br>METHODS: Spectral domain OCT volumes prior to conversion and the corresponding clinical data (age, best-corrected visual acuity, sex, and fellow-eye status) were collected and used for model training or testing. ResNet-50 and classical ML (Random Forest and XGBoost) models were trained to predict imminent conversion to eAMD within 6 months on an eye level. For the multilayer perceptron (MLP) framework, the trained ResNet-50 model was used as the feature encoder, and a downsampled feature vector concatenated with corresponding clinical tabular data was passed through the MLP (prediction head). Data were partitioned at the patient level (75% training, 15% validation, and 10% testing). Model performance was evaluated using the area under the operating characteristic curve (AUC) and 95% confidence interval (CI) for the model AUC was calculated using the percentile method after bootstrapping the test set 10 000 times. Model comparisons were made using modified paired t test. P < 0.05 was considered statistically significant.<br><br>MAIN OUTCOME MEASURES: Area under the operating characteristic curve.<br><br>RESULTS: Thirty-three thousand one hundred eighty-nine OCT volumes from 2084 patients (63% female; 89.1% White, 4.8% Black, and 2.3% Asian) were included. The mean age at the time of first-eye conversion was 78.9 (&#xb1; 9.3) years. Our best-performing models, "MLP multimodal" (trained with both OCT and clinical data; AUC: 0.76, 95% CI: 0.71-0.80) and "CNN OCT" (trained with only OCT data; AUC: 0.75, 95% CI: 0.70-0.79), had a DL (ResNet-50) architecture; "MLP multimodal" outperformed "CNN OCT" in predicting both all-eye (P < 0.05) and first-eye conversion (P < 0.001).<br><br>CONCLUSIONS: The 3-dimensional DL models, trained with OCT volumes, are capable of predicting both first-eye and fellow-eye imminent conversion to eAMD. The addition of clinical data further improved the model performance. These models, if validated prospectively, could serve as screening tools and allow retinal specialists to prioritize patients with more acute retinal issues.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40503074, year = {2025}, author = {Medoro, A and Davinelli, S and Scuderi, L and Scuderi, G and Scapagnini, G and Fragiotta, S}, title = {Targeting Senescence, Oxidative Stress, and Inflammation: Quercetin-Based Strategies for Ocular Diseases in Older Adults.}, journal = {Clinical interventions in aging}, volume = {20}, number = {}, pages = {791-813}, pmid = {40503074}, issn = {1178-1998}, mesh = {Humans ; *Quercetin/pharmacology/therapeutic use/administration &amp; dosage ; *Oxidative Stress/drug effects ; *Antioxidants/therapeutic use/pharmacology ; Inflammation/drug therapy ; Aged ; *Eye Diseases/drug therapy ; *Cellular Senescence/drug effects ; Macular Degeneration/drug therapy ; Aging ; Anti-Inflammatory Agents/pharmacology/therapeutic use ; Drug Delivery Systems ; Neuroprotective Agents/pharmacology/therapeutic use ; }, abstract = {Quercetin, a flavonol abundant in fruits and vegetables, has attracted significant attention for its senotherapeutic effects, which involve the selective elimination of senescent cells and the modulation of pro-inflammatory phenotypes that contribute to age-related dysfunctions. These actions, together with its antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties, make quercetin a promising strategy for ocular diseases associated with visual impairment in older adults such as age-related macular degeneration, cataract, diabetic retinopathy, and glaucoma. This review emphasizes the mechanisms by which quercetin exerts its protective effects, with particular attention to its ability to target cellular senescence, reduce oxidative stress, and modulate inflammation. Despite extensive preclinical evidence, the clinical application of quercetin remains limited due to challenges related to poor bioavailability, rapid degradation, and the absence of standardized ocular formulations. Progress in drug delivery systems, including nanoparticles, nanoemulsions, and solid lipid carriers, provides promising strategies to overcome these barriers. In addition, combining quercetin with established treatments, such as anti-vascular endothelial growth factor (VEGF) agents and neuroprotective drugs, may enhance its therapeutic potential in managing and possibly reversing age-related ophthalmic disorders.}, }
@article {pmid40503367, year = {2025}, author = {Sorrentino, FS and Parmeggiani, F and Gardini, L and Fontana, L and Musa, M and Gagliano, C and Zeppieri, M}, title = {Stem cell therapy for retinal pigment epithelium disorders.}, journal = {World journal of stem cells}, volume = {17}, number = {5}, pages = {103100}, pmid = {40503367}, issn = {1948-0210}, abstract = {Retinal pigment epithelium (RPE) dysfunction is involved in the advancement of numerous degenerative retinal illnesses, such as age-related macular degeneration and hereditary retinal abnormalities. Transplantation of RPE produced from stem cells has emerged as a promising therapeutic strategy to restore retinal function and prevent vision loss. However, other obstacles impede its clinical application, including immunological rejection, cell viability, functional integration, and the necessity for consistent differentiation techniques. This review offers a thorough examination of the molecular processes regulating RPE integrity, investigates recent progress in stem cell-derived RPE therapeutics, and addresses significant challenges to their broad implementation. Furthermore, we emphasize prospective avenues intended to enhance the safety, efficacy, and enduring success of RPE transplantation in clinical environments.}, }
@article {pmid40504424, year = {2025}, author = {Lee, SH and Lee, MY}, title = {Factors determining timing of first recurrence after three loading aflibercept injections in newly diagnosed neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {69}, number = {6}, pages = {876-885}, pmid = {40504424}, issn = {1613-2246}, mesh = {Humans ; Retrospective Studies ; Female ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Male ; *Recombinant Fusion Proteins/administration &amp; dosage ; Intravitreal Injections ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis ; Fluorescein Angiography/methods ; Aged ; *Visual Acuity ; Recurrence ; Fundus Oculi ; Follow-Up Studies ; Aged, 80 and over ; Time Factors ; Angiogenesis Inhibitors/administration &amp; dosage ; Treatment Outcome ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Dose-Response Relationship, Drug ; }, abstract = {PURPOSE: To investigate factors affecting timing of the first recurrence after three loading aflibercept injections in patients with newly diagnosed neovascular age-related macular degeneration (NAMD).<br><br>STUDY DESIGN: Retrospective chart review.<br><br>METHODS: A retrospective study was conducted on 193 eyes from 193 patients newly diagnosed with NAMD who received monthly three loading aflibercept injections and a fourth injection by pro-re-nata therapy regimen for recurrence between January 2016 and May 2023. Recurrence was defined as reaccumulation of subretinal or intraretinal fluid or new or increased retinal or subretinal hemorrhage. Patients were divided into two groups. One group received a fourth injection within 12 weeks after the third dose of aflibercept (Group A) and the other group received a fourth injection after 12 weeks (Group B).<br><br>RESULTS: In group A (65 eyes) compared to group B (128 eyes), the frequency of polypoidal choroidal vasculopathy (PCV) was higher (60.0%: 36.7%), the frequency of retinal angiomatous proliferation was lower (6.2%: 18.0%), and the optical coherence tomography (OCT) findings showed that pigment epithelial detachment (PED) of hollow type was more likely to be observed compared to solid type (OR=3.14, p=0.013) or mixed type (OR=3.67, p=0.003) of PED; sharply peaked PED was more common (OR=2.05, p=0.045) and less likely to be seen in females (OR=0.46, p=0.034).<br><br>CONCLUSION: In patients with newly diagnosed NAMD who received three injection loading doses of aflibercept, earlier recurrence was predicted when PCV was present, when a hollow type of PED was observed on OCT, and when the patient was a man.}, }
@article {pmid40504425, year = {2025}, author = {Yanagi, Y and Mori, R and Teo, KYC and Park, KH and Ngah, NF and Chen, SJ and Ruamviboonsuk, P and Kondo, N and Lee, WK and Rajagopalan, R and Obata, R and Wong, IYH and Chee, C and Terasaki, H and Sekiryu, T and Chen, SC and Lai, TYY and Cheung, G and Honda, S}, title = {Six-year findings of polypoidal choroidal vasculopathy in the EVEREST II study: Japanese subgroup analysis.}, journal = {Japanese journal of ophthalmology}, volume = {69}, number = {6}, pages = {894-901}, pmid = {40504425}, issn = {1613-2246}, support = {NMRC/LCG/004/2018//National Medical Research Council Singapore Open Fund Large Collaborative Grant/ ; }, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Choroid/blood supply ; *Choroid Diseases/drug therapy/diagnosis/epidemiology ; Cross-Sectional Studies ; Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; Intravitreal Injections ; Japan/epidemiology/ethnology ; *Photochemotherapy/methods ; Photosensitizing Agents/therapeutic use ; Polypoidal Choroidal Vasculopathy ; *Polyps/drug therapy/diagnosis/epidemiology ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Time Factors ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Verteporfin ; *Visual Acuity ; East Asian People/statistics &amp; numerical data ; }, abstract = {PURPOSE: To evaluate long-term outcomes for polypoidal choroidal vasculopathy (PCV) in Japanese patients in the EVEREST II study.<br><br>STUDY DESIGN: A multicenter, cross-sectional study of the long-term outcomes of a cohort of patients originally treated with ranibizumab alone (monotherapy group) or in combination with photodynamic therapy PDT (combination group) in the EVEREST II study (ClinicalTrials.gov identifier, NCT01846273).<br><br>METHODS: Ninety participants from the six-year EVEREST II follow-up: 20 Japanese and 70 non-Japanese were included. Long-term changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) were reported in the Japanese compared to non-Japanese participants. Number of injections, types of anti-vascular endothelial growth factor (VEGF) agents used, and cases with equal visits and injections, indicating fixed dosing or treat-and-extend (TAE) administration were investigated. Outcomes were also compared between those who had verteporfin PDT during the six-year period (n=14) and those who did not (n=6).<br><br>RESULTS: The Japanese and non-Japanese participants had similar baseline characteristics. The mean age for Japanese participants was 76&#xb1;4.47 years, with 25% being women. BCVA improved from baseline to year 2 in both groups (P < 0.05). At six years, BCVA was maintained in the Japanese (67.2 ETDRS letters) but decreased in the non-Japanese participants (from 68.8 to 53.5 letters). The Japanese participants received more injections than the non-Japanese (12.5 vs. 7.57, P=0.017). Aflibercept was the most frequently used anti-VEGF agent, and the number of fixed dosing or TAE administration was higher in the Japanese participants. No significant differences were found in functional and anatomical outcomes between those who received PDT and those who did not (all P > 0.05). However, non-PDT participants had numerically worse BCVA at the final visit.<br><br>CONCLUSIONS: This study highlights positive long-term outcomes for Japanese PCV patients and underscores the need for further research to validate these findings in broader patient populations.}, }
@article {pmid40504540, year = {2025}, author = {Lynch, AM and Grove, NC and Wagner, BD and Palestine, AG and Holers, VM and Frazer-Abel, AA and Gnanaraj, R and Lisker-Cervantes, A and Patnaik, JL and de Carlo Forest, TE and Auer, EA and McReynolds, AJ and Mathias, MT and Manoharan, N and Rodriquez De Cordoba, S and Mandava, N}, title = {Dynamic Risk of Systemic Complement Activation With Time to Progression to Advanced Age-Related Macular Degeneration.}, journal = {JAMA ophthalmology}, volume = {143}, number = {8}, pages = {634-642}, pmid = {40504540}, issn = {2168-6173}, support = {R01 EY032456/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Female ; Male ; Disease Progression ; Aged ; *Complement Activation/physiology ; Follow-Up Studies ; *Wet Macular Degeneration/diagnosis/blood ; Aged, 80 and over ; Risk Factors ; *Geographic Atrophy/diagnosis/blood ; Retrospective Studies ; Time Factors ; Tomography, Optical Coherence ; }, abstract = {IMPORTANCE: Understanding the relationship between longitudinally measured systemic complement factors and intermediate AMD (iAMD) progression may enable the introduction of systemic therapeutics earlier in the disease course, before vision loss occurs.<br><br>OBJECTIVE: To determine the contribution of longitudinal measures of systemic complement factors and ratios to time to progression to advanced AMD (geographic atrophy [GA] or neovascular AMD [NVAMD]).<br><br>This cohort study was conducted at Sue Anschutz Rodgers Eye Center, Aurora, Colorado, from 2014 to 2022. Participants were patients with iAMD and at least 1 month of follow-up. Data analysis was performed from September to December 2024.<br><br>EXPOSURES: Complement factors.<br><br>MAIN OUTCOMES AND MEASURES: Time to progression to advanced AMD, either GA or NVAMD. Joint models were used to estimate the relationship between the exposures and the outcomes. The hazard ratio (HR) was a measure of association.<br><br>RESULTS: Among 325 participants, the mean (SD) age was 76 (7.0) years; 212 participants (65%) were female and 113 (35%) male. During the 8-year follow-up period (mean, 3.9 years), 110 participants (34%) progressed to any advanced AMD. Sixty-four participants (20%) progressed to GA and 46 (14%) to NVAMD. Higher systemic levels of C4 (HR, 6.8; 95% credible interval [CrI], 1.7-26.2; P&#x2009;=&#x2009;.03), C4b (HR, 60.4; 95% CrI, 6.5-544; P&#x2009;<&#x2009;.001), C3a/C3 (HR, 49.4; 95% CrI, 5.2-675; P&#x2009;<&#x2009;.001), C5a/C5 (HR, 29.3; 95% CrI, 4.8-258; P&#x2009;<&#x2009;.001), sC5b-9/C5 (HR, 297; 95% CrI, 10-14&#x202f;877; P&#x2009;=&#x2009;.003), and factor I (HR, 525.9; 95% CrI, 5.5-107&#x202f;589; P&#x2009;=&#x2009;.02) were associated with shorter time to progression to any AMD. Levels of C3a/C3 (HR, 9.5; 95% CrI, 1.9-55.9; P&#x2009;=&#x2009;.01) and C5a/C5 (HR, 28.6; 95% CrI, 5.7-157.9; P&#x2009;<&#x2009;.001) were associated with the hazard of GA.<br><br>CONCLUSIONS AND RELEVANCE: Continued dysregulation of complement pathways appears to increase the hazard of iAMD progression. This supports the possibility of identifying a high-risk group of patients with iAMD for personalized ophthalmic care and targeted treatments to attenuate the risk of iAMD progression.}, }
@article {pmid40505850, year = {2025}, author = {Dhoot, DS}, title = {Treatment of Retinal/Choroidal Vascular Diseases by Sustained Delivery of Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors.}, journal = {American journal of ophthalmology}, volume = {277}, number = {}, pages = {570-579}, doi = {10.1016/j.ajo.2025.06.010}, pmid = {40505850}, issn = {1879-1891}, mesh = {Animals ; Humans ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Choroid Diseases/drug therapy ; Delayed-Action Preparations ; Drug Delivery Systems ; Intravitreal Injections ; *Protein Kinase Inhibitors/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/antagonists &amp; inhibitors ; *Retinal Diseases/drug therapy ; Tyrosine Kinase Inhibitors ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; }, abstract = {PURPOSE: To review current investigational strategies using sustained delivery of vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (TKIs) for the treatment of retinal and choroidal vascular diseases.<br><br>DESIGN: Narrative review.<br><br>METHODS: A comprehensive review of preclinical and clinical studies evaluating the safety, efficacy, and durability of VEGF receptor TKIs delivered via sustained-release platforms, including intravitreal hydrogel implants, suprachoroidal injections, subcutaneous delivery systems, and oral formulations.<br><br>RESULTS: Multiple VEGF receptor TKIs, including axitinib, sunitinib, vorolanib, and dendranib, are under evaluation for sustained treatment of neovascular age-related macular degeneration, diabetic macular edema, and diabetic retinopathy. Delivery platforms such as bioerodible implants (OTX-TKI/axitinib, EYP-1901/vorolanib), suprachoroidal injections (CLS-AX/axitinib), microparticle suspensions (GB-102/sunitinib), and oral or subcutaneous therapies (X-82, D-4517.2) have demonstrated variable degrees of treatment durability, reduction in anti-VEGF injection burden, and maintenance of anatomic and functional outcomes in early phase studies. Safety profiles have generally been favorable, although certain formulations showed dose-dependent adverse effects.<br><br>CONCLUSIONS: Sustained delivery of VEGF receptor TKIs represents a promising therapeutic paradigm for retinal and choroidal vascular diseases, potentially reducing treatment burden while maintaining efficacy. Continued evaluation through larger, controlled clinical trials is essential to validate these early findings and define the role of these agents in clinical practice.}, }
@article {pmid40506926, year = {2025}, author = {Yim, AC and Azzouz, L and Paulus, YM}, title = {Novel Handheld Device for Remote Monitoring of Dry Macular Degeneration and Patient Usability Assessment.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {11}, pages = {}, pmid = {40506926}, issn = {2075-4418}, support = {1R01EY034325-23A1/NH/NIH HHS/United States ; R01 EY034325/EY/NEI NIH HHS/United States ; 1K08EY027458-18A1/NH/NIH HHS/United States ; FFSGIA16002//Fight for Sight/ ; K08 EY027458/EY/NEI NIH HHS/United States ; unrestricted departmental support//Research to Prevent Blindness/ ; }, abstract = {Background/Objectives: A novel, handheld, standalone device using shape discrimination hyperacuity has been developed to remotely monitor age-related macular degeneration (AMD). Methods: We clinically validated the device in an outpatient dry AMD population to evaluate its usability and comfort. A cross-sectional study was conducted with subjects aged 50 years or older with dry AMD at the University of Michigan Kellogg Eye Center outpatient clinic after approval from the UM IRB (HUM00187177). Subjects used the device and then completed a device survey and System Usability Scale (SUS). Results: Thirty-one subjects completed the study, and one subject withdrew post-study completion (mean age 77 years, STD 8 years). The mean testing time was 126 s (STD 56 s), and the median was 116 s. Most patients reported that the use of the device occurred for an acceptable duration (97%), was easy (97%), and was comfortable (90%). The mean SUS score was 77.7 (STD 11.9). Conclusions: A handheld, standalone device can provide a rapid, easy, and comfortable testing solution for patients with dry AMD. The usability of the device supports further clinical trials to demonstrate the device's ability to reliably detect the progression of AMD.}, }
@article {pmid40506954, year = {2025}, author = {Gawęcki, M and Kiciński, K and Grzybowski, A and Teper, S}, title = {Posterior Vitreous Detachment in Healthy Versus AMD Eyes Assessed by Widefield Optical Coherence Tomography.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {11}, pages = {}, pmid = {40506954}, issn = {2075-4418}, abstract = {Introduction: This study aimed to determine the frequency of posterior vitreous detachment (PVD) in dry and wet age-related macular degeneration (AMD) patients compared with healthy eyes via ultrawide field optical coherence tomography (UWF-OCT). Additionally, the retinal thicknesses in the central and peripheral zones of AMD patients and the control group were compared. Methods: We included 123 eyes from 83 participants with dry AMD, 123 from 87 participants with wet AMD, and 85 from 53 healthy controls. All three study groups were compared according to age, sex, best corrected visual acuity (BCVA), PVD stage, axial length, and retinal thickness in the central, perifoveal, and peripheral zones. Additional analyses included correlations between the BCVA and PVD stage and between retinal thickness and the PVD stage. Results: Complete separation of the vitreous from the macula was significantly more common in AMD patients than in the control group, as noted in 47 eyes (55.29%) in the control group, 92 eyes (74.80%) in the wet AMD group, and 93 eyes (75.61%) in the dry AMD group. The PVD stage did not significantly influence retinal thickness. BCVA in AMD patients did not correlate with the PVD stage. Conclusions: Complete PVD is more common in AMD patients than in healthy controls, as evaluated by UWF-OCT. No relationship between the PVD stage and AMD type or BCVA was observed.}, }
@article {pmid40507384, year = {2025}, author = {Di Pippo, M and Rullo, D and Maugliani, E and Lotery, AJ and Abdolrahimzadeh, S}, title = {Short-Term Morphological and Quantitative Changes in Non-Exudative Macular Neovascularization Using Spectral-Domain OCT and OCT Angiography: A Pilot Study.}, journal = {Journal of clinical medicine}, volume = {14}, number = {11}, pages = {}, pmid = {40507384}, issn = {2077-0383}, support = {RP12117A34924689//Sapienza University of Rome/ ; }, abstract = {Background/Objectives: The aim of the current investigation was to assess the short-term changes in retinal-choroidal vasculature and the morphological complexity of non-exudative macular neovascularization (NE-MNV) using optical coherence tomography angiography (OCTA) and spectral-domain optical coherence tomography (SD-OCT). Methods: Sixteen eyes of 12 patients with NE-MNV underwent baseline and six-month follow-up examinations, including comprehensive ophthalmological assessment and imaging. Central macular thickness, foveal avascular zone, vessel density, flow area, and choroidal vascularity index were analyzed. NE-MNV morphology was quantitatively assessed for area, vessel characteristics, and fractal dimensions. Results: Significant changes in NE-MNV morphology were noted over six months, especially in fractal dimensions, vessel junctions, and vessel length (p-values: 0.01, 0.037, and 0.036, respectively). While there was an increase in the NE-MNV area, it did not reach statistical significance. No significant changes were shown regarding the standard SD-OCT and OCTA output parameters or choroidal measurements. Conclusions: The increase in NE-MNV fractal dimensions suggests rising complexity in the neovascular network and may indicate possible implications for clinical management. The correlation between baseline and follow-up measures underscores a trend toward complexity, pointing to the necessity for closer monitoring of patients with higher NE-MNV fractal dimensions.}, }
@article {pmid40507429, year = {2025}, author = {Fieß, A and Gißler, S and Mildenberger, E and Pfeiffer, N and Hartmann, A and Schuster, AK}, title = {Long-Term Ocular Outcomes of Prematurity: Morphological Alterations, Visual Aspects and Implications for Age-Related Ocular Diseases.}, journal = {Journal of clinical medicine}, volume = {14}, number = {11}, pages = {}, pmid = {40507429}, issn = {2077-0383}, support = {//Ernst und Berta Grimmke-Stiftung/ ; //Else Kr&#xf6;ner-Fresenius-Stiftung/ ; }, abstract = {The impact of prematurity has been reported to affect ocular development during infancy and childhood. Research into long-term ocular outcomes in adults born preterm is highly relevant due to a possible impact on the development of age-related ocular diseases such as macular degeneration. The aim was to review the currently available literature regarding outcomes of prematurity on ocular morphology in adults to provide a summary of the long-term effects of prematurity and associated factors such as low birth weight (BW) and retinopathy of prematurity (ROP) and its treatment. Adults formerly born preterm have a higher prevalence of refractive error, lower visual acuity, a higher prevalence of strabismus, shorter axial length, a steeper corneal radius, increased macular thickness, and a thinner peripapillary retinal nerve fiber layer thickness (RNFL), as well as changes in vessel anatomy and the foveal avascular zone. Adults who suffered from ROP have a high risk of myopic refractive error, amblyopia, shallower anterior chambers and thicker crystalline lenses, higher corneal aberrations, thinner RNFL thickness, and foveal hypoplasia. Individuals with advanced ROP requiring treatment also have higher rates of astigmatism, an increased temporal RNFL thickness, altered macular curvature, and reduced visual acuity. Prematurity leads to lifelong ocular morphological and functional changes, suggesting that fetal origins may contribute to age-related ocular diseases. This could have implications for ophthalmologic monitoring and the frequency of check-ups in adulthood.}, }
@article {pmid40507504, year = {2025}, author = {Bakdalieh, A and Khawaja, LM and Yu, M}, title = {Dark Adaptometry as a Diagnostic Tool in Retinal Diseases: Mechanisms and Clinical Utility.}, journal = {Journal of clinical medicine}, volume = {14}, number = {11}, pages = {}, pmid = {40507504}, issn = {2077-0383}, support = {P30 EY025585/EY/NEI NIH HHS/United States ; P30-EY025585/GF/NIH HHS/United States ; }, abstract = {Dark adaptometry is a non-invasive functional test that assesses the retina's ability to recover sensitivity in low-light conditions following photobleaching. This review explores the physiological mechanisms underlying dark adaptation (DA), including photopigment regeneration and the critical role of the retinal pigment epithelium in the visual cycle. We detail clinical protocols for dark adaptometry using modern instruments such as the AdaptDx, highlighting methodological advances that improve testing efficiency and reproducibility. The clinical utility of dark adaptometry is examined across a range of inherited and acquired retinal disorders, including age-related macular degeneration (AMD), retinitis pigmentosa (RP), Stargardt disease, diabetic retinopathy (DR), cone-rod dystrophy (CRD), vitamin A deficiency, and congenital stationary night blindness (CSNB). Dark adaptometry has emerged as a sensitive biomarker capable of detecting functional deficits before structural changes are evident, making it a valuable tool for early diagnosis and monitoring disease progression. However, limitations such as age-related variability, patient compliance, and lack of standardization remain challenges to broader clinical adoption. Continued refinement of dark adaptometry protocols and instrumentation is essential to maximize its diagnostic potential in ophthalmic practice.}, }
@article {pmid40507802, year = {2025}, author = {Callan, A and Heckman, J and Tah, G and Lopez, S and Valdez, L and Tsin, A}, title = {VEGF in Diabetic Retinopathy and Age-Related Macular Degeneration.}, journal = {International journal of molecular sciences}, volume = {26}, number = {11}, pages = {}, pmid = {40507802}, issn = {1422-0067}, support = {R13 CA278054/CA/NCI NIH HHS/United States ; R15 EY033551/EY/NEI NIH HHS/United States ; CA278054/GF/NIH HHS/United States ; EY033551/GF/NIH HHS/United States ; DA056203/GF/NIH HHS/United States ; R13 DA056203/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; *Diabetic Retinopathy/metabolism/drug therapy/pathology ; *Vascular Endothelial Growth Factor A/metabolism/antagonists &amp; inhibitors ; *Macular Degeneration/metabolism/drug therapy/pathology ; Animals ; Angiogenesis Inhibitors/therapeutic use ; Choroidal Neovascularization/metabolism ; }, abstract = {Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis throughout the human body, influencing countless physiological and pathological processes, including tumor growth, preeclampsia, and retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). In DR, VEGF promotes retinal neovascularization and intraretinal fluid accumulation, leading to complications like diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Regular intravitreal anti-VEGF injections are commonly used to manage PDR and DME, though repeated treatments are often required, and efficacy can be limited. AMD, a major cause of vision loss in older adults, is characterized by either dry or wet forms. While the dry form has not been shown to be influenced by VEGF, the choroidal neovascularization of wet AMD has strong associations with VEGF. Current treatment for wet AMD consists primarily of anti-VEGF injections, the gold standard of care, but is limited by varying patient responses, as treatments are often repeated every 4-8 weeks indefinitely. This review explores the pathogenic role of VEGF in both DR and AMD, discussing the molecular mechanisms underlying these diseases and the therapeutic approaches targeting VEGF. Despite advancements, the variability in treatment responses highlights the need for continued research to develop more effective therapies to prevent vision loss and blindness associated with these retinal diseases.}, }
@article {pmid40509232, year = {2025}, author = {Lin, S and Guo, MS and Tang, RW and Ye, Y and Wu, J and Ho, YM and Duan, R and Leung, KW and Dong, TT and Tsim, KW}, title = {Design, Synthesis, and Biological Evaluations of a Novel Resveratrol-Type Analogue Against VEGF.}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {11}, pages = {}, pmid = {40509232}, issn = {1420-3049}, support = {2019AG035//Zhongshan Municipal Bureau of Science and Technology/ ; T13-605/18-W//Hong Kong RGC Theme-based Research Scheme/ ; }, mesh = {*Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Resveratrol/analogs &amp; derivatives/pharmacology/chemistry/chemical synthesis ; Humans ; *Drug Design ; Signal Transduction/drug effects ; *Stilbenes/pharmacology/chemistry/chemical synthesis ; }, abstract = {Vascular endothelial growth factor (VEGF), also known as VEGF-A, has been reported to mediate various diseases, including cancer and wet age-related macular degeneration (wAMD). Despite the fact that VEGF inhibitors are commercially available and appear to be effective in clinical applications, adverse effects have been caused by these treatments. There is an unmet need for developing novel VEGF-targeted treatments against these diseases. Resveratrol, a phytochemical derived from fruits and vegetables, has shown promising potency in suppressing VEGF-mediated bioactivities through a series of in vitro and in vivo testing models. Herein, we report that RE-1, a synthetic resveratrol-type analog, displays robust inhibitory activities against VEGF and its downstream signaling pathways, surpassing its parental molecule, resveratrol. In addition, the drug capabilities of RE-1 were evaluated. As a newly synthesized chemical, RE-1 could be considered for subsequent pharmacological development targeting VEGF-related diseases.}, }
@article {pmid40510741, year = {2025}, author = {Ch, S and Lim, RR and Low, SWY and Grant, DG and Patterson, S and Ramasubramanian, A and Gadicherla, AK and Chaurasia, SS}, title = {A comprehensive overview of focused ion beam-scanning electron microscopy (FIB-SEM) applications for the evaluation of outer retina.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1586029}, pmid = {40510741}, issn = {2296-634X}, support = {R01 EY029795/EY/NEI NIH HHS/United States ; R01 EY030077/EY/NEI NIH HHS/United States ; }, abstract = {The retina is the light-sensitive inner layer of the eye, consisting of multiple cell types organized into ten distinct layers of neurons interconnected by synapses that play a crucial role in visual function. Any pathological alterations in this intricate structure can lead to vision impairment. Conventional electron microscopy techniques, including scanning electron microscopy (SEM) and transmission electron microscopy (TEM), provide our current understanding of ultrastructural defects in the retina. However, they are limited by their inability to image the complex three-dimensional (3D) structure layer-by-layer at a nanoscale resolution. Advanced electron microscopy techniques, including serial block face scanning (SBF), have emerged as a superior alternative to traditional imaging methods for enhancing the understanding of 3D segmentation at the nanoscale and revealing the ultrastructural architecture of the retina under both physiological and pathological conditions. This article provides a comprehensive overview of the advancements in SBF electron microscopy, emphasizing focused ion beam (FIB)-SEM for studying the interdigitation zone (IZ), which connects the cone outer segments to the retinal pigment epithelium (RPE) to enhance the understanding of retinal degenerative diseases such as inherited retinal disorders (IRDs), age-related macular degeneration (AMD), and diabetic retinopathy (DR). We have collated and discussed current literature alongside our recent work on FIB-SEM applications, particularly in examining the structural integrity of the outer retina. FIB-SEM can bridge the knowledge gap between structural insights and functional impairments through its state-of-the-art imaging and 3D segmentation capabilities. Additionally, it offers various applications for the pathological evaluation of retinal degenerative diseases.}, }
@article {pmid40512025, year = {2025}, author = {Agostini, H and Baumane, K and Balčiūnienė, VJ and Ozols, K and Soni, R and Hamdi, S and Cirillo, S and Rai, M and Otto, H and Leutz, S and Sattar, A and Berti, F}, title = {A randomized, double-masked parallel-group, multicenter clinical study evaluating the efficacy and safety of the biosimilar candidate AVT06 compared to the reference product aflibercept in participants with neovascular age-related macular degeneration.}, journal = {Expert opinion on biological therapy}, volume = {25}, number = {7}, pages = {773-787}, doi = {10.1080/14712598.2025.2519531}, pmid = {40512025}, issn = {1744-7682}, mesh = {Humans ; Double-Blind Method ; *Recombinant Fusion Proteins/adverse effects/pharmacokinetics/administration &amp; dosage/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Biosimilar Pharmaceuticals/adverse effects/pharmacokinetics/administration &amp; dosage/therapeutic use ; Male ; Female ; Aged ; Visual Acuity/drug effects ; Intravitreal Injections ; *Angiogenesis Inhibitors/adverse effects/pharmacokinetics/administration &amp; dosage/therapeutic use ; Aged, 80 and over ; Middle Aged ; Treatment Outcome ; *Macular Degeneration/drug therapy ; }, abstract = {BACKGROUND: This study compared efficacy, pharmacokinetics (PK), immunogenicity, and safety between AVT06, proposed biosimilar to reference product (RP) aflibercept (Eylea®), in participants with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: In this randomized, double-masked, multicenter, active-controlled trial, treatment na&#xef;ve participants received intravitreal injections of AVT06 or RP (2&#x2009;mg) over 48&#x2009;weeks. The primary endpoint was the change from baseline to Week 8 in best-corrected visual acuity (BCVA). Secondary endpoints included BCVA improvements and changes in Central Subfield Thickness (CST). PK, immunogenicity, and safety were also assessed.<br><br>RESULTS: The 90% and 95% confidence intervals (-0.60, 2.14 and -0.86, 2.40, respectively) in least squares mean difference in BCVA letter score from baseline to Week 8 were contained within the pre-specified equivalence margin of ETDRS BCVA letter score of [-3.5 to 3.5], supporting the demonstration of comparative efficacy. Secondary efficacy outcomes were also comparable. PK analyses supported systemic safety. There were no clinically meaningful differences in immunogenicity profiles. Safety profiles were similar; most treatment-emergent adverse events were mild and unrelated to the study drug.<br><br>CONCLUSIONS: Results supported a demonstration of comparable efficacy between AVT06 and RP aflibercept. Similar PK, immunogenicity, and safety profiles were also shown.<br><br>CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier is NCT05155293; ClinicalTrialsRegister.eu identifier is 2021-003651-42.}, }
@article {pmid40512437, year = {2025}, author = {Brandl, C and Heid, IM and Helbig, H and Holz, FG and Finger, RP and Mauschitz, MM}, title = {[Risk factors for age-related macular degeneration : Lessons learned from current data].}, journal = {Die Ophthalmologie}, volume = {122}, number = {7}, pages = {510-517}, pmid = {40512437}, issn = {2731-7218}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Genetic Predisposition to Disease/epidemiology/genetics ; *Macular Degeneration/epidemiology/prevention &amp; control/genetics ; Prevalence ; Risk Factors ; *Smoking/epidemiology/adverse effects ; }, abstract = {BACKGROUND: Identifying risk factors for age-related macular degeneration (AMD) is crucial for patient counseling and the development of potential prevention strategies.<br><br>OBJECTIVES: This study summarizes the current epidemiological evidence on AMD risk factors, analyzes their clinical relevance, and discusses potential preventive measures.<br><br>MATERIALS AND METHODS: A&#xa0;systematic literature review was conducted to assess demographic, genetic, and modifiable risk factors for AMD, including smoking, diet, and physical activity.<br><br>RESULTS: Age is the strongest risk factor for early and advanced AMD. Genetic predisposition also plays a&#xa0;critical role, particularly from genetic variants in the complement and lipid metabolism pathways and extracellular matrix. Modifiable factors such as smoking, dietary habits, and physical activity significantly influence the risk of AMD. Recent studies further suggest a&#xa0;potentially beneficial effect of medication intake, such as metformin and statins.<br><br>CONCLUSION: Epidemiological data indicate that smoking cessation, adherence to a&#xa0;Mediterranean diet, and regular physical activity are associated with a&#xa0;reduced risk of AMD over time. These factors should be integral to patient counseling. The continued extension of longitudinal study data will be key to refining individual risk profiles and optimizing prevention strategies.}, }
@article {pmid40512487, year = {2025}, author = {Ulla, L and Foti, C and Arrigo, A and Battaglia Parodi, M and Cicinelli, MV and Marolo, P and Miserocchi, E and Peronetti, M and Bandello, F and Borrelli, E and Reibaldi, M}, title = {Choroidal Hyperreflective Foci Represent a Common Finding Across Different Types of Macular Atrophy.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {6}, pages = {42}, pmid = {40512487}, issn = {1552-5783}, mesh = {Humans ; Retrospective Studies ; Tomography, Optical Coherence/methods ; Female ; Male ; Middle Aged ; *Choroid/pathology ; Aged ; Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis/complications ; Adult ; *Geographic Atrophy/diagnosis ; *Macula Lutea/pathology ; Aged, 80 and over ; Visual Acuity ; Fundus Oculi ; *Choroid Diseases/diagnosis ; }, abstract = {PURPOSE: To evaluate the presence, distribution, and potential implications of choroidal hyperreflective foci (HRFs) across different types of macular atrophy and their relationship with the size of atrophic regions.<br><br>METHODS: This retrospective case series analyzed 95 eyes from 87 patients with macular atrophy caused by various conditions, including geographic atrophy due to age-related macular degeneration, pachychoroid disease, punctate inner choroidopathy, angioid streaks, and Stargardt disease. Structural optical coherence tomography (OCT) images were evaluated to identify HRFs in different choroidal layers. HRF counts were correlated with the size of macular atrophy and underlying conditions using multiple regression analysis.<br><br>RESULTS: HRFs were observed in all cases, with their number significantly associated with the size of macular atrophy (P < 0.001). The highest HRF counts were found in Stargardt disease, while the lowest were in pachychoroid disease. However, no association was identified between HRF quantity and specific disease type (P = 0.2). HRFs were primarily located in the choriocapillaris, Sattler's layer, and near Bruch's membrane but were absent within choroidal vessels.<br><br>CONCLUSIONS: HRFs represent a common OCT finding in various disorders associated with macular atrophy. Their quantity correlates with atrophy size rather than disease type, suggesting they are likely normal choroidal components rendered visible by RPE loss. Future studies are warranted to elucidate their origin and potential implications for disease progression.}, }
@article {pmid40512794, year = {2025}, author = {Toomey, CB and Pflugmacher, S and Park, K and Pihl, J and Weiser Novak, S and Rodriguez, J and Jalali, M and Jung, J and Mozafari, M and Omran, SP and Pormir, CK and Hauer, J and Painter, C and Walker, E and Huang, AS and Boassa, D and Handa, JT and Aastrup, T and Gordts, PLSM and Esko, JD}, title = {Bruch's membrane heparan sulfate retains lipoproteins in the early stages of age-related macular degeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {24}, pages = {e2500727122}, pmid = {40512794}, issn = {1091-6490}, support = {R01 EY035805/EY/NEI NIH HHS/United States ; RMF-IRRF-001-2022//International Retinal Research Foundation (IRRF)/ ; EY024225//HHS | NIH | National Eye Institute (NEI)/ ; Unrestricted Grant//Research to Prevent Blindness (RPB)/ ; CD-CL-0824-0886-UCSD//Foundation Fighting Blindness (FFB)/ ; EY030501//HHS | NIH | National Eye Institute (NEI)/ ; HL131474//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; unrestricted grant//Research to Prevent Blindness (RPB)/ ; 30342012//Novartis AG | Alcon | Alcon Research Institute (ARI)/ ; EY035322//HHS | NIH | National Eye Institute (NEI)/ ; EY033765//HHS | NIH | National Eye Institute (NEI)/ ; RPB CDA 2023//Research to Prevent Blindness (RPB)/ ; EY031594//HHS | NIH | National Eye Institute (NEI)/ ; A-013//Larry L. Hillblom Foundation (LLHF)/ ; R01 EY031594/EY/NEI NIH HHS/United States ; K08 EY035322/EY/NEI NIH HHS/United States ; K12 EY024225/EY/NEI NIH HHS/United States ; R21 AI185519/AI/NIAID NIH HHS/United States ; R01 EY030501/EY/NEI NIH HHS/United States ; P01 HL131474/HL/NHLBI NIH HHS/United States ; EY035805//HHS | NIH | National Eye Institute (NEI)/ ; R01 EY033765/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Heparan Sulfate/metabolism ; *Macular Degeneration/metabolism/pathology ; *Bruch Membrane/metabolism/pathology/ultrastructure ; *Lipoproteins/metabolism ; Aged ; Aged, 80 and over ; Retinal Pigment Epithelium/metabolism ; }, abstract = {Lipoprotein retention in Bruch's membrane is a key event in the pathobiology of early and intermediate age-related macular degeneration (AMD). However, the mechanism of lipoprotein retention in BrM is unknown. Given the established role of glycosaminoglycans (GAG) in binding lipoproteins, our laboratory sought to determine the role of GAGs in AMD BrM. In this study, BrM GAG content in AMD pathobiology was analyzed in human postmortem tissue. Strikingly, increased levels of highly sulfated heparan sulfate were present in AMD Bruch's membrane as compared to non-AMD samples. In addition, using scanning electron microscopy of postmortem AMD tissue, we show aggregates of lipoprotein-like particles on the retinal pigmented epithelium side of Bruch's membrane adjacent to heparan sulfate. We also show that heparin displaces lipoproteins rich in apolipoprotein A1 from human BrM, suggesting their identity as high-density lipoproteins. Using human BrM immobilized to quartz crystal microbalance biosensor (QCM) chips, we show that heparan sulfate is required for lipoprotein binding to BrM and soluble heparan sulfate can remove lipoproteins bound to BrM. Thus, our data establish that heparan sulfate regulates lipoprotein deposition in AMD BrM. These findings provide a foundation for targeted therapies capable of either preventing lipoprotein accumulation or removing drusen in the early and intermediate stages of AMD prior to vision loss.}, }
@article {pmid40512945, year = {2025}, author = {Gupta, AK and Meng, R and Duelk, M and Wald, K and Srinivasan, VJ}, title = {High-resolution visible light OCT of the human retina with combined superluminescent diodes.}, journal = {Optics letters}, volume = {50}, number = {12}, pages = {4070-4073}, pmid = {40512945}, issn = {1539-4794}, support = {P41 EB032840/EB/NIBIB NIH HHS/United States ; OT2 OD038130/OD/NIH HHS/United States ; R01 EY031469/EY/NEI NIH HHS/United States ; R01 EB035762/EB/NIBIB NIH HHS/United States ; R01 EY036192/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Tomography, Optical Coherence/instrumentation/methods ; *Retina/diagnostic imaging ; *Light ; *Semiconductors ; }, abstract = {High-resolution optical coherence tomography (OCT) requires broadband, spatially coherent light sources. Today, the source of choice for visible light OCT, the supercontinuum (SC), is bulky, expensive, and prone to excess noise. Here we demonstrate high-resolution visible light OCT of the human retina with a combined superluminescent diode (SLD) source. The source is longer in wavelength than the high blue light hazard range but shorter in wavelength than the high photopic efficiency range, ensuring subject safety and comfort. We report an axial resolution of 3.2 µm in the retina. We find that Bruch's membrane is well-delineated in subjects without ocular pathology, even though the axial resolution is ∼3× coarser than SC visible light OCT. Imaging of intermediate age-related macular degeneration is also shown. Within the cyan-green wavelength range of the SLD, optical density spectra resemble those of macular pigments. While the combined SLD approach does not achieve the micrometer-scale resolution of the SC, it potentially reduces the cost and complexity of visible light OCT while providing novel disease-relevant biomarkers, to the best of our knowledge, in human retina.}, }
@article {pmid40514020, year = {2025}, author = {Coletto, A and Serafino, S and Olivieri, C and Marica, V and Viggiano, P and Vallino, V and Marolo, P and Borrelli, E and Reibaldi, M}, title = {Macular fibrosis in neovascular AMD: inter-reader and intermodality variability across four imaging modalities.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {60}, number = {6}, pages = {e906-e914}, doi = {10.1016/j.jcjo.2025.05.019}, pmid = {40514020}, issn = {1715-3360}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Cross-Sectional Studies ; Prospective Studies ; Male ; Female ; Aged ; *Wet Macular Degeneration/diagnosis/drug therapy/complications ; Fibrosis/diagnosis ; *Macula Lutea/pathology ; Fluorescein Angiography/methods ; Aged, 80 and over ; Reproducibility of Results ; Observer Variation ; Middle Aged ; Fundus Oculi ; }, abstract = {OBJECTIVE: To assess inter-reader and intermodality variability in quantifying macular fibrosis in patients with neovascular age-related macular degeneration (AMD) using 4 imaging modalities: color fundus photography (CFP), near-infrared reflectance (NIR), structural optical coherence tomography (OCT), and MultiColor imaging.<br><br>DESIGN: Prospective, cross-sectional case series.<br><br>PARTICIPANTS: Thirty eyes of 30 patients with neovascular AMD and macular fibrosis, previously treated with anti-vascular endothelial growth factor therapy.<br><br>METHODS: Imaging was performed using CFP, NIR, structural OCT, and MultiColor modalities. Two masked graders evaluated the size of macular fibrosis using each modality. The study assessed inter-reader agreement using the intraclass correlation coefficient (ICC), coefficient of variation (CV), and 95% coefficient of repeatability. Intermodality variability was analyzed using repeated measures ANOVA and pairwise comparisons.<br><br>RESULTS: Structural OCT demonstrated the highest inter-reader agreement (ICC&#x202f;=&#x202f;0.983; CV&#x202f;=&#x202f;0.04), while NIR exhibited the lowest (ICC&#x202f;=&#x202f;0.461; CV&#x202f;=&#x202f;0.26). The median macular fibrosis size was largest on structural OCT (4.87 mm&#xb2;) and smallest on MultiColor imaging (2.03 mm&#xb2;). Significant differences were observed between imaging modalities, with fibrosis measurements from different modalities not consistently comparable.<br><br>CONCLUSIONS: Structural OCT is the most reliable modality for quantifying macular fibrosis in neovascular AMD. The observed intermodality variability highlights the need for standardized criteria in fibrosis assessment across imaging techniques, as differences can impact clinical interpretation and management.}, }
@article {pmid40515543, year = {2025}, author = {Ly, A and Herse, S and Williams, MA and Stapleton, F}, title = {Artificial intelligence for age-related macular degeneration diagnosis in Australia: A Novel Qualitative Interview Study.}, journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)}, volume = {45}, number = {6}, pages = {1282-1292}, pmid = {40515543}, issn = {1475-1313}, support = {//Roche Products, Australia/ ; }, mesh = {Humans ; *Artificial Intelligence ; Australia/epidemiology ; *Macular Degeneration/diagnosis/epidemiology ; Qualitative Research ; Interviews as Topic ; Female ; Male ; }, abstract = {INTRODUCTION: Artificial intelligence (AI) systems for age-related macular degeneration (AMD) diagnosis abound but are not yet widely implemented. AI implementation is complex, requiring the involvement of multiple, diverse stakeholders including technology developers, clinicians, patients, health networks, public hospitals, private providers and payers. There is a pressing need to investigate how AI might be adopted to improve patient outcomes. The purpose of this first study of its kind was to use the AI translation extended version of the non-adoption, abandonment, scale-up, spread and sustainability of healthcare technologies framework to explore stakeholder experiences, attitudes, enablers, barriers and possible futures of digital diagnosis using AI for AMD and eyecare in Australia.<br><br>METHODS: Semi-structured, online interviews were conducted with 37 stakeholders (12 clinicians, 10 healthcare leaders, 8 patients and 7 developers) from September 2022 to March 2023. The interviews were audio-recorded, transcribed and analysed using directed and summative content analysis.<br><br>RESULTS: Technological features influencing implementation were most frequently discussed, followed by the context or wider system, value proposition, adopters, organisations, the condition and finally embedding the adaptation. Patients preferred to focus on the condition, while healthcare leaders elaborated on organisation factors. Overall, stakeholders supported a portable, device-independent clinical decision support tool that could be integrated with existing diagnostic equipment and patient management systems. Opportunities for AI to drive new models of healthcare, patient education and outreach, and the importance of maintaining equity across population groups were consistently emphasised.<br><br>CONCLUSIONS: This is the first investigation to report numerous, interacting perspectives on the adoption of digital diagnosis for AMD in Australia, incorporating an intentionally diverse stakeholder group and the patient voice. It provides a series of practical considerations for the implementation of AI and digital diagnosis into existing care for people with AMD.}, }
@article {pmid40515626, year = {2025}, author = {O'Neil, A and Welikala, RA and Barman, S and Owen, CG and Rudnicka, AR and Rakesh, M and Roy-Gagnon, MH and Maberley, D and Freeman, EE}, title = {Retinal Vessel Traits and Age-Related Eye Disease in the Canadian Longitudinal Study on Aging.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {53}, number = {7}, pages = {764-772}, pmid = {40515626}, issn = {1442-9071}, support = {//Canada Foundation for Innovation/ ; LSA 94473/CAPMC/CIHR/Canada ; PJT-183690/CAPMC/CIHR/Canada ; LSA 94473/CAPMC/CIHR/Canada ; PJT-183690/CAPMC/CIHR/Canada ; }, mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; Canada/epidemiology ; Aged ; Intraocular Pressure/physiology ; *Aging/physiology ; *Retinal Vessels/pathology ; Follow-Up Studies ; *Macular Degeneration/epidemiology/physiopathology/diagnosis ; Middle Aged ; Longitudinal Studies ; Aged, 80 and over ; *Glaucoma/physiopathology/epidemiology/diagnosis ; Tomography, Optical Coherence/methods ; Optic Disk/pathology ; }, abstract = {BACKGROUND: To cross-sectionally and longitudinally examine whether retinal vessel traits are associated with glaucoma-related outcomes (glaucoma, cup-to-disc ratio [CDR] and intraocular pressure [IOP]) and age-related macular degeneration (AMD).<br><br>METHODS: Baseline and 3-year follow-up data from the 30&#x2009;097 participants of the Canadian Longitudinal Study on Aging were used. The follow-up rate was 92%. QUARTZ, a deep learning algorithm, was used to extract data from retinal images including arteriolar and venular diameter, tortuosity and vertical CDR. Glaucoma and AMD were self-reported. IOP was measured. Multiple linear and logistic regression were used to adjust for demographic, lifestyle and clinical factors.<br><br>RESULTS: Having wider arterioles was associated with a lower odds of glaucoma (OR&#x2009;=&#x2009;0.36, 95% CI: 0.20, 0.65) at baseline but there was no association using longitudinal data. Instead, glaucoma at baseline was strongly associated with 3-year change in arteriolar diameter (&#x3b2;&#x2009;=&#x2009;-0.21, 95% CI: -0.37, -0.05) indicating that the cross-sectional association may have been due to reverse causality. Using longitudinal data, greater venular tortuosity was associated with a reduced 3-year development of glaucoma (OR&#x2009;=&#x2009;0.52, 95% CI: 0.31, 0.87) and a 3-year reduction in the CDR (&#x3b2;&#x2009;=&#x2009;-0.006, 95% CI: -0.010, -0.002). Wider venular diameter was associated with a higher odds of AMD at baseline (OR&#x2009;=&#x2009;2.77, 95% CI: 1.50, 5.15) and a higher odds of the 3-year development of AMD (OR&#x2009;=&#x2009;4.15, 95% CI: 1.95, 8.82).<br><br>CONCLUSIONS: Understanding the temporal relationship of changes in the retinal microvasculature and the development of eye disease may lead to better treatment and prevention strategies.}, }
@article {pmid40515815, year = {2025}, author = {Torrell-Belzach, N and Souied, EH and Le, HM and Benlahbib, M and Dobbels, Z and Gounfle, AE and Wang, XX and Jung, C and Miere, A}, title = {Comparison of choriocapillaris perfusion between swept-source optical coherence tomography angiography and spectral-domain optical coherence tomography angiography in five different choriocapillaris slabs in patients with intermediate age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {263}, number = {9}, pages = {2495-2504}, pmid = {40515815}, issn = {1435-702X}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Choroid/blood supply ; Cross-Sectional Studies ; Female ; Male ; Aged ; Capillaries/physiopathology/diagnostic imaging ; Fundus Oculi ; *Retinal Vessels/physiopathology/diagnostic imaging ; Regional Blood Flow/physiology ; Aged, 80 and over ; Middle Aged ; Visual Acuity ; Retrospective Studies ; }, abstract = {PURPOSE: To analyze choriocapillaris (CC) perfusion using swept-source optical coherence tomography angiography (SS-OCTA) and spectral-domain optical coherence tomography angiography (SD-OCTA) in five CC slabs in patients with intermediate age-related macular degeneration (iAMD).<br><br>METHODS: This is a cross-sectional study of 23 eyes of 20 patients who underwent three 3&#x2009;&#xd7;&#x2009;3&#xa0;mm OCTA, one with SS-OCTA and two with SD-OCTA, a non-averaged scan (V1) and a four-scan volume (V4). Percentage of flow deficits (FD%), average size of FD (&#xb5;m2), total area of FD (mm2) and number of FD were calculated in different CC slabs (automatic, 11-21&#xa0;&#x3bc;m, 21-31&#xa0;&#x3bc;m, 31-41&#xa0;&#x3bc;m, 16-31&#xa0;&#x3bc;m).<br><br>RESULTS: There was a statistically significant difference in all parameters and all slabs analyzed, when comparing SS-OCTA versus SD-OCTA V1 and SD-OCTA V1 versus SD-OCTA V4. Nevertheless, when comparing SS-OCTA versus SD-OCTA V4, significant differences were only found for the automatic and the 31-41&#xa0;&#x3bc;m slab. When comparing the FD% between different slabs on the same device, significant differences were also found.<br><br>CONCLUSION: Quantification of CC FD% is impacted by the CC slab, the type of OCTA used, and volume averaging in SD-OCTA. Given the significant impact on quantitative results, comparisons between studies and instruments and/or with/without averaging are difficult, even at the same slab depth.}, }
@article {pmid40517179, year = {2025}, author = {Ma, K and Nakajima, H and Basak, N and Barman, A and Ratnapriya, R}, title = {Integrating explainable machine learning and transcriptomics data reveals cell-type specific immune signatures underlying macular degeneration.}, journal = {NPJ genomic medicine}, volume = {10}, number = {1}, pages = {48}, pmid = {40517179}, issn = {2056-7944}, abstract = {Genome-wide association studies (GWAS) have established key role of immune dysfunction in Age-related Macular Degeneration (AMD), though the precise role of immune cells remains unclear. Here, we develop an explainable machine-learning pipeline (ML) using transcriptome data of 453 donor retinas, identifying 81 genes distinguishing AMD from controls (AUC-ROC of 0.80, CI 0.70-0.92). Most of these genes were enriched in their expression within retinal glial cells, particularly microglia and astrocytes. Their role in AMD was further strengthened by cellular deconvolution, which identified distinct differences in microglia and astrocytes between normal and AMD. We corroborated these findings using independent single-cell data, where several ML genes exhibited differential expression. Finally, the integration of AMD-GWAS data identified a regulatory variant, rs4133124 at PLCG2, as a novel AMD association. Collectively, our study provides molecular insights into the recurring theme of immune dysfunction in AMD and highlights the significance of glial cell differences in AMD progression.}, }
@article {pmid40517351, year = {2025}, author = {Mhmud, H and Vermeulen, JP and Tigchelaar-Besling, OAM and Verbraak, FD and Barthelmes, D and Gillies, M and Ponsioen, TL and Klaver, CCW}, title = {Real-World 5-Year Outcomes of Age-Related Macular Degeneration with Bevacizumab as First-Line Anti-VEGF.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {8}, pages = {1813-1826}, pmid = {40517351}, issn = {2193-8245}, abstract = {INTRODUCTION: To evaluate long-term outcomes of anti-VEGF therapy for neovascular age-related macular degeneration (nAMD) in the Netherlands (NL), where bevacizumab is the mandated first-line drug, compared to high-income countries using ranibizumab or aflibercept as initial treatments.<br><br>METHODS: Five-year data from the Fight Retinal Blindness! (FRB) registry, a real-world prospective registry, were analyzed. Outcomes from 1473 Dutch eyes (1229 patients) treated with bevacizumab were compared with 7144 eyes (5884 patients) in a reference group (RG) from 13 socioeconomically similar countries. The primary outcome was mean visual acuity (VA) at yearly intervals; secondary outcomes included injection frequency and switching rates to alternative anti-VEGF agents.<br><br>RESULTS: Throughout the 60&#xa0;months, mean VA was consistently higher in Dutch eyes (baseline: NL 60.2 vs. RG 59.2; 60&#xa0;months: NL 64.9 vs. RG 62.6). The Dutch group cumulatively received 14.5 more injections over 5&#xa0;years and had a higher rate of switching (70.9% vs. 50.9%) with a shorter median time to switching (11.9&#xa0;months vs. 17.7&#xa0;months).<br><br>CONCLUSIONS: Patients treated in Dutch FRB! clinics have good long-term outcomes with a 2.3-letter higher mean VA at the 60-month timepoint compared to FRB! clinics in the RG. The Dutch patients, who began treatment with bevacizumab, received 14.5 more injections over 5&#xa0;years and had a 40% higher rate of switching to an alternative drug, with switching occurring 5.8&#xa0;months earlier. This study highlights the benefits of early and more intensive management to optimize visual outcomes, which appear more important than the choice and price of the first-line drug.}, }
@article {pmid40517987, year = {2025}, author = {He, HL and An, GQ and Qi, Y and Yu, XB and Zhao, MW and Song, ZM and Jin, XM and Du, LP and Jin, ZB}, title = {Clinical characteristics of atrophic macular hole in pathologic myopia: A multicenter study.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {54}, number = {}, pages = {104680}, doi = {10.1016/j.pdpdt.2025.104680}, pmid = {40517987}, issn = {1873-1597}, mesh = {Humans ; Female ; *Retinal Perforations/diagnostic imaging/etiology/pathology ; Male ; Retrospective Studies ; Middle Aged ; *Myopia, Degenerative/complications ; Aged ; Visual Acuity ; Tomography, Optical Coherence/methods ; Choroidal Neovascularization ; }, abstract = {PURPOSE: This study aims to describe and analyze the clinical characteristics of atrophic macular hole (AMH), a severe complication in patients with pathologic myopia (PM).<br><br>METHODS: A multicenter, retrospective analysis was conducted involving 17 patients (17 eyes) diagnosed with AMH and 52 patients (52 eyes) diagnosed with simple macular hole (SMH) in PM from January 2023 to December 2023. Clinical data and multimodal images were collected. The age, gender, spherical equivalent (SE), axial length (AL), and best-corrected visual acuity (BCVA) of patients with AMH were described and their imaging characteristics analyzed.<br><br>RESULTS: Of the 17 patients diagnosed with AMH, 15 (88.24 %) were female; the mean age was 64.59&#xb1;12.61 years; the SE was -17.85&#xb1;4.15 D; the AL was 30.40&#xb1;1.67 mm; and the BCVA was 1.30 (1.00, 1.35) logMAR. Eleven eyes (64.71 %) exhibited myopic foveoschisis, seven eyes showed choroidal neovascularization (Fuchs spot), one eye had a concomitant epiretinal membrane, and no cases of retinal detachment involving the macula were observed. Axial length and neovascularization were significant correlates of BCVA in AMH patients (P < 0.05). Compared with SMH in PM, patients with AMH were older (t = 2.247, P = 0.028) and had worse BCVA (Z = 375, P = 0.037); no significant differences were found between the two groups in terms of gender, SE, and AL (P > 0.05).<br><br>CONCLUSION: We propose the term "atrophic macular hole" to describe a condition resembling a macular hole accompanied by atrophy of the RPE and choroid, caused by progressive degeneration of the outer retina or traction of the eyeball, which severely impairs central vision in patients.}, }
@article {pmid40518488, year = {2026}, author = {Huang, C and Tian, H and Li, W}, title = {Age-independent anti-angiogenic therapy for choroidal neovascularization by targeting secretogranin III.}, journal = {GeroScience}, volume = {48}, number = {1}, pages = {1313-1321}, pmid = {40518488}, issn = {2509-2723}, support = {R44EY027665/EY/NEI NIH HHS/United States ; R01 EY027749/EY/NEI NIH HHS/United States ; R01 EY036417/EY/NEI NIH HHS/United States ; R24 EY028764/EY/NEI NIH HHS/United States ; R21EY035421/EY/NEI NIH HHS/United States ; R44 EY027665/EY/NEI NIH HHS/United States ; R43 EY032827/EY/NEI NIH HHS/United States ; R43EY032827/EY/NEI NIH HHS/United States ; R21 EY035421/EY/NEI NIH HHS/United States ; R01EY027749/EY/NEI NIH HHS/United States ; R24EY028764/EY/NEI NIH HHS/United States ; R01EY036417/EY/NEI NIH HHS/United States ; R01EY036417/EY/NEI NIH HHS/United States ; R01EY027749/EY/NEI NIH HHS/United States ; R24EY028764/EY/NEI NIH HHS/United States ; R21EY035421/EY/NEI NIH HHS/United States ; R44EY027665/EY/NEI NIH HHS/United States ; R43EY032827/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Choroidal Neovascularization/drug therapy/metabolism ; Mice ; *Angiogenesis Inhibitors/pharmacology/therapeutic use ; *Chromogranins ; Disease Models, Animal ; Mice, Inbred C57BL ; Vascular Endothelial Growth Factor A/metabolism/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/pharmacology ; Receptors, Vascular Endothelial Growth Factor ; }, abstract = {Recent studies reported that anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) alleviate choroidal neovascularization (CNV) in young but not aged animals. We recently developed a disease-targeted anti-angiogenic therapy against secretogranin III (Scg3), which selectively binds to diseased but not healthy vessels in young mice. Herein, using a unique in vivo ligand binding assay, we predicted and confirmed that Scg3 selectively binds CNV vessels in both young and aged mice. In contrast, VEGF with minimal increased binding to CNV vessels exhibited an age-dependent decline in binding to both CNV and healthy vessels with negligible binding in aged mice. Based on these binding activity patterns, we further predicted and confirmed that a humanized anti-Scg3 antibody effectively alleviated laser-induced CNV in both young and aged mice, whereas the anti-VEGF drug aflibercept was effective only in young mice. These findings suggest that enhanced binding of Scg3 to CNV vessels in both age groups provides a molecular basis for an age-independent anti-Scg3 therapy, offering potential to address anti-VEGF resistance in clinical treatment of wet age-related macular degeneration with CNV.}, }
@article {pmid40519319, year = {2025}, author = {Yao, J and Liu, Y and Zheng, J and Li, H and Lv, X}, title = {Association between dyslipidemia and neovascular age-related macular degeneration: a case-control study.}, journal = {International journal of clinical and experimental pathology}, volume = {18}, number = {5}, pages = {191-198}, pmid = {40519319}, issn = {1936-2625}, abstract = {OBJECTIVES: Neovascular age-related macular degeneration (nAMD) is an advanced stage of AMD and is associated with an increased risk of visual impairment. Disturbances in lipid metabolism have been proposed as a major contributing factor to the pathogenesis of AMD. This study aims to investigate whether lipid profiles in the serum and components of dyslipidemia can be used as indicators for predicting progression to nAMD.<br><br>METHODS: A retrospective analysis was conducted involving 125 participants with nAMD. 125 non-AMD controls, matched by age, sex, and BMI, were incorporated into the study. The comparative analysis between the groups involved six lipid biomarkers in the serum: HDL-C, LDL-C TG, TC, ApoA1, and ApoB. Moreover, the existence of dyslipidemia and its constituents was assessed through t-tests, as well as univariate and multivariable logistic regression models.<br><br>RESULTS: Individuals with nAMD exhibited significantly higher serum HDL-C (P = 0.02) compared to the controls without AMD. Furthermore, the concentrations of ApoB were significantly less in the nAMD cohort (P < 0.01) when compared to the control group. During the investigation of the correlation between levels of serum HDL-C (P < 0.01) and serum ApoB (P < 0.01) with nAMD through logistic regression analysis, notable findings indicated a significant association between both variables and nAMD. However, by multivariate logistic regression analysis, neither serum HDL-C nor serum ApoB was an independent risk factor for nAMD.<br><br>CONCLUSIONS: While individuals with nAMD demonstrated elevated serum HDL-C and reduced serum ApoB levels, these lipid markers may not be suitable as biomarkers for monitoring or preventing nAMD.}, }
@article {pmid40520173, year = {2025}, author = {Yang, N and Xiong, C and Feng, S and Gao, M and Zhou, S and Hui, Q and Zhou, X and Jin, Q and Shao, Y and Xu, X}, title = {Modified ZhuJing pill protects retinal pigment epithelium against oxidative stress-induced epithelial-mesenchymal transition through Nrf2-mediated Akt/GSK3β pathway.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1545731}, pmid = {40520173}, issn = {1663-9812}, abstract = {BACKGROUND: The modified ZhuJing pill (mZJP) has been widely used in China as a classical prescription for treating retinal diseases for years. Our preliminary experiment showed that mZJP exerted an antioxidant effect in treating dry age-related macular degeneration (AMD). Nevertheless, the specific mechanism underpinning the impact of mZJP on dry AMD remains obscure.<br><br>METHODS: The chemical metabolites of mZJP were qualitatively analyzed using LC-Q-TOF-MS. Dry AMD model mice were used to assess the efficacy of mZJP through optical coherence tomography (OCT), fundus autofluorescence (FAF), and immunofluorescence. Epithelial-mesenchymal transition (EMT) in OxLDL-induced ARPE-19 cells was evaluated by monitoring cellular integrity and quantifying EMT-related markers. Cell migration capacity was determined via wound healing and transwell assays. To investigate molecular mechanisms, cells were transfected with Nrf2 siRNA and analyzed through Western blotting, immunofluorescence, and migration assays under Nrf2 inhibition.<br><br>RESULTS: A total of 113 major metabolites were identified in mZJP. Our findings revealed that mZJP alleviated retinal pathological alterations and inhibited EMT progression. Furthermore, mZJP upregulated Nrf2 and HO-1 expression levels while downregulating Akt and GSK-3&#x3b2; phosphorylation levels. Notably, the EMT-suppressing effect of mZJP was significantly attenuated upon Nrf2 silencing, as evidenced by enhanced cell migration, decreased epithelial marker expression (E-cadherin), increased mesenchymal marker expression (vimentin and &#x3b1;-SMA), suppression of the Nrf2 pathway, and activation of the Akt/GSK3&#x3b2; pathway.<br><br>CONCLUSION: Our study suggested that RPE protection by mZJP against oxidative stress induced EMT through Nrf2 activation and inhibition of the Akt/GSK3&#x3b2; pathway. MZJP could be a potential candidate drug for the treatment of dry AMD.}, }
@article {pmid40520473, year = {2025}, author = {Hunt, PW and Olshen, AB and Murad, N and Ambayec, GC and Sezgin, E and Schneider, MF and Jabs, DA}, title = {Plasma Proteomic Markers of Interleukin-1β Pathway Associated with Incident Age-Related Macular Degeneration in Persons with AIDS.}, journal = {Ophthalmology science}, volume = {5}, number = {5}, pages = {100794}, pmid = {40520473}, issn = {2666-9145}, support = {R01 EY025093/EY/NEI NIH HHS/United States ; }, abstract = {OBJECTIVE: To evaluate the associations of plasma inflammatory proteins with age-related macular degeneration (AMD) in persons with the AIDS, using a discovery-based proteomics approach.<br><br>DESIGN: A nested case-control study (analysis 1) and nested cohort study (analysis 2).<br><br>PARTICIPANTS: Persons with AIDS enrolled in the Longitudinal Study of the Ocular Complications with AIDS (LSOCA).<br><br>METHODS: Cryopreserved plasma specimens obtained at baseline were assayed for inflammatory proteins using the Olink Inflammation Explore Panel 1. In analysis 1, baseline proteomic profiles for 26 persons with AIDS and incident intermediate-stage AMD 5 to 10 years after baseline and 49 matched controls (matched for age, biologic sex, race/ethnicity, and follow-up) without AMD were compared. In analysis 2, 475 persons from LSOCA with baseline plasma inflammatory proteomic profile measurements were followed for incident cataract and mortality.<br><br>MAIN OUTCOME MEASURES: Incident intermediate-stage AMD; incident cataract; and mortality.<br><br>RESULTS: Of 365 measurable plasma inflammatory proteins, 118 (32%) were associated with incident intermediate-stage AMD at the false discovery rate-adjusted Q < 0.05 level after adjustment for smoking, CD4+ T count, and plasma human immunodeficiency virus RNA level. Gene ontology pathway enrichment analysis identified the interleukin (IL)-1&#x3b2; pathway and wound healing pathways, including tissue inhibitor of metalloproteinase 3, as significantly associated with incident AMD. These associations were qualitatively different from those associated with incident cataracts, where elevated levels of inflammatory proteins were associated with a decreased risk of cataracts. A much broader number of inflammatory pathways, including those related to the adaptive immune system, were associated with mortality.<br><br>CONCLUSIONS: Upregulation of the IL-1&#x3b2; pathway appears to be associated with an increased risk of incident AMD in persons with AIDS. Given the availability of inhibitors of this pathway, inhibition of the IL-1&#x3b2; pathway may provide a therapeutic avenue for treatment of AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40521080, year = {2025}, author = {Jia, Q and Zha, Z and Li, S and Zhang, Y and Ke, L and Liu, S}, title = {Genetic Correlation and Mendelian Randomization Analyses Support Causal Relationships Between Instant Coffee and Age-Related Macular Degeneration.}, journal = {Food science &amp; nutrition}, volume = {13}, number = {6}, pages = {e70439}, pmid = {40521080}, issn = {2048-7177}, abstract = {Coffee is a popular beverage, and previous cohort studies suggest it may reduce the risk of age-related macular degeneration (AMD). However, confounding factors in these studies necessitate further exploration of causal relationships using advanced methods. We obtained data on coffee consumption from genome-wide association studies (GWAS) and the latest AMD-related GWAS summary data from the Finngen consortium R11. We assessed their genetic correlation using linkage disequilibrium score regression (LDSC), explored causal associations using Mendelian randomization (MR), and identified shared genetic loci via colocalization. Our results revealed a genetic correlation between instant coffee consumption and dry AMD, with each standard deviation (SD) increase in instant coffee intake associated with a corresponding odds ratio (OR) of approximately 6.92 for dry AMD, indicating a 6.92-fold increased risk. However, colocalization analysis did not show shared genetic variants between instant coffee consumption and AMD. Instant coffee may increase the risk of AMD, and reducing its intake could help prevent dry AMD. People at high-risk for AMD should avoid instant coffee. This study aids clinicians in identifying dietary factors, particularly instant coffee consumption, as potential risks for AMD. By providing genetically based causal evidence, our findings support the development of personalized AMD prevention strategies. Clinicians can advise patients to reduce instant coffee intake based on genetic risk profiles, offering a precision approach to reduce dry AMD risk. These interventions may significantly contribute to AMD prevention and treatment.}, }
@article {pmid40521981, year = {2025}, author = {Yang, R and Zong, T and Wang, N and Wang, F and Su, Y}, title = {NR4A1 Alleviates Subretinal Fibrosis by Inhibiting Macrophage to Myofibroblast Transition.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {6}, pages = {47}, pmid = {40521981}, issn = {1552-5783}, mesh = {Animals ; *Nuclear Receptor Subfamily 4, Group A, Member 1/genetics/physiology/biosynthesis/metabolism ; Mice ; *Macrophages/pathology/metabolism ; Fibrosis/metabolism ; *Myofibroblasts/pathology/metabolism ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Retinal Pigment Epithelium/pathology/metabolism ; Male ; Extracellular Matrix/metabolism ; Macular Degeneration/metabolism/pathology ; RNA, Small Interfering/genetics ; }, abstract = {PURPOSE: Subretinal fibrosis (SF) secondary to neovascular age-related macular degeneration (nAMD) is the most predominant cause of central visual impairment in all patients with AMD. NR4A1 is a member of the nuclear orphan receptor superfamily, and has shown inhibitory effects on fibrosis in tissues such as the dermis, intestines, and heart. Cytosporone B (Csn-B) is a natural agonist of NR4A1. This study aims to explore whether NR4A1 plays a role in SF associated with nAMD.<br><br>METHODS: Mice RPE-choroid-sclera flat mounts were prepared for serial observation of changes in macrophage infiltration, as well as macrophage to myofibroblast transformation (MMT). The morphology of MMT cells and differences in extracellular matrix (ECM) expression were further observed in TGF-&#x3b2;1-induced THP-1 cells. The role of NR4A1 in MMT was confirmed by small interfering RNA (siRNA) after changes in NR4A1 were observed. To determine whether NR4A1 could be a target for SF treatment, we intervened with the Csn-B and observed the MMT and SF changes.<br><br>RESULTS: Macrophages were rapidly recruited in the early stage and gradually decreased after the second week. MMT was observed in the lesions and the maximum number of MMT cells was observed at the third week. NR4A1 was transiently upregulated with induction, followed by a gradual decrease and a continuous phosphorylation. The knockdown of NR4A1 promoted MMT and ECM expression, whereas treatment with Csn-B had an inhibitory effect. P-NR4A1 expression was significantly suppressed in Csn-B-treated MMT cells. Finally, MK-2206 was found to inhibit sustained TGF-&#x3b2;1-induced NR4A1 phosphorylation and also ECM expression.<br><br>CONCLUSIONS: NR4A1 inhibits MMT and reduces ECM deposition in SF. Its agonist Csn-B inhibits MMT by inhibiting AKT-induced NR4A1 phosphorylation, which then attenuates SF.}, }
@article {pmid40522574, year = {2025}, author = {Chen, X and Bian, H and Wu, Z}, title = {Validation of the Chinese version of the financial toxicity scale in patients with wet age-related macular degeneration.}, journal = {Journal of patient-reported outcomes}, volume = {9}, number = {1}, pages = {69}, pmid = {40522574}, issn = {2509-8020}, mesh = {Humans ; Female ; Male ; Aged ; *Wet Macular Degeneration/economics/drug therapy ; Reproducibility of Results ; China ; Surveys and Questionnaires/standards ; Aged, 80 and over ; Middle Aged ; }, abstract = {OBJECTIVE: to confirm the validity of the Comprehensive Score for Financial Toxicity (COST) Scale in Chinese patients with wet age-related macular degeneration.<br><br>METHODS: A tertiary hospital in Wuxi's ophthalmology outpatient clinic treated 217 patients with wet age-related macular degeneration (wAMD) were chosen using the convenience sample approach for a questionnaire survey between October 2023 and February 2024. The Chinese version of the COST and general patient information were included in the survey. Critical ratio analysis and correlation analysis were used to examine the items on the scale. The structural validity of the scale was evaluated using factor analysis, the reliability of the scale was evaluated using Cronbach's &#x3b1; coefficient and retest reliability, and the content validity of the scale was evaluated using the Content Validity Index (CVI).<br><br>RESULTS: The item analysis results demonstrated that high and low subgroups could be identified using The COST scale's Chinese translation (P&#x2009;<&#x2009;0.01).; A linear positive correlation was observed between the scores of each item and the scale's overall scores (r values of 0.243&#x2009;~&#x2009;0.878, P&#x2009;<&#x2009;0.01), and the scores of factor 1, factor 2, and factor 3 showed a linear positive correlation with the total scores of the scale (accordingly, r values were 0.974, 0.505, and 0.300; P&#x2009;<&#x2009;0.01). and the scores of each item were linearly and positively correlated with the scores of the common factors to which they belonged (r values of 0.642 to 1.000, P&#x2009;<&#x2009;0.01). Content validity showed that the I-CVI of each item was 0.857&#x2009;~&#x2009;1.00, and the S-CVI was 0.974. Three metrics in all, with a cumulative variance contribution rate of 67.739%, were obtained through exploratory factor analysis. Each item's loading on the corresponding dimensions varied from 0.638 to 0.954. The Cronbach's &#x3b1; coefficient for the entire scale was 0.876(95% CI: 0.85-0.899). The reliability of the retest was 0.970 (95% CI: 0.936-0.990).<br><br>CONCLUSION: The Chinese version of the COST scale shows potential applicability pending further validation.}, }
@article {pmid40523155, year = {2025}, author = {Patel, P and Smith, BT}, title = {Extensive Network of Outer Retinal Tubulations.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {12}, pages = {e90-e91}, doi = {10.1097/IAE.0000000000004546}, pmid = {40523155}, issn = {1539-2864}, }
@article {pmid40523306, year = {2025}, author = {Sina, EM and Pena, J and Zafar, S and Bommakanti, NK and Kuriyan, AE and Yonekawa, Y}, title = {AUTOMATED MACHINE LEARNING CLASSIFICATION OF OPTICAL COHERENCE TOMOGRAPHY IMAGES OF RETINAL CONDITIONS USING GOOGLE CLOUD VERTEX ARTIFICIAL INTELLIGENCE.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {10}, pages = {1984-1990}, doi = {10.1097/IAE.0000000000004555}, pmid = {40523306}, issn = {1539-2864}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Machine Learning ; Male ; Female ; Aged ; Macular Edema ; *Diabetic Retinopathy ; *Retinal Vein Occlusion ; Artificial Intelligence ; Middle Aged ; *Retinal Diseases/diagnosis ; *Retina ; Aged, 80 and over ; Retrospective Studies ; *Epiretinal Membrane ; }, abstract = {PURPOSE: Automated machine learning is an artificial intelligence tool that streamlines image recognition model development. This study evaluates the diagnostic performance of Google Vertex AI automated machine learning in differentiating age-related macular degeneration (AMD), diabetic macular edema, epiretinal membrane, retinal vein occlusion, and healthy controls using optical coherence tomography images.<br><br>METHODS: A publicly available, validated optical coherence tomography data set of 1965 deidentified images from 759 patients was used. Images were labeled and uploaded to Vertex AI. A single-label classification model was trained, validated, and tested using an 80%-10%-10% split. Diagnostic metrics included area under the precision-recall curve (AUPRC), sensitivity, specificity, and positive and negative predictive value. A subanalysis evaluated neovascular versus nonneovascular AMD.<br><br>RESULTS: The automated machine learning model achieved high accuracy (AUPRC = 0.991), with sensitivity, specificity, and PPV of 95.9%, 96.9%, and 95.9%, respectively. AMD classification performed best (AUPRC = 0.999, precision = 98.4%, recall = 99.2%). Epiretinal membrane (AUPRC = 0.978, precision = 92.9%, recall = 86.7%) and diabetic macular edema (AUPRC = 0.895, precision = 81.3%, recall = 86.7%) followed. Retinal vein occlusion recall was 80% despite 100% precision. Neovascular AMD outperformed nonneovascular AMD (AUPRC = 0.963 vs. 0.915).<br><br>CONCLUSION: Our automated machine learning model accurately classifies optical coherence tomography images of retinal conditions, demonstrating performance comparable or superior to traditional ML methods. Its user-friendly design supports scalable AI-driven clinical integration.}, }
@article {pmid40523530, year = {2025}, author = {Tamaddon, M and Fazel, M and Rezaee, D and Khalilzad, MA and Majidpoor, J and Ahmadieh, H and Fattahi, MD and Namakin, K and Suri, F and Najafi, S}, title = {The role of microRNAs in the pathophysiology of the aging eye.}, journal = {Ageing research reviews}, volume = {111}, number = {}, pages = {102805}, doi = {10.1016/j.arr.2025.102805}, pmid = {40523530}, issn = {1872-9649}, mesh = {Humans ; *MicroRNAs/genetics/metabolism/physiology ; *Aging/genetics/pathology/physiology ; Animals ; *Eye Diseases/genetics/physiopathology/metabolism ; *Eye/physiopathology/metabolism ; }, abstract = {The human eye is a complex organ integral to visual perception, comprising multiple structures, including the retina, cornea, and lens. Vision loss affects over 2.2 billion individuals globally, with conditions, such as age-related macular degeneration, cataracts, glaucoma, and diabetic retinopathy, recognized as responsible for a majority of visual-impairing conditions. Recent research highlights the critical roles of microRNAs (miRNAs)-small non-coding RNAs involved in post-transcriptional gene regulation-in ocular physiology and pathophysiology. miRNAs regulate gene expression by binding to target mRNA, modulating multiple processes like cell growth, apoptosis, and differentiation. Dysregulation of miRNAs has been implicated in various age-related ocular disorders like retinopathy, glaucoma and age-related macular degeneration, thereby disrupting cellular homeostasis and promoting disease progression. Experimental evidence, primarily from murine models, reveals that miRNAs regulate photoreceptor differentiation, retinal development, and the survival of postmitotic retinal cells. Additionally, miRNA dysregulation offers potential diagnostic and therapeutic insights. This study explores the roles of miRNAs in ocular pathophysiology, emphasizing their involvement in the maintenance of retinal cell integrity and visual system homeostasis. Furthermore, the significance of miRNAs in the pathogenesis of various human ophthalmic diseases associated with advancing age is reviewed.}, }
@article {pmid40525639, year = {2025}, author = {Yildiz, E and Bozuyuk, U and Yildiz, E and Wang, F and Han, M and Karacakol, AC and Sheehan, D and Yu, Y and Sitti, M}, title = {Magnetically Controllable and Degradable Milliscale Swimmers as Intraocular Drug Implants.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {34}, pages = {e07569}, pmid = {40525639}, issn = {2198-3844}, support = {834531//HORIZON EUROPE European Research Council/ ; 101059593//H2020 Marie Sk&#x142;odowska-Curie Actions/ ; }, mesh = {*Drug Implants ; Humans ; *Absorbable Implants ; Hydrogels/chemistry ; Polyethylene Glycols/chemistry ; Animals ; *Drug Delivery Systems/methods ; Printing, Three-Dimensional ; Indoles ; Polymers ; }, abstract = {Intraocular drug implants are increasingly used for retinal treatments, such as age-related macular degeneration and diabetic macular edema, due to the rapidly aging global population. Although these therapies show promise in arresting disease progression and improving vision, intraocular implant-based therapies can cause unexpected complications that require further surgery due to implant dislocation or uncontrolled drug release. These frequent complications of intraocular drug implants can be overcome using magnetically controllable degradable milliscale swimmers (MDMS) with a double-helix body morphology. A biodegradable hydrogel, polyethylene glycol diacrylate, is employed as the primary 3D printing material of MDMS, and it is magnetized by decorating it with biocompatible polydopamine-encapsulated iron-platinum nanoparticles. MDMS have comparable dimensions to commercial intraocular implants that achieve translational motions in both aqueous and vitreous bodies. They can be imaged in real-time using optical coherence tomography, ultrasound, and photoacoustic imaging. Thanks to their biodegradable hydrogel-based structure, they can be loaded with anti-inflammatory drug molecules and release the medications without disrupting retinal epithelial viability and barrier function, and decrease proinflammatory cytokine release significantly. These magnetically controllable swimmers, which degrade in a couple of months, can be used for less invasive and more precise intraocular drug delivery compared to commercial intraocular drug implants.}, }
@article {pmid40525920, year = {2025}, author = {Ji, R and Ishikawa, K and Tan, W and Mori, K and Tsukamoto, R and Matsunaga, N and Kiyohara, K and Fukuda, Y and Wada, I and Isobe, T and Tanihara, T and Yoshida, Y and Mayanagi, K and Oyama, K and Terada, Y and Otsuki, K and Hamamura, K and Kikuchi, H and Nakao, S and Yoshida, S and Kannan, R and Ohdo, S and Sonoda, KH}, title = {Liposome Encapsulation Enhances Ripasudil Therapeutic Efficacy Against Proliferative Vitreoretinal Diseases: Implications in Advanced Ocular Treatment.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {6}, pages = {56}, pmid = {40525920}, issn = {1552-5783}, support = {R01 EY030141/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Vitreoretinopathy, Proliferative/drug therapy/metabolism ; Liposomes ; Rabbits ; *Isoquinolines/pharmacokinetics/administration &amp; dosage ; Retinal Pigment Epithelium/drug effects/pathology ; *Sulfonamides/pharmacokinetics/administration &amp; dosage ; Disease Models, Animal ; Humans ; Epithelial-Mesenchymal Transition/drug effects ; Intravitreal Injections ; }, abstract = {PURPOSE: Proliferative vitreoretinal diseases, such as proliferative vitreoretinopathy (PVR) and neovascular age-related macular degeneration (nAMD), pose substantial challenges in their advanced stages owing to the development of retinal fibrous membranes. Current therapeutic modalities, including surgical interventions for PVR and antivascular endothelial growth factor therapy for nAMD, cannot effectively manage intraocular fibrosis associated with epithelial-to-mesenchymal transition (EMT) in retinal pigment epithelium (RPE) cells. Through drug screening, we identified ripasudil, a Rho-kinase inhibitor, as a remarkable suppressor of RPE-EMT. However, the short vitreal half-lives of small-molecule drugs, coupled with the limited stability of ripasudil in the ocular environment, impede its application in vitreoretinal diseases. Considering the advances in nanotechnology-assisted improvement in drug stability and cellular uptake as well as controlled release, we aimed to enhance the efficacy of ripasudil through liposome encapsulation.<br><br>METHODS: After ripasudil encapsulation, we performed comprehensive in vivo and in vitro analyses and pharmacokinetic studies.<br><br>RESULTS: Liposome-encapsulated ripasudil (Lipo-Ripa) demonstrated a substantial reduction in subretinal fibrosis in an advanced AMD model and more effective inhibition of PVR progression in rabbits than that induced by ripasudil alone. Pharmacokinetic studies revealed that Lipo-Ripa exhibited improved retention capacity in the vitreous and retina, alongside reduced permeability through the RPE barrier and increased cellular uptake. These characteristics resulted in a sustained elevation of drug concentration within the ocular tissues over time.<br><br>CONCLUSIONS: Our findings suggest that liposomal encapsulation of ripasudil supports enhanced bioavailability and effectiveness of the drug, presenting a promising innovative therapeutic approach for the treatment of proliferative vitreoretinopathy.}, }
@article {pmid40526023, year = {2025}, author = {Lee, H and Sharma, A and Woo, SJ}, title = {Clinical Trials of Aflibercept Biosimilars: A Review.}, journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics}, volume = {41}, number = {7}, pages = {363-369}, doi = {10.1089/jop.2025.0040}, pmid = {40526023}, issn = {1557-7732}, mesh = {Humans ; *Biosimilar Pharmaceuticals/therapeutic use/administration &amp; dosage/pharmacology ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage/pharmacology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Retinal Diseases/drug therapy ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage/pharmacology ; Clinical Trials, Phase III as Topic ; }, abstract = {Anti-vascular endothelial growth factor (VEGF) biologics have revolutionized the management of VEGF-driven retinal diseases, significantly improving visual outcomes for patients. Following the patent expiration of ranibizumab, multiple anti-VEGF biosimilars have been developed, with the first approved for ophthalmic use entering the market in 2022. More recently, the expiration of aflibercept market exclusivity in 2024 has led to the rapid development of aflibercept biosimilars-some already approved and others pending regulatory decisions. By offering clinically equivalent and cost-effective alternatives to reference biologics, biosimilars can lessen financial burdens and improve treatment adherence. Understanding the study designs of biosimilars can mitigate negative perceptions of biosimilars and promote their active implementation. In this review, we provide a comprehensive comparison of the designs of phase III clinical trials of aflibercept biosimilars, including recently published results.}, }
@article {pmid40526904, year = {2025}, author = {Rouvas, A and Datseris, I and Malvina-Efthymia, T and Kardara, M and Theodossiadis, P and Gouliopoulos, N}, title = {LONG-TERM NATURAL COURSE OF AVASCULAR SEROUS PIGMENT EPITHELIAL DETACHMENT IN AGE-RELATED MACULAR DEGENERATION.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {10}, pages = {1854-1861}, doi = {10.1097/IAE.0000000000004558}, pmid = {40526904}, issn = {1539-2864}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Retinal Detachment/diagnosis/etiology ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Aged ; *Visual Acuity ; *Retinal Pigment Epithelium/pathology ; Follow-Up Studies ; Aged, 80 and over ; Disease Progression ; *Choroidal Neovascularization/diagnosis/etiology ; Fundus Oculi ; Middle Aged ; Risk Factors ; *Macular Degeneration/complications/diagnosis ; Time Factors ; *Wet Macular Degeneration/complications/diagnosis ; Indocyanine Green/administration &amp; dosage ; }, abstract = {PURPOSE: To investigate the long-term natural history of avascular serous pigment epithelial detachment (PED) in age-related macular degeneration and identify risk factors for choroidal neovascularization (CNV) development.<br><br>METHODS: This retrospective study analyzed 71 eyes from 50 patients with pure avascular serous PED because of age-related macular degeneration, diagnosed via fluorescein angiography and indocyanine-green angiography. Patients were followed for at least 12 months (mean follow-up: 54.9 months). Baseline and follow-up assessments included best-corrected visual acuity and optical coherence tomography measurements of PED height and diameter. Disease progression was categorized as stable, atrophic, or CNV development, and statistical analyses identified CNV risk factors.<br><br>RESULTS: Among studied eyes, 15.5% developed CNV, 21.1% progressed to atrophy, and 63.4% remained stable. Larger baseline PED height and diameter significantly correlated with CNV risk (P = 0.004 and P = 0.003, respectively). Every 100 &#xb5; m increase in PED height and diameter raised CNV risk by 50% and 10%, respectively. Best-corrected visual acuity declined in all groups, with greater deterioration in CNV and atrophic cases.<br><br>CONCLUSION: Larger PED height and diameter are significant CNV risk factors in avascular serous PED. OCT-based monitoring is crucial for early detection of high-risk cases, optimizing clinical management, and preventing vision loss in age-related macular degeneration patients.}, }
@article {pmid40528210, year = {2025}, author = {Heinke, A and Warter, A and Nagel, ID and Agnihotri, A and Mehta, NN and Galang, CMB and Deussen, DN and Bartsch, DG and Cheng, L and Ferreyra, HA and Freeman, WR}, title = {Faricimab for treatment-resistant choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD): seven-months results using artificial intelligence and OCTA.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {68}, pmid = {40528210}, issn = {2056-9920}, support = {OT2OD032644/GF/NIH HHS/United States ; R01EY016323/GF/NIH HHS/United States ; R01EY033847/GF/NIH HHS/United States ; }, abstract = {BACKGROUND: To analyze the therapeutic response to faricimab 6 mg/0.05 ml in eyes with neovascular AMD (nAMD) with refractory intra- and/or subretinal fluid due to choroidal neovascularization (CNV), previously unresponsive to 4 mg monthly aflibercept and combination therapy with anti-VEGF and long-acting steroids.<br><br>METHODS: A retrospective case series study of 22 eyes with unresponsive CNV, despite monthly intravitreal treatment (mean number of pre-faricimab injections: 35.52&#x2009;&#xb1;&#x2009;17.12). We evaluated therapeutic response in eyes with persistent intra/subretinal fluid (IRF/SRF) unresponsive to anti-VEGF double-dose (DD) monotherapy (4-mg aflibercept) and/or simultaneous DD anti-VEGF (4-mg aflibercept) with steroids (triamcinolone). Best-corrected visual acuity (BCVA), intraocular pressure (IOP), and optical coherence tomography (OCT) measurements of central retinal thickness (CRT) were recorded for 7 follow-ups. Baseline and follow-up OCTs were examined by an AI-developed platform (Discovery OCT Fluid and Biomarker Detector, RetinAI AG, Switzerland) to measure the volume of IRF, SRF, and pigment epithelium detachment (PED) in nanoliters (nL) and CRT in micrometers (&#x3bc;m). Paired t-test compared these parameters at baseline and after treatment. OCTA analysis of CNV before and after treatment with faricimab was conducted using Angio-Tool software.<br><br>RESULTS: Anatomic outcomes included mean CRT reduction of -25.3&#xa0;&#x3bc;m (p&#x2009;=&#x2009;0.0118) at month-1, -16.15&#xa0;&#x3bc;m (p&#x2009;=&#x2009;0.0414) at month-4, and -26.36&#xa0;&#x3bc;m (p&#x2009;=&#x2009;0.0129) after the 7th follow-up. AI-assisted software analysis showed a significant reduction of IRF, SRF, and PED volume at multiple time points after initiating faricimab. There was a non-significant improvement in BCVA.<br><br>CONCLUSIONS: Switching to faricimab improved anatomy in highly treatment-resistant CNV eyes, indicating its potential when other therapeutic options have failed.}, }
@article {pmid40528396, year = {2025}, author = {He, N and Wu, D and Luo, R and Cao, Z and Shan, S and Fei, Q and Wu, J and Bai, S}, title = {Development and optimisation of esculin-loaded chitosan microspheres for intravitreal injection.}, journal = {Journal of microencapsulation}, volume = {42}, number = {6}, pages = {593-612}, doi = {10.1080/02652048.2025.2515840}, pmid = {40528396}, issn = {1464-5246}, mesh = {*Chitosan/chemistry/pharmacokinetics ; *Microspheres ; Intravitreal Injections ; *Esculin/pharmacokinetics/administration &amp; dosage/chemistry ; Animals ; Particle Size ; Macular Degeneration/drug therapy ; Drug Liberation ; Drug Delivery Systems ; *Drug Carriers/chemistry ; Vitreous Body/metabolism ; }, abstract = {This study was to prepare the esculin-loaded chitosan microspheres for intravitreal injection and explore the feasibility of the treatment of macular degeneration. The microspheres were fabricated using an emulsification crosslinking technique. The drug loading, encapsulation efficiency, and mean particle diameter of the optimised esculin-loaded chitosan microspheres were 8.03 ± 1.30%, 93.03 ± 2.16%, and 4.81 ± 1.60 μm, respectively. The thermal stability evaluation at 25 °C demonstrated consistent particle diameter maintenance, with microspheres retaining sizes of 4.73 ± 1.75 μm and 4.89 ± 1.55 μm after 15 and 30 days' storage periods, respectively. The in vitro release profile demonstrated 80% cumulative drug release from the microspheres over a 72 h period. Subsequent pharmacokinetic analysis revealed significantly enhanced parameters in the vitreous humour following intravitreal administration, with the half-life (t1/2) reaching 879.88 ± 44.00 min and the area under curve (AUC) attaining 150.18 ± 2.28 × 10[3] mg·min/mL. Intravitreal injection of esculin-loaded chitosan microspheres offers a promising drug delivery system for the treatment of macular degeneration.}, }
@article {pmid40528953, year = {2025}, author = {Su, W and Gao, Y and Jia, X and Chen, X and Wu, J and Wen, Y and Shi, Y and Zhu, Y and Zhuo, Y}, title = {Single-cell transcriptome atlas of spontaneous dry age-related macular degeneration in macaques.}, journal = {Fundamental research}, volume = {5}, number = {3}, pages = {1034-1046}, pmid = {40528953}, issn = {2667-3258}, abstract = {Age-related macular degeneration is the leading cause of irreversible visual impairment in the elderly. It manifests in two forms, wet and dry. However, the mechanisms underlying spontaneous dry age-related macular degeneration (SD-AMD) remain unclear. Herein, we constructed a single-cell retinal transcription atlas in aged non-human primates with SD-AMD. Retinal tissues affected by SD-AMD exhibited a more degenerative and dysfunctional transcriptomic landscape, with global activation of the oxidative stress response and apoptotic signaling pathway. We found two distinct Müller glia subtypes in normal aged and SD-AMD macaques, one exhibiting a photoreceptor-like transcriptome and the other exhibiting a typical Müller glia transcriptome. As SD-AMD progressed, the proportion of photoreceptor-like Müller glial cells decreased, and photoreceptor-function-associated genes were downregulated, indicating weaker Müller glia potential to transit into photoreceptor-like functional states. Microglial cells showed activated features, and the complement system was activated during disease pathogenesis. We also found that the disruption of iron homeostasis and ferroptosis could promote SD-AMD pathogenesis in neural cells. Further experimentation revealed that a ferroptosis inhibitor exerted a profound rescuing effect in SD-AMD mouse models. Based on these results, our study introduces a path toward understanding the pathogenesis of SD-AMD in a non-human primate model at single-cell resolution.}, }
@article {pmid40529115, year = {2025}, author = {Agrawal, V and Gupta, A and Agrawal, V and Sheth, JU}, title = {Faricimab Outcomes in Chorioretinal Disorders: Indian Real-World Analysis (FOCUS Study).}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {1855-1862}, pmid = {40529115}, issn = {1177-5467}, abstract = {PURPOSE: To assess the real-world efficacy and safety of intravitreal faricimab in treating Diabetic Macular Edema (DME), neovascular Age-related Macular Degeneration (nAMD), and Central Macular Edema (CME) secondary to retinal vein occlusion (RVO) in an Indian population.<br><br>PATIENTS AND METHODS: This single&#x2011;center, retrospective observational study reviewed the records of 49 patients (49 eyes) diagnosed with DME, nAMD, or cystoid macular edema secondary to RVO, who received a total of 150 intravitreal faricimab injections and were followed for at least 24&#x202f;weeks. Patients received intravitreal faricimab injections, with follow-up at four-week intervals. Outcome measures included changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT), along with resolution of intraretinal (IRF) and subretinal fluid (SRF) in nAMD patients.<br><br>RESULTS: Faricimab significantly improved BCVA and reduced CMT across all groups after a mean follow-up period of 33.31 (&#xb1; 7.41) weeks. DME patients' BCVA improved from 0.71 (&#xb1; 0.36) LogMAR to 0.46 (&#xb1; 0.35) LogMAR (P<0.0001), nAMD from 1.24 (&#xb1; 0.73) to 0.43 (&#xb1; 0.43) LogMAR (P=0.00003), and RVO from 0.78 (&#xb1; 0.32) to 0.38 (&#xb1; 24) LogMAR (P=0.02). CMT decreased from 454.43 (&#xb1; 164.76) &#xb5;m to 255.3 (&#xb1; 81.17) &#xb5;m (P<0.00001) overall. Significant reductions were also observed in IRF and SRF in nAMD patients, with IRF decreasing from 48% to 16% (P=0.008) and SRF from 100% to 20% (P<0.00001). No significant adverse events, including intraocular inflammation (IOI), were reported.<br><br>CONCLUSION: Faricimab demonstrated significant visual and anatomical improvements across all diagnostic groups, including off&#x2011;label use in RVO&#x2011;associated CME during the study period, showing promise as an effective treatment for DME, nAMD, and RVO. These real-world outcomes align with clinical trial data (TENAYA, LUCERNE, YOSEMITE, RHINE), underscoring faricimab's potential as an effective, dual-action therapy for chorioretinal disorders.}, }
@article {pmid40532855, year = {2025}, author = {Owsley, C and McGwin, G and Clark, ME and Gao, L and Gooden, L and Thomas, TN and Goerdt, L and Curcio, CA}, title = {Delayed Rod-Mediated Dark Adaptation Is Associated with Incidence and Early Progression of Age-Related Macular Degeneration: Alabama Study on Early Age-Related Macular Degeneration 2.}, journal = {Ophthalmology}, volume = {132}, number = {11}, pages = {1273-1283}, pmid = {40532855}, issn = {1549-4713}, support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Dark Adaptation/physiology ; Incidence ; Male ; Female ; Disease Progression ; Aged ; Visual Acuity/physiology ; Middle Aged ; *Retinal Rod Photoreceptor Cells/physiology ; Follow-Up Studies ; Alabama/epidemiology ; *Macular Degeneration/physiopathology/epidemiology/diagnosis ; Contrast Sensitivity/physiology ; Aged, 80 and over ; Longitudinal Studies ; }, abstract = {PURPOSE: To examine whether delayed rod-mediated dark adaptation (RMDA) in healthy older eyes and those with early age-related macular degeneration (AMD) is associated with AMD incidence and progression at follow-up, as compared with other visual functions reliant on rods, cones, or mixed rod-cone mediation.<br><br>DESIGN: Longitudinal study over 3 years.<br><br>PARTICIPANTS: Eyes from adults &#x2265;60 years of age with normal macular health or with early AMD at baseline.<br><br>METHODS: At baseline, eyes underwent fundus photography to establish AMD presence and severity using the Age-Related Eye Disease Study (AREDS) 9-step classification system. The following visual functions were tested in 1 eye at baseline (the study eye): RMDA, scotopic sensitivity, low-luminance acuity, mesopic contrast sensitivity, mesopic light sensitivity, visual acuity, and contrast sensitivity. Three years later at follow-up, fundus photography and the AREDS classification were repeated. Age-adjusted relative risks and 95% confidence intervals measured the association between visual functions and AMD incidence and progression for the study eye and the fellow eye at follow-up.<br><br>MAIN OUTCOME MEASURES: Presence and severity of AMD at the 3-year follow-up visit in the study and fellow eyes.<br><br>RESULTS: Healthy older eyes at baseline with delayed RMDA were 3.54 or 3.40 times more likely to have incident AMD at the 3-year follow-up in the study eye and the fellow eye, respectively, compared with eyes without delays. No other visual functions were associated with AMD incidence, except for low-luminance visual acuity in the study eye. Eyes with early AMD at baseline with delayed RMDA were 3.89 or 2.65 times more likely to have progressed at follow-up for the study and fellow eye, respectively. No other visual functions were associated with AMD progression at follow-up.<br><br>CONCLUSIONS: Rod-mediated dark adaptation is the only visual function of those tested that was associated with AMD incidence and progression over 3 years in healthy eyes or those with early AMD at baseline. Our results suggest that other visual functions are not useful for understanding AMD incidence and early progression risk. Interventions that eventually are designed to arrest early AMD progression or preventative measures in those at risk should consider RMDA a functional outcome measure.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40533834, year = {2025}, author = {Wang, TI and Qu, J and Tang, R and Shi, X and Ying, X and Tao, Y and Li, X}, title = {Prognostic factors in the treatment of polypoidal choroidal vasculopathy with conbercept: a post hoc analysis of the STAR study.}, journal = {Eye and vision (London, England)}, volume = {12}, number = {1}, pages = {24}, pmid = {40533834}, issn = {2326-0254}, support = {7232192//Natural Science Foundation of Beijing Municipality/ ; }, abstract = {BACKGROUND: A post hoc analysis of the STAR study, which was a 48-week, phase IV, multicenter randomized controlled multicenter clinical trial was performed. This study aims to identify the baseline factors associated with visual and anatomic changes over 48 weeks in the treatment of active polypoidal choroidal vasculopathy (PCV) with conbercept.<br><br>METHODS: In the STAR study, 249 participants were randomized to either the 3&#x2009;+&#x2009;Q12W (3 monthly injections followed by injections every 12&#xa0;weeks) or 3&#x2009;+&#x2009;TAE (3 monthly injections followed by treat and extend regimen) group. The association of 27 baseline factors with three outcomes-changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and maximum retinal thickness (MRT) from baseline to 48&#xa0;weeks-was investigated using univariate regression analysis followed by multivariate linear regression analysis.<br><br>RESULTS: The final multivariate model indicated that worse baseline BCVA (P&#x2009;<&#x2009;0.01), CRT&#x2009;&#x2264;&#x2009;400&#xa0;&#x3bc;m (P&#x2009;<&#x2009;0.01), fewer polypoidal lesions (P&#x2009;<&#x2009;0.01), and younger age at baseline (P&#x2009;=&#x2009;0.04) were associated with greater BCVA gain at week 48. Higher CRT and MRT at baseline were associated with a greater reduction in CRT and MRT at week 48, separately (P&#x2009;<&#x2009;0.01 and P&#x2009;<&#x2009;0.01, respectively). Smaller pigment epithelial detachment (PED) volume at baseline was associated with greater reductions in CRT and MRT at week 48 (both P&#x2009;<&#x2009;0.01). Eyes with relatively good BCVA (>&#x2009;73 letters) at baseline exhibited lower reductions in CRT and MRT at week 48 (P&#x2009;<&#x2009;0.01 and P&#x2009;=&#x2009;0.02, respectively). At week 48, eyes with hemorrhagic PEDs showed greater reductions in CRT and MRT than those with fibrovascular PEDs (P&#x2009;=&#x2009;0.02 and P&#x2009;=&#x2009;0.03, respectively). Furthermore, eyes with shallow irregular or sharp-peaked PEDs exhibited greater reductions in CRT (both P&#x2009;<&#x2009;0.01) and MRT (P&#x2009;=&#x2009;0.01 and P&#x2009;<&#x2009;0.01, respectively) than those with multilobular PEDs from baseline to week 48.<br><br>CONCLUSIONS: In Chinese patients with PCV receiving intravitreal injections of conbercept, baseline characteristics, including age, BCVA, CRT, MRT, number of polypoidal lesions, PED volume, and PED types and morphology, served as predictors of visual and anatomical changes over 48&#xa0;weeks.}, }
@article {pmid40534793, year = {2025}, author = {Yuan, YX and Wu, HY and Yuan, WJ and Zhong, YL and Xu, Z}, title = {Macular pigment optical density and measurement technology based on artificial intelligence: a narrative review.}, journal = {International journal of ophthalmology}, volume = {18}, number = {6}, pages = {1152-1162}, pmid = {40534793}, issn = {2222-3959}, abstract = {Macular pigment (MP) is a crucial pigment in the macular region. It plays an important role in filtering blue light, and exhibits anti-inflammatory and antioxidant properties. Macular pigment optical density (MPOD) is a key indicator for assessing the density of MP in the macular area and is closely associated with eye diseases, including age-related macular degeneration, diabetic retinopathy, and glaucoma. This review aims to explore the clinical significance of MPOD and its research value in ophthalmology and other medical fields. It summarizes the current MPOD measurement techniques, categorizing them into two main types (in vivo and in vitro), and discusses their respective advantages and limitations. Additionally, given the advancements in artificial intelligence (AI) and deep-learning technologies that offer new opportunities for improving MPOD assessment, this review analyzes the significant potential and future prospects of AI-based fundus image analysis in MPOD measurement. The goal of AI-based analysis is to provide faster and more accurate detection methods, thereby promoting further research and new clinical applications of MPOD in the field of ophthalmology.}, }
@article {pmid40537005, year = {2026}, author = {Zhang, H and Mu, Y and Li, H and Li, X}, title = {Unfolded protein response in endoplasmic reticulum stress associated with retinal degenerative diseases: A promising therapeutic target.}, journal = {Neural regeneration research}, volume = {21}, number = {4}, pages = {1339-1352}, pmid = {40537005}, issn = {1673-5374}, support = {R01 DK126662/DK/NIDDK NIH HHS/United States ; R01 DK129241/DK/NIDDK NIH HHS/United States ; }, abstract = {The unfolded protein response is a cellular pathway activated to maintain proteostasis and prevent cell death when the endoplasmic reticulum is overwhelmed by unfolded proteins. However, if the unfolded protein response fails to restore endoplasmic reticulum homeostasis, it can trigger pro-inflammatory and pro-death signals, which are implicated in various malignancies and are currently being investigated for their role in retinal degenerative diseases. This paper reviews the role of the unfolded protein responsein addressing endoplasmic reticulumstress in retinal degenerative diseases. The accumulation of ubiquitylated misfolded proteins can lead to rapid destabilization of the proteome and cellular demise. Targeting endoplasmic reticulum stress to alleviate retinal pathologies involves multiple strategies, including the use of chemical chaperones such as 4-phenylbutyric acid and tauroursodeoxycholic acid, which enhance protein folding and reduce endoplasmic reticulum stress. Small molecule modulators that influence endoplasmic reticulum stress sensors, including those that increase the expression of the endoplasmic reticulum stress regulator X-box binding protein 1, are also potential therapeutic agents. Additionally, inhibitors of the RNAse activity of inositol-requiring transmembrane kinase/endoribonuclease 1, a key endoplasmic reticulum stress sensor, represent another class of drugs that could prevent the formation of toxic aggregates. The activation of nuclear receptors, such as PPAR and FXR, may also help mitigate ER stress. Furthermore, enhancing proteolysis through the induction of autophagy or the inhibition of deubiquitinating enzymes can assist in clearing misfolded proteins. Combination treatments that involve endoplasmic-reticulum-stress-targeting drugs and gene therapies are also being explored. Despite these potential therapeutic strategies, significant challenges remain in targeting endoplasmic reticulum stress for the treatment of retinal degeneration, and further research is essential to elucidate the mechanisms underlying human retinal diseases and to develop effective, well-tolerated drugs. The use of existing drugs that target inositol-requiring transmembrane kinase/endoribonuclease 1 and X-box binding protein 1 has been associated with adverse side effects, which have hindered their clinical translation. Moreover, signaling pathways downstream of endoplasmic reticulum stress sensors can contribute to therapy resistance. Addressing these limitations is crucial for developing drugs that can be effectively used in treating retinal dystrophies. In conclusion, while the unfolded protein response is a promising therapeutic target in retinal degenerative diseases, additional research and development efforts are imperative to overcome the current limitations and improve patient outcomes.}, }
@article {pmid40537856, year = {2025}, author = {Lynn, SA and Pandi, SPS and Sanchez-Bretano, A and Muir, AM and Parker, L and Chatelet, DS and Newall, T and Scott, JA and Keeling, E and Smyth, NR and Self, JE and Lotery, AJ and Lee, H and Ratnayaka, JA}, title = {A longitudinal study of the 5xFAD mouse retina delineates Amyloid beta (Aβ)-mediated retinal pathology from age-related changes.}, journal = {Alzheimer's research &amp; therapy}, volume = {17}, number = {1}, pages = {136}, pmid = {40537856}, issn = {1758-9193}, support = {NC3R Fellowship to S.A.L (NC/T002336/1)/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; Seed award and PhD studentship//Sight Research UK/ ; }, mesh = {Animals ; Mice, Transgenic ; *Retina/pathology/metabolism/physiopathology ; *Amyloid beta-Peptides/metabolism ; Male ; Female ; Longitudinal Studies ; *Aging/pathology ; Mice ; Disease Models, Animal ; Tomography, Optical Coherence ; *Macular Degeneration/pathology/genetics/metabolism ; Electroretinography ; Humans ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the commonest cause of irreversible blindness in developed societies. AMD coincides with advanced age to which genetic and lifestyle factors contribute additional risks. High levels of the Alzheimer's-linked Amyloid beta (Aβ) proteins are correlated with aged/AMD retinas. To delineate the role of Aβ in retinopathy from age-related changes, we used transgenic 5xFAD mice in a longitudinal study to recapitulate the aged/AMD Aβ-burden of the human retina.<br><br>METHODS: Mice were genotyped to exclude the retinal degeneration alleles Pde6b[rd1], Pde6brd8, Agouti, Tyr and Oca2. Retinas of 5xFAD and wildtype littermates (97 males/females in total) were longitudinally assessed until 15 months using non-invasive retinal scans: multi-focal electroretinography, optokinetic tracking, optical coherence tomography (OCT), colour fundus photography and fluorescein angiography. Mice were killed at 4, 8 and 15 months, and eyes enucleated for analyses by light, confocal and electron microscopy.<br><br>RESULTS: Age-related changes included a gradual decline of retinal activity in all mice. Subretinal/drusen-like deposits increased with age, but, like retinal vessel morphology and vessel integrity, showed no differences between cohorts. Diminished PSD95 levels indicated impaired photoreceptor-bipolar connectivity which correlated with age. Ultrastructural imaging showed increased electron-dense granules and undigested outer segments within retinal pigment epithelial cells with age. 5xFAD pathology included significant weight reduction vs. wildtype/littermates, which were pronounced in females. 8 month old 5xFAD mice had diminished A and B waves, though the age-related decline in wildtype mice abolished these subsequently. Visual acuity/function was also reduced in 14 month 5xFAD eyes. OCT revealed thickened photoreceptor nuclei and inner segments in 8 month 5xFAD retinae. Scrutiny of chorioretinal tissues revealed diminished photoreceptor nuclei in 4 month 5xFAD eyes, though differences were abolished as both cohorts aged. From 8 months onwards, 5xFAD mice possessed fewer bipolar cell nuclei.<br><br>CONCLUSIONS: Chronic A&#x3b2; exposure led to the earlier development of retinopathy-linked features, the identification of which advances our understanding of how A&#x3b2; contributes to multifaceted retinopathies. These were distinguishable from wider age-related changes and non-specific influences of retinal degeneration alleles in 5xFAD mice. Longitudinal analyses revealed sex and age-related limitations and important 3Rs considerations for future studies using 5xFAD mice.}, }
@article {pmid40538770, year = {2025}, author = {Pearlman, JA and Sheth, VS and Khanani, AM and Indjeian, VB and Brunstein, F and Kuruvilla, D and Maia, M and Dere, R and Ma, L and Chen, H and Datta, S and Willis, JR and Wiley, HE}, title = {Phase I Study of the Anti-interleukin 33 Fragment Antigen-Binding Region RO7303359 in Geographic Atrophy Secondary to Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {5}, number = {5}, pages = {100800}, pmid = {40538770}, issn = {2666-9145}, abstract = {PURPOSE: Interleukin (IL) 33 is a potent proinflammatory cytokine and a potential target in age-related macular degeneration (AMD) pathophysiology. This study evaluated RO7303359, an anti-IL-33 fragment antigen-binding region (Fab) targeting the IL-33/serum stimulation-2 (ST2) pathway, in patients with geographic atrophy (GA) secondary to AMD.<br><br>DESIGN: Phase I, open-label, multicenter, single-dose, dose-escalation study.<br><br>PARTICIPANTS: Patients with GA secondary to AMD.<br><br>METHODS: Patients received a single intravitreal (IVT) injection of RO7303359 (dose range, 1-20 mg).<br><br>MAIN OUTCOME MEASURES: The primary objective was to evaluate the safety and tolerability of RO7303359. The secondary objectives included assessing pharmacokinetics (PK), immune response, and pharmacodynamic (PD) biomarker activity. Pharmacodynamic biomarkers assessed in aqueous humor included CC motif chemokine ligand 2, CXC motif chemokine ligand 10, IL-6, and intercellular adhesion molecule 1.<br><br>RESULTS: Thirty-seven patients enrolled in the dose cohorts. Single IVT doses of RO7303359 demonstrated an acceptable safety profile up to 20 mg, with mild ocular adverse events reported. Pharmacokinetics analysis revealed dose-proportional exposure within expected ranges for an IVT-administered Fab. No treatment-emergent antidrug antibodies were observed. Evaluation of changes in aqueous humor PD biomarker levels failed to demonstrate a discernible effect on IL-33/ST2 pathway activity.<br><br>CONCLUSIONS: In this trial (ClinicalTrials.gov identifier, NCT04615325), while RO7303359 exhibited acceptable safety and PK profiles, absence of demonstrable effects on the IL-33/ST2 pathway using aqueous PD biomarkers resulted in discontinuation of development in GA. Further work is needed to evaluate the relevance of the IL-33/ST2 pathway in the pathophysiology of AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40540142, year = {2025}, author = {Hoy, SM}, title = {Revakinagene Taroretcel: First Approval.}, journal = {Molecular diagnosis &amp; therapy}, volume = {29}, number = {4}, pages = {553-561}, pmid = {40540142}, issn = {1179-2000}, mesh = {Humans ; *Genetic Therapy/methods ; Retinal Pigment Epithelium/cytology/metabolism ; *Ciliary Neurotrophic Factor/genetics/therapeutic use ; Animals ; Drug Approval ; United States ; }, abstract = {Revakinagene taroretcel (revakinagene taroretcel-lwey; ENCELTO™) is an encapsulated cell-based gene therapy containing 200,000-440,000 allogeneic retinal pigment epithelial (RPE) cells expressing recombinant human ciliary neurotrophic factor (rhCNTF). Available as a single-dose intravitreal implant, it has been developed by Neurotech Pharmaceuticals, Inc. for the treatment of chronic retinal diseases. In March 2025, revakinagene taroretcel received its first approval for the treatment of adults with idiopathic macular telangiectasia (MacTel) type 2 in the USA. It is the first US FDA-approved treatment for this disease. Revakinagene taroretcel has been granted Orphan Drug Designation for retinitis pigmentosa and Fast Track Designation for retinitis pigmentosa and dry age-related macular degeneration in the USA. This article summarises the milestones in the development of revakinagene taroretcel leading to this first approval for the treatment of adults with idiopathic MacTel type 2 in the USA.}, }
@article {pmid40540493, year = {2025}, author = {Loke, JY and Rampal, S and Che Hamzah, J and Lim, YW and Kamalden, TA}, title = {Visual impairment in any eye adversely affects quality of life: Psychometric validation of the Malay NEI VFQ-25.}, journal = {PloS one}, volume = {20}, number = {6}, pages = {e0324979}, pmid = {40540493}, issn = {1932-6203}, mesh = {Humans ; Male ; Female ; *Quality of Life ; *Psychometrics ; Middle Aged ; Malaysia ; Aged ; Cross-Sectional Studies ; Surveys and Questionnaires ; *Vision Disorders/psychology ; Reproducibility of Results ; Visual Acuity ; Adult ; }, abstract = {PURPOSE: To cross-culturally translate and adapt the National Eye Institute Visual Functioning Questionnaire (NEIVFQ-25) into Malay or Bahasa Malaysia, and to analyze its psychometric properties in a cohort of Malaysian patients with visual impairment from various causes.<br><br>DESIGN: Cross-sectional validation study.<br><br>METHODS: The NEI-VFQ 25 was translated and cross-culturally adapted into the Malay version. Total of 324 visually impaired patients caused by cataracts, glaucoma, age-related macular degeneration (ARMD) or diabetic macular edema (DME), and a control group were included. Psychometric analysis was performed including test-retest and internal consistency reliability, convergent validity, discriminant validity, and factor analysis. Clinical validity was measured by correlation of clinical measurements with subdomain scores and known-groups comparison.<br><br>RESULTS: Participants' average age was 60.4 years (SD 15.4) and 47.2% were male. The internal consistency was high in most subdomains, with Cronbach alpha ranging from 0.66-0.89. The test-retest reliability was high (intraclass correlation coefficient 0.92). Even when just one eye had impaired vision, participants scored much lower on the Malay NEIVFQ 25, highlighting how well the questionnaire reflects the real impact of visual impairment. Moderate correlations were detected between visual acuity and the 'General vision', 'Near Activities', 'Distance Activities', 'Social Functioning', 'Mental Health', 'Role Difficulties', 'Dependency' and 'Driving' subdomains suggesting that these subdomains were associated with central vision. Factor analysis demonstrated that 4 factors can be extracted from 12 subdomains.<br><br>CONCLUSIONS: This study revealed that the Malay version of the NEIVFQ-25 is a valid, reliable, and reproducible instrument to measure the vision-related quality of life in patients with visual impairment. Quality of life was adversely affected even with only one eye having poor vision.}, }
@article {pmid40541565, year = {2025}, author = {Cui, T and Ou, Q and Wang, Z and Zhou, Y and Xu, J and Liu, Y and Bi, Y and Jin, X and Chen, J and Gao, F and Wang, J and Zhang, J and Lu, L and Xu, GT and Jin, C and Tian, H and Xu, JY}, title = {Naphthalene Metabolites From Long-Term Environmental Tobacco Smoke Induce the Aging of Retinal Pigment Epithelium.}, journal = {Aging cell}, volume = {24}, number = {9}, pages = {e70150}, pmid = {40541565}, issn = {1474-9726}, support = {82373482//The National Natural Science Foundation of China/ ; 82271108//The National Natural Science Foundation of China/ ; 20234Y0113//Shanghai Municipal Health Commission/ ; 2023YFC2506100//The National Key Research and Development Program of China/ ; }, mesh = {Animals ; *Retinal Pigment Epithelium/drug effects/pathology/metabolism ; *Naphthalenes/metabolism/toxicity ; Rats ; Male ; *Tobacco Smoke Pollution/adverse effects ; Cellular Senescence/drug effects ; Humans ; Rats, Sprague-Dawley ; DNA Damage ; *Smoke/adverse effects ; }, abstract = {Tobacco use is the main source of indoor air pollution and contains a variety of toxic components. The smoke from burning cigarettes is a key environmental risk factor that leads to accelerated aging and the occurrence of numerous diseases. Meanwhile, cigarette smoke and aging are both prominent risk factors for age-related macular degeneration (AMD). This study demonstrates that long-term exposure to cigarette smoke can impair retinal function and induce the aging of retinal pigment epithelium (RPE). Meanwhile, the plasma of rats after long-term exposure to cigarette smoke can trigger DNA damage and cellular senescence in vitro. In addition, naphthalene and its metabolites (1,2-dihydroxynaphthalene and 1,2-naphthoquinone) derived from cigarette smoke have been identified as an important factor contributing to RPE damage caused by cigarette exposure. Finally, we found that the aging of RPE induced by smoking can be alleviated through smoking cessation, probably because quitting smoking reduces the accumulation of these toxic chemicals in plasma and within the eyes.}, }
@article {pmid40542004, year = {2025}, author = {Liermann, YN and Behning, C and Isselmann, B and Schmid, M and Dunbar, HMP and Luhmann, UFO and Finger, RP and Schmitz-Valckenberg, S and Holz, FG and Pfau, M and Luu, CD and Saßmannshausen, M and Thiele, S and , }, title = {Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study report.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {20093}, pmid = {40542004}, issn = {2045-2322}, mesh = {Humans ; Aged ; Female ; *Macular Degeneration/diagnostic imaging/physiopathology/pathology ; Male ; *Tomography, Optical Coherence/methods ; Biomarkers ; Visual Acuity/physiology ; Middle Aged ; *Retina/diagnostic imaging/physiopathology ; Aged, 80 and over ; Contrast Sensitivity ; Visual Field Tests ; }, abstract = {This study evaluated the functional relevance of relative ellipsoid zone reflectivity (rEZR) on spectral-domain optical coherence tomography as a structural biomarker for retinal integrity, focusing on its association with retinal function. Participants with age-related macular degeneration (AMD) and controls from the MACUSTAR study underwent functional testing, including mesopic fundus-controlled perimetry, best-corrected visual acuity, low-luminance visual acuity, low-luminance deficit, Moorfields Acuity Test, and Pelli-Robson contrast sensitivity, along with spectral-domain optical coherence tomography imaging. Structural and functional data were analyzed globally and spatially aligned for topographic analysis. Linear-mixed effects models, adjusted for age, sex, and eccentricity of the rEZR, assessed associations between rEZR and functional metrics. A total of 275 eyes (early AMD, n = 34; intermediate AMD, n = 152; late AMD, n = 36; controls, n = 53) from 275 participants (mean ± standard deviation age: 71.1 ± 7.2 years; 63.3% female) were included. In global analyses, rEZR was associated with the mean average threshold in mesopic fundus-controlled perimetry (coefficient estimate 0.0492, 95% confidence interval 0.0190-0.0794, p = 0.0015), low-luminance visual acuity (coefficient estimate - 0.0015, 95% confidence interval - 0.0026 to - 0.0004, p = 0.0092), Moorfields Acuity Test (coefficient estimate 0.0092, 95% confidence interval - 0.0022 to - 0.0001, p = 0.0285), and Pelli-Robson contrast sensitivity (coefficient estimate 0.0030, 95% confidence interval 0.0015-0.0045, p = 0.0001). Topographic analysis further revealed an association of rEZR with mesopic retinal sensitivity (coefficient estimate 0.0065, 95% confidence interval 0.0026-0.0104, p < 0.0001). Higher outer retinal reflectivity is linked to better retinal function in AMD and controls, supporting its potential as a biomarker for retinal integrity and function.}, }
@article {pmid40542208, year = {2025}, author = {Kojima, H and Shiragami, C and Yamashita, A and Miyoshi, Y and Osaka, R and Ono, A and Suzuma, K}, title = {Increased macular atrophy area with photodynamic therapy over intravitreal aflibercept at 2-year follow-up of pachychoroid neovasculopathy.}, journal = {Japanese journal of ophthalmology}, volume = {69}, number = {4}, pages = {529-535}, pmid = {40542208}, issn = {1613-2246}, mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Intravitreal Injections ; *Recombinant Fusion Proteins/administration &amp; dosage ; Retrospective Studies ; *Photochemotherapy/methods/adverse effects ; Female ; Male ; Follow-Up Studies ; Tomography, Optical Coherence/methods ; *Visual Acuity ; Fluorescein Angiography ; Aged ; Fundus Oculi ; *Macula Lutea/pathology ; *Choroid/pathology/blood supply ; *Choroidal Neovascularization/drug therapy/diagnosis ; Middle Aged ; Atrophy ; Time Factors ; Angiogenesis Inhibitors/administration &amp; dosage ; Treatment Outcome ; Photosensitizing Agents/therapeutic use ; }, abstract = {PURPOSE: To compare the therapeutic outcomes of intravitreal aflibercept injection (IVA) and reduced-fluence photodynamic therapy (rfPDT) for pachychoroid neovasculopathy (PNV) over 2 years.<br><br>STUDY DESIGN: Observational, retrospective case series. Single-center study.<br><br>METHODS: This study involved 36 eyes of 36 patients with PNV. The IVA group comprised 18 eyes treated with IVA monotherapy (injection every 3 months followed by a pro re nata regimen), whereas the rfPDT group consisted of 18 eyes treated with rfPDT monotherapy. Post-treatment changes in best-corrected visual acuity (BCVA), macular atrophy (MA) area, central retinal thickness (CRT) and subfoveal choroidal thickness (SFCT) were compared between the 2 groups.<br><br>RESULTS: The IVA group received 8.94&#xa0;&#xb1;&#xa0;4.77 injections, whereas the rfPDT group received rfPDT 1.06 &#xb1; 0.24 times. The logMAR BCVA improved in both groups but did not differ between the 2 groups. The MA area increased from 0.163 &#xb1; 0.418&#xa0;mm[2] to 0.227 &#xb1; 0.480&#xa0;mm[2] (P = .024) and from 0.139 &#xb1; 0.402&#xa0;mm[2] to 0.597 &#xb1; 0.939&#xa0;mm[2] (P < .001) in the IVA and rfPDT groups, respectively, with the rfPDT group showing a greater increase than the IVA group (P = .013). The CRT was reduced in both groups but did not differ between the 2 groups. The SFCT was reduced in both groups, but the reduction was higher in the rfPDT group than in the IVA group (P = .027). The factors affecting change in the MA area were the treatment method and patient age.<br><br>CONCLUSIONS: The increase in the MA area and the decrease in the SFCT were greater in the rfPDT group than in the IVA group for PNV, suggesting that IVA may be preferred over rfPDT for PNV treatment.}, }
@article {pmid40543257, year = {2025}, author = {Couturier, A and Souied, EH and Creuzot-Garcher, C and Cohen, SY and Kodjikian, L and Baillif, S and Delyfer, MN and Weber, M and Aubry-Quenet, I and Ponthieux, A and Devin, F}, title = {Disease control, visual and anatomic outcomes at week 48 of brolucizumab treatment in patients with previously suboptimal anatomically controlled neovascular age-related macular degeneration - The SWIFT study.}, journal = {Journal francais d'ophtalmologie}, volume = {48}, number = {7}, pages = {104574}, doi = {10.1016/j.jfo.2025.104574}, pmid = {40543257}, issn = {1773-0597}, mesh = {Humans ; Aged ; Female ; Male ; Visual Acuity/drug effects ; Middle Aged ; Treatment Outcome ; Intravitreal Injections ; Aged, 80 and over ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use/adverse effects ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use/adverse effects ; *Wet Macular Degeneration/drug therapy/pathology/epidemiology ; Prospective Studies ; France/epidemiology ; *Macular Degeneration/drug therapy/pathology ; Tomography, Optical Coherence ; *Choroidal Neovascularization/drug therapy/pathology ; }, abstract = {PURPOSE: Neovascular age-related macular degeneration (nAMD) patients refractory to one anti-vascular endothelial growth factor (VEGF) agent often switch to another anti-VEGF for better disease control. Our objective is to assess nAMD control with brolucizumab 6mg treatment in previously treated patients with suboptimal anatomical control.<br><br>METHODS: SWIFT was a 48-week, prospective, single-arm, open-label clinical trial at 52&#xa0;sites in France (NCT04264819). Participants were adults (&#x2265;&#xa0;50&#xa0;years) with active CNV lesions secondary to nAMD, diagnosed<18&#xa0;months, previously treated with either ranibizumab or aflibercept with a 4- or 8-week interval treatment, with baseline BCVA 38-83&#xa0;letters. Eyes were treated with intravitreal brolucizumab 6mg at weeks 0, 4 and 8 (loading phase), followed by treat-to-control dosing with intervals up to 16&#xa0;weeks, depending on investigator-assessed disease activity. The main outcome is the proportion of eyes without investigator-assessed disease activity at week 16.<br><br>RESULTS: Two hundred and eighty-nine patients were included and analyzed (mean age 76.3&#xa0;years, 61.9% female). Eyes were previously treated for a mean of 9.1&#xa0;months. Baseline mean BCVA was 68.9&#xa0;letters, and central subfield foveal thickness (CSFT) was 417&#x3bc;m. Over the course of the study, patients received a median of 6&#xa0;brolucizumab injections (range: 1-8) with a mean (SD) treatment duration of 32.1 (14.1) weeks. The mean last brolucizumab treatment interval (SD) was 8.7 (3.5) weeks, notably longer than the interval of 6.2 (2.8) weeks with the previous anti-VEGF agent before inclusion in SWIFT. The proportion of eyes with no disease activity was 41.0% (95% CI: 34.4-47.9) at week 16 and 52.0% at week 48 (47.0 and 43.4%, respectively, using last observation carried forward sensitivity analysis). Improvements were observed from baseline to week 48 in BCVA (mean +3.2 [9.2] letters; P<0.0001), CFST (-66 [101] &#x3bc;m; P<0.0001). At week 48, 22% of eyes were on a regimen of every 12&#xa0;weeks or more, and 40.4% of eyes had no retinal fluid (36.0 and 42.4% had intraretinal and subretinal fluid respectively). Intraocular inflammation (IOI) was confirmed in 29/295 (9.8%) eyes. Four of these patients had BCVA losses of&#x2265;15&#xa0;letters at or after IOI resolution.<br><br>CONCLUSIONS: In patients with refractory nAMD, brolucizumab allowed control of disease activity for up to 41.0% of patients, with visuals gains, anatomical improvements and extended treatment interval, despite poor response and discontinuation for some patients in addition to a 9.8% rate of IOI.}, }
@article {pmid40543797, year = {2025}, author = {Finger, RP}, title = {Can interventional clinical trials be implemented in intermediate age-related macular degeneration?.}, journal = {Experimental eye research}, volume = {258}, number = {}, pages = {110493}, doi = {10.1016/j.exer.2025.110493}, pmid = {40543797}, issn = {1096-0007}, }
@article {pmid40544279, year = {2025}, author = {Huang, X and Li, T and Zhang, G and Chen, J and Li, T and Yang, S and Bo, Q and Zhao, X and Wan, X and Zhu, X and Yu, B and Sun, X and Sun, J}, title = {AIM2 activation mediated by RIPK1/3-dependent mitochondrial DNA release drives Aβ1-40-Induced retinal pigment epithelium injury.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {301}, pmid = {40544279}, issn = {1478-811X}, support = {82101159//National Natural Science Foundation of China/ ; 82101168//National Natural Science Foundation of China/ ; 82000882//National Natural Science Foundation of China/ ; 82301220//National Natural Science Foundation of China/ ; 82201223//National Natural Science Foundation of China/ ; 82471091//National Natural Science Foundation of China/ ; U22A20311, 82388101 and 82171076//National Natural Science Foundation of China/ ; 23YF1434100//"YangFan Program" of Shanghai Municipal Committee of Science and Technology/ ; 22PJ1412200//Shanghai Pujiang Program/ ; 2022YFC2502800//National Key R&amp;D Program/ ; 2023ZKZD18//Shanghai Municipal Education Commission/ ; 2023YFC2506100//National Key R&amp;D Program of China/ ; }, mesh = {Animals ; *Retinal Pigment Epithelium/pathology/metabolism/injuries ; *Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; *Amyloid beta-Peptides/toxicity/metabolism ; Mice ; *DNA, Mitochondrial/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; Mice, Inbred C57BL ; Humans ; Inflammasomes/metabolism ; Male ; *Peptide Fragments ; Signal Transduction ; }, abstract = {BACKGROUND: The retinal pigment epithelium (RPE) degeneration and subsequent retinal atrophy are hallmarks of age-related macular degeneration (AMD). Amyloid-beta (Aβ), the primary component of amyloid plaques in Alzheimer's disease (AD), is also present within drusen and is considered a critical factor contributing to RPE degeneration in AMD. Recent findings indicate that Aβ-induced inflammation plays a role in RPE degeneration. The aim of this study was to explore the molecular players and the precise mechanisms involved in this process, particularly the potential role of the absent in melanoma 2 (AIM2)-like receptors (ALRs) inflammasome.<br><br>METHODS: An animal model of A&#x3b2;1-40-induced RPE injury was established. Fundus photography, electrophysiology and hematoxylin-eosin staining were used to evaluate the morphological and functional RPE damage. Transcriptome sequencing was used to detect the differentially expressed genes between A&#x3b2;1-40 group and control group. The transcriptional and protein expression levels of AIM2 pathway and RIPK family members were detected. Adeno-associated virus vector 2/2 (AAV2/2)-shAIM2 was constructed to knockdown AIM2 expression in mice RPE cells. A&#x3b2;1-40-treated ARPE-19 cells and hRPE cells were employed to analyze the regulatory effects of RIPK family on mitochondrial DNA (mtDNA) release and AIM2 pathway activation.<br><br>RESULTS: A&#x3b2; induces RPE damage through stimulation of AIM2 inflammasome and augmentation of caspase-1 and interleukin-1&#x3b2; (IL-1&#x3b2;). Knocking down AIM2 inhibits the release of inflammatory cytokines and alleviates the degeneration of the retina and RPE. Simultaneously, A&#x3b2; triggers the activation of RIPK1/RIPK3 kinases, as manifested by heightened protein expression and phosphorylation. Inhibiting RIPK1/RIPK3 phosphorylation dampens AIM2 inflammasome activity and curtails IL-1&#x3b2; secretion. Mechanistically, RIPK1/RIPK3 inhibition attenuates A&#x3b2;-induced Drp1(S616) hyperphosphorylation, consequently reducing mitochondrial fission and the efflux of mitochondrial DNA (mtDNA) into the cytosol. The diminished mtDNA release is responsible for attenuated AIM2 activation and subsequent inactivation of the stimulator of interferon genes (STING)/nuclear factor-kappa-B (NF-&#x3ba;B) signaling cascade.<br><br>CONCLUSIONS: Our study is the first to validate AIM2's contribution in A&#x3b2;-induced RPE pathology and underscore the significance of the RIPK1/RIPK3-induced mtDNA release in modulating inflammatory responses, shedding light on the underlying mechanisms and potential therapeutics of AMD.}, }
@article {pmid40545017, year = {2025}, author = {Ramirez, M and Kitayama, K and Puran, A and Tseng, VL and Yu, F and Coleman, AL}, title = {The Associations Between Glaucoma and Circadian Rhythm Sleep Disorders in California Medicare Beneficiaries.}, journal = {American journal of ophthalmology}, volume = {278}, number = {}, pages = {250-256}, doi = {10.1016/j.ajo.2025.06.021}, pmid = {40545017}, issn = {1879-1891}, mesh = {Humans ; Female ; Male ; Aged ; Cross-Sectional Studies ; United States ; Aged, 80 and over ; *Glaucoma/epidemiology/complications/physiopathology ; California/epidemiology ; *Sleep Disorders, Circadian Rhythm/epidemiology ; *Medicare/statistics &amp; numerical data ; Intraocular Pressure/physiology ; Retrospective Studies ; }, abstract = {PURPOSE: To examine the associations between glaucoma, circadian rhythm sleep disorders (CRSD), and any sleep-wake disorders in California (CA) Medicare beneficiaries.<br><br>DESIGN: Cross-sectional study.<br><br>SUBJECTS: All 2019 CA Medicare beneficiaries who were &#x2265;65 years old, had both Parts A &amp; B coverage, and had &#x2265;1 Part B claim.<br><br>METHODS: The primary exposure was a diagnosis of glaucoma as defined by International Classification of Diseases, 10th revision codes. The primary outcome was CRSD, and the secondary outcome was any sleep-wake disorder, defined by International Classification of Diseases, 10th revision codes. The associations between glaucoma, CRSD, and any sleep-wake disorders were estimated using multivariable logistic regression models adjusting for age, sex, race and ethnicity, age-related macular degeneration, diabetic retinopathy, cataracts, pseudophakia, and systemic disease burden defined by Charlson Comorbidity Index score. The effect estimate was expressed as an adjusted odds ratio (aOR) with a 95% confidence interval (CI).<br><br>MAIN OUTCOME MEASURES: Odds ratios between exposures and outcomes.<br><br>RESULTS: The study population included 2,717,346 CA Medicare beneficiaries meeting inclusion criteria. Of those, 220,662 (8.1%) had glaucoma, 3,202 (0.12%) had CRSD, and 355,390 (13.1%) had any sleep-wake disorder. In the adjusted logistic regression models, beneficiaries with glaucoma had greater adjusted odds of CRSD (aOR: 1.20; 95% CI: 1.06-1.35; P = .0031) and of any sleep-wake disorder (aOR: 1.12; 95% CI: 1.11-1.13; P < .001) compared to beneficiaries without glaucoma.<br><br>CONCLUSIONS: In the 2019 CA Medicare population, beneficiaries with glaucoma had increased likelihood of CRSD and of any sleep-wake disorder. Further investigations are needed to characterize mechanisms of these associations and to examine the impact of glaucoma treatment on sleep-wake disorders.}, }
@article {pmid40546332, year = {2025}, author = {Arbab, A and Habibi, A and Rabbani, H and Tajmirriahi, M}, title = {From Image to Sequence: Exploring Vision Transformers for Optical Coherence Tomography Classification.}, journal = {Journal of medical signals and sensors}, volume = {15}, number = {}, pages = {18}, pmid = {40546332}, issn = {2228-7477}, abstract = {BACKGROUND: Optical coherence tomography (OCT) is a pivotal imaging technique for the early detection and management of critical retinal diseases, notably diabetic macular edema and age-related macular degeneration. These conditions are significant global health concerns, affecting millions and leading to vision loss if not diagnosed promptly. Current methods for OCT image classification encounter specific challenges, such as the inherent complexity of retinal structures and considerable variability across different OCT datasets.<br><br>METHODS: This paper introduces a novel hybrid model that integrates the strengths of convolutional neural networks (CNNs) and vision transformer (ViT) to overcome these obstacles. The synergy between CNNs, which excel at extracting detailed localized features, and ViT, adept at recognizing long-range patterns, enables a more effective and comprehensive analysis of OCT images.<br><br>RESULTS: While our model achieves an accuracy of 99.80% on the OCT2017 dataset, its standout feature is its parameter efficiency-requiring only 6.9 million parameters, significantly fewer than larger, more complex models such as Xception and OpticNet-71.<br><br>CONCLUSION: This efficiency underscores the model's suitability for clinical settings, where computational resources may be limited but high accuracy and rapid diagnosis are imperative.Code Availability: The code for this study is available at https://github.com/Amir1831/ViT4OCT.}, }
@article {pmid40548258, year = {2025}, author = {Sun, Y and Wang, J and Zhang, Y and Shang, J and Liu, JX}, title = {ACOCMPMI: An Ant Colony Optimization Algorithm Based on Composite Multiscale Part Mutual Information for Detecting Epistatic Interactions.}, journal = {Human mutation}, volume = {2025}, number = {}, pages = {7656300}, pmid = {40548258}, issn = {1098-1004}, mesh = {*Epistasis, Genetic ; *Algorithms ; Humans ; Polymorphism, Single Nucleotide ; Bayes Theorem ; Models, Genetic ; Macular Degeneration/genetics ; *Computational Biology/methods ; Computer Simulation ; }, abstract = {Epistatic interaction detection plays a pivotal role in understanding the genetic mechanisms underlying complex diseases. The effectiveness of epistatic interaction detection methods primarily depends on their interaction quantification measures and search strategies. In this study, a two-stage ant colony optimization algorithm based on composite multiscale part mutual information (ACOCMPMI) is proposed for detecting epistatic interactions. In the first stage, composite multiscale part mutual information is developed to quantify epistatic interactions, and an improved ant colony optimization algorithm incorporating filter and memory strategies is employed to search for potential epistatic interactions. In the second stage, an exhaustive search strategy and a Bayesian network score are adopted to further identify epistatic interactions within the candidate SNP set obtained in the first stage. ACOCMPMI is compared with five state-of-the-art methods, including epiACO, FDHE-IW, AntEpiSeeker, SIPSO, and MACOED, using simulation data generated from 11 epistatic interaction models. Furthermore, ACOCMPMI is applied to detect epistatic interactions in a real dataset of age-related macular degeneration. The experimental results show that ACOCMPMI is a promising method for epistatic interaction detection.}, }
@article {pmid40548629, year = {2025}, author = {Tran, E and Rakesh, M and Li, G and Freeman, EE and Roy-Gagnon, MH}, title = {Does the Association Between Eye Disease and Cognitive Function Vary by Genetic Risk of Cognitive Decline? An Analysis of Hospital Data With Replication in the Canadian Longitudinal Study on Aging.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {6}, pages = {71}, pmid = {40548629}, issn = {1552-5783}, mesh = {Humans ; Male ; Female ; *Polymorphism, Single Nucleotide ; Cross-Sectional Studies ; Aged ; *Aging/physiology ; Aged, 80 and over ; *Cognition/physiology ; Canada/epidemiology ; Longitudinal Studies ; *Genetic Predisposition to Disease ; Middle Aged ; *Intracellular Signaling Peptides and Proteins/genetics ; *Phosphoproteins/genetics ; Risk Factors ; *Macular Degeneration/genetics ; Genotype ; *Cognition Disorders/genetics/epidemiology ; *Glaucoma/genetics ; }, abstract = {PURPOSE: Age-related eye diseases are inconsistently associated with cognitive decline which could be due to effect modification. The purpose of this study was to investigate whether two genetic factors previously found to be associated with cognitive decline, the KIBRA (WWC1) and PDE7A/MTFR1 genes, modify the association between eye disease and cognitive function.<br><br>METHODS: Data from a Montreal hospital-based cross-sectional study (n = 302) were used for the primary analysis. Candidate single-nucleotide polymorphisms (SNPs) rs17070145 (KIBRA gene) and rs10808746 (PDE7A/MTFR1 gene) were included in linear regression models to test for effect modification of the relationship between eye disease (glaucoma or age-related macular degeneration [AMD]) and cognitive function. Six oral cognitive tests were used. A replication analysis was done using the Quebec data from the Canadian Longitudinal Study on Aging (CLSA) (n = 4238). Effect modifications by expanded genomic regions around the candidate SNPs were tested.<br><br>RESULTS: Three statistically significant interactions with two cognitive function measures -category verbal fluency and immediate story recall-were found in the Montreal study: glaucoma and AMD with rs17070145 and verbal fluency (P < 0.03) and glaucoma with rs10808746 with immediate story recall (P < 0.05). Similar interactions, although not with the same cognitive measure, were found in the CLSA: AMD with KIBRA and glaucoma with PDE7A/MTFR1.<br><br>CONCLUSIONS: Our results suggest that the KIBRA and PDE7A/MTFR1 genes may modify the association between eye disease and cognitive function. This knowledge may help to better understand the mechanism by which glaucoma and AMD are related to cognitive function.}, }
@article {pmid40548636, year = {2025}, author = {Hang, A and Shao, A and Shea, M and Roux, MJ and Imai-Leonard, DM and Adams, DJ and Amano, T and Amarie, OV and Berberovic, Z and Bour, R and Bower, L and Leonard, BC and Brown, SD and Cho, SY and Clementson-Mobbs, S and D'Souza, AJ and Dickinson, M and Eskandarian, M and Flenniken, AM and Fuchs, H and Gailus-Durner, V and Heaney, J and Hérault, Y and Hrabe de Angelis, M and Hsu, CW and Jin, S and Joynson, R and Kang, YK and Kim, H and Masuya, H and Nam, KH and Noh, H and Nutter, LMJ and Palkova, M and Prochazka, J and Raishbrook, MJ and Riet, F and Salazar, J and Seavitt, JR and Sedlacek, R and Selloum, M and Seo, KY and Seong, JK and Shin, HS and Shiroishi, T and Sorg, T and Stewart, M and Tamura, M and Tolentino, H and Udensi, U and Wells, S and Wurst, W and Yoshiki, A and Meziane, H and Yiu, G and Sieving, PA and Lanoue, L and Lloyd, KCK and McKerlie, C and Moshiri, A and , }, title = {Ocular Phenotyping of Knockout Mice Identifies Genes Associated With Late Adult Retinal Phenotypes.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {6}, pages = {64}, pmid = {40548636}, issn = {1552-5783}, support = {K08 EY027463/EY/NEI NIH HHS/United States ; R03 OD032622/OD/NIH HHS/United States ; U42 OD011175/OD/NIH HHS/United States ; U54 HG006364/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Mice, Knockout ; Mice ; Phenotype ; Disease Models, Animal ; Humans ; *Retina/pathology/metabolism ; *Macular Degeneration/genetics ; *Eye Proteins/genetics ; }, abstract = {PURPOSE: Analyze phenotypic data from knockout mice with late-adult retinal pathologic phenotypes to identify genes associated with development of adult-onset retinal diseases.<br><br>METHODS: The International Mouse Phenotyping Consortium (IMPC) database was queried for genes associated with abnormal retinal phenotypes in the late-adult knockout mouse pipeline (49-80 weeks postnatal age). We identified human orthologs and performed protein-protein analysis and biological pathways analysis with known inherited retinal disease (IRD) and age-related macular degeneration (AMD) genes using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), PLatform for Analysis of single cell Eye in a Disk (PLAE), Protein Analysis Through Evolutionary Relationships (PANTHER), and Kyoto Encyclopedia of Genes and Genomes (KEGG).<br><br>RESULTS: Screening of 587 late-adult mouse genes yielded 12 with abnormal retinal phenotypes, which corresponded to 20 human orthologs. Three of the 12 mouse genes and two of the 20 human orthologs were previously implicated in retinal pathology or physiology in a literature review. Although all of the genes demonstrated retinal pathology when deleted from the mouse genome, most do not have established roles in human retinal disease. Furthermore, human protein-protein analysis and biological pathway analysis yielded only a few relationships between the candidate gene list and that of known IRD and AMD genes, suggesting they may represent novel retinal functions.<br><br>CONCLUSIONS: We identified 12 mouse genes with significant late-adult abnormal retinal pathology, eight of which have not been previously implicated in either mouse or human retinal physiology or pathology. These serve as novel retinal disease gene candidates for late-onset retinal disease.}, }
@article {pmid40549132, year = {2025}, author = {Gunderson, I and Burale, A and Best, BJ and Tung, CI and Huber, J and Marsh, L}, title = {Clinical Trial Simulation in Geographic Atrophy: Patient, Caregiver, and Trial Site Staff Perspectives.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {8}, pages = {1855-1868}, pmid = {40549132}, issn = {2193-8245}, abstract = {INTRODUCTION: The perspectives of patients with geographic atrophy (GA) should be considered when planning new clinical trials to ensure that real-world patient needs are addressed. The purpose of this study was to explore the perspectives of patients, caregivers, and trial site staff on designing and planning a phase 2 clinical trial in GA.<br><br>METHODS: This cross-sectional study included patients with GA and their caregivers, trial site staff, and investigators from Germany, the UK, and the USA. Participants were asked to spend 30&#xa0;min reviewing a simulated trial design communicated as a simple video animation with a voiceover. Subsequently, a 90-min web-assisted telephone interview and survey was conducted to identify problems with the design of the simulated trial and explore potential solutions and improvements.<br><br>RESULTS: Patients (n&#x2009;=&#x2009;11), caregivers (n&#x2009;=&#x2009;11), and site staff (n&#x2009;=&#x2009;16) completed the survey after reviewing the simulated trial design. Survey responses suggested that study recruitment could be facilitated via widespread advertisement and by including a short washout period, i.e., the time period during which patients receive no medication prior to commencing the study drug to ensure that other treatments do not impact the study results. Survey suggestions for reducing the burden of trial participation included minimizing the number and frequency of trial visits, enabling assessments to be completed at home, and making the schedule of trial visits flexible. Appropriate investment in study center facilities was recommended. In addition, survey respondents proposed that providing transport could be highly beneficial, potentially enabling patients and caregivers to attend trial visits more easily.<br><br>CONCLUSIONS: This study provides valuable information on the viewpoints of patients, caregivers, and trial site staff regarding trial design. Accounting for these perspectives when designing future clinical trials may help ensure successful trial completion and promote positive perceptions of clinical research.}, }
@article {pmid40549133, year = {2025}, author = {Küçükerdönmez, C and Tedford, SE}, title = {Multiwavelength Photobiomodulation Improves Multiple Aspects of Visual Function in Early-Stage Dry Age-Related Macular Degeneration.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {8}, pages = {1843-1853}, pmid = {40549133}, issn = {2193-8245}, abstract = {INTRODUCTION: This study aimed to evaluate the safety and efficacy of multiwavelength photobiomodulation (PBM) treatment (Tx) in earlier stages of nonexudative (dry) age-related macular degeneration (AMD).<br><br>METHODS: Participants were enrolled with a diagnosis of dry AMD. Participants were treated with a single or repeated series of multiwavelength PBM treatment (LumiThera Valeda[&#xae;] Light Delivery System; 590, 660, and 850&#xa0;nm) delivered three times per week over 3-5&#xa0;weeks every 4&#xa0;months with follow-up extending out to 16&#xa0;months. Outcomes analyzed included visual acuity (VA), contrast sensitivity (CS), and electroretinography (ERG).<br><br>RESULTS: A total of 41 eyes (27 participants) were evaluated after single (1 series of Tx, n&#x2009;=&#x2009;41 eyes) and repeat (2-4 series of Tx, n&#x2009;=&#x2009;26 eyes) PBM treatment with up to 16&#xa0;months of follow-up. Participants were mostly female (n&#x2009;=&#x2009;22, 81.5%) with a mean time since AMD diagnosis of 5.6&#xa0;years. Participants enrolled had earlier stage dry AMD with better vision (~&#x2009;20/32 Snellen) and a mean baseline VA of 76.5 letters. Single and repeated PBM Tx improved VA, CS, multi-luminance ERG, and fixed luminance ERG parameters. No significant visual decline was noted in any outcome measure or signs of phototoxicity.<br><br>CONCLUSIONS: PBM treatment of patients with earlier stage dry AMD showed improvements on multiple visual outcome measures and no adverse effects. Earlier stage AMD populations may not show robust magnitude effects as their starting vision does not show serious deficits, however; as a result of the degenerative and progressive nature of the disease, repeat treatment and continued monitoring of these outcomes are of interest. These beneficial effects were improved with repeated PBM treatment series.}, }
@article {pmid40550377, year = {2025}, author = {Shui, M and Yang, G and Jiang, J and Wang, S and Liao, R}, title = {Mendelian randomization study of lipid metabolites reveals causal associations with age-related macular degeneration.}, journal = {Experimental gerontology}, volume = {208}, number = {}, pages = {112817}, doi = {10.1016/j.exger.2025.112817}, pmid = {40550377}, issn = {1873-6815}, mesh = {Humans ; *Macular Degeneration/genetics/metabolism/epidemiology ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; *Lipid Metabolism/genetics ; Aged ; Middle Aged ; Genome-Wide Association Study ; Male ; Female ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly, affecting approximately 8.7 % of individuals over 55 years old. Increasing evidence suggests that lipid metabolism plays a significant role in AMD pathogenesis, yet the causal relationships remain unclear. This study aims to elucidate the causal relationship between lipid metabolites and AMD using Mendelian randomization (MR) methodology.<br><br>METHODS: A two-sample MR analysis was conducted to explore the associations between specific lipid metabolites (such as bile acids, fatty acids, sphingolipids, and steroid hormones) and the incidence of AMD, as well as the potential causal effect of AMD on these lipid metabolites. Genetic variants significantly associated with these lipid metabolites were selected as instrumental variables (IVs). Data for AMD and lipid metabolites were sourced from the IEU GWAS database, covering over 209,000 cases and >16 million single nucleotide polymorphisms (SNPs). The MR analysis employed inverse-variance weighted (IVW), MR-Egger regression, and weighted median methods to estimate causal relationships and address potential pleiotropy and heterogeneity.<br><br>RESULTS: IVW analysis revealed significant associations between several lipid metabolites and AMD. Specifically, higher levels of laurate were found to increase the risk of AMD by 3.532 times (OR&#xa0;=&#xa0;3.532, 95%CI 1.498-8.328, P&#xa0;<&#xa0;0.010). In contrast, dehydroepiandrosterone sulfate (DHEA-S) (OR&#xa0;=&#xa0;0.551, 95%CI 0.311-0.977, P&#xa0;=&#xa0;0.042) and palmitoyl sphingomyelin (OR&#xa0;=&#xa0;0.213, 95%CI 0.053-0.863, P&#xa0;=&#xa0;0.030) were protective, with DHEA-S and palmitoyl sphingomyelin levels reducing the risk of AMD by 44.9&#xa0;% and 78.7&#xa0;%, respectively. Sensitivity analyses using MR-Egger and weighted median methods supported these findings, highlighting consistent trends across different analytical approaches.<br><br>CONCLUSION: By clarifying these causal relationships, this research aims to provide insights that could inform the development of therapeutic strategies targeting lipid metabolism, ultimately improving outcomes for individuals at risk of AMD.}, }
@article {pmid40550705, year = {2025}, author = {Gualino, V and Sohier, C and Sibert, M and Erginay, A and Varenne, F and Butterworth, J and Couturier, A and Gabrielle, PH and Soler, V and Creuzot-Garcher, C}, title = {Real-world faricimab switch in France: artificial intelligence-based detection of changes in exudative signs in difficult-to-treat neovascular age-related macular degeneration.}, journal = {BMJ open ophthalmology}, volume = {10}, number = {1}, pages = {}, pmid = {40550705}, issn = {2397-3269}, mesh = {Humans ; Male ; Female ; Intravitreal Injections ; France/epidemiology ; Retrospective Studies ; *Artificial Intelligence ; Aged, 80 and over ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence/methods ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; Exudates and Transudates ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; Subretinal Fluid/diagnostic imaging ; Fluorescein Angiography/methods ; Drug Substitution ; Follow-Up Studies ; Antibodies, Bispecific ; }, abstract = {PURPOSE: Some patients with neovascular age-related macular degeneration (nAMD) have persistent signs of exudation under treatment with intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents. We examined the real-world anatomical responses among patients with suboptimal response and switched to faricimab using artificial intelligence (AI)-based retinal fluid quantification.<br><br>METHODS: A retrospective, multicentric, cohort study of patients in France with exudative signs and switched to faricimab without a new loading phase, maintaining the same prior injection interval. The RetInSight Fluid Monitor AI software quantified subretinal (SRF) and intraretinal (IRF) fluid on spectral domain optical coherence tomography. The primary outcome was change in SRF and IRF volumes in the central 1 and 6&#x2009;mm retinal areas after one and two injections of faricimab.<br><br>RESULTS: 74 patients (74 eyes) were included (mean age: 81.5&#xb1;8.4 years, 49% male). Significant reductions were observed in mean 1&#x2009;mm IRF (-2.9&#xb1;18.3&#x2009;nl; p=0.002), mean 6&#x2009;mm IRF (-17.7&#xb1;71.1&#x2009;nl; p<0.001) and mean 6&#x2009;mm SRF (-24.8&#xb1;156.3&#x2009;nl; p<0.001) volumes after one injection. The proportion of dry eyes (<5&#x2009;nl for SRF and IRF in the 1 and 6&#x2009;mm areas) increased from 0% at baseline to 32.4% after one injection and 48.4% after two injections. Lower baseline SRF volumes were predictive of dry response after one injection (adjOR 0.965; p=0.028) and lower baseline IRF volumes were predictive of dry response after two injections (adjOR 0.373; p=0.051).<br><br>CONCLUSION: Nearly half of patients achieved a dry response after two injections. AI-assisted fluid quantification provided objective monitoring, identifying lower baseline SRF and IRF as predictive factors for good response. Limited patient inclusion means longer-term and larger prospective studies are now required using automated retinal fluid quantification to further refine the baseline characteristics of good switch responders to better adapt switch protocols.}, }
@article {pmid40551957, year = {2025}, author = {Aljuhani, HS and Hubayni, RA and Qedair, J and Bukhari, ZM and Alzahrani, A and Bawazir, RO and Badghaish, OS and Alqahtani, F}, title = {Efficacy and Safety of Aflibercept Biosimilars Relative to Reference Aflibercept Therapy for Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {1911-1918}, pmid = {40551957}, issn = {1177-5467}, abstract = {PURPOSE: To assess the efficacy and safety of aflibercept biosimilars compared to reference aflibercept therapy for neovascular age-related macular degeneration (nAMD) through a systematic review and meta-analysis.<br><br>METHODS: A comprehensive literature search was conducted across multiple databases. Randomized controlled trials comparing intravitreal aflibercept biosimilars with reference aflibercept in patients with nAMD were included. The outcomes were changes in best-corrected visual acuity (BCVA), retinal thickness, choroidal neovascularization (CNV) leakage area from baseline based on fluorescein angiography, and adverse events.<br><br>RESULTS: Five studies involving 2,039 patients were included. No statistically significant differences were found between aflibercept biosimilars and reference aflibercept in terms of BCVA (weighted mean difference [WMD]: 1.05; 95% CI: -0.62 to 2.71; p = 0.22), central subfield thickness (WMD: 3.33; 95% CI: -14.48 to 21.14; p = 0.71), or CNV (WMD: -0.23; 95% CI: -0.58 to 0.12; p = 0.20). SThe incidence of treatment-emergent adverse events was similar between groups.<br><br>CONCLUSION: Aflibercept biosimilars demonstrated comparable efficacy and safety profiles to reference aflibercept in the treatment of nAMD. These findings suggest that biosimilars may serve as a cost-effective alternative without compromising patient outcomes.}, }
@article {pmid40551979, year = {2025}, author = {Zhou, J and Zhao, D and Niu, S and Meng, W and Chen, Z and Li, H and Liu, Y and Zou, L and Li, W}, title = {RGD-Functionalized Ginsenoside Rg3 Liposomes for Alleviating Oxidative Stress and Choroidal Neovascularization in Age-Related Macular Degeneration.}, journal = {International journal of nanomedicine}, volume = {20}, number = {}, pages = {7915-7933}, pmid = {40551979}, issn = {1178-2013}, mesh = {Animals ; *Choroidal Neovascularization/drug therapy ; *Ginsenosides/administration &amp; dosage/chemistry/pharmacology ; *Oxidative Stress/drug effects ; *Oligopeptides/chemistry ; *Macular Degeneration/drug therapy/metabolism ; Mice ; Liposomes/chemistry ; Humans ; Cell Line ; Disease Models, Animal ; Angiogenesis Inhibitors/pharmacology/administration &amp; dosage/chemistry ; Vascular Endothelial Growth Factor A/metabolism ; Mice, Inbred C57BL ; Antioxidants/pharmacology/administration &amp; dosage/chemistry ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Reactive Oxygen Species/metabolism ; Intravitreal Injections ; Male ; }, abstract = {BACKGROUND AND AIM: Age-related macular degeneration (AMD) is a leading cause of vision loss owing to choroidal neovascularization (CNV) and retinal vascular abnormalities. Current anti-VEGF therapies often exhibit limited efficacy in approximately 50% of patients owing to the complex pathological microenvironment, including elevated reactive oxygen species (ROS) levels. This study aimed to develop a multitargeted therapeutic strategy for AMD by leveraging the antioxidant and anti-angiogenic properties of ginsenoside Rg3 (Rg3).<br><br>METHODS: RGD-Rg3@Lips was formulated to encapsulate Rg3 and modified with (Arginine-Glycine-Aspartic Acid, RGD) peptides for targeted delivery. In vitro studies have evaluated the cellular internalization, anti-angiogenic effects, and suppression of oxidative stress and inflammation in ARPE-19 cells. In vivo efficacy was assessed using a laser-induced AMD mouse model, in which an intravitreal injection of RGD-Rg3@Lips was administered. Mechanistic studies have focused on the hypoxia-inducible factor 1-&#x3b1;, (HIF-1&#x3b1;) / vascular endothelial growth factor, (VEGF) signaling pathway and the expression of inflammatory cytokines.<br><br>RESULTS: RGD-Rg3@Lips demonstrated superior cellular internalization and anti-angiogenic efficacy compared to Rg3@Lips and free Rg3 in vitro, significantly reducing oxidative stress and inflammation. In vivo, RGD-Rg3@Lips markedly reduced CNV formation and vascular leakage in an AMD mouse model. Mechanistically, RGD-Rg3@Lips attenuated oxidative stress, inhibited the HIF-1&#x3b1;/VEGF pathway, and downregulated key inflammatory cytokines including tumor necrosis factor &#x3b1; (TNF-&#x3b1;) and VEGF. RGD modification significantly improved the targeting of CNV lesions, enhancing therapeutic efficacy by specifically binding to vascular surface integrin receptors compared to non-modified liposomes and free Rg3.<br><br>CONCLUSION: This study highlights the potential of RGD-Rg3@Lips as a novel multitargeted therapeutic strategy for wet AMD. By combining the antioxidant and antiangiogenic properties of Rg3 with targeted drug delivery, RGD-Rg3@Lips offers a promising approach to address the limitations of current AMD therapies. These findings underscore the value of natural-product-based nanomedicine for the treatment of complex ocular diseases.}, }
@article {pmid40552706, year = {2025}, author = {Weissenbacher, LM and Schmidt, R and Vécsei-Marlovits, PV and Weingessel, B}, title = {Comparative treatment burden of intravitreal injection versus visit frequency in patients with exudative age-related macular degeneration.}, journal = {Acta ophthalmologica}, volume = {103}, number = {7}, pages = {e533-e535}, doi = {10.1111/aos.17538}, pmid = {40552706}, issn = {1755-3768}, }
@article {pmid40552927, year = {2025}, author = {Rudeen, KM and Maloney, CM and Lydon, KL and Teixeria, LBC and Mieler, WF and Kang-Mieler, JJ}, title = {Treatment Efficacy of a Dual Release of Aflibercept and Dexamethasone From a Single Hydrogel Drug Delivery System in a Rodent Model.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {6}, pages = {31}, pmid = {40552927}, issn = {2164-2591}, support = {R01 EY029298/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Dexamethasone/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Choroidal Neovascularization/drug therapy ; Disease Models, Animal ; *Drug Delivery Systems ; Tomography, Optical Coherence ; Fluorescein Angiography ; Rats ; Hydrogels ; Intravitreal Injections ; Electroretinography ; Intraocular Pressure/drug effects ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; Treatment Outcome ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of vision loss for the elderly population. Wet AMD, which accounts for approximately 15% of AMD cases, is characterized by abnormal blood vessel growth from the choroid into the subretinal space. Although intravitreal anti-vascular endothelial growth factor (VEGF) agents have become the standard of care for wet AMD, there is a growing subset of patients who do not fully respond to monotherapy anti-VEGF treatment. In previously published reports, corticosteroids have shown improvements in treatment efficacy when administered with anti-VEGF in a subset of non-responders to anti-VEGF monotherapy.<br><br>METHODS: A combination dexamethasone and aflibercept drug delivery system (Combo-DDS) was evaluated in a laser-induced rodent model of choroidal neovascularization (CNV). Longitudinal monitoring was done through week 22 using fluorescein angiography (FA) and spectral domain optical coherence tomography (SD-OCT). Multi-Otsu thresholding was used to quantify the lesion area based on late-phase FA images. In addition, preliminary safety and biocompatibility of the Combo-DDS were evaluated by intraocular pressure (IOP) measurements, electroretinogram (ERG), and histology (n = 6 eyes/group).<br><br>RESULTS: In the laser-induced CNV model, CNV lesions (n = 28-36 lesions/group) were monitored longitudinally. Combo-DDS showed a regression in lesion size starting at week 2 that continued through the end of study. IOP, ERG, and histology showed preliminary safety and biocompatibility of the Combo-DDS.<br><br>CONCLUSIONS: This study demonstrated that Combo-DDS maintained treatment efficacy in a laser-induced CNV rodent model for 6 months.<br><br>TRANSLATIONAL RELEVANCE: The Combo-DDS shows the potential to eliminate the need for separate dosing regiments of anti-VEGF and corticosteroids for non-responders to anti-VEGF monotherapy.}, }
@article {pmid40553257, year = {2025}, author = {Mathivanan, I and Volker, E and Thyagarajan, K and Sivasubramanian, AT and Raju, K and Thangaraj, A}, title = {Age-Related Macular Degeneration: Therapeutic Strategies Based on Stem Cells.}, journal = {Stem cell reviews and reports}, volume = {21}, number = {7}, pages = {1867-1882}, pmid = {40553257}, issn = {2629-3277}, support = {BT/HRD/35/02/2006 dated 30/03/2021//Department of Biotechnology, Ministry of Science and Technology, India/ ; }, mesh = {Humans ; *Macular Degeneration/therapy/pathology ; *Stem Cell Transplantation/methods ; Retinal Pigment Epithelium/cytology ; Animals ; Induced Pluripotent Stem Cells/transplantation/cytology ; Cell Differentiation ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly in developed countries, manifesting in two primary forms: neovascular (wet) AMD and non-neovascular (dry) AMD. Current treatments, such as anti-VEGF therapy, offer limited efficacy, particularly for dry AMD, highlighting the urgent need for alternative strategies. Advancements in contemporary treatment strategies for these eye conditions are a pressing medical concern. Stem cell-based therapies have emerged as a promising approach for retinal regeneration due to their capacity for self-renewal and differentiation into retinal cell types, including retinal pigment epithelial (RPE) cells and photoreceptors, two key cell populations damaged in AMD. Among the various sources, pluripotent stem cells such as human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) show significant potential in generating functional RPE cells and restoring retinal architecture and function. Preclinical and early clinical studies have demonstrated promising outcomes, including improved visual acuity and anatomical integration. However, challenges such as immune rejection, tumorigenicity, limited long-term integration, and ethical concerns continue to impede clinical translation. This review critically evaluates current stem cell-based therapeutic strategies for AMD, including advances in mesenchymal stem cells, retinal organoids, and combinatorial approaches with gene and nanotherapy. Furthermore, this review outlines the translational bottlenecks and future directions required to advance these therapies toward clinical application.}, }
@article {pmid40555396, year = {2025}, author = {Han, YE and Choi, HI and Lee, J and Kim, YJ and Lee, JY and Sadda, SR and Yoon, YH}, title = {Geographic atrophy in Korean patients with dry age-related macular degeneration: incidence, phenotypes, and progression.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {60}, number = {6}, pages = {e925-e933}, doi = {10.1016/j.jcjo.2025.05.026}, pmid = {40555396}, issn = {1715-3360}, mesh = {Humans ; *Geographic Atrophy/epidemiology/diagnosis ; Incidence ; Disease Progression ; Male ; Female ; Retrospective Studies ; Republic of Korea/epidemiology ; Aged ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Phenotype ; Follow-Up Studies ; Fundus Oculi ; Middle Aged ; *Macular Degeneration/epidemiology/diagnosis ; *Visual Acuity ; Aged, 80 and over ; }, abstract = {OBJECTIVE: To evaluate the characteristics of geographic atrophy (GA) in Korean patients, including incidence, phenotypes, progression patterns, and factors associated with progression rates.<br><br>DESIGN: Retrospective longitudinal cohort study.<br><br>PARTICIPANTS: Korean patients with intermediate and advanced (prevalent GA) dry AMD, followed for &#x2265;3 years.<br><br>METHODS: GA incidence was defined as the percentage of new GA emerging from the intermediate dry AMD group during the follow-up. Baseline phenotypes were evaluated in the prevalent GA group at the initial visit using fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence (FAF). Progression patterns were assessed by growth rates (mm[2]/year and mm/year using square-root treansformation [SQRT]), and the centripetal growth direction (foveal involvement of extrafoveal lesions). Linear regression was used to identify factors associated with progression rates.<br><br>RESULTS: In intermediate dry AMD group (395 eyes/241 patients), GA incidence was 6.8%, while wet conversion was 14.4%, during 60.5 &#xb1; 13.5 months. In prevalent GA group (70 eyes/46 patients), the mean lesion size was 7.2 &#xb1; 7.1 mm[2] (2.4 &#xb1; 1.3 mm [SQRT]), with bilateral involvement in 68.6%, banded/diffuse FAF patterns in 81.4%, extrafoveal and multifocal locations in 51.4% and 84.3%, and drusen and reticular pseudodrusen in 87.1% and 34.3%. The progression rate was 2.0 &#xb1; 1.3 mm[2]/year (0.3 &#xb1; 0.2 mm/year [SQRT]), with 69.4% exhibiting centripetal direction during 61.2 &#xb1; 14.5 months. Large lesion size, banded/diffuse FAF patterns, and extrafoveal locations were positively associated with progression rates (p&#x202f;=&#x202f;0.006, 0.007, and 0.008).<br><br>CONCLUSIONS: The 5-year incidence of GA in Korean patients with intermediate dry AMD was 6.8%, approximately half of the rate of wet conversion. The mean GA progression rate was 2.0 mm[2]/year (0.3 mm/year [SQRT]). Risk factors for fast progression were banded/diffuse FAF patterns, extrafoveal locations, and large lesion size.}, }
@article {pmid40555726, year = {2025}, author = {Lee, TJ and Santeford, A and Pitts, KM and Ripoll, CV and Terao, R and Guo, Z and Ozcan, M and Kratky, D and Christoffersen, C and Javaheri, A and Apte, RS}, title = {Apolipoprotein M attenuates age-related macular degeneration phenotypes via sphingosine-1-phosphate signaling and lysosomal lipid catabolism.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {5331}, pmid = {40555726}, issn = {2041-1723}, support = {P30 EY002687/EY/NEI NIH HHS/United States ; R01 EY019287/EY/NEI NIH HHS/United States ; R01 HL155344/HL/NHLBI NIH HHS/United States ; P30 DK056341/DK/NIDDK NIH HHS/United States ; P30 DK020579/DK/NIDDK NIH HHS/United States ; K08 HL138262/HL/NHLBI NIH HHS/United States ; }, mesh = {*Lysophospholipids/metabolism ; *Macular Degeneration/metabolism/pathology/genetics ; Animals ; *Sphingosine/analogs &amp; derivatives/metabolism ; *Apolipoproteins M/metabolism/genetics ; Humans ; *Lysosomes/metabolism ; Retinal Pigment Epithelium/metabolism/pathology ; Signal Transduction ; *Lipid Metabolism ; Mice ; Mice, Knockout ; Male ; Female ; Phenotype ; Mice, Inbred C57BL ; Cholesterol/metabolism ; Aged ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in people over 50. AMD and cardiovascular disease share risk factors including age, impaired lipid metabolism, and extracellular lipid deposition. Because of its importance in age-related diseases, we hypothesize that apolipoprotein M (ApoM), a lipocalin that binds sphingosine-1-phosphate (S1P), might restore lipid homeostasis and retinal function in AMD. In support, we find that human patients with AMD demonstrate significantly reduced ApoM compared to controls. In mice with impaired retinal cholesterol efflux, ApoM improves retinal pigment epithelium (RPE) function and lipotoxicity in an S1P- and S1P receptor 3-dependent manner. Ultrastructural evidence of enhanced melanosome-lipid droplet interactions led us to hypothesize and demonstrate that ApoM-S1P signaling drives RPE-specific lysosomal lipid catabolism. RPE-specific knockout of lysosomal acid lipase recapitulates features of AMD. Our study defines a novel role for ApoM/S1P signaling in AMD driven by RPE lipotoxicity, mediated by cell-autonomous lysosomal lipid catabolism.}, }
@article {pmid40557781, year = {2025}, author = {Trinh, M and Cheung, R and Nam, J and Ng, D and Nivison-Smith, L and Ly, A}, title = {High risk does not guarantee high accuracy-Evaluating the prognostic accuracy of OCT biomarkers for predicting late AMD.}, journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)}, volume = {45}, number = {6}, pages = {1293-1301}, pmid = {40557781}, issn = {1475-1313}, support = {1174385//NHMRC/ ; }, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Female ; Male ; Prognosis ; Biomarkers ; Aged ; ROC Curve ; *Macular Degeneration/diagnosis ; *Retinal Pigment Epithelium/pathology ; Disease Progression ; Middle Aged ; Aged, 80 and over ; Follow-Up Studies ; }, abstract = {PURPOSE: The translation of high-risk biomarkers into accurate predictions of late age-related macular degeneration (AMD) may be limited by biomarker prevalence, subjective identification and competing risks from concurrent biomarkers. This study evaluates the prognostic performance of key optical coherence tomography (OCT) biomarkers for progression to late AMD, with colour fundus photography (CFP) as the reference standard.<br><br>METHODS: This retrospective study included 78 single eyes with intermediate AMD, propensity-score matched by age and sex between converters and non-converters to late AMD. Ten OCT biomarkers empirically derived from recent meta-analysis, alongside CFP biomarkers of large drusen and pigmentary abnormality, were independently graded by three clinician-researchers. Biomarkers' associated risk (odds ratios) and prognostic performance (area under the receiver operating characteristic curve (AUC), sensitivity, specificity) were evaluated for predicting late AMD.<br><br>RESULTS: The adjusted risk was highest for OCT-detected nascent geographic atrophy, shallow irregular retinal pigment epithelium (RPE) elevations, drusenoid pigment epithelium detachment and RPE reflective abnormality (odds ratios, 6.66 [1.32, 42.71] to 28.27 [2.44, 545.3], p&#x2009;<&#x2009;0.05). However, CFP-detected pigmentary abnormalities demonstrated the highest individual prognostic accuracy (77.69 [68.11, 87.27]% AUC, p&#x2009;<&#x2009;0.0001), with excellent sensitivity (92.31%) but moderate specificity (63.08%). Adding at least three OCT biomarkers was required to improve prognostic performance significantly (91.01 [84.66, 97.36]%, p&#x2009;<&#x2009;0.0001), and at least eight additional biomarkers to yield both excellent sensitivity (94.62%) and specificity (90.77%).<br><br>CONCLUSIONS: CFP-detected pigmentary abnormality remains a mainstay of clinical AMD prognostication, likely due to its higher prevalence and interpretability than high-risk OCT biomarkers. Integrating OCT biomarkers into clinical prognostic models is promising but complex and may require automated identification to aid efficiency.}, }
@article {pmid40558523, year = {2025}, author = {Muraleva, NA and Tikhonov, DI and Zhdankina, AA and Plotnikov, MB and Khlebnikov, AI and Logvinov, SV and Kolosova, NG}, title = {Alterations of JNK Signaling Pathway Activity in the Rat Retina: Effects of Age, Age-Related Macular Degeneration-like Pathology, and a JNK Inhibitor (IQ-1S).}, journal = {Cells}, volume = {14}, number = {12}, pages = {}, pmid = {40558523}, issn = {2073-4409}, support = {24-25-00030//Russian Science Foundation/ ; }, mesh = {Animals ; *Macular Degeneration/pathology/drug therapy/metabolism ; *Retina/pathology/drug effects/metabolism ; Rats, Wistar ; *MAP Kinase Signaling System/drug effects ; Rats ; *Aging/pathology/metabolism ; Male ; *Quinoxalines/pharmacology ; *Protein Kinase Inhibitors/pharmacology ; *Oximes/pharmacology ; Disease Models, Animal ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment worldwide. AMD development is associated with inflammation, oxidative stress, and a progressive proteostasis imbalance, in whose regulation, c-Jun N-terminal kinases (JNKs) play a crucial role. JNK inhibition is being discussed as a new way to prevent and treat AMD, but there are no data on JNK signaling in the retina and its changes with age and with AMD development. Here, for the first time, we assessed JNK-signaling activity in the retina and did not detect its age-related changes in healthy Wistar rats. By contrast, manifestation and progression of the AMD-like pathology in OXYS rats occurred simultaneously with JNK pathway activation. We also confirmed that selective JNK3 inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt (IQ-1S) can suppress neurodegenerative changes in the OXYS rat retina. Its effects were prevention of the destructive changes in retinal synapses and the suppression of the JNK signaling pathway activity during active progression of AMD signs in OXYS rats.}, }
@article {pmid40558564, year = {2025}, author = {Bisen, S and Singh, NK}, title = {Implications of Fatty Acids for Age-Related Macular Degeneration: Evidence and Recommendations.}, journal = {Cells}, volume = {14}, number = {12}, pages = {}, pmid = {40558564}, issn = {2073-4409}, support = {R01 EY029709/EY/NEI NIH HHS/United States ; EY029709//National Eye Institute, NIH/ ; }, mesh = {Humans ; *Macular Degeneration/metabolism/pathology/diet therapy ; *Fatty Acids/metabolism/therapeutic use ; Fatty Acids, Omega-3 ; Animals ; }, abstract = {Age-related macular degeneration (AMD) is an ocular pathology in humans characterized by the buildup of lipid-rich extracellular deposits, which leads to retinal degeneration. In recent years, considerable effort has been made to observe the effect of dietary fatty acids on oxidative stress and inflammation. In continuation of this, much effort has been made to study the effect of dietary fatty acids on the pathogenesis of AMD. Although studies have shown that dietary fatty acids are effective against few forms of AMD, particularly wet AMD or neovascular AMD, no dietary lipids have shown any conclusive results for dry AMD or geographic AMD. It is therefore important to look for new lipids and lipoproteins that can be helpful in treating various stages of AMD. This article reviews the impact of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) on retinal health and the progression of AMD. Furthermore, this manuscript discusses all studies investigating the implications of fatty acids on AMD, which may be beneficial for future treatment strategies and dietary guidelines related to it. In conclusion, studies suggest that omega-3 PUFAs, particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), might provide protection against AMD, highlighting the necessity for additional clinical trials to evaluate their efficacy in the prevention and treatment of AMD.}, }
@article {pmid40559108, year = {2025}, author = {Grün, M and Rothaus, K and Ziegler, M and Lommatzsch, A and Lange, C and Faatz, H}, title = {Morphology of Macular Neovascularization in Age-Related Macular Degeneration Influences Treatment Requirement and Visual Outcome After 1 Year.}, journal = {Journal of personalized medicine}, volume = {15}, number = {6}, pages = {}, pmid = {40559108}, issn = {2075-4426}, support = {//Voltmann Foundation/ ; }, abstract = {Background/Objectives: To evaluate the potential of Optical Coherence Tomography (OCT) and OCT angiography parameters in predicting treatment requirements and visual outcomes after one year in therapy-naïve eyes with neovascular age-related macular degeneration (nAMD). Methods: A retrospective study of 96 therapy-naïve eyes newly diagnosed with nAMD was carried out. All eyes received baseline OCT and OCTA. Follow-up OCT after initial upload was then carried out, involving three intravitreal injections (IVIs) with anti-Vascular Endothelial Growth Factor (anti-VEGF) at four-week intervals. OCT parameters, including intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelium detachment (PED), and central retinal thickness (CRT), were assessed qualitatively and quantitatively. Macular Neovascularization (MNV) morphology at baseline was described in terms of area, total vessel length, flow density, and fractal dimension. OCT and OCTA parameters were correlated with best corrected visual acuity (BCVA) and number of administered IVIs after 1 year of treatment. Results: Eyes with persistent subretinal fluid (SRF) or both intraretinal fluid (IRF) and SRF after upload showed a significantly higher need for IVIs (p < 0.01). Also, pigment epithelium detachment (PED) presence at baseline (p < 0.05), PED height at baseline (p < 0.01), PED presence after upload (p < 0.01), and PED height after upload (p < 0.01) were each correlated with a greater number of IVIs. Decrease in PED height during upload was accompanied by a lower number of IVIs (p < 0.01). All the aforementioned parameters had no influence on BCVA after 1 year (p > 0.05). Baseline central retinal thickness (CRT) was linked to worse BCVA at 12 months (p < 0.05), but not the number of IVIs. Follow-up CRT correlated with worse BCVA (p < 0.01) and more IVIs (p < 0.01), while CRT decrease was associated with better BCVA (p < 0.05) and fewer IVIs (p < 0.01) at 1 year. In OCTA, area and total vessel length of MNVs were correlated with BCVA after 1 year (p < 0.01) but had no influence on number of IVIs (p > 0.05). Flow density had no influence on either outcome parameter (p > 0.05). Fractal dimension was associated with BCVA (p < 0.01) and number of IVIs (p < 0.05) after 1 year. Conclusions: MNV area, vessel length, and fractal dimension in OCTA, along with fluid distribution in OCT at baseline and after follow-up, may serve as indicators of treatment needs and visual outcomes after one year. Further studies with longer observation periods and the use of deep learning models are needed to improve analyses and to verify the applicability of these findings to clinical practice.}, }
@article {pmid40560103, year = {2025}, author = {Durmaz Engin, C and Beşenk, U and Özizmirliler, D and Selver, MA}, title = {Comparative Analysis of Automated vs. Expert-Designed Machine Learning Models in Age-Related Macular Degeneration Detection and Classification.}, journal = {Turkish journal of ophthalmology}, volume = {55}, number = {3}, pages = {120-126}, pmid = {40560103}, issn = {2149-8709}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Machine Learning ; *Macular Degeneration/diagnosis/classification ; Aged ; *Wet Macular Degeneration/diagnosis/classification ; }, abstract = {OBJECTIVES: To compare the effectiveness of expert-designed machine learning models and code-free automated machine learning (AutoML) models in classifying optical coherence tomography (OCT) images for detecting age-related macular degeneration (AMD) and distinguishing between its dry and wet forms.<br><br>MATERIALS AND METHODS: Custom models were developed by an artificial intelligence expert using the EfficientNet V2 architecture, while AutoML models were created by an ophthalmologist utilizing LobeAI with transfer learning via ResNet-50 V2. Both models were designed to differentiate normal OCT images from AMD and to also distinguish between dry and wet AMD. The models were trained and tested using an 80:20 split, with each diagnostic group containing 500 OCT images. Performance metrics, including sensitivity, specificity, accuracy, and F1 scores, were calculated and compared.<br><br>RESULTS: The expert-designed model achieved an overall accuracy of 99.67% for classifying all images, with F1 scores of 0.99 or higher across all binary class comparisons. In contrast, the AutoML model achieved an overall accuracy of 89.00%, with F1 scores ranging from 0.86 to 0.90 in binary comparisons. Notably lower recall was observed for dry AMD vs. normal (0.85) in the AutoML model, indicating challenges in correctly identifying dry AMD.<br><br>CONCLUSION: While the AutoML models demonstrated acceptable performance in identifying and classifying AMD cases, the expert-designed models significantly outperformed them. The use of advanced neural network architectures and rigorous optimization in the expert-developed models underscores the continued necessity of expert involvement in the development of high-precision diagnostic tools for medical image classification.}, }
@article {pmid40563040, year = {2025}, author = {Ahmed, F and Bhuiyan, MAN and Coskunuzer, B}, title = {Topo-CNN: Retinal Image Analysis with Topological Deep Learning.}, journal = {Journal of imaging informatics in medicine}, volume = {}, number = {}, pages = {}, pmid = {40563040}, issn = {2948-2933}, support = {P20 GM121307/GM/NIGMS NIH HHS/United States ; P20GM121307 to M.A.N.B/GF/NIH HHS/United States ; }, abstract = {The analysis of fundus images is vital for early detection of retinal diseases such as diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (AMD), but traditional methods are resource-intensive. We propose an automated and interpretable diagnostic framework that leverages novel feature representations to improve performance. Our main contribution is a topological feature extraction technique based on Topological Data Analysis (TDA), which captures geometric and structural patterns in fundus images. These features are computationally efficient and interpretable. We integrate them with pretrained CNN features (e.g., ResNet-50) into a hybrid deep model, Topo-CNN, combining global image context with topological structure. We evaluate Topo-CNN on three benchmarks: APTOS (binary and five-class DR), ORIGA (Glaucoma), and IChallenge-AMD. Our model achieves 98.7% accuracy/98.9 AUC on binary DR, 95.5 AUC on five-class DR, 93.8% accuracy/93.6 AUC on AMD, and 82.3% accuracy/95.8 specificity on glaucoma. Ablation studies confirm the added value of topological features, and our Topo-CNN consistently outperforms existing methods across tasks.}, }
@article {pmid40563282, year = {2025}, author = {Antemie, RG and Marc, G and Pele, R and Fizeșan, I and Creștin, IV and Borlan, R and Theodosis-Nobelos, P and Rekka, EA and Oniga, O and Crișan, O and Pîrnău, A and Vlase, L and Clichici, SV}, title = {Antioxidant Activity and Cytotoxicity Evaluation of New Catechol Hydrazinyl-Thiazole Derivatives as Potential Protectors in Retinal Degenerative Processes.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, pmid = {40563282}, issn = {2076-3921}, support = {PCD 881/3/12 January 2022 and PCD 772/1/11 January 2023//"Iuliu Ha&#x163;ieganu" University of Medicine and Pharmacy Cluj-Napoca, Romania/ ; 27N/03.01.2023, component project code PN 23 24 01 05//"Nucleu" Program within the National Research Development and Innovation Plan 2022-2027, Romania, carried out with the support of MEC/ ; Installations and Special Objectives of National Interest (IOSIN), IZOSTAB//Romanian Ministry of Education and Research/ ; }, abstract = {Retinal degenerative processes such as age-related macular degeneration are at the center of many ongoing research studies, as their impact on the general population is significant, with severe visual impairment and even irreversible vision loss if left untreated. Currently, there are few efficient treatments available to stop or limit its progression. In the present paper, a molecular hybridization approach was employed to develop novel compounds that address this issue. By adding either 2-butenal or a β-ionone-derived residue to the hydrazone-catechol-thiazole scaffold, two compounds were designed and synthesized: 5a and 5b. After being characterized by mass spectrometry and nuclear magnetic resonance, and proving potent antioxidant activity in the in vitro assays, the cytotoxicity evaluation using the ARPE-19, BJ, and A549 cell lines revealed a surprisingly low-dose effect of 5a and the unexpected cytotoxic activity of 5b, despite its β-ionone moiety, known for its significant therapeutic properties.}, }
@article {pmid40563363, year = {2025}, author = {Boo, YC}, title = {Restoring Glutathione Homeostasis in Glycation-Related Eye Diseases: Mechanistic Insights and Therapeutic Interventions Beyond VEGF Inhibition.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, pmid = {40563363}, issn = {2076-3921}, support = {RS-2024-00437643//Korea Health Industry Development Institute/Republic of Korea ; }, abstract = {Advanced glycation end-products (AGEs) and oxidative stress are recognized as central contributors to the pathogenesis of age-related or diabetic cataracts, diabetic retinopathy (DR), and age-related macular degeneration (AMD). These glycation-related diseases are characterized by impaired redox balance and decreased glutathione (GSH) levels. This review aims to examine the mechanistic links between AGEs and GSH depletion across ocular tissues by integrating in vitro, ex vivo, in vivo, and clinical studies relevant to this topic. The multiple levels of evidence highlight GSH homeostasis as both a biomarker and therapeutic target in glycation-related ocular disorders. Therapeutic strategies aimed at restoring GSH homeostasis under glycation stress are categorized into four mechanistic domains: (I) promoting GSH supply and synthesis, (II) enhancing GSH recycling, (III) mitigating glycation stress, and (IV) reducing oxidative and nitrosative stress. Most of these strategies have been explored via different approaches, and experimental findings with various interventions have shown promise in restoring GSH balance and mitigating AGE-induced damage. A pathological link between GSH depletion and vascular endothelial growth factor (VEGF) overexpression is observed in DR and wet AMD. GSH-centered interventions act upstream to modulate redox homeostasis while anti-VEGF therapies target downstream angiogenesis. This study supports the rationale for a dual-targeting strategy that combines redox-based interventions with VEGF inhibition in glycation-related ocular diseases.}, }
@article {pmid40563412, year = {2025}, author = {Wang, N and Wang, Y and Zhang, L and Yang, W and Fu, S}, title = {Molecular Mechanisms of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelial Cells: Implications for Age-Related Macular Degeneration (AMD) Progression.}, journal = {Biomolecules}, volume = {15}, number = {6}, pages = {}, pmid = {40563412}, issn = {2218-273X}, support = {22JR5RA914//the Construction Plan of the Gansu Province Natural Science Foundation Project/ ; 22ZSCQD02//Gansu Provincial Intellectual Property Program/ ; 23JRRA1490//Gansu Province Joint Research Fund Project/ ; 2023YFC3503400//National Key R&amp;D program of China/ ; 2019-ZD-38//Lanzhou Municipal Science and Technology Development Guidance Plan Project/ ; }, mesh = {Humans ; *Epithelial-Mesenchymal Transition ; *Macular Degeneration/pathology/metabolism/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; Disease Progression ; Animals ; Oxidative Stress ; Signal Transduction ; Epigenesis, Genetic ; Autophagy ; }, abstract = {Age-related macular degeneration (AMD), the leading cause of irreversible blindness worldwide, represents a complex neurodegenerative disorder whose pathogenesis remains elusive. At the core of AMD pathophysiology lies the retinal pigment epithelium (RPE), whose epithelial-mesenchymal transition (EMT) has emerged as a critical pathological mechanism driving disease progression. This transformative process, characterized by RPE cell dedifferentiation and subsequent extracellular matrix remodeling, is orchestrated through a sophisticated network of molecular interactions and cellular signaling cascades. Our review provides a comprehensive analysis of the molecular landscape underlying RPE EMT in AMD, with particular emphasis on seven interconnected pathological axes: (i) oxidative stress and mitochondrial dysfunction, (ii) hypoxia-inducible factor signaling, (iii) autophagic flux dysregulation, (iv) chronic inflammatory responses, (v) complement system overactivation, (vi) epigenetic regulation through microRNA networks, and (vii) key developmental signaling pathway reactivation. Furthermore, we evaluate emerging therapeutic strategies targeting EMT modulation, providing a comprehensive perspective on potential interventions to halt AMD progression. By integrating current mechanistic insights with therapeutic prospects, this review aims to bridge the gap between fundamental research and clinical translation in AMD management.}, }
@article {pmid40564380, year = {2025}, author = {Wu, J and Liu, X and Liu, Y and Su, W and Zhuo, Y}, title = {New Insights into the Role of Cellular Senescence and Its Therapeutic Implications in Ocular Diseases.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {12}, number = {6}, pages = {}, pmid = {40564380}, issn = {2306-5354}, support = {82171057//the National Natural Science Foundation of China/ ; BX20240440//China National Postdoctoral Program for Innovative Talents/ ; 202206080005//Science and Technology Program of Guangzhou, China/ ; }, abstract = {The process of aging exerts profound effects on various physiological systems, leading to the progression of chronic degenerative disorders and pathologies associated with advancing age. Cellular senescence plays a central role in the aging process and the onset of various eye conditions associated with advancing age, including age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, cataracts, and ocular surface disorders. The accumulation of senescent cells (SnCs) and their secretion of pro-inflammatory and tissue-remodeling factors, collectively known as the senescence-associated secretory phenotype (SASP), exacerbate chronic inflammation, oxidative stress, and tissue dysfunction, contributing to disease progression. This study is the first to systematically integrate the multifaceted mechanisms of cellular senescence in ocular diseases, revealing differential regulatory mechanisms of specific signaling pathways across different ocular pathologies, thereby providing novel insights into the pathogenesis of these disorders. SnC-targeted therapies such as senolytics, senomorphics, SASP modulators, mitochondrial-targeted antioxidants, and epigenetic reprogramming are emerging as regenerative therapies, demonstrating potent anti-inflammatory effects, restoration of normal tissue physiology, and successful regeneration of ocular defects in preclinical models and clinical trials, while slowing senescence-associated disease progression. This review not only summarizes the role of cellular senescence in ocular diseases but also delves into potential therapeutic strategies, particularly highlighting novel perspectives for root-cause-targeted therapies from the unique angle of senescence biology, which may pioneer new directions for the treatment of ocular pathologies.}, }
@article {pmid40565235, year = {2025}, author = {Pinelli, R and Lazzeri, G and Berti, C and Biagioni, F and Scaffidi, E and Ferrucci, M and Bumah, VV and Fornai, F}, title = {Retinal Autophagy for Sustaining Retinal Integrity as a Proof of Concept for Age-Related Macular Degeneration.}, journal = {International journal of molecular sciences}, volume = {26}, number = {12}, pages = {}, pmid = {40565235}, issn = {1422-0067}, support = {RC 2024-2025//Ministero della Salute/ ; }, mesh = {*Autophagy ; *Macular Degeneration/pathology/metabolism ; Humans ; Animals ; *Retina/pathology/metabolism ; Retinal Pigment Epithelium/pathology/metabolism ; }, abstract = {Current evidence indicates that most types of autophagy represent a pivot in promoting retinal integrity. In healthy conditions, autophagy acts on multiple pathways, which are fundamental for the biochemistry and the fine structure of the retina. Autophagy is essential in granting visual processes. On the other hand, autophagy dysfunction characterizes several retinal disorders. This is mostly evident in age-related macular degeneration (AMD), which represents the most common degenerative disease leading to blindness. The involvement of autophagy in AMD is documented in vitro and in vivo experiments, and it is strongly suggested by clinical findings in humans. The present manuscript provides an overview of the specific types of autophagy, which prevail in the retina and their alterations in retinal degeneration with an emphasis on AMD. The dysfunction of specific autophagy steps was analyzed in relation to hallmarks of AMD pathology and symptoms. An extended session of the manuscript analyzes the connection between altered autophagy and cell pathology within retinal pigment epithelium, as well as the site and structure of extracellular aggregates named drusen. The significance of the drusen in relation to visual function is discussed in the light of the role of autophagy in regulating key steps of phototransduction.}, }
@article {pmid40565279, year = {2025}, author = {Zibetti, C}, title = {Molecular Determinants of the Human Retinal Pigment Epithelium Cell Fate and Potential Pharmacogenomic Targets for Precision Medicine.}, journal = {International journal of molecular sciences}, volume = {26}, number = {12}, pages = {}, pmid = {40565279}, issn = {1422-0067}, support = {801133//Horizon H2020 MSCA CoFUND/ ; }, mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/cytology ; *Precision Medicine/methods ; Epithelial-Mesenchymal Transition/genetics ; *Macular Degeneration/genetics/pathology/metabolism ; *Pharmacogenetics/methods ; Gene Regulatory Networks ; Transcription Factors/metabolism/genetics ; Cell Differentiation ; }, abstract = {Age-related macular degeneration (AMD) is a common cause of blindness worldwide, and it is projected to affect several million individuals by 2040. The human retinal pigment epithelium (hRPE) degenerates in dry AMD, prompting the need to develop stem cell therapies to replace the lost tissue by autologous transplantation and restore the visual function. Nevertheless, the molecular factors behind the hRPE cell fate determination have not been elucidated. Here we identify all molecular determinants of the hRPE cell fate identity by comprehensive and unbiased screening of predicted pioneer factors in the human genome: such TFs mediate coordinated transitions in chromatin accessibility and transcriptional outcome along three major stages of the hRPE genesis. Furthermore, we compile a complete census of all transcription factor-specific binding sites by footprinting analysis of the human epigenome along the RPE developmental trajectory. Gene regulatory networks were found to be involved in cellular responses to glucose and hypoxia, RPE nitrosative stress, type II epithelial-to-mesenchymal transition (EMT), and type III tumorigenic EMT, providing routes for therapeutic intervention on pleiotropic targets dysregulated in AMD, diabetic retinopathy, and cancer progression. Genome editing technologies may leverage this repository to devise functional screenings of regulatory elements and pharmacogenomic therapies in complex diseases, paving the way for strategies in precision medicine.}, }
@article {pmid40565365, year = {2025}, author = {Lu, Z and Liu, S and Morales, MG and Whitlock, A and Ramkumar, R and Ramkumar, HL}, title = {Retinal BMI1 Expression Preserves Photoreceptors in Sodium-Iodate-Induced Oxidative Stress Models.}, journal = {International journal of molecular sciences}, volume = {26}, number = {12}, pages = {}, pmid = {40565365}, issn = {1422-0067}, mesh = {Animals ; *Iodates/toxicity ; *Oxidative Stress/drug effects ; Mice ; *Polycomb Repressive Complex 1/genetics/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; *Retina/metabolism ; Electroretinography ; Mice, Inbred BALB C ; *Macular Degeneration/metabolism/genetics/pathology ; Retinal Pigment Epithelium/metabolism/pathology ; Tomography, Optical Coherence ; Dependovirus/genetics ; *Photoreceptor Cells, Vertebrate/metabolism ; Proto-Oncogene Proteins ; }, abstract = {Dry age-related macular degeneration (AMD) is a leading cause of vision loss in individuals over 50, yet no approved therapies exist for early or intermediate stages of the disease. Oxidative stress is a central driver of retinal degeneration in AMD, and sodium iodate (NaIO3)-induced injury serves as a well-characterized model of oxidative damage to the retinal pigment epithelium (RPE) and photoreceptors. BMI1, a poly-comb group protein involved in DNA repair, mitochondrial function, and cellular renewal, has emerged as a promising therapeutic target for retinal neuroprotection. We evaluated the efficacy of AAV-mediated BMI1 gene delivery in murine models using two administration routes: subretinal (SR) and suprachoroidal (SC). AAV5.BMI1 (1 × 10[9] vg/eye) was delivered SR in Balb/c mice and evaluated at 4 and 15 weeks post-injection. AAV8.BMI1 (5 × 10[9] or 1 × 10[10] vg/eye) was administered SC in C57BL/6 mice and assessed at 4 weeks. Control groups received BSS or AAV8.stuffer. Following NaIO3 exposure, retinal structure and function were analyzed by optical coherence tomography (OCT), electroretinography (ERG), histology, and molecular assays. SC delivery of AAV8.BMI1 achieved the highest levels of retinal BMI1 expression with no evidence of local or systemic toxicity. Treated eyes showed dose-dependent preservation of outer nuclear layer (ONL) thickness and significantly improved ERG responses indicating structural and functional protection. These findings support SC AAV.BMI1 gene therapy as a promising, minimally invasive, and translatable approach for early intervention in intermediate AMD.}, }
@article {pmid40565902, year = {2025}, author = {Luttrull, JK and Sinclair, SH and Kozak, I}, title = {Laser Prophylaxis for Dry Age-Related Macular Degeneration: Current Evidence.}, journal = {Journal of clinical medicine}, volume = {14}, number = {12}, pages = {}, pmid = {40565902}, issn = {2077-0383}, abstract = {PURPOSE: To review the role of prophylactic panmacular laser treatment for age-related macular degeneration (AMD).<br><br>METHOD: A narrative review of studies employing laser treatment for non-exudative ("dry") AMD listed in the PubMed database.<br><br>RESULTS: In multiple published studies, macular laser treatment that causes laser-induced retinal damage (LIRD) has shown either no overall benefit or has accelerated disease progression and vision loss in eyes with dry AMD, particularly in high-risk eyes with more severe pre-treatment disease. Conversely, other studies, including randomized and matched propensity-scored real-world-data (RWD) clinical studies, indicate that avoidance of LIRD may allow laser to be used safely and effectively to prevent vision loss from AMD by slowing disease progression and preventing neovascular conversion without adverse treatment effects, benefiting the highest-risk eyes most.<br><br>CONCLUSIONS: AMD is the leading cause of irreversible vision loss worldwide. Current evidence suggests that laser prophylaxis for dry AMD may hold great promise in preventing age-related vision loss. More studies, especially prospective clinical trials, from more investigators, are needed. If current evidence is confirmed, laser prophylaxis would rise to a preeminent position as the safest, most effective, and most economical and accessible approach to reducing vision loss from AMD.}, }
@article {pmid40566556, year = {2025}, author = {Musadiq, M and Musadiq, M and Latif, F and Ng, B and Azzopardi, M and Gilead, N and Needham, A and Chong, YJ}, title = {Early Real-World Outcomes of Switching to 8 mg Aflibercept for Neovascular Age-Related Macular Degeneration in the United Kingdom.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {6}, pages = {}, pmid = {40566556}, issn = {2075-1729}, abstract = {(1) Aim: To evaluate early real-world outcomes of switching to aflibercept 8 mg in eyes with neovascular age-related macular degeneration (nAMD) in the United Kingdom. (2) Methods: This retrospective, observational study included 59 eyes from 50 patients with treatment-refractory nAMD previously treated with multiple anti-vascular endothelial growth factor (anti-VEGF) agents. Eyes were switched to aflibercept 8 mg without loading doses and treated using a treat-and-extend regimen. Functional, anatomical, and safety outcomes were evaluated over a mean (SD) follow-up of 33.5 (10.4) weeks. (3) Results: The mean (SD) age was 80.2 (6.3) years, and 28 (56.0%) of 50 patients were male. At baseline, the mean (SD) best corrected visual acuity (BCVA) was 66.0 (14.4) letters, with 33 (55.9%) eyes achieving ≥70 letters. The mean (SD) baseline central subfield thickness (CST) was 367.2 (100.7) µm. Prior to switching to aflibercept 8 mg, the mean (SD) number of injections for each eye was 26.9 (19.0), with the most recent mean (SD) treatment interval of 7.7 (1.7) weeks. Switching to aflibercept 8 mg resulted in extension of the mean (SD) injection interval from 7.7 (1.7) weeks to 8.7 (2.2) weeks (p < 0.01). BCVA and CST remained stable, with a significant reduction in pigment epithelial detachment (PED) height (232.5 µm to 211.6 µm, p < 0.01). No serious ocular adverse events or intraocular pressure (IOP) elevations requiring treatment were reported. (4) Conclusion: Aflibercept 8 mg demonstrated early treatment durability, anatomical benefit, and a favourable short-term safety profile in eyes with treatment-refractory nAMD. Further prospective studies are warranted.}, }
@article {pmid40569499, year = {2025}, author = {Lu, X and Kataoka, K and Kumagai, M and Nochi, Y and Yamamoto, A and Ko, R and Okada, AA}, title = {Comparison of intraocular pressure elevation following intravitreal injection of 70 µl aflibercept 8 mg.}, journal = {Japanese journal of ophthalmology}, volume = {69}, number = {6}, pages = {926-931}, pmid = {40569499}, issn = {1613-2246}, mesh = {Humans ; Intravitreal Injections/adverse effects ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage/adverse effects ; *Intraocular Pressure/drug effects ; Retrospective Studies ; Male ; Female ; Aged ; *Ocular Hypertension/chemically induced/physiopathology/diagnosis ; Middle Aged ; Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; Tonometry, Ocular ; Aged, 80 and over ; Dose-Response Relationship, Drug ; }, abstract = {PURPOSE: To assess the effect of increased injection volume on intraocular pressure (IOP) following intravitreal injections of aflibercept 8 mg (70 µl) compared to conventional anti-vascular endothelial growth factor drugs.<br><br>STUDY DESIGN: Retrospective observational study METHODS: This retrospective observational study included eyes treated with 50 &#xb5;l of either aflibercept 2 mg or faricimab 6 mg, followed by a switch to 70 &#xb5;l of aflibercept 8 mg. IOP was measured before and 30 minutes after intravitreal injections. IOP changes in treated and fellow eyes were analyzed, with potential associations examined between IOP changes and clinical parameters.<br><br>RESULTS: A total of 88 eyes from 85 patients were switched to aflibercept 8 mg during the study period. Due to incomplete data, 17 eyes from 15 patients were excluded, leaving 71 eyes from 70 patients for the analysis. IOP significantly increased from 13.2 &#xb1; 2.9 mmHg to 19.1&#xb1; 5.4 mmHg (P< 0.001) with 50 &#xb5;l injections and from 13.3 &#xb1; 2.9 mmHg to 19.8 &#xb1; 4.8 mmHg (P<0.001) with 70 &#xb5;l injections. The IOP increases were 6.0 &#xb1; 5.0 mmHg with 50 &#xb5;l injections and 6.5 &#xb1; 4.3 mmHg with 70 &#xb5;l injections, with no statistically significant difference (P = 0.20). An IOP exceeding 26 mmHg was observed in 6 eyes treated with 50 &#xb5;l injections and 10 eyes with 70 &#xb5;l injections, with no significant difference in IOP distribution between the volumes (P = 0.20).<br><br>CONCLUSION: There was no additional increase in IOP 30 minutes after intravitreal injections when switching from 50 &#xb5;l to 70 &#xb5;l volumes.}, }
@article {pmid40570232, year = {2025}, author = {Zhang, X and Huang, Y and Ma, M and Zhou, C and Jiang, Y and Zhang, Z and Zhu, X and Li, C and Xu, X and Fan, Y and Han, C and Zheng, Z and Zhao, S}, title = {Childhood obesity directly increases age-related macular degeneration risk: the role of physiobiological and immune-metabolic function.}, journal = {Journal of global health}, volume = {15}, number = {}, pages = {04164}, pmid = {40570232}, issn = {2047-2986}, mesh = {Humans ; *Macular Degeneration/epidemiology/etiology ; *Pediatric Obesity/epidemiology/complications ; Child ; Female ; Male ; Body Mass Index ; Middle Aged ; Risk Factors ; Aged ; Adult ; Mendelian Randomization Analysis ; Incidence ; }, abstract = {BACKGROUND: Childhood obesity is a growing global concern and is associated with cardiometabolic comorbidities in adulthood. However, the association between childhood body size and age-related macular degeneration (AMD) in late life remains to be investigated. We aimed to explore the association between childhood obesity and incident AMD and the underlying anatomical and physiobiological mechanisms.<br><br>METHODS: We investigated the association between childhood body size and incident AMD using multivariable Cox regression models and its relation to retinal layer thickness using linear regression. We performed four-way decomposition mediation analyses to explore the underlying mechanism. Lastly, we used univariable Mendelian randomisation (UVMR) and multivariable Mendelian randomisation (MVMR) to evaluate and differentiate the causal effect of childhood and adulthood body mass index (BMI).<br><br>RESULTS: Over a median follow-up of 12.8 years, 5026 incident AMD cases occurred among 487&#x2009;009 participants. Plumper childhood body size at age 10 conferred independent risk to incident AMD in later life (adjusted hazards ratio (aHR)&#x2009;=&#x2009;1.13; 95% confidence interval (CI)&#x2009;=&#x2009;1.03, 1.24, P&#x2009;=&#x2009;0.007) and was associated with photoreceptor outer segment layer thinning. Adulthood BMI mediated the association between childhood plumper body size and incident AMD (pure indirect effect&#x2009;=&#x2009;33%; 95% CI&#x2009;=&#x2009;9.9, 56.9, P&#x2009;=&#x2009;0.05). Mediation analysis of adulthood physiobiological and immuno-metabolic function showed that 17 peripheral biomarkers of 7 categories significantly mediated the aforementioned pathway, with HbA1c and cystatin C showing the two largest effects. Mendelian randomisation suggested a potential causal association between childhood BMI and AMD (UVMR inverse variance weighted (IVW) odd ratio (OR)&#x2009;=&#x2009;1.50; 95% CI&#x2009;=&#x2009;1.09, 2.08, P&#x2009;=&#x2009;0.013), independent of adulthood BMI (MVMR adulthood BMI-adjusted IVW OR&#x2009;=&#x2009;1.29; 95% CI&#x2009;=&#x2009;1.03, 1.61, P&#x2009;=&#x2009;0.024).<br><br>CONCLUSIONS: Childhood obesity may be a causal risk factor for incident AMD in later life, partially mediated by persistent obesity and physiobiological memory. Prevention of retinal degenerative diseases should therefore begin in childhood, whereby children should be encouraged and supported to maintain a normal body size.}, }
@article {pmid40570933, year = {2025}, author = {Nanji, K and Grad, J and Hatamnejad, A and McKechnie, T and Phillips, M and Gemmy Cheung, CM and Patel, PJ and Marco, RD and Borrelli, E and Steel, DH and Sadda, SR and Wong, TY and Sivaprasad, S and Guymer, R and Wykoff, CC and Chaudhary, V}, title = {Baseline OCT Biomarkers Predicting Visual Outcomes in Neovascular Age-Related Macular Degeneration: A Meta-Analysis.}, journal = {Ophthalmology}, volume = {132}, number = {11}, pages = {1241-1252}, doi = {10.1016/j.ophtha.2025.06.018}, pmid = {40570933}, issn = {1549-4713}, mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; *Biomarkers ; Intravitreal Injections ; Prognosis ; *Tomography, Optical Coherence/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity/physiology ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; }, abstract = {TOPIC: To determine the effect estimates and certainty of evidence for baseline OCT biomarkers predicting visual acuity (VA) and changes in VA from baseline at 6, 12, and 24 months after anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration.<br><br>CLINICAL RELEVANCE: Understanding the prognostic utility of biomarkers can improve treatment decisions.<br><br>METHODS: Results were reported in ETDRS letters. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines for prognostic studies informed certainty of evidence. Results were interpreted using a 5-letter minimally important difference.<br><br>RESULTS: Twenty-nine reports (8863 eyes) evaluating 80 biomarkers were included. Two biomarkers predicted better VA at 12 months with a low-certainty: the presence of an intact external limiting membrane (+14.0; 95% confidence interval [CI], +3.1 to +24.8) and the presence of an intact ellipsoid zone (+6.8; 95% CI, +2.8 to +10.8). Three biomarkers predicted worse VA at 12 months with a low certainty; the presence of intraretinal fluid (IRF; -5.6; 95% CI, -9.7 to -1.5), the presence of IRF in the foveal center point (-7.4; 95% CI, -10.1 to -4.7), and the presence of subretinal hyperreflective material (-8.7; 95% CI, -19.0 to 1.6). No other biomarker predicted an effect size that crossed the minimally important difference. However, noteworthy results occurred when interpreting biomarkers with statistically significant findings relative to a threshold of 0 letters and moderate certainty: the presence of a pigment epithelial detachment, geographic atrophy (GA), and both IRF and subretinal fluid (SRF) predicted reduced vision at 12 months. The presence of SRF predicted a positive change in VA at 12 months. The absence of a posterior vitreous detachment predicted a negative change in VA at 12 months. Finally, the presence of IRF in the central 1 mm, retinal pigment epithelial elevation, and GA predicted negative changes in VA at 24 months.<br><br>DISCUSSION: With low-certainty evidence, the baseline presence of an intact external limiting membrane and ellipsoid zone predicted better VA at 12 months, and the presence of IRF, IRF in the foveal center point, and subretinal hyperreflective material predicted worse VA at 12 months. Improved standardization in biomarker classification and control of confounding variables is needed.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40571871, year = {2025}, author = {Li, X and Ibrahim, KS and Baran, MR and Tchivelekete, GM and Zhou, X and Wu, Y and Reilly, J and Tan, Z and He, Z and Shu, X}, title = {Traditional Chinese Medicine, Ziyin-Mingmu Decoction, Regulates Cholesterol Metabolism, Oxidative Stress, Inflammation and Gut Microbiota in Age-related Macular Degeneration Models.}, journal = {Pharmaceutical research}, volume = {42}, number = {7}, pages = {1101-1118}, pmid = {40571871}, issn = {1573-904X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Oxidative Stress/drug effects ; *Macular Degeneration/drug therapy/metabolism/microbiology/pathology ; *Cholesterol/metabolism ; Humans ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Diet, High-Fat/adverse effects ; Mice ; Inflammation/drug therapy/metabolism ; Disease Models, Animal ; Male ; Medicine, Chinese Traditional/methods ; Retinal Pigment Epithelium/drug effects/metabolism ; Antioxidants/pharmacology ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the commonest cause of retinal disorders in the aged population. Ziyin-Mingmu decoction (ZD) has been widely used to treat AMD patients over thousands of years, however the underlying functional mechanisms of ZD are largely elusive. In this study, we aim to elucidate the therapeutic mechanisms of ZD in AMD models.<br><br>METHODS: An in vivo AMD mouse model and&#xa0;an in vitro AMD model were established. Cholesterol level in mouse tissues was measured. Expression of antioxidant genes and proinflammatory cytokines in mouse tissues and in human retinal pigment epithelial (RPE) cells were detected using biochemical approaches. Gut microbiota community and functional pathways were analysed using bioinformatics approach. Compounds in ZD were identified using HPLC/MS.<br><br>RESULTS: High fat diet (HFD)-fed mice had significantly higher levels of cholesterol in the retina, RPE, liver and serum, and markedly decreased expression of cholesterol metabolism-associated genes in those tissues, compared to mice fed with normal diet. Similarly, expression of antioxidant and inflammation genes was dysregulated in HFD-fed mouse tissues. ZD treatment reversed these HFD-induced pathological effects. HFD also altered the composition of cecum bacterial communities and associated metabolic pathways, which returned to control levels by ZD. In vitro assays showed that H2O2 significantly increased oxidative stress and enhanced expression of proinflammatory cytokines. Co-treatment with ZD significantly counteracted these changes. HPLC/MS identified 105 compound in water extracted ZD and most are polyphenols.<br><br>CONCLUSION: Our data suggests that protection of ZD against AMD is possibly through mitigating cholesterol level, oxidative stress and inflammation, and modulating gut microbiota by polyphenols.}, }
@article {pmid40572507, year = {2025}, author = {Rykowska, I and Nowak, I and Nowak, R and Michałkiewicz, O}, title = {Biodegradable Contact Lenses for Targeted Ocular Drug Delivery: Recent Advances, Clinical Applications, and Translational Perspectives.}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {12}, pages = {}, pmid = {40572507}, issn = {1420-3049}, mesh = {Humans ; *Drug Delivery Systems/methods ; *Contact Lenses ; Polymers/chemistry ; Ophthalmic Solutions/chemistry ; Administration, Ophthalmic ; Animals ; Drug Liberation ; Translational Research, Biomedical ; Dry Eye Syndromes/drug therapy ; }, abstract = {Ocular drug delivery presents a persistent clinical challenge due to the protective anatomical structure of the eye, physiological barriers such as reflex blinking, and continuous tear fluid turnover. These factors significantly limit the bioavailability of topically applied medications, reducing the therapeutic effectiveness of conventional formulations, such as eye drops, ointments, and suspensions, particularly in the management of chronic ocular disorders, including dry eye syndrome, diabetic retinopathy, and age-related macular degeneration. Drug-eluting contact lenses (DECLs) offer a promising alternative, enabling sustained, localized, and controlled drug release directly at the ocular surface. While several reviews have addressed contact lenses as drug delivery platforms, this work provides a distinct perspective by focusing specifically on biodegradable polymer-based systems. Emphasis is placed on recent advances in the design and fabrication of DECLs using natural and synthetic biodegradable polymers, which offer superior biocompatibility, customizable degradation kinetics, and the capacity for programmable drug release. This review discusses the selection criteria for polymer matrices, strategies for drug incorporation, and key factors influencing release profiles. Moreover, this study highlights innovative methodologies and therapeutic approaches that differentiate it from the existing literature, providing a timely and comprehensive resource for researchers developing next-generation polymeric ocular drug delivery systems.}, }
@article {pmid40573278, year = {2025}, author = {Rusciano, D}, title = {A Personal Scientific Journey in Ophthalmology: Twenty-Five Years of Translating Research into Novel Therapies.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {6}, pages = {}, pmid = {40573278}, issn = {1424-8247}, abstract = {Ocular diseases including glaucoma, diabetic retinopathy and age-related macular degeneration represent a growing global health burden, with current treatments often providing only symptomatic relief. Through an integrated approach combining preclinical models, molecular biology, and clinical insights, this review synthesizes 25 years of my translational research to advance therapeutic strategies for these conditions. Key findings demonstrate the following: (1) the dual neuroprotective and intraocular pressure-lowering effects of natural compounds (EGCG, forskolin) in glaucoma models; (2) successful development of Uparant, a first-in-class peptide inhibitor of pathological angiogenesis with efficacy in retinal disease models; and (3) innovative drug delivery systems (melatonin nanomicelles, liposomal sprays) that enhance ocular bioavailability. Notably, some of these approaches have progressed to early-phase clinical trials, demonstrating translational potential. Significant challenges remain in optimizing sustained drug delivery and addressing the heterogeneity of ocular diseases through personalized approaches. Future directions include combinatorial therapies and the application of artificial intelligence for treatment optimization. Collectively, this work establishes a framework for developing multi-target therapies that address both the molecular mechanisms and clinical needs in ophthalmology.}, }
@article {pmid40575145, year = {2025}, author = {Kammer, RL and Federici, R and Gormley, S}, title = {Topical Review: Clinical, Physiological, and Functional Benefits of Home-based Telerehabilitation with Occupational Therapists for Low Vision.}, journal = {International journal of telerehabilitation}, volume = {17}, number = {1}, pages = {6703}, pmid = {40575145}, issn = {1945-2020}, abstract = {For patients with low vision, rehabilitation enables the performance of daily activities and the acquisition of skills while enhancing quality of life, despite vision loss. Access to comprehensive low vision rehabilitation services, however, is often limited. The rise of telehealth during the COVID-19 pandemic has facilitated innovative delivery of healthcare, including telerehabilitation for low vision. This literature review was undertaken to evaluate the current evidence regarding telerehabilitation conducted by occupational therapists for patients with low vision. In this review, studies investigating the effects of new programs largely found significant improvements in outcomes. Results of a multicenter, randomized controlled trial found that reading ability significantly improved and results did not differ between therapies conducted through telerehabilitation or in-office. Additionally, studies surveying providers and patients regarding their sentiments about telehealth found that comfort level and overall satisfaction were similar between in-office visits and telerehabilitation.}, }
@article {pmid40576434, year = {2025}, author = {Swan, J and Toomey, CB and Bergstrand, M and Cuello, HA and Robie, J and Yu, H and Yuan, Y and Kooner, AS and Chen, X and Shaughnessy, J and Ram, S and Varki, A and Gagneux, P}, title = {The Sialome of the Retina, Alteration in Age-Related Macular Degeneration Pathology, and Potential Impacts on Complement Factor H.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {6}, pages = {81}, pmid = {40576434}, issn = {1552-5783}, support = {R01 AI130684/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Complement Factor H/metabolism ; *Macular Degeneration/metabolism/pathology ; *Retina/metabolism/pathology ; Aged ; Retinal Pigment Epithelium/metabolism ; Aged, 80 and over ; Female ; Bruch Membrane/metabolism ; Male ; Middle Aged ; *N-Acetylneuraminic Acid/metabolism ; *Sialic Acids/metabolism ; }, abstract = {PURPOSE: Little is known about sialic acids of the human retina, despite their integral role in self /non-self-discrimination by complement factor H (FH), the alternative complement pathway inhibitor.<br><br>METHODS: A custom sialoglycan microarray was used to characterize the sialic acid-binding specificity of native FH or recombinant molecules where IgG Fc was fused to FH domains 16 to 20 (which contains a sialic acid-binding site), domains 6 and 7 (which contains a glycosaminoglycan-binding site), or the FH-related proteins (FHRs) 1 and 3. We analyzed macular and peripheral retinal tissue from postmortem ocular globes for the amount, type, and presentation (glycosidic linkage type) of sialic acid in individuals with age-related macular degeneration (AMD) and age-matched controls using fluorescent lectins and antibodies to detect sialic acid and endogenous FH. Released sialic acids from neural retina, retinal pigmented epithelium (RPE) cells, and the Bruch's membrane (BrM) were labeled with 1,2-diamino-4,5-methylenedioxybenzene-2HCl (DMB), separated and quantified by high-performance liquid chromatography (HPLC).<br><br>RESULTS: Both native FH and the recombinant FH domains 16 to 20 recognized Neu5Ac and Neu5Gc that is &#x3b1;2-3-linked to the underlying galactose. 4-O-Actylation of sialic acid and sulfation of GlcNAc did not inhibit binding. Different linkage types of sialic acid were localized at different layers of the retina. The greatest density of &#x3b1;2-3-sialic acid, which is the preferred ligand of FH, did not colocalize with endogenous FH. The level of sialic acids at the BrM/choroid interface of the macula and peripheral retina of individuals with AMD were significantly reduced.<br><br>CONCLUSIONS: The sialome of the human retina is altered in AMD. This may affect FH binding and, consequently, alternative complement pathway regulation.}, }
@article {pmid40576874, year = {2025}, author = {Sun, X and Li, Y and Song, Z and Ma, X and Yan, H and Yu, S and Zhang, J and Wu, Y and Huang, Z and Wang, H and Bai, T and Hu, J and Tan, J and Lin, X}, title = {Challenges and Opportunities for Improving Management of Patients with nAMD and DME in China: Insights from a Global Survey on Anti-VEGF Therapy.}, journal = {Advances in therapy}, volume = {42}, number = {9}, pages = {4390-4402}, pmid = {40576874}, issn = {1865-8652}, mesh = {Humans ; China ; *Angiogenesis Inhibitors/therapeutic use/economics/administration &amp; dosage ; *Macular Edema/drug therapy ; Male ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Female ; *Diabetic Retinopathy/drug therapy ; Surveys and Questionnaires ; Aged ; Middle Aged ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy ; Practice Patterns, Physicians' ; }, abstract = {INTRODUCTION: This survey investigated the challenges and opportunities during anti-vascular endothelial growth factor (VEGF) therapy in Chinese patients.<br><br>METHODS: The survey was conducted in six&#xa0;hospitals from different regions in China, as part of the Barometer global survey. Paper-based optical mark recognition (OMR) questionnaires were answered by 498 and 527 patients who had been diagnosed with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), respectively, and were currently receiving or had previously received anti-VEGF injections, and by physicians who prescribe and/or administer anti-VEGF injections for the treatment of nAMD/DME. A total of 105 nAMD physicians and 105 DME physicians completed the questionnaire.<br><br>RESULTS: More than half of patients with DME (60.7%) and doctors (69.5%) identified long periods of waiting during the appointment as a challenge. Over 85% of physicians and 55% of patients identified the limitation on number of treatments covered by insurance plans as another main challenge. The main opportunities to improve patient care agreed upon by physicians and patients were the provision of financial assistance with drug/prescription costs and lifting of reimbursement restrictions (84.3-94.3%), less frequent appointments, longer time in between treatments without compromising vision (82.9-95.2%), and increasing predictability of the injection schedule (83.9-95.2%). Over 90% of doctors and patients agreed that more time for doctors to answer questions/concerns during each appointment is an important need to strengthen communication.<br><br>CONCLUSION: Lifting reimbursement limits, reducing appointments and extending the time between treatments without compromising vision, and increasing the time available to answer patient questions at each visit are key opportunities to improve patients' adherence and persistence for anti-VEGF therapy.}, }
@article {pmid40576882, year = {2025}, author = {Hikichi, T and Kurabe, H and Notoya, A and Oguro, Y and Hirano, M and Doi, Y}, title = {Short‑term outcomes of switching to faricimab for macular edema secondary to retinal vein occlusion.}, journal = {Japanese journal of ophthalmology}, volume = {69}, number = {6}, pages = {918-925}, pmid = {40576882}, issn = {1613-2246}, mesh = {Humans ; *Retinal Vein Occlusion/complications/diagnosis/drug therapy ; Retrospective Studies ; *Macular Edema/drug therapy/etiology/diagnosis ; Male ; Female ; Intravitreal Injections ; *Visual Acuity ; Tomography, Optical Coherence ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; Follow-Up Studies ; Middle Aged ; *Drug Substitution ; Treatment Outcome ; Fluorescein Angiography ; Time Factors ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Aged, 80 and over ; Macula Lutea/pathology ; Antibodies, Bispecific ; }, abstract = {PURPOSE: This study evaluated the anatomical and functional outcomes in patients with macular edema (ME) secondary to retinal vein occlusion (RVO) who were switched from conventional anti-vascular endothelial growth factor (VEGF) agents to faricimab.<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: This study included 42 eyes from 42 patients treated at Hikichi Eye Clinic between April and August 2024. All patients had relapsed ME despite prior treatment with aflibercept and were switched to intravitreal faricimab (6.0 mg). The primary endpoints included best-corrected visual acuity (BCVA), central foveal thickness (CFT), and intravitreal injection intervals over six months.<br><br>RESULTS: The mean (&#xb1; standard error) CFT significantly decreased from 356 &#xb1; 23 &#x3bc;m to 214 &#xb1; 3 &#x3bc;m at one month (p < 0.01) and remained stable at the final visit (205 &#xb1; 4 &#x3bc;m). Logarithm of the minimum angle of resolution (logMAR) BCVA improved from 0.16 &#xb1; 0.03 to 0.04 &#xb1; 0.03 at one month (p < 0.01) and remained at 0.02 &#xb1; 0.02 at the final visit. The mean injection interval was significantly extended from 12.3 &#xb1; 0.4 weeks to 16.2 &#xb1; 0.5 weeks (p < 0.01).<br><br>CONCLUSION: Faricimab improved anatomical and functional outcomes while extending treatment intervals in ME secondary to RVO. Further large-scale, prospective, and long-term follow-up studies are needed to confirm these findings.}, }
@article {pmid40577617, year = {2025}, author = {Hsu, J and Cappellani, F and Nguyen, MK and Momenaei, B and Regillo, CD and Xu, D and Garg, SJ and Kuriyan, AE and Chiang, A and Ho, AC}, title = {ATROPHY GROWTH RATES IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION COMPARED WITH FELLOW EYES WITH DRY AGE-RELATED MACULAR DEGENERATION.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {10}, pages = {1833-1841}, doi = {10.1097/IAE.0000000000004567}, pmid = {40577617}, issn = {1539-2864}, support = {//J. Arch McNamara, MD Fund for Retina Research and Education, Philadelphia, PA/ ; }, mesh = {Humans ; Retrospective Studies ; Male ; Female ; Aged ; *Wet Macular Degeneration/diagnosis/drug therapy/complications ; *Geographic Atrophy/diagnosis/drug therapy ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged, 80 and over ; Disease Progression ; Intravitreal Injections ; Fluorescein Angiography/methods ; Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Follow-Up Studies ; Atrophy ; Middle Aged ; Ranibizumab/administration &amp; dosage ; *Macula Lutea/pathology ; Fundus Oculi ; }, abstract = {PURPOSE: To study the natural history and anatomical characteristics of geographic atrophy in eyes with dry age-related macular degeneration (dAMD) compared with fellow eyes with macular atrophy and concurrent neovascular AMD (nAMD) treated with anti-vascular endothelial growth factor injections.<br><br>METHODS: This is a single-center, retrospective chart review. Data were recorded at two time points (#1 and #2) one year apart. Two independent graders reviewed the images to measure atrophy area and grade it based on the Consensus on Atrophy Meeting group criteria. Difference in atrophy area between the two time points was calculated. A square root transformation was also performed to report the change in atrophy progression.<br><br>RESULTS: Two hundred eight eyes of 104 patients were included: 104 eyes had dAMD and 104 fellow eyes had nAMD. The mean (SD) atrophy area was 14.05 (9.96) mm 2 in dAMD eyes and 14.14 (9.26) mm 2 in nAMD eyes (P = 0.95) at time point #1, and 16.92 (10.83) mm 2 in dAMD eyes and 17.35 (11.03) mm 2 in nAMD eyes (P = 0.78) at time point #2. The mean (SD) atrophy growth rate was 3.08 (2.52) mm 2 /year in the nAMD eyes and 2.77 (1.88) mm 2 /year in the dAMD eyes (P = 0.32). Using the square root transformation, the growth rates were 0.40 (0.24) mm/year in nAMD and 0.38 (0.22) mm/year in dAMD (P = 0.55).<br><br>CONCLUSION: Geographic atrophy in eyes with dAMD and macular atrophy in fellow eyes with nAMD exhibit similar growth rates, suggesting a high degree of concordance and potentially a similar mechanism of atrophy development and progression.}, }
@article {pmid40577635, year = {2025}, author = {Oka, A and Murakami, R and Machida, A and Hirata, Y and Miyagi, S and Kurihara, J and Oishi, A}, title = {PACHYCHOROID NEITHER PROMOTES NOR INHIBITS THE FORMATION OF FIBROSIS IN MACULAR NEOVASCULARIZATION.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {11}, pages = {2035-2041}, doi = {10.1097/IAE.0000000000004569}, pmid = {40577635}, issn = {1539-2864}, support = {no. 22K09793//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; Male ; Female ; Aged ; Fibrosis ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/therapeutic use/adverse effects/administration &amp; dosage ; Retrospective Studies ; Fluorescein Angiography/methods ; *Choroid/pathology ; Visual Acuity ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Retinal Neovascularization/drug therapy/diagnosis ; Middle Aged ; Intravitreal Injections ; Fundus Oculi ; Aged, 80 and over ; *Choroidal Neovascularization/drug therapy/diagnosis ; Ranibizumab ; *Macula Lutea/pathology ; }, abstract = {PURPOSE: Subretinal fibrosis is a major cause of vision loss during macular neovascularization (MNV) treatment. This study investigated the effect of the pachychoroid phenotype on subretinal fibrosis development after antivascular endothelial growth factor therapy for MNV.<br><br>METHODS: A total of 107 eyes from 107 patients (63 males, 44 females; mean age 72.9 &#xb1; 8.8 years) treated with antivascular endothelial growth factor therapy for MNV and followed for at least 4 years were included. Univariate and multivariate analyses identified factors associated with subretinal fibrosis at 4 years.<br><br>RESULTS: Subretinal fibrosis developed in 18 eyes (16.8%) after 4 years of therapy. Fibrosis occurred more frequently in eyes with type 2 MNV (44.4%) and subretinal hemorrhage (88.9%) (P = 0.026 and 0.001, respectively). The incidence of fibrosis did not differ between eyes with and without pachychoroid features (14.8% vs. 18.9%, P = 0.614). Logistic regression identified subretinal hemorrhage, type 2 MNV, and taller pigment epithelium detachment as significant factors (P = 0.0424, 0.0193, and 0.0149, respectively).<br><br>CONCLUSION: In addition to subretinal hemorrhage and type 2 MNV, taller pigment epithelium detachment was associated with subretinal fibrosis. The pachychoroid phenotype was neither a promoting nor protective factor for fibrosis.}, }
@article {pmid40577636, year = {2025}, author = {Kato, N and Haruta, M and Matsuo, Y and Dake, S and Kojima, Y and Arai, R and Sato, K and Furushima, K and Yoshida, S}, title = {COMPARISON OF OCULAR BLOOD FLOW CHANGES AT 30 MINUTES AFTER INTRAVITREAL INJECTION OF FARICIMAB, BROLUCIZUMAB, AND AFLIBERCEPT 2 mg FOR NEOVASCULAR AGE-RELATED MACULAR.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {11}, pages = {2042-2048}, doi = {10.1097/IAE.0000000000004561}, pmid = {40577636}, issn = {1539-2864}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Intravitreal Injections ; Retrospective Studies ; Male ; Female ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Regional Blood Flow/physiology/drug effects ; Aged, 80 and over ; *Choroid/blood supply ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Visual Acuity ; Fluorescein Angiography ; *Optic Disk/blood supply ; Tomography, Optical Coherence ; Blood Flow Velocity/physiology ; Time Factors ; Fundus Oculi ; Follow-Up Studies ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To investigate ocular blood flow before and 30 minutes postinjection of antivascular endothelial growth factor agents in eyes with neovascular age-related macular degeneration and to compare the reduction rates of ocular blood flow among three groups: intravitreal faricimab injections (faricimab-treated), intravitreal brolucizumab injections (brolucizumab-treated), and intravitreal aflibercept 2 mg injections (aflibercept-treated).<br><br>METHODS: This retrospective observational case series included 45 eyes of 45 Japanese patients with neovascular age-related macular degeneration treated with faricimab, brolucizumab, or aflibercept 2 mg. Ocular blood flow at the optic nerve head (ONH MV) and the choroid (choroid mean blur rate) was analyzed before and 30 minutes after injections using laser speckle flowgraphy.<br><br>RESULTS: The mean optic nerve head MV and choroid mean blur rate decreased significantly 30 minutes postinjection by 12.0% &#xb1; 15.3% and 9.7% &#xb1; 8.8% in the faricimab-treated group, 9.5% &#xb1; 7.9% and 18.2% &#xb1; 12.9% in the brolucizumab-treated group, and 10.4% &#xb1; 11.9% and 6.0% &#xb1; 7.7% in the aflibercept-treated group. There were no significant differences in the reduction rates of optic nerve head MV among the three groups. However, the brolucizumab-treated group showed a greater reduction in choroid mean blur rate than the aflibercept-treated group (faricimab vs. brolucizumab: P = 0.161; faricimab vs. aflibercept: P = 0.631; brolucizumab vs. aflibercept: P = 0.027).<br><br>CONCLUSION: Ocular blood flow significantly decreased 30 minutes postinjection in faricimab-treated, brolucizumab-treated, or aflibercept-treated eyes with neovascular age-related macular degeneration. Brolucizumab-treated eyes showed a significantly greater reduction in choroidal blood flow than aflibercept-treated eyes.}, }
@article {pmid40578594, year = {2025}, author = {Shen, W and Tan, Y and Luo, Z and Jin, K and Ye, J}, title = {Elucidating the genetic and metabolomic underpinnings of age-related macular degeneration through two-sample Mendelian randomization.}, journal = {Experimental eye research}, volume = {258}, number = {}, pages = {110491}, doi = {10.1016/j.exer.2025.110491}, pmid = {40578594}, issn = {1096-0007}, mesh = {Humans ; *Mendelian Randomization Analysis/methods ; Genome-Wide Association Study ; *Metabolomics/methods ; *Polymorphism, Single Nucleotide ; Aged ; *Wet Macular Degeneration/genetics/metabolism ; Male ; Female ; *Geographic Atrophy/genetics/metabolism ; *Macular Degeneration/genetics/metabolism ; Linkage Disequilibrium ; }, abstract = {Age-related macular degeneration (AMD), a chronic and progressive retinal disorder, is a leading cause of severe and irreversible visual impairment. The pathogenesis of AMD is multifactorial and intricate. Mendelian randomization (MR) serves as a popular approach of instrumental variable analysis to decipher the causality of associations. We applied a two-sample MR to assess the causal effects of 1400 serum metabolites and two subtypes of AMD (dry AMD and wet AMD) using the genome-wide association study statistics. We performed the inverse variance weighted method, weighted median algorithm, and sensitivity analyses including Cochran Q test, MR-Egger intercept test, MR-PRESSO, radial MR, leave-one-out examination, and Steiger test. Meanwhile, we utilized the linkage disequilibrium score regression analysis to consolidate the genetic correlation analysis. 18 identified metabolites for dry AMD and 16 for wet AMD were confirmed to have significant associations with the risk of dry AMD and wet AMD, respectively. Among these metabolites, 13 and 12 genetically established metabolites had prominent correlations after strict sensitivity assessments. 4 and 3 metabolites were identified prominent heritability for two subtypes of AMD, respectively. After excluding one metabolite which displayed shared genetic interrelation with wet AMD, our results demonstrates 4 identified serum metabolites are related to a reduced risk of dry AMD (N-acetyl-2-aminooctanoate, N-acetyl-L-glutamine, N-acetylphenylalanine, and N2,N5-diacetylornithine); 2 chemically known serum metabolites are linked with a decreased risk of wet AMD (pregnenetriol disulfate and N2-acetyl,N6,N6-dimethyllysine), respectively. The results manifested their potential protective roles in the development of AMD, underlines the distinct genetic inferences between metabolomics and AMD, and provide a novel ponder angle for clinical screening, preventive measures, and therapeutic strategy exploration of distinct subtypes of AMD.}, }
@article {pmid40580349, year = {2025}, author = {Nilsson, I and Senra, H and Baskaran, K and Mohlin, C and Macedo, AF}, title = {Perceived stress levels among patients treated for neovascular age-related macular degeneration with anti-VEGF injections.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {263}, number = {9}, pages = {2523-2531}, pmid = {40580349}, issn = {1435-702X}, mesh = {Humans ; Aged ; Male ; Female ; Intravitreal Injections ; Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/psychology/diagnosis ; *Stress, Psychological/psychology/etiology ; Surveys and Questionnaires ; Aged, 80 and over ; *Ranibizumab/administration &amp; dosage ; *Bevacizumab/administration &amp; dosage ; Tomography, Optical Coherence ; Follow-Up Studies ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Middle Aged ; }, abstract = {PURPOSE: The aim of this study was to assess perceived stress levels in patients with nAMD undergoing treatment with anti-VEGF injections, and to investigate psychosocial and visual factors that can be associated with perceived stress among these patients.<br><br>METHODS: We recruited 202 patients diagnosed with nAMD (mean age of 78 years) who had received three or more anti-VEGF injections and had been scheduled for further treatments. To measure perceived stress, participants completed the Perceived Stress Scale-10 (PSS10). For the associated factors, the participants also completed the National Eye Institute Visual Function Questionnaire-25 and Multidimensional Perceived Social Support. Participants completed the questionnaires at home before an upcoming treatment scheduled at the hospital. Best corrected visual acuity was measured at the hospital before the treatment. Factors associated with PSS10 scores were examined using multiple regression models.<br><br>RESULTS: Participants with near vision impairment perceived higher stress levels than those without near vision impairment (p&#x2009;=&#x2009;0.034). Younger age (&#x3b2; = -0.15, p&#x2009;=&#x2009;0.003), better visual acuity (&#x3b2; = -4.20, p&#x2009;=&#x2009;0.036), poorer perceived social support (&#x3b2; = -1.21, p&#x2009;<&#x2009;0.001), and poorer self-reported visual function (&#x3b2; = -0.16, p&#x2009;<&#x2009;0.001) were significantly associated with increased levels of perceived stress.<br><br>CONCLUSIONS: Our study highlighted factors potentially associated with increased perceived stress in nAMD patients undergoing anti-VEGF treatment. Self-reported visual function, in particular near-vision, and perceived social support are factors that can be addressed to reduce the levels of stress and risk of mental health disorders in this patient group.}, }
@article {pmid40580375, year = {2025}, author = {Tabano, D and Watane, A and Gale, R and Cox, O and Hill, SR and Longworth, L and Oluboyede, Y and Ahmed, A and Patel, NA}, title = {The Economic Burden of Anti-Vascular Endothelial Growth Factor on Patients and Caregivers in the UK, Europe, and North America.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {8}, pages = {1869-1892}, pmid = {40580375}, issn = {2193-8245}, abstract = {INTRODUCTION: Intravitreal (IVT) injections of anti-vascular endothelial growth factor (VEGF) agents are the standard of care for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). While demonstrated to be effective, these treatments potentially place a significant burden on patients owing to their cost and frequency of treatment visits required for administration. The objective of this study was to investigate the economic burden of treatment on patients with nAMD/DME and their informal caregivers in seven countries.<br><br>METHODS: Data were collected from patients and caregivers in the USA, UK, Canada, Italy, Spain, Germany, and France using a survey between September and December 2022. Each survey collected data to facilitate calculating economic burden, combining the total financial costs (i.e., direct costs to receive treatment) and productivity losses associated with attending treatment appointments over a 6-month period. Quality of life data were collected using validated instruments.<br><br>RESULTS: In total, 194 patients and 194 caregivers reported currently receiving (or caring for someone who receives) anti-VEGF treatment. Across all countries, the modal frequency of anti-VEGF treatment was every 4&#xa0;weeks, except for patients with DME (every 8&#xa0;weeks). The largest, mean 6-month economic burden on the pooled population of patients with nAMD/DME was reported in Italy (&#x20ac;1244) and on caregivers it was in the USA (&#x20ac;3069). Economic burden was lower for respondents receiving fewer anti-VEGF injections.<br><br>CONCLUSIONS: More durable therapies for nAMD/DME would reduce treatment burden and have a sizeable impact financially on patients with nAMD/DME and their caregivers.}, }
@article {pmid40580986, year = {2025}, author = {, }, title = {Global burden of vision impairment due to age-related macular degeneration, 1990-2021, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2021.}, journal = {The Lancet. Global health}, volume = {13}, number = {7}, pages = {e1175-e1190}, pmid = {40580986}, issn = {2214-109X}, mesh = {Humans ; *Macular Degeneration/epidemiology/complications ; *Global Burden of Disease/trends ; *Global Health/statistics &amp; numerical data ; Male ; Female ; Aged ; Disability-Adjusted Life Years ; Middle Aged ; Risk Factors ; Prevalence ; Forecasting ; *Vision Disorders/epidemiology/etiology ; Aged, 80 and over ; Quality-Adjusted Life Years ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a growing public health concern worldwide, as one of the leading causes of vision impairment. We aimed to estimate global, national, and region-specific prevalence and disability-adjusted life-years (DALYs) along with tobacco as a modifiable risk factor to aid public policy addressing AMD.<br><br>METHODS: Data on AMD were extracted from the Global Burden of Disease, Injuries, and Risk Factor Study 2021 database in 204 countries and territories, 1990-2021. Vision impairment was defined and categorised by severity as follows: moderate to severe vision loss (visual acuity from <6/18 to 3/60) and blindness (visual acuity <3/60 or a visual field <10 degrees around central fixation). The burden of vision impairment attributable to AMD was subsequently estimated. These estimates were further stratified by geographical region, age, year, sex, Healthcare Access and Quality (HAQ) Index, and Socio-demographic Index (SDI) levels. Additionally, the effect of tobacco use, a modifiable risk factor, on the burden of AMD was analysed, and projections of AMD burden were estimated through to 2050. These projections also included scenario modelling to assess the potential effects of tobacco elimination.<br><br>FINDINGS: Globally, the number of individuals with vision impairment due to AMD more than doubled, rising from 3&#xb7;64 million (95% uncertainty inverval [UI] 3&#xb7;04-4&#xb7;35) in 1990 to 8&#xb7;06 million (6&#xb7;71-9&#xb7;82) in 2021. Similarly, DALYs increased by 91% over the same period, from 0&#xb7;30 million (95% UI 0&#xb7;21-0&#xb7;42) to 0&#xb7;58 million (0&#xb7;40-0&#xb7;80). By contrast, age-standardised prevalence and DALY rates declined, with prevalence rates decreasing by 5&#xb7;53% (99&#xb7;50 per 100&#x2008;000 of the population [95% UI 83&#xb7;16-118&#xb7;04] in 1990 to 94&#xb7;00 [78&#xb7;32-114&#xb7;42] in 2021) and DALY rates dropping by 19&#xb7;09% (8&#xb7;38 [5&#xb7;70-11&#xb7;53] to 6&#xb7;78 [4&#xb7;70-9&#xb7;32]). These rates showed a consistent decrease in higher SDI quintiles, reflecting the negative correlation between HAQ Index and AMD burden. A general downward trend was observed from 1990 to 2021, with the largest age-standardised reduction occurring in the low-middle SDI quintile. The global contribution of tobacco to age-standardised DALYs decreased by 20%, declining from 12&#xb7;45% (95% UI 7&#xb7;73-17&#xb7;37) in 1990 to 9&#xb7;96% (6&#xb7;12-14&#xb7;06) in 2021. By 2050, the number of individuals affected by AMD is projected to increase from 3&#xb7;40 million males (95% UI 2&#xb7;81-4&#xb7;17) in 2021 to 9&#xb7;02 million (5&#xb7;72-14&#xb7;20) and from 4&#xb7;66 million females (3&#xb7;88-5&#xb7;65) to 12&#xb7;32 million (8&#xb7;88-17&#xb7;08). Eliminating tobacco use could reduce these numbers to 8&#xb7;17 million males (5&#xb7;59-11&#xb7;92) and 11&#xb7;15 million females (8&#xb7;58-14&#xb7;48) in 2050.<br><br>INTERPRETATION: While the total prevalence and DALYs due to AMD have steadily increased from 1990 to 2021, age-standardised prevalence and DALY rates have declined, probably reflecting the effect of population ageing and growth. The consistent decrease in age-standardised rates with higher SDI levels highlights the crucial role of health-care resources and public policies in mitigating AMD-related vision impairment. The downward trend observed from 1990 to 2021 might also be partially attributed to the reduced effect of tobacco as a modifiable risk factor, with declines in tobacco use seen globally and across all SDI quintiles. The burden of vision impairment due to AMD is projected to increase to about 21&#xb7;34 million in 2050. However, effective tobacco regulation has the potential to substantially reduce AMD-related vision impairment, particularly in lower SDI quintiles where health-care resources are limited.<br><br>FUNDING: Gates Foundation.}, }
@article {pmid40581140, year = {2025}, author = {Hammer, M and Oertel, J and Alderzy, H and Tarhan, M and Meller, D and Curcio, CA}, title = {Fundus autofluorescence intensity, lifetime, and spectral imaging in age-related macular degeneration.}, journal = {Experimental eye research}, volume = {258}, number = {}, pages = {110500}, doi = {10.1016/j.exer.2025.110500}, pmid = {40581140}, issn = {1096-0007}, mesh = {Humans ; *Macular Degeneration/diagnosis ; *Fluorescein Angiography/methods ; *Optical Imaging/methods ; Fundus Oculi ; Retinal Pigment Epithelium/pathology ; }, abstract = {Fundus autofluorescence (FAF) imaging is a well-established retinal imaging technique that is widely used in the diagnostics of age-related macular degeneration (AMD). It facilitates the classification of distinct autofluorescence patterns, which may be predictive of AMD progression, the quantification of atrophic zones and their development over time and serves as a clinical endpoint in various studies. However, beyond autofluorescence intensity, emission spectra and fluorescence lifetime can be utilized to further investigate specific fluorophores, their changes in association with AMD, and their potential prognostic value in disease progression and therapy monitoring. In this review, we present the current state of spectrally and temporally resolved retinal FAF imaging in AMD. We explain the underlying principles, review the applied techniques, propose possible fluorophores contributing to FAF, summarize results from clinical studies as well as from histology and investigations in both in vivo and in vitro AMD models, and discuss the limitations of current techniques along with perspectives for technical development and clinical application.}, }
@article {pmid40581196, year = {2025}, author = {Icoz, SGG and Usta, SA and Icoz, M}, title = {Post-phacoemulsification examination of intraocular pathologies that could not bedetected by fundus biomicroscopy or OCT in eyes with dense cataract: trying to avoid intra- and post-operative complications.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {54}, number = {}, pages = {104696}, doi = {10.1016/j.pdpdt.2025.104696}, pmid = {40581196}, issn = {1873-1597}, mesh = {Humans ; Female ; Aged ; Male ; Middle Aged ; *Phacoemulsification/adverse effects/methods ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Aged, 80 and over ; *Postoperative Complications/prevention &amp; control ; *Cataract/complications ; Adult ; Lens Implantation, Intraocular ; Risk Factors ; }, abstract = {PURPOSE: To investigate postoperative intraocular pathologies in eyes with dense cataracts that preclude fundus evaluation.<br><br>DESIGN: Retrospective study.<br><br>METHODS: This study was conducted on 88 eyes from 88 patients.All participants underwent uncomplicated phacoemulsification and intraocular lens implantation due to dense cataracts that prevented fundus evaluation in biomicroscopic dilated fundus examination. In the postoperative first-month follow-up, intraocular pathologies were assessed via dilated biomicroscopic fundus examination, color fundus photography, and optical coherence tomography.Potential risk factors were identified using univariate and multivariate regression analyses.<br><br>RESULTS: The mean age of the patients was 69 &#xb1; 11 (range:28-92) years, with 49 being female. Intraocular pathologies were detected in 33 patients (37 %).The most frequently observed pathologies were diabetic retinopathy (n = 11, 13 %), followed by age-related macular degeneration (n = 7, 8 %), epiretinal membrane (n = 6, 7 %), full-thickness or lamellar macular holes (n = 3, 3 %), photoreceptor damage (n = 2, 2 %), glaucomatous changes (n = 2, 2 %), myopic degeneration (n = 1, 1 %), and vitreomacular traction (n = 1, 1 %).Both univariate and multivariate regression analyses revealed diabetes mellitus and the presence of pathology in the fellow eye as significant risk factors for postoperative intraocular pathologies in patients with dense cataracts (p < 0.05 and p < 0.001,respectively).<br><br>CONCLUSION: A considerable proportion of intraocular pathologies were detected postoperatively in eyes with dense cataracts.Diabetes mellitus and the presence of pathology in the fellow eye were found to be significant risk factors for postoperative intraocular pathologies in both univariate and multivariate regression analyses.These findings provide valuable evidence for clinicians and patients regarding postoperative intraocular pathologies in eyes with mature cataracts.}, }
@article {pmid40581633, year = {2025}, author = {Salkar, A and Palanivel, V and Basavarajappa, D and Mirzaei, M and Schulz, A and Yan, P and Gupta, V and Graham, S and You, Y}, title = {Glial and immune dysregulation in glaucoma independent of retinal ganglion cell loss: a human post-mortem histopathology study.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {141}, pmid = {40581633}, issn = {2051-5960}, abstract = {UNLABELLED: Glaucoma is characterized by progressive retinal ganglion cell (RGC) loss and optic nerve head (ONH) changes, but the roles of glial activation and immune responses remain unclear. This study examines gliosis, microglial diversity, and inflammation in postmortem retinal tissues. Postmortem retinal and ONH samples (total n = 50) from patients with open-angle glaucoma (G, n = 18) were compared with those from age-matched controls (n = 32), including healthy individuals (Ctrl) and disease controls (patients with early age-related macular degeneration [AMD] and diabetes mellitus [DM]). Immunostaining was performed to assess glial activation, blood–retinal barrier (BRB) integrity, and immune infiltration, which were quantified via ImageJ and Zen lite. Generalized estimating equations (GEEs) with Bonferroni correction accounted for intrapatient variability. G retinae presented significant RGC loss accompanied by widespread gliosis, with activation of microglia (Iba1), astrocytes (GFAP), and Müller cells (Vimentin). This gliotic response differed across conditions, with astrocyte activation being more prominent in DM and microglial activation predominating in AMD. In glaucoma, gliosis is evident even in early-stage disease, regardless of the severity of retinal ganglion cell (RGC) loss or structural changes in the ONH. Furthermore, microglia showed a marked shift in morphological diversity, transitioning to hyperramified, bushy, and amoeboid forms, along with an increased distribution of activation markers such as CD45, CD11b, and CD163. Additionally, biochemical evidence of alterations to the BRB integrity, characterized by reduced tight junction protein expression, facilitates immune cell infiltration, as indicated by the minimal and inconsistent presence of CD3/CD4+ T cells. Gliosis persisted regardless of RGC loss severity, suggesting that gliosis progresses independently of neuronal degeneration. Unlike AMD and DM, where specific glial subtypes dominate, glaucoma exhibits widespread gliosis. Microglial heterogeneity indicates the existence of a continuum of functional states. Furthermore, dysregulation of the BRB, inconsistent immune infiltration, and multimodal microglial activation indicate that the inflammatory response in glaucoma patients is driven primarily by resident microglia, with limited interactions with infiltrating immune cells. These findings highlight the need for further research into glial modulation as a potential therapeutic strategy.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-025-02066-0.}, }
@article {pmid40582342, year = {2025}, author = {Zur, D and Wright, DM and Shahar Gonen, M and Shor, R and Wen, Q and Benyamini, G and Havilio, M and Ben-Nun, M and Look, S and Dor, O and Chakravarthy, U and Loewenstein, A and Peto, T}, title = {The British-Israeli Project for Algorithm-Based Management of Age-Related Macular Degeneration: Deep Learning Integration for Real-World Data Management and Analysis.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {248}, number = {4}, pages = {294-307}, pmid = {40582342}, issn = {1423-0267}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Angiogenesis Inhibitors/administration &amp; dosage ; *Deep Learning ; *Disease Management ; *Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; Intravitreal Injections ; Israel/epidemiology ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; United Kingdom/epidemiology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy/epidemiology ; Feasibility Studies ; }, abstract = {INTRODUCTION: The aim of this study was to describe the development of an integrative dataset, combining clinical and optical coherence tomography (OCT) imaging data by applying a deep learning (DL) algorithm for automated, objective, and comprehensive quantification of OCT scans in two large real-world datasets of eyes with neovascular age-related macular degeneration (nAMD). We further report baseline characteristics of the study population, focusing on demographics, clinical parameters, and quantitative retinal morphological features.<br><br>METHODS: This retrospective study analyzed data from 5,207 eyes of 4,265 nAMD patients treated at two centers in the UK and Israel. Longitudinal clinical data and OCT scans were analyzed using a DL algorithm (NOA&#x2122;, Notal Ltd.) to quantify retinal fluid volumes and morphological features. Baseline characteristics were compared between the cohorts.<br><br>RESULTS: The dataset included 134,340 visual acuity (VA) measurements, 79,457 OCT scans, and 73,218 anti-vascular endothelial growth factor injections. Median follow-up was 4.54 years (UK) and 3.12 years (Israel). Baseline VA differed significantly between cohorts due to varying treatment criteria. Fluid distribution patterns were similar, with most eyes showing combined intraretinal and subretinal fluid. Age-related trends in fluid volumes were observed. Weak correlations were found between baseline OCT measurements and VA.<br><br>CONCLUSION: This study demonstrates the feasibility of integrating large-scale clinical and imaging data for automated analysis in nAMD. The comprehensive baseline characterization provides insights into real-world presentations and lays the groundwork for enabling personalized decision-making and optimizing outcomes based on individual patient profiles and fluid distribution patterns.}, }
@article {pmid40584705, year = {2025}, author = {Elvira, JC and Devesa, P and Elvira-Giner, B and Tañá-Sanz, P and Orts-Vila, P and Tañá-Rivero, P}, title = {Visual outcomes with a non-diffractive enhanced depth-of-focus IOL in patients with age-related macular degeneration.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1505401}, pmid = {40584705}, issn = {2296-858X}, abstract = {PURPOSE: To evaluate visual function in eyes with age-related macular degeneration (AMD) implanted with a non-diffractive enhanced depth-of-focus (EDOF) intraocular lens (IOL) after cataract surgery.<br><br>DESIGN: Prospective, observational, non-randomized clinical study.<br><br>METHODS: Twenty-two eyes from 22 patients diagnosed with AMD and cataracts were submitted to standard cataract surgery with a non-diffractive EDOF IOL implantation (AcrySof IQ Vivity). We measured monocular uncorrected and best-corrected-distance visual acuity (UDVA and CDVA), uncorrected- and distance-corrected-intermediate visual acuity (UIVA and DCIVA), uncorrected- and distance-corrected-near visual acuity (UNVA and DCNVA), manifest refractive spherical equivalent (MRSE) and cylinder, monocular defocus curve and patient-reported outcome questionnaires (Catquest-9SF and NEI VFQ-25). Follow-up visits were carried out at 1, 3 and 6 months post-surgery.<br><br>RESULTS: At 6 months post-surgery all eyes were within &#xb1; 0.50 D with a mean MRSE of -0.19 &#xb1; 0.20 D, 95.45% had a refractive cylinder of &#x2264; 0.50 D with a mean cylinder of -0.24 &#xb1; 0.27 D. The mean values of postoperative monocular CDVA, DCIVA, and DCNVA were 0.02 &#xb1; 0.08, 0.16 &#xb1; 0.11, and 0.26 &#xb1; 0.15 logMAR, respectively. The defocus curve showed good visual acuity at distance and intermediate with a depth-of-focus of about 1.60 D. A total of 81.82% of patients did not report any difficulty with their vision in their everyday-life and 86.36% reported being quite satisfied to very satisfied with their current vision. The NEI VFQ-25 showed that all values improved significantly (p < 0.05) after the surgery in the different parameters analyzed except for ocular pain (p = 0.390) and color vision (p = 0.333).<br><br>CONCLUSION: The use of a non-diffractive EDOF IOL in AMD eyes with cataracts is a safe and effective surgical approach for visually correcting aphakia, providing good visual acuity at far and intermediate distances. Our outcomes support the use of non-diffractive EDOF IOLs in patients with AMD diagnosed with cataracts aiming to obtain spectacle-independence at far and intermediate distances.}, }
@article {pmid40584817, year = {2025}, author = {Wang, W and Wang, N and Zhao, X and Su, X and Liu, Z}, title = {Recent advancements in polymer science for retinal diseases: New frontiers in drug delivery systems.}, journal = {APL bioengineering}, volume = {9}, number = {2}, pages = {020902}, pmid = {40584817}, issn = {2473-2877}, abstract = {Retinal diseases, such as age-related macular degeneration and diabetic macular edema, are significant contributors to vision loss. While injection of anti-vascular endothelial growth factors is the current gold standard treatment, their invasive nature reduces patient compliance and treatment outcomes and increases the risk of complications. In this review, we explore the recent advancements in drug delivery systems designed to overcome ocular barriers to effectively deliver drugs to the retina. We examine advancements in intravitreal injections, such as novel formulations, therapeutic molecules, and sustained-release implants. Moreover, we discuss innovations in noninvasive strategies, such as topical delivery systems incorporating cell-penetrating peptides, solid lipid nanoparticles, dendrimers, and nano-micelles. These technologies aim to enhance drug penetration, stability, and bioavailability. Although preclinical and clinical trials have yielded promising results, challenges remain in ensuring long-term safety and efficacy. This review highlights future research directions to optimize these approaches and develop more effective, patient-friendly therapies for retinal diseases.}, }
@article {pmid40585168, year = {2025}, author = {Seddon, JM and De, D and Rosner, B}, title = {Quantifying Effects of Lifestyle Changes on Progression to Advanced Age-Related Macular Degeneration in High Genetic Risk Individuals.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {40585168}, support = {R01 EY011309/EY/NEI NIH HHS/United States ; R01 EY022445/EY/NEI NIH HHS/United States ; R01 EY028602/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE: We examined the extent to which adopting healthy lifestyle behaviors could offset high genetic risk for progression to advanced age-related macular degeneration (AMD), to address concerns of family members of affected patients.<br><br>DESIGN: Prospective longitudinal study.<br><br>PARTICIPANTS: Eyes with early or intermediate AMD at baseline were defined based on the Age-Related Eye Disease Study severity scale. High genetic risk was defined as the third tertile of a genetic risk score for progression, adjusted for age, race and sex.<br><br>METHODS: Information on lifestyle behaviors was obtained from baseline risk and food frequency questionnaires. Risk-inducing and health-promoting lifestyle profiles were defined based on dichotomous categorizations of smoking, body-mass index (BMI), and dietary caloric intake, green leafy vegetables and fish, in never and ever smokers. Cox proportional hazard ratios (HRs), relative risks (RRs) and population attributable risks (PARs) were calculated, adjusting for inter-eye correlation, demographic factors, macular status and family history.<br><br>MAIN OUTCOME MEASURES: Progression to advanced AMD (AAMD) and subtypes geographic atrophy (GA) and neovascular (NV), confirmed at 2 consecutive visits over 5 years of follow-up.<br><br>RESULTS: Among 898 high genetic risk eyes, 207 eyes progressed to AAMD (23%). Among never smokers, a high risk-inducing lifestyle profile conferred a 3-fold increased incidence of AAMD, compared to an ideal health-promoting lifestyle profile [HR = 3.3 (CI 1.8, 6.4), P <0.001]. In ever smokers, a risk-inducing profile was independently associated with a 5-fold increased incidence of AAMD [HR = 5.3 (CI 2.3,11.9), P <0.001]. Stronger effects of these lifestyle behaviors were seen for GA compared to NV. Estimated PARs suggested adopting an ideal health-promoting profile could prevent 56% of incident AAMD in never smokers and 60% in ever smokers.<br><br>CONCLUSION: Unhealthy behaviors increased incidence of AAMD by 3 to 5-fold among a highly genetically susceptible population, and 56-60% of AAMD incidence was attributed to the modifiable factors of smoking, high BMI, high caloric intake and low intake of foods rich in lutein-zeaxanthin and omega-3 fatty acids. These results underscore the importance of lifestyle interventions even in high genetic risk populations, such as relatives of affected patients, to reduce progression from early and intermediate AMD to advanced vision-threatening stages.}, }
@article {pmid40587704, year = {2025}, author = {Polat Gültekin, B and Çomçali, S and Şahin, E}, title = {Assessment of inflammation levels through the modified systemic inflammation score in patients with nonneovascular and neovascular age-related macular degeneration.}, journal = {Medicine}, volume = {104}, number = {26}, pages = {e43047}, pmid = {40587704}, issn = {1536-5964}, mesh = {Humans ; Male ; Female ; Aged ; *Inflammation/blood/diagnosis ; *Macular Degeneration/blood/complications ; Severity of Illness Index ; Middle Aged ; Aged, 80 and over ; Serum Albumin/analysis ; *Wet Macular Degeneration ; Body Mass Index ; }, abstract = {This study assesses the inflammation levels through the modified systemic inflammation score (mSIS) in patients with nonneovascular and neovascular age-related macular degeneration (AMD). A total of 90 participants were categorized into 3 groups: a control group, individuals with nonneovascular AMD under follow-up, and individuals with neovascular AMD who had not yet started injection treatment. Demographic and clinical parameters, including body mass index, were analyzed. The mSIS, based on serum albumin levels and the lymphocyte-to-monocyte ratio, was used to determine the level of systemic inflammation. There were no significant differences between the groups in terms of age (P = .08) or gender (P = .06). Regarding body mass index, no significant differences were observed between the groups (P = .06). When comparing mSIS scores between the groups, no significant differences were found for mSIS scores 0 and 1 across the groups. However, for mSIS 2, the proportion of participants with an mSIS score of 2 was significantly higher in the neovascular AMD group compared with the control group (P = .01). These findings suggest that mSIS may be a valuable tool for assessing systemic inflammation in AMD. The higher mSIS scores in the neovascular AMD group may indicate that disease severity is associated with increased inflammation. Further large-scale studies are needed to confirm the utility and clinical relevance.}, }
@article {pmid40588359, year = {2025}, author = {Weatherby, TJM and Boyle, M and Madhusudhan, S}, title = {Charles Bonnet syndrome in adults with inherited retinal disease: prevalence and patient perspectives.}, journal = {BMJ open ophthalmology}, volume = {10}, number = {1}, pages = {}, pmid = {40588359}, issn = {2397-3269}, mesh = {Humans ; Female ; Male ; Prevalence ; Adult ; Cross-Sectional Studies ; Middle Aged ; Surveys and Questionnaires ; *Charles Bonnet Syndrome/epidemiology/psychology/etiology/diagnosis ; Prospective Studies ; *Retinal Diseases/epidemiology/complications/diagnosis ; Aged ; Visual Acuity ; United Kingdom/epidemiology ; Young Adult ; *Hallucinations/epidemiology/etiology ; }, abstract = {OBJECTIVE: To assess the prevalence of symptoms associated with Charles-Bonnet syndrome (CBS) in adult patients with inherited retinal disease (IRD) and explore patient perspectives and need for support.<br><br>METHODS AND ANALYSIS: This was a prospective single-centre cross-sectional service evaluation and improvement project that involved adult patients with a clinical diagnosis of IRD under the care of the specialist IRD service at a tertiary NHS healthcare provider in the UK. Information was gathered from a survey questionnaire completed by participants remotely or at a hospital appointment and electronic patient records.<br><br>RESULTS: There were 103 surveys returned of which 94 were suitable for inclusion in the analysis. Visual hallucinations were reported by 18.6% of patients overall. Patients with visual acuity worse than 0.3 logMAR made up 76% of those reporting CBS symptoms.Of the patients who experienced visual hallucinations, 59% reported that their visual hallucinations had no effect on them, while 29% reported a negative effect, with 12% not commenting; only 12% said that they require further support.<br><br>CONCLUSION: CBS symptoms were reported by almost one in six patients in our IRD practice.Only a small proportion of patients included in this survey felt that they required additional support, but they did express that being informed early on of an explanation for their visual hallucinations was helpful.The limitations of our study are the small number of patients included in the survey, the lack of external validation of the questionnaire used, the risk of selection bias and the two different methods/phases of data collection used.}, }
@article {pmid40588392, year = {2025}, author = {Lin, C and Jivraj, S}, title = {Are diabetes and blood sugar control associated with the diagnosis of eye diseases? An English prospective observational study of glaucoma, diabetic eye disease, macular degeneration and cataract diagnosis trajectories in older age.}, journal = {BMJ open}, volume = {15}, number = {6}, pages = {e091816}, pmid = {40588392}, issn = {2044-6055}, mesh = {Humans ; Female ; Male ; Aged ; Prospective Studies ; England/epidemiology ; *Cataract/epidemiology/diagnosis ; *Glaucoma/epidemiology/diagnosis ; *Macular Degeneration/epidemiology/diagnosis ; Risk Factors ; *Diabetic Retinopathy/epidemiology/diagnosis ; Middle Aged ; Glycated Hemoglobin/analysis ; Blood Glucose ; Aged, 80 and over ; *Glycemic Control ; *Diabetes Mellitus/epidemiology/blood ; Logistic Models ; Longitudinal Studies ; }, abstract = {BACKGROUND: The growing global burden of diabetes suggests a currently unrealised growth in prevalence of eye disease. This prospective observational study addresses gaps in evidence of blood sugar control as a risk factor for the diagnosis of glaucoma, diabetic eye disease, macular degeneration and cataract using waves 2-9 (2004-2019) of the English Longitudinal Study of Ageing.<br><br>METHODS: Logistic regression modelling is used to predict the probability of self-reported diagnosis of four eye conditions separately over a 14-year period in a community-dwelling sample in England. Analysis of approximately 29&#x2009;000 person observations over eight study waves from around 5600 participants for each eye disease is conducted with an average of 5.7 waves per participant. Participants' baseline blood sugar control is categorised as non-diabetic (diabetes not previously diagnosed and glycated haemoglobin (HbA1c)<6.5), controlled (diabetes previously diagnosed and HbA1c<6.5), uncontrolled (diabetes previously diagnosed and HbA1c&#x2265;6.5) and undiagnosed (diabetes not previously diagnosed and HbA1c&#x2265;6.5). Controls at baseline for age, sex, physical activity level, body mass index and smoking status are included in the regression analysis.<br><br>RESULTS: The mean age of the sample is 66 and 53% are female. The main finding from this study is that older adults in England who are controlling a diabetes diagnosis have a lower probability of developing glaucoma, diabetic eye disease or macular degeneration compared with those either without a diabetes diagnosis or with uncontrolled diabetes. Compared with those with controlled diabetes, the adjusted odds of developing glaucoma was 1.29 times higher (95%&#x2009;CI 1.01 to 1.65) among those not diabetic; the adjusted odds of developing diabetic eye disease was 1.20 times higher (95%&#x2009;CI 1.00 to 1.45) among those with uncontrolled diabetes; and the adjusted odds of developing macular degeneration was 1.38 times higher (95%&#x2009;CI 1.04 to 1.82) among those with undiagnosed diabetes. There was no statistically significant difference in the probability of developing cataracts by category of blood sugar control.<br><br>CONCLUSION: This study illustrates the importance of blood sugar control in the development of eye diseases and therefore supports more regular screening measures for eye disease in older age among groups at risk of diabetes.}, }
@article {pmid40588681, year = {2025}, author = {Shu, Y and Li, Z and Zong, T and Mu, T and Zhou, H and Yang, Q and Wu, M and Liu, Y and Xie, T and Tan, C and Zhuang, M and Wang, X and Yao, Y}, title = {MiR-21-5p promotes RPE cell necroptosis by targeting Peli1 in a rat model of AMD.}, journal = {In vitro cellular &amp; developmental biology. Animal}, volume = {61}, number = {7}, pages = {801-815}, pmid = {40588681}, issn = {1543-706X}, support = {2020-THRCTD-1//Wuxi Taihu Lake Talent Plan, Supports for Leading Talents in Medical and Health Profession/ ; HRC-DJ-1//Wuxi Taihu Lake Talent Plan, Supports for Leading Talents in Medical and Health Profession/ ; BJ2023001//Top Talent Support Program for young and middle-aged people of Wuxi Health Committee/ ; HB2023014//Top Talent Support Program for young and middle-aged people of Wuxi Health Committee/ ; WMCG202347//General Program of Wuxi Medical Center, Nanjing Medical University/ ; WMCG202345//General Program of Wuxi Medical Center, Nanjing Medical University/ ; ZDXK2021001//Medial Key Discipline Program of Wuxi Health Commission/ ; NMUB20230240//The Science and Technology Development Fund Project of Nanjing Medical University/ ; }, mesh = {Animals ; *MicroRNAs/genetics/metabolism ; *Retinal Pigment Epithelium/pathology/metabolism ; Disease Models, Animal ; *Necroptosis/genetics/drug effects ; *Macular Degeneration/genetics/pathology ; Rats ; Male ; Rats, Sprague-Dawley ; Iodates ; Humans ; }, abstract = {Nonexudative age-related macular degeneration (dry AMD) is characterized by the progressive degeneration of retinal pigment epithelial (RPE) cells and photoreceptors, resulting in central vision loss. The disease is primarily marked by the accumulation of drusen and RPE atrophy. Given the emerging role of miR-21-5p in various ocular diseases, including diabetic retinopathy, glaucoma, pterygium, and choroidal neovascularization, we hypothesized that miR-21-5p may also impact RPE cell integrity in AMD. To test this hypothesis, we employed a rat model of dry AMD induced by sodium iodate (NaIO3) and evaluated the effects of miR-21-5p modulation via intravitreal injections of miR-21-5p agomir or antagomir. Comprehensive assessments were performed using optical coherence tomography (OCT), fundus imaging, histopathology, and biochemical markers. Our results demonstrated an upregulation of miR-21-5p in response to NaIO3 treatment. Administration of miR-21-5p agomir exacerbated RPE damage, while pretreatment with miR-21-5p antagomir mitigated these detrimental effects. Furthermore, in vitro experiments revealed that miR-21-5p regulates necroptosis in CoCl2-treated RPE cells by targeting Pellino1 (Peli1) via its 3' untranslated region, thereby inhibiting Peli1 expression. Overexpression of Peli1 effectively counteracted the necroptotic effects induced by CoCl2. These findings highlight the potential of miR-21-5p as a therapeutic target in dry AMD, expanding our understanding of miRNA-mediated regulation of RPE cells and suggesting new avenues for treatment strategies.}, }
@article {pmid40591046, year = {2025}, author = {Cukurova, F and Izgi, B and Cebeci, Z and Kir, N}, title = {Long-term observational data on neovascular age-related macular degeneration: a 10-year follow-up study.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {273}, pmid = {40591046}, issn = {1573-2630}, mesh = {Humans ; Male ; Follow-Up Studies ; Female ; *Visual Acuity ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Intravitreal Injections ; Tomography, Optical Coherence/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retrospective Studies ; Time Factors ; Middle Aged ; *Ranibizumab/administration &amp; dosage ; Fluorescein Angiography/methods ; Fundus Oculi ; *Bevacizumab/administration &amp; dosage ; Aged, 80 and over ; Treatment Outcome ; *Macula Lutea/pathology ; }, abstract = {AIM: To report real-life data of eyes with neovascular age-related macular degeneration (nAMD) treated with vascular endothelial growth factor (VEGF) inhibitors for an average of 10 years.<br><br>METHODS: Anti-VEGF na&#xef;ve eyes with nAMD and had at least 7-year follow-up at a tertiary center were evaluated. The primary outcome was a change in best-corrected visual acuity (BCVA) at 10&#xa0;years; secondary outcomes included anatomical outcomes, number of injections, and examinations.<br><br>RESULTS: The study included 102 eyes of 82 patients, with a mean initial age of 69.2&#x2009;&#xb1;&#x2009;9.7&#xa0;years. The average follow-up duration was 116.19&#x2009;&#xb1;&#x2009;24.98&#xa0;months, and the mean number of injections was 37.42&#x2009;&#xb1;&#x2009;15.81. Initial mean BCVA was 59.0&#x2009;&#xb1;&#x2009;18.3 letters, increasing to 70.55&#x2009;&#xb1;&#x2009;12.72 in the first year, then gradually declining to 60.44&#x2009;&#xb1;&#x2009;17.55 by the tenth year. Patients had an average of 6.13&#x2009;&#xb1;&#x2009;1.72 exams in the first year and 4.61&#x2009;&#xb1;&#x2009;2.60 in the last year, with 6.02&#x2009;&#xb1;&#x2009;1.70 injections in the first year and 3.18&#x2009;&#xb1;&#x2009;2.17 in the tenth year. Patients were classified as increasing, decreasing, or stable based on changes in VA by 2 lines or 10 letters. Significant variables among the groups included age (p&#x2009;=&#x2009;0.018), baseline BCVA (p&#x2009;=&#x2009;0.001), prior photodynamic therapy (PDT) (p&#x2009;=&#x2009;0.025), and retinal hemorrhage due to macular neovascularization (MNV) (p&#x2009;=&#x2009;0.049).<br><br>CONCLUSION: Eyes with nAMD maintained their initial BCVA after treatment with VEGF inhibitors for 10&#xa0;years. With regular and prompt treatment, functional vision can be achieved over a long period of time in nAMD.}, }
@article {pmid40591387, year = {2025}, author = {Fursova, AZ and Nikulich, IF and Vasilyeva, MA and Derbeneva, AS and Karlash, YA}, title = {[New options determining the success of treatment for neovascular age-related macular degeneration].}, journal = {Vestnik oftalmologii}, volume = {141}, number = {3}, pages = {71-78}, doi = {10.17116/oftalma202514103171}, pmid = {40591387}, issn = {0042-465X}, mesh = {Humans ; Angiogenesis Inhibitors/administration &amp; dosage ; Dose-Response Relationship, Drug ; Intravitreal Injections/methods ; *Macular Degeneration/drug therapy/diagnosis ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; Treatment Outcome ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; }, abstract = {Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that can lead to severe and irreversible vision loss despite the availability of effective anti-VEGF agents. One of the potential causes of suboptimal treatment outcomes in nAMD is undertreatment, which may result from the need for frequent injections and follow-up visits, limitations in public healthcare funding, and challenges in achieving sustained and long-term control of disease activity (DA). Aflibercept 8 mg is a novel formulation with a higher concentration and improved molecular stability, enabling a fourfold increase in the molar dose of the active substance delivered to the vitreous body. The phase III PULSAR trial, a 96-week randomized, double-masked, active-controlled study, evaluated the efficacy and safety of 8 mg aflibercept compared with the standard 2 mg dose in treatment-naïve patients with nAMD. Participants were randomized 1:1:1 into three groups: aflibercept 2 mg every 8 weeks (2q8), 8 mg every 12 weeks (8q12), or 8 mg every 16 weeks (8q16) after three initial monthly loading doses. The study demonstrated the benefits of the 8 mg dose in extending interinjection intervals. By week 96, 88% of patients achieved an interval of ≥12 weeks, 71% ≥16 weeks, and 47% ≥20 weeks; in the 8q16 group, 53% of patients reached an interval of ≥20 weeks and 31% - 24 weeks. Over the 2-year period, patients in the 8q16 group received approximately 8 injections, compared to around 13 in the 2q8 group, with comparable anatomical and functional outcomes and no additional safety concerns. Given the proven effectiveness in improving best-corrected visual acuity (BCVA), superior outcomes in resolving intra- and/or subretinal fluid (IRF/SRF), and reduced treatment burden, it appears optimal to broadly transition patients already receiving aflibercept 2 mg to the higher molar concentration (aflibercept 8 mg) regardless of treatment phase or the interinjection interval. This approach aims to achieve a longer anti-VEGF effect duration and sustained DA control with the fewest possible injections.}, }
@article {pmid40591950, year = {2025}, author = {Ferro Desideri, L and Anguita, R and Sacconi, R and Beretta, F and Corradetti, G and Feo, A and Dobovsek, D and Parravano, M and Capuano, V and Souied, E and Sarraf, D and Zinkernagel, M and Querques, G}, title = {UNILATERAL RETICULAR PSEUDODRUSEN: Clinical Features and Potential Protective Factors.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {11}, pages = {2049-2056}, doi = {10.1097/IAE.0000000000004575}, pmid = {40591950}, issn = {1539-2864}, mesh = {Humans ; Retrospective Studies ; *Retinal Drusen/diagnosis ; Male ; Female ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Aged, 80 and over ; *Choroid/blood supply/pathology ; Aged ; Fundus Oculi ; *Visual Acuity ; Multimodal Imaging ; Protective Factors ; }, abstract = {PURPOSE: To describe the demographic and clinical data of patients with rare unilateral reticular pseudodrusen (RPD) presentation and investigate features that may play a protective role against their formation.<br><br>METHODS: This retrospective, multicenter case series included patients with unilateral RPD from multiple tertiary care centers. Demographic, longitudinal clinical, and multimodal imaging (MMI) data were collected and compared between the study eye showing the presence of RPD and the fellow eye. Central macular thickness, subfoveal choroidal thickness, and choroidal vascular index were measured.<br><br>RESULTS: Ten eyes of 10 patients with unilateral RPD were included, with a mean age of 87.3 years (&#xb1;5.9). Fellow eyes exhibited four cases of retinal vein occlusion and one case of macular microaneurysm. Average baseline subfoveal choroidal thickness was 168.4 &#xb5; m (&#xb1;79.1) in the eyes presenting RPD, where it was 194.4 &#xb5; m (&#xb1;88.3) in the fellow eyes. Average choroidal vascular index at baseline was lower in RPD eyes (0.39, &#xb1;0.11) as opposed to 0.48 (&#xb1;0.03) in fellow eyes.<br><br>CONCLUSION: Our study highlights potential protective factors associated with unilateral RPD in age-related macular degeneration, emphasizing the crucial role played by the choroid and the choriocapillaris-retinal pigment epithelium complex.}, }
@article {pmid40592385, year = {2025}, author = {Wang, Z and Chen, L and Li, L and Wu, M and Zheng, B and Fan, Y}, title = {Aging reprograms the rhythmic transcriptome in the retina.}, journal = {Experimental eye research}, volume = {258}, number = {}, pages = {110504}, doi = {10.1016/j.exer.2025.110504}, pmid = {40592385}, issn = {1096-0007}, mesh = {Animals ; *Aging/physiology/genetics ; Mice, Inbred C57BL ; Mice ; *Circadian Rhythm/physiology/genetics ; *Transcriptome ; *Retina/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation/physiology ; }, abstract = {PURPOSE: Aging is a significant risk factor for various retinal degenerative diseases. However, its impact on diurnal transcriptional profile of the retina remains largely unexplored. Addressing this knowledge gap is crucial given the rising prevalence of age-related retinal diseases.<br><br>METHODS: We conducted high-throughput RNA sequencing on retinal samples collected at 4-h intervals (n&#xa0;=&#xa0;24 per group) from young (6-week-old) and aged (20-month-old) C57BL/6 mice maintained under a 12h:12h light-dark cycle. Differential expression analysis was performed using edgeR (FDR <0.05, |FC|&#xa0;>&#xa0;1.5). Rhythmicity analysis was conducted using the MetaCycle package, which integrates JTK_CYCLE and Lomb-Scargle algorithms, while differential rhythmicity analysis was performed using the CircaCompare package.<br><br>RESULTS: A total of 361 differentially expressed genes (DEGs) were identified between young and aging retinas, with enrichment in immunity-related pathways, including antigen processing and presentation, as well as the AGE-RAGE signaling pathway. A total of 4151 genes (16&#xa0;%) were identified as rhythmic expressed genes (REGs) in the young group, whereas 2999 genes (11&#xa0;%) were detected in the aging group. Notably, aging reduced rhythmic gene proportion by 28&#xa0;% (1152 genes). Additionally, aging altered rhythmic pathway dynamics: genes associated with RNA degradation and the proteasome pathway lost rhythmicity, whereas genes related to immune responses, and age-related macular degeneration (AMD)-associated pathways, including MAPK and WNT signaling, exhibited rhythmicity in the aging retina. In the differential rhythmicity analysis of 2036 overlapping rhythmic genes, 387 genes exhibited differences in MESOR, 78 showed differences in amplitude, and 72 displayed phase shifts.<br><br>CONCLUSIONS: Aging significantly reshapes the rhythmic transcriptome in the retina, altering both the composition and temporal distribution of rhythmic pathways. This study provides a valuable dataset elucidating the interplay between aging, diurnal rhythms, and gene expression in the retina, offering insights into potential molecular mechanisms underlying age-related retinal diseases.}, }
@article {pmid40593839, year = {2025}, author = {Reeve, MP and Loomis, S and Nissilä, E and Soare, TW and Rausch, T and Zheng, Z and Della Briotta Parolo, P and Ben-Isvy, D and Aho, E and Cesetti, E and Okunuki, Y and McLaughlin, H and Mäkelä, J and ,  and Kurki, M and Talkowski, ME and Korbel, JO and Connor, K and Meri, S and Daly, MJ and Runz, H}, title = {Loss of CFHR5 function reduces the risk for age-related macular degeneration.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {5766}, pmid = {40593839}, issn = {2041-1723}, support = {R01 MH115957/MH/NIMH NIH HHS/United States ; R56 MH115957/MH/NIMH NIH HHS/United States ; U24 HG011450/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; *Macular Degeneration/genetics ; Aged ; Male ; Female ; Complement Factor H/genetics ; Genetic Predisposition to Disease ; Haplotypes ; Aged, 80 and over ; Complement Activation/genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; *Complement C3b Inactivator Proteins/genetics ; Frameshift Mutation ; Case-Control Studies ; Retina/pathology ; Mutation, Missense ; Complement System Proteins ; }, abstract = {Age-related macular degeneration (AMD) is a prevalent cause of vision loss in the elderly with limited therapeutic options. A single chromosomal region around the complement factor H gene (CFH) is reported to explain nearly 25% of genetic AMD risk. Here, we used association testing, statistical finemapping and conditional analyses in 12,495 AMD cases and 461,686 controls to deconvolute four major CFH haplotypes that convey protection from AMD. We show that beyond CFH, two of these are explained by Finn-enriched frameshift and missense variants in the CFH modulator CFHR5. We demonstrate through a FinnGen sample recall study that CFHR5 variant carriers exhibit dose-dependent reductions in serum levels of the CFHR5 gene product FHR-5 and two functionally related proteins at the locus. Genetic reduction in FHR-5 correlates with higher complement activation capacity and a thicker retinal photoreceptor layer. Our results propose therapeutic downregulation of FHR-5 as promising to prevent or treat AMD.}, }
@article {pmid40594270, year = {2025}, author = {Davari, A and Piroozkhah, M and Iranpour, A and Nejadghaderi, SA}, title = {The burden of age-related macular degeneration and its socioeconomic associates in the Eastern Mediterranean Region from 1990 to 2021.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {21950}, pmid = {40594270}, issn = {2045-2322}, support = {403000696//Kerman University of Medical Sciences/ ; }, mesh = {Humans ; *Macular Degeneration/epidemiology ; Female ; Male ; Aged ; Prevalence ; Mediterranean Region/epidemiology ; Middle Aged ; Aged, 80 and over ; Global Burden of Disease ; Socioeconomic Factors ; *Cost of Illness ; Adult ; }, abstract = {This research aimed to assess the trends in the burden of age-related macular degeneration (AMD) in the Eastern Mediterranean Region (EMR) by age, sex, socio-demographic index (SDI), and location. We extracted data on the prevalence and years lived with disability (YLDs) of AMD from the Global Burden of Disease (GBD) study 2021. The data included all 22 countries in the EMR from 1990 to 2021. Estimates were presented as counts, age-standardized rates per 100,000, and their corresponding 95% uncertainty intervals (UIs). In 2021, the EMR had an age-standardized point prevalence for AMD of 196.8 (95% UI: 161.5 to 240.2) and a YLD rate of 14.9 (10.3 to 20.5) per 100,000 individuals, which represents a decline of 8.1% (from - 11.1% to -5.0%) and 13.3% (from - 16.7% to -9.7%), respectively, when compared to the data from 1990. In 2021, Iran exhibited the highest age-standardized YLD rate at 25.0 (17.2 to 34.9), while Somalia recorded the lowest rate at 8.0 (5.2 to 11.8). Notably, all countries within the EMR demonstrated a reduction in their age-standardized YLD rates from 1990 to 2021, except Yemen. We found an M-shaped relationship between AMD burden and the SDI during 1990-2021. The burden initially increased until reaching an SDI of 0.3, followed by a decline to 0.4, then rose again, peaking at an SDI of 0.6, before showing a final descending trend at SDI values. Despite a reduction in the burden of AMD over the past thirty years, its prevalence continues to be remarkable. Our findings revealed that women experienced a greater burden of AMD than men in the EMR. Additionally, this study highlighted a reduction in age-standardized prevalence and YLD rates. These insights can serve as a foundational basis for developing policies aimed at preventing and treating AMD.}, }
@article {pmid40596765, year = {2025}, author = {Kim, J and Han, LS and Robinson, L and Young-Zvandasara, T}, title = {Randomised Controlled Trial: Influence of Subconjunctival Anaesthesia Duration on Pain Perception During Intravitreal Injections.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {53}, number = {8}, pages = {918-924}, doi = {10.1111/ceo.14579}, pmid = {40596765}, issn = {1442-9071}, mesh = {Humans ; *Intravitreal Injections ; Female ; Male ; *Anesthesia, Local/methods ; Pain Measurement ; *Anesthetics, Local/administration &amp; dosage ; Conjunctiva/drug effects ; *Lidocaine/administration &amp; dosage ; Single-Blind Method ; Aged ; Middle Aged ; *Pain Perception/physiology ; Time Factors ; *Eye Pain/diagnosis ; Angiogenesis Inhibitors/administration &amp; dosage ; *Procedural Pain ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; }, abstract = {BACKGROUND: The intravitreal injection (IVI) is one of the most performed vitreoretinal procedures in ophthalmology. Subconjunctival anaesthesia (SCA) with 2% lidocaine is a commonly used modality to reduce procedural pain and patient distress. Currently, there is no unifying recommended wait time between SCA and IVI. The purpose of this study is to determine the optimal wait time between the two, whilst maintaining clinical efficiency.<br><br>METHODS: Single-blinded randomised clinical trial. Two hundred and forty patients were randomly assigned to one of four groups: wait time of 2, 3, 4 or 5&#x2009;min. The primary outcome was pain level graded by the patient on a 10-point visual analogue scale. The secondary outcome was the willingness to receive further IVI with the current pain level. Data points were collected on patient demographics and characteristics.<br><br>RESULTS: The mean pain scores showed a decreasing trend with increasing wait times, 2.27 (2&#x2009;min), 1.03 (3&#x2009;min), 0.67 (4&#x2009;min) and 0.58 (5&#x2009;min). More patients were willing to receive further IVI with increasing wait times, 92% (2&#x2009;min), 97% (3 and 4&#x2009;min), and 100% (5&#x2009;min). These differences were statistically significant at each time interval.<br><br>CONCLUSION: Longer wait times post-SCA were associated with better anaesthetic effect and higher patient acceptance to continue receiving IVI. The most marked difference was observed between 2- and 3-min groups. Based on our findings, a minimum wait time of 3&#x2009;min should be recommended as the group had reported acceptably low pain scores (1.03) while maintaining high patient satisfaction (97%).}, }
@article {pmid40597124, year = {2025}, author = {Erkan, E and Bayhan, SA and Bayhan, HA}, title = {Evaluation of the effects of phacoemulsification surgery in patients with wet age-related macular degeneration using optical coherence tomography angiography.}, journal = {BMC ophthalmology}, volume = {25}, number = {1}, pages = {354}, pmid = {40597124}, issn = {1471-2415}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Phacoemulsification/methods ; Male ; Female ; Prospective Studies ; Aged ; *Wet Macular Degeneration/surgery/complications/diagnosis/physiopathology ; *Fluorescein Angiography/methods ; Visual Acuity/physiology ; Aged, 80 and over ; Choroidal Neovascularization ; Follow-Up Studies ; Choroid/blood supply ; *Cataract/complications ; Middle Aged ; Fundus Oculi ; }, abstract = {PURPOSE: To assess the impact of uncomplicated phacoemulsification surgery in patients with wet age-related macular degeneration (AMD) using optical coherence tomography-angiography (OCTA).<br><br>DESIGN: Prospective study.<br><br>METHOD: The study included eyes from 44 patients diagnosed with AMD who underwent phacoemulsification surgery and 44 eyes from 44 patients without an indication for cataract surgery. Patients who had received anti-vascular endothelial growth factor therapy within the last six months were excluded. Best-corrected visual acuity measurements, optical coherence tomography, and OCTA were performed preoperatively and at postoperative months 1, 3, and 6. During the same sessions, choroidal neovascular membrane area was evaluated manually with OCTA.<br><br>RESULTS: Throughout follow-up, no significant differences were observed between the surgical and control groups regarding membrane area (p&#x2009;>&#x2009;0.05). However, the change in membrane area in the surgical group, measured as an increase of 0.17&#x2009;&#xb1;&#x2009;0.14 mm[2], was statistically significant (p&#x2009;<&#x2009;0.05). No significant difference was found between the two groups in terms of flow area (p&#x2009;>&#x2009;0.05). Vessel density measurements in the superficial capillary plexus did not significantly differ between the groups (p&#x2009;>&#x2009;0.05). At the six-month visit, a significant decrease was observed in small-caliber vessels (p&#x2009;<&#x2009;0.05) within the surgical group, along with a significant increase in the perilesional halo (p&#x2009;<&#x2009;0.05); however, no significant changes were noted in other activation criteria (p&#x2009;>&#x2009;0.05).<br><br>CONCLUSION: Phacoemulsification was determined to induce changes in certain parameters of the choroidal neovascularization in patients with wet AMD. Therefore, the timing of surgical intervention should be carefully planned, considering patients' daily life activities.}, }
@article {pmid40597158, year = {2025}, author = {Yang, Y and Chen, L and Liu, Q and Mu, M and Huang, J and Zhang, G and Song, Q}, title = {Long-term exposure to multiple air pollutants and multi-level socioeconomic status: joint effects on age-related macular degeneration, subsequent ocular comorbidity, and death in middle-aged and older adults.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {354}, pmid = {40597158}, issn = {1741-7015}, support = {2021QNRC001//China Association for Science and Technology/ ; }, mesh = {Humans ; *Macular Degeneration/epidemiology/mortality ; Male ; Aged ; Female ; Middle Aged ; *Air Pollutants/adverse effects ; *Air Pollution/adverse effects ; *Social Class ; Comorbidity ; *Environmental Exposure/adverse effects ; Life Expectancy ; United Kingdom/epidemiology ; Aged, 80 and over ; Incidence ; }, abstract = {BACKGROUND: Both air pollution and socioeconomic status (SES) are recognized as significant determinants of health outcomes. However, no study has explored the combined effects of air pollutants and SES on (1) age-related macular degeneration (AMD) incidence; (2) trajectories from baseline to AMD, subsequent ocular comorbidity (OCMD), and mortality; and (3) life expectancy in middle-aged and older adults.<br><br>METHODS: Using UK Biobank data, we created two composite air pollution scores (APS) and assessed SES at individual and neighborhood levels. OCMD was defined as glaucoma or cataract occurrence after AMD diagnosis. Cox proportional hazard regression models, multistate models, and life tables were used to assess associations and calculate life expectancy.<br><br>RESULTS: Over a median of 12.5 years, 3859 participants developed AMD, 2907 participants developed OCMD, and 23,363 died. Compared to those with low APS and favorable SES, individuals with high APS and unfavorable SES had highest risk (APS1: individual-level SES HR 1.41, 95% CI: 1.18-1.67, area-level SES HR 1.31, 95% CI: 1.15-1.49; APS2: individual-level SES HR 1.51, 95% CI: 1.27-1.80; area-level SES HR 1.31, 95% CI: 1.15-1.49), after adjusting for all potential covariates. Among five transitions, the combined effects were significant in transitions from baseline to incident AMD, from AMD to OCMD, and from baseline to death. Significant life expectancy disparities were observed; individuals with low individual-level SES had shortest life expectancies across APS tertiles, with similar but less pronounced effects for area-level SES.<br><br>CONCLUSIONS: Our study underscores the need for interventions addressing air pollution and SES to reduce AMD risk, improve ocular health, and enhance life expectancy in aging populations.}, }
@article {pmid40598116, year = {2025}, author = {Yufeng, X and Ningxi, H and Mingzhi, S and Weixin, Z and Panpan, Y}, title = {Real-world outcomes of a loading phase with intravitreal faricimab in refractory Neovascular Age-Related Macular Degeneration (nAMD) patients.}, journal = {BMC ophthalmology}, volume = {25}, number = {1}, pages = {347}, pmid = {40598116}, issn = {1471-2415}, support = {LTGY24H120002//Zhejiang Provincial Natural Science Foundation of China/ ; 2025-KYY-518052-0055//Chen Jumei Foundation/ ; }, mesh = {Humans ; Intravitreal Injections ; Male ; Female ; *Visual Acuity ; Aged ; Prospective Studies ; Tomography, Optical Coherence ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Aged, 80 and over ; Follow-Up Studies ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Fluorescein Angiography ; Antibodies, Bispecific ; }, abstract = {BACKGROUND: Intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents is the standard of care for neovascular age-related macular degeneration (nAMD), but treatment resistance and incomplete fluid resolution remain challenges in refractory cases. This study investigates the real-world outcomes of faricimab in patients with previously treated refractory nAMD.<br><br>METHODS: A prospective single center study was conducted involving patients with refractory nAMD treated with a loading dose of 3 IVI of faricimab 6 mg/0.05 ml, administered every four weeks. All patients included in this study had previously received a minimum of 3 consecutive intravitreal injections of other anti-VEGF. Main outcome measures included best-corrected visual acuity (BCVA) and OCT outcomes at follow-up time for 3 months.<br><br>RESULTS: Thirty-five eyes of 35 patients were included. The BCVA (logMAR) improved from 0.84&#xb1;0.49 to 0.76&#xb1;0.49 at 3 months (P = 0.025). The central macular thickness (CMT) decreased significantly from 447.65&#xb1;161.46 &#xb5;m to 327.33&#xb1;147.78 &#xb5;m at 3 months (P < 0.001). The correlation analysis revealed that age and ellipsoid zone (EZ) discontinuity exhibited a weak positive correlation with the final BCVA (P < 0.05). Baseline BCVA demonstrated a strong positive correlation with the final BCVA (P < 0.05). Meanwhile, baseline CMT, intraretinal fluid (IRF), scar, and subretinal hyperreflective material (SHRM) showed a moderate positive correlation with the final BCVA (P < 0.05). Multivariate logistic regression analysis demonstrated that baseline BCVA (P = 0.032) and age (P = 0.047) were independent predictors of final BCVA.<br><br>CONCLUSION: In the short term, faricimab led to significant improvements in BCVA and CMT, as well as reductions in retinal fluid, making it an effective treatment option for previously treated refractory nAMD with minimal adverse effects. Limitations include the single-arm design, small sample size, and lack of long-term durability assessment.}, }
@article {pmid40599631, year = {2025}, author = {Villicana, J and Joseph, A and Goldstein, O and Luu, K and Matta, E and Ngo, D and Nakawaki, K and Siebein, K and Sustek, R and Tang, K and Shiraishi, M and Mayorga, A and Moon, SH and Rajagopal, S and Chauhan, RK and Soangra, R}, title = {THE ROLE OF PERIPHERAL VISION IN ENHANCING BALANCE AND POSTURAL STABILITY: INSIGHTS FROM CENTRAL VISION OBSTRUCTION.}, journal = {Biomedical sciences instrumentation}, volume = {61}, number = {1}, pages = {1-8}, pmid = {40599631}, issn = {0067-8856}, support = {R15 HD110941/HD/NICHD NIH HHS/United States ; }, abstract = {This study examines the role of peripheral vision in maintaining postural stability, particularly when central vision is obstructed, using Sensory Organization Testing (SOT) with computer dynamic posturography. Ten participants (5 males, 5 females, aged 21-34 years) were tested under three conditions: full vision, full occlusion, and central vision obstruction allowing only peripheral vision access. Results revealed significantly better balance performance in the peripheral vision condition during somatosensory perturbations (Condition 4), with equilibrium scores higher than in the full vision condition (p = 0.02). Similarly, visual preference (VIS) scores, indicating reliance on visual input, were significantly elevated under peripheral vision conditions (p = 0.03). These findings highlight peripheral vision's critical role in improving postural sway and maintaining balance when central vision is impaired, as seen in conditions such as age-related macular degeneration (AMD). While central vision is vital for daily tasks requiring focused attention, peripheral vision provides crucial environmental cues for balance and stability. This research underscores the need for targeted interventions and balance training programs to mitigate fall risks in individuals with central vision loss. Future studies will explore these effects in populations with visual impairments to enhance clinical relevance and applicability of central vision on balance.}, }
@article {pmid40601510, year = {2025}, author = {Zhou, HW and Kim, LA}, title = {Gene Therapy in Age-related Macular Degeneration.}, journal = {International ophthalmology clinics}, volume = {65}, number = {3}, pages = {48-55}, doi = {10.1097/IIO.0000000000000567}, pmid = {40601510}, issn = {1536-9617}, mesh = {Humans ; *Genetic Therapy/methods ; *Macular Degeneration/therapy/genetics ; Genetic Vectors ; }, abstract = {Recent advances in gene therapy and salient features of the current AMD therapeutic landscape have led to increased interest in applying gene therapy approaches to AMD. This review will discuss approaches to drug administration, viral and non-viral delivery vectors, and current trials in gene therapy for both wet and dry AMD. Drug administration routes include subretinal, intravitreal, and suprachoroidal approaches. Viral vectors include adenoviral, lentiviral, and adeno-associated viral (AAV) vectors. Non-viral vectors include lipid nanoparticle (LNP) and polymer-based vectors. Current trials in wet AMD include ADVM-022 and RGX-314. Current trials in dry AMD include GT-005 and JNJ-1887.}, }
@article {pmid40601512, year = {2025}, author = {Bagheri, S and Ntentakis, DP and Emfietzoglou, M and Ashourizadeh, H and Grinspan, N and Ploumi, I and Armstrong, GW and Miller, JB}, title = {Sterile Intraocular Inflammation Following Intravitreal Injections: Pathogenesis, Clinical Features, and Management.}, journal = {International ophthalmology clinics}, volume = {65}, number = {3}, pages = {63-70}, pmid = {40601512}, issn = {1536-9617}, mesh = {Humans ; *Intravitreal Injections/adverse effects ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; *Endophthalmitis/diagnosis/etiology/therapy/chemically induced ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Retinal Vasculitis/chemically induced/diagnosis ; }, abstract = {Intravitreal injections have revolutionized the treatment of retinal diseases, yet there are possible complications, such as noninfectious intraocular inflammation, a complication that may threaten vision and mimic infectious endophthalmitis. This review synthesizes current knowledge on inflammation after intravitreal therapy, with particular focus on sterile intraocular inflammation and retinal vasculitis associated with anti-VEGF agents such as brolucizumab and newer complement inhibitors like pegcetacoplan. The pathogenesis is multifactorial, involving patient-specific immune responses, drug-specific properties including aggregation or impurities, and deviations in preparation or delivery techniques. Clinical presentations range from anterior uveitis and vitritis to occlusive retinal vasculitis. Visual outcomes vary and depend on prompt recognition and appropriate management. Epidemiologic data show variable incidence across agents, with brolucizumab demonstrating higher rates of inflammation compared with ranibizumab or aflibercept. Treatment includes corticosteroids and discontinuation of the offending agent, with rare cases requiring surgical intervention. As the therapeutic landscape expands, heightened awareness and standardized evaluation of postinjection inflammation are critical to improving safety and preserving vision.}, }
@article {pmid40601515, year = {2025}, author = {Harris, J and Wu, D}, title = {The Role of Inflammation in Age-Related Macular Degeneration.}, journal = {International ophthalmology clinics}, volume = {65}, number = {3}, pages = {82-113}, pmid = {40601515}, issn = {1536-9617}, support = {//Gragoudas-Folkman Research Award/ ; }, mesh = {Humans ; *Inflammation/complications ; *Macular Degeneration/etiology ; }, abstract = {Age-related macular degeneration (AMD) is a common neurodegenerative disease that results in significant morbidity and economic cost to patients and society. While advances in our understanding of the mechanisms of neovascularization have led to breakthrough vision-saving treatments for "wet" AMD, the "dry" variant of AMD, geographic atrophy, still poses significant clinical and scientific challenges. Many genetic and environmental factors have been linked with AMD, providing clues for understanding the disease mechanisms driving "dry" AMD. Evidence of neuroinflammation has been found across a wide spectrum of neurodegenerative diseases including AMD and therapies targeting inflammation, including recent complement inhibitors, have been investigated as treatments for "dry" AMD. Here we survey the evidence from human patients of the potential role of inflammation in AMD and review the efforts to treat AMD with therapeutic interventions targeting mediators of inflammation.}, }
@article {pmid40601523, year = {2025}, author = {Choe, BS and C, A and Mk, P and Kim, J and Baek, KS and Park, YK}, title = {Enhanced Oral Bioavailability of Lutein and Zeaxanthin via a Self-Emulsifying Delivery System: A Randomized, Double-Blind Cross-Over Study.}, journal = {Journal of medicinal food}, volume = {28}, number = {8}, pages = {824-832}, doi = {10.1089/jmf.2025.k.0060}, pmid = {40601523}, issn = {1557-7600}, mesh = {Humans ; *Lutein/pharmacokinetics/blood/administration &amp; dosage ; Male ; *Zeaxanthins/pharmacokinetics/blood/administration &amp; dosage ; Double-Blind Method ; Cross-Over Studies ; Biological Availability ; Adult ; *Dietary Supplements/analysis ; Young Adult ; Administration, Oral ; Emulsions/chemistry ; *Drug Delivery Systems ; }, abstract = {This study was conducted to evaluate and verify the improved bioavailability, as determined by the plasma concentrations of lutein and zeaxanthin, of the test supplement, XanMax® 2002 plus LuZeAbility™, as compared to the reference supplement, XanMax® 2002. For this purpose, this study was designed as a randomized, double-blind, two-group, two-period cross-over clinical trial research. A total of 24 male subjects participated in the clinical trial. They were randomized 1:1 into group 1 or 2 to consume two types of supplements in two separate periods. This study aimed to propose and demonstrate that the bioavailability and the plasma concentrations of lutein and zeaxanthin in the test supplement were significantly higher (110-132.8%) than in the reference supplement in all consecutive periods, such as 12 to 72 h after intake and at the time of maximum concentration. These results are expected to strengthen macular pigment optical density levels, ultimately providing a safe and effective intervention for comprehensively promoting eye health. Therefore, the findings of this study have significant pharmacokinetic implications and offer valid theoretical and practical insights for both academic research and the industrial development in the supplement market.}, }
@article {pmid40601621, year = {2025}, author = {Anderer, S}, title = {GLP-1 Drugs Linked to Higher Risk of Age-Related Macular Degeneration.}, journal = {JAMA}, volume = {334}, number = {5}, pages = {383}, doi = {10.1001/jama.2025.10318}, pmid = {40601621}, issn = {1538-3598}, }
@article {pmid40606666, year = {2025}, author = {Luo, Q and Huang, J and Shi, L and Zhang, G and Xue, L and Wu, K and Li, X and Yang, L and Li, D and Mao, L and Luo, J}, title = {Identification and functional characterization of ABCA4 gene variants in three patients with Stargardt disease or retinitis pigmentosa.}, journal = {Frontiers in genetics}, volume = {16}, number = {}, pages = {1516872}, pmid = {40606666}, issn = {1664-8021}, abstract = {INTRODUCTION: The diversity of phenotypes, ranging from inherited retinal dystrophies (such as Stargardt disease 1, cone-rod dystrophy 3, and retinitis pigmentosa 19) to late-onset age-related macular degeneration 2, has been attributed to loss-of-function variants in the ABCA4 gene. In this study, we aimed to identify and analyze potential pathogenic ABCA4 variants in patients with Stargardt disease or retinitis pigmentosa and to explore the impact of an intronic variant (NM_000350.3:c.6386 + 4A>G) on mRNA splicing.<br><br>METHODS: We enrolled three patients from unrelated families with Stargardt disease or retinitis pigmentosa after comprehensive ophthalmological evaluations were performed. Whole-exome sequencing and Sanger sequencing were applied for mutation screening, focusing on inherited retinal dystrophy-related genes. Additionally, the splicing alteration caused by c.6386 + 4A>G was functionally characterized by a minigene splicing assay.<br><br>RESULTS: Five ABCA4 germline variants were detected in three patients: one frameshift, one nonsense, one splicing, and two missense variants. Furthermore, two pathogenic and two likely pathogenic variants and one variant of uncertain significance were determined according to ACMG/AMP and ClinGen sequence variant interpretation (SVI) guidelines. The minigene splicing assay result proved that c.6386 + 4A>G affected the wild-type donor splice-site recognition of intron 46 and yielded a truncated transcript with a 47-bp deletion in exon 46.<br><br>DISCUSSION: Our study identified two novel ABCA4 variants, expanding the mutational spectrum of the ABCA4 gene in Stargardt disease and retinitis pigmentosa while providing new insights into the molecular pathology of ABCA4 splicing defects.}, }
@article {pmid40608095, year = {2025}, author = {Liu, JY and Cheng, CK and Bai, CH and Chiu, CY}, title = {Long-term remission and incidence of recurrence of neovascularization in intravitreal injection treated exudative age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {263}, number = {9}, pages = {2541-2550}, pmid = {40608095}, issn = {1435-702X}, mesh = {Humans ; Intravitreal Injections ; Retrospective Studies ; Male ; Female ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/epidemiology ; Recurrence ; Incidence ; Tomography, Optical Coherence/methods ; *Visual Acuity ; Follow-Up Studies ; Fluorescein Angiography/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; Time Factors ; Fundus Oculi ; Taiwan/epidemiology ; Remission Induction ; Aged, 80 and over ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; *Macula Lutea/pathology ; }, abstract = {PURPOSE: This study evaluates the long-term remission (LTR) rate, recurrence rate, and prognostic factors of extended remission and recurrence in macular neovascularization (MNV) eyes treated with aflibercept.<br><br>METHODS: This was a retrospective cohort of treatment-na&#xef;ve MNV eyes treated in Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan with intravitreal aflibercept between 2015 and 2023. Patients followed pro re nata (PRN) or Treat-and-Extend (T&amp;E) protocols. Long-term remission (LTR) was defined as over 6 months of disease inactivity without injection. Binary logistic regression and Cox proportional hazard regression assessed associations with LTR and time to recurrence.<br><br>RESULTS: Of 144 eyes, 68.75% achieved LTR after an average of 21.32 months after treatment, with no difference between PRN and T&amp;E groups. Among LTR cases, 69.7% experienced recurrence after a median 15 months (range: 6&#x2009;~&#x2009;67). Firth multinomial logistic regression found younger age [OR, 0.898 (0.836 to 0.946; p&#x2009;=&#x2009;0.032)], fewer injections per year [OR, 0 (0.000 to 0.001; p&#x2009;=&#x2009;0.004)], polypoid choroidal vasculopathy (PCV) [OR, 6.170 (1.811 to 21.039; p&#x2009;=&#x2009;0.033)], and retinal angiomatous proliferation (RAP) [OR, 24 450.658 (24 450.657 to 24 450.658; p&#x2009;<&#x2009;0.001)] associated with LTR. Cox regression showed more yearly injections [HR, 7.621(0.376 to 0.972; p&#x2009;=&#x2009;0.038)] led to earlier recurrence, while baseline subretinal fluid (SRF) [HR, 0.604 (0.376 to 0.972; p&#x2009;=&#x2009;0.038)] delayed recurrence.<br><br>CONCLUSION: Implementing our exit strategies, 68.75% of eyes achieved LTR across the two injection protocols. Age, disease subtype, baseline anatomical features, and yearly injection numbers may predict sustained remission and a longer time to experience recurrence.}, }
@article {pmid40608114, year = {2025}, author = {Brown, HDH and Vernon, RJW and Baseler, HA and Morland, AB}, title = {Reduced functional connectivity between central representations of V1 and foveal-biased face-selective region in central vision loss.}, journal = {Brain structure &amp; function}, volume = {230}, number = {6}, pages = {111}, pmid = {40608114}, issn = {1863-2661}, support = {1523/1524//Fight for Sight UK/ ; }, mesh = {Humans ; Male ; Female ; Magnetic Resonance Imaging ; *Visual Cortex/physiopathology/diagnostic imaging ; Middle Aged ; Aged ; *Fovea Centralis/physiopathology ; *Visual Pathways/physiopathology/diagnostic imaging ; Brain Mapping ; Visual Fields/physiology ; *Macular Degeneration/physiopathology/diagnostic imaging ; Adult ; Pilot Projects ; *Facial Recognition/physiology ; }, abstract = {Individuals with central visual deficits exhibit atrophy of the visual cortex in regions representing the central visual field and show little or no functional response there. Information in the central and peripheral visual field appear to be represented preferentially in extrastriate regions that are selective to faces and places, respectively. We recruited individuals with bilateral macular degeneration (age-related or juvenile) and age-matched sighted controls. We used resting state fMRI (RS-fMRI) to examine functional connectivity between striate (V1) and extrastriate face and place selective areas as it allows better comparison between those with unaffected vision and those with visual loss, whose stimulus related signals are already known to differ from those of controls. Selective deficits emerged in our central loss group, showing reduced functional connectivity between regions with foveal biases (central V1-face area) compared to sighted controls, whereas no such difference emerged in the peripheral biased regions (peripheral V1-place area). This result was evident regardless of whether eyes were closed or open and fixating, but was only significant in the right hemisphere, supporting the functional lateralisation of face processing. This pilot study provides some evidence for reduced functional connectivity between foveal-biased visual areas in central vision loss, suggesting that communication within the posterior visual pathway may be selectively affected in partial vision loss. Functional connectivity differences did not appear to be driven by changes in viewing condition. RS-fMRI is a valuable tool that allows us to explore functional brain changes without the need for retinal input.}, }
@article {pmid40608264, year = {2025}, author = {Khodor, A and Caranfa, JT and Nanda, T and Ruiz-Lozano, RE and Quiroga-Garza, ME and Choi, S and Chehab, A and Ramos-Dávila, EM and Heier, JS and Shah, CP and Witkin, AJ}, title = {Functional and Anatomical Outcomes of Faricimab in Previously Treated Wet Age-Related Macular Degeneration: Systematic Review and Pooled Analysis.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {8}, pages = {1965-1984}, pmid = {40608264}, issn = {2193-8245}, abstract = {INTRODUCTION: To evaluate the outcomes of intravitreal faricimab (IVF; Vabysmo[®]) in previously treated patients with wet age-related macular degeneration (wAMD), focusing on best available visual acuity (BAVA), central subfield thickness (CST), injection interval, complications, fluid resolution, and reversion rates to prior therapies.<br><br>METHODS: The PubMed, Embase, and Google Scholar databases were searched for studies reporting outcomes of treatments for previously treated cases of wAMD. Mean differences (MD) with 95% confidence intervals (CI) were used to compute the effect size of the change in outcomes.<br><br>RESULTS: A total of 29 studies with 2070 patients (1003 women, mean age 78.9&#xa0;years) and 2128 eyes were included. BAVA and CST were reported in 28 studies, fluid status in 21, injection interval in 14, and reversion rates in 6. Pooled analysis showed significant but modest improvement in BAVA when IVF was given for&#x2009;>&#x2009;6&#xa0;months (MD&#x2009;= -0.026 LogMAR, p&#x2009;<&#x2009;0.05) but not at earlier follow-ups. A similar trend was noted with injection interval extension when IVF was given beyond 6&#xa0;months (MD&#x2009;= +2.1&#xa0;weeks, p&#x2009;<&#x2009;0.05). CST reduction was observed at all time points (overall MD&#x2009;= -37.7&#xa0;&#x3bc;m, p&#x2009;<&#x2009;0.05). Complication rates were reported in nine studies, with an overall rate of 1.2%, including retinal pigment epithelium tear, intraocular inflammation, endophthalmitis, and subretinal hemorrhage. Reversion to prior or other anti-vascular endothelial growth factor (anti-VEGF) therapy was reported in six studies, occurring in 23% of eyes.<br><br>CONCLUSIONS: We reported the outcomes of utilizing IVF in previously treated cases of wAMD. IVF showed a significant improvement in CST at all time points and in the extension of injection interval. Visual outcomes remained unchanged when followed for less than 6&#xa0;months but improved significantly but modestly when followed for more than 6&#xa0;months. Switching to intravitreal faricimab may be a useful treatment option for previously treated patients with wAMD, with a goal of reducing treatment burden and improving treatment efficacy.}, }
@article {pmid40609263, year = {2025}, author = {Yanagi, Y and Ichikawa, H and Nguyen, LBT and Hayashi, A and Abe, N and Abe, H and Uchida, S}, title = {mRNA vaccination mitigates pathological retinochoroidal neovascularization in animal models.}, journal = {Vaccine}, volume = {61}, number = {}, pages = {127451}, doi = {10.1016/j.vaccine.2025.127451}, pmid = {40609263}, issn = {1873-2518}, mesh = {Animals ; Disease Models, Animal ; *RNA, Messenger/immunology/administration &amp; dosage/genetics ; Mice, Knockout ; Mice ; *Choroidal Neovascularization/prevention &amp; control ; Mice, Inbred C57BL ; *Vaccination/methods ; Receptors, LDL/genetics ; *Retinal Neovascularization/prevention &amp; control ; Female ; }, abstract = {Retinochoroidal neovascularization (NV), involved in macular degeneration, diabetic retinopathy, and other ocular diseases, causes vision impairment and blindness. Current treatments rely on repeated intraocular injections of anti-angiogenic drugs, which are burdensome for patients and clinicians, and some patients fail to respond to the treatments. This study investigates the potential of mRNA vaccination to mitigate NV and treat ocular pathologies. The vaccine targets leucine-rich alpha-2-glycoprotein 1 (LRG1), a protein specifically expressed in pathological neovascularization, inducing anti-LRG1 antibody responses in mice. In a laser-induced NV model, the LRG1 mRNA vaccine reduces NV area and leakage while inhibiting microglial cell infiltration. Histological analysis shows no adverse effects on retinal architecture or glial cell activation. Additionally, in Vldlr knockout mice, LRG1 mRNA administration suppresses ongoing neovascularization and downregulates key angiogenic mediators. These findings highlight the therapeutic potential of LRG1 mRNA as a novel strategy for CNV-associated diseases.}, }
@article {pmid40609554, year = {2025}, author = {Pan, H and Miao, J and Yu, J and Li, J and Wang, X and Feng, J}, title = {Multi-modal classification of retinal disease based on convolutional neural network.}, journal = {Biomedical physics &amp; engineering express}, volume = {11}, number = {4}, pages = {}, doi = {10.1088/2057-1976/adeb92}, pmid = {40609554}, issn = {2057-1976}, mesh = {Humans ; Algorithms ; *Convolutional Neural Networks ; Deep Learning ; Diabetic Retinopathy/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Macular Degeneration/diagnostic imaging ; *Multimodal Imaging ; Neural Networks, Computer ; Retina/diagnostic imaging ; *Retinal Diseases/diagnostic imaging/classification ; *Tomography, Optical Coherence/methods ; }, abstract = {Retinal diseases such as age-related macular degeneration and diabetic retinopathy will lead to irreversible blindness without timely diagnosis and treatment. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images provide complementary views of the retina, and the integration of the two imaging modalities can improve the accuracy of retinal disease classification. We propose a multi-modal classification model consisting of two branches to automatically diagnose retinal diseases, in which OCT and OCTA images are efficiently integrated to improve both the accuracy and efficiency of disease diagnosis. A bright line cropping is used to remove the useless black edge region while preserving the lesion features and reducing the calculation load. To solve the insufficient data issue, data enhancement and loose matching methods are adopted to increase the data amount. A two-step training method is used to train our proposed model, alleviating the limited training images. Our model is tested on an external test set instead of a training set, making the classification results more rigorous. The intermediate fusion and two-step training methods are adopted in our multiple classification model, achieving 0.9667, 0.9418, 0.8569, 0.9422, and 0.8921 in average accuracy, precision, recall, specificity, and F1-Score, respectively. Our multi-modal model outperforms the single-modal model, the early, and late fusion multi-modal model in accuracy. Our model offers doctors less human error, lower cost, more uniform, and effective mass screening, thus providing a solution to improve deep learning performance in terms of a relatively fewer number of training data and even more imbalanced classes.}, }
@article {pmid40610024, year = {2025}, author = {Trinh, M and Duong, A and Cheung, R and Chen, S and Ng, D and Friedrich, J and Hodge, C and Nivison-Smith, L and Ly, A}, title = {Proposal of a Simpler Eye-Level Risk Model Incorporating Reticular Pseudodrusen for the Clinical Prediction of Late Age-Related Macular Degeneration.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {53}, number = {8}, pages = {936-945}, pmid = {40610024}, issn = {1442-9071}, support = {//Future Vision Foundation/ ; }, mesh = {Humans ; Retrospective Studies ; *Retinal Drusen/diagnosis ; Female ; Male ; Aged ; Prognosis ; Disease Progression ; Risk Assessment/methods ; Aged, 80 and over ; Risk Factors ; *Macular Degeneration/diagnosis ; Follow-Up Studies ; Tomography, Optical Coherence/methods ; Middle Aged ; Fluorescein Angiography ; Visual Acuity ; }, abstract = {BACKGROUND: The updated simplified AREDS risk model predicts progression to late age-related macular degeneration (AMD) by person, describing up to nine observations across both eyes and 10 annual risk scores (0-4, with/without reticular pseudodrusen [RPD]). This study proposes an abridged model to enable inter-eye comparisons and potentially enhance clinical efficiency.<br><br>METHODS: This retrospective cohort study included 269 participants with early/intermediate AMD over 7&#x2009;years. The full, person-level updated simplified AREDS risk model was compared to eye-level candidate risk models, derived by removing the least predictive biomarkers. The main outcomes were prognostic performance (AUC) and risk score separability (&#x3c7; [2]).<br><br>RESULTS: At 1-3&#x2009;years, the full model showed prognostic performance (AUC&#x2009;&#xb1;&#x2009;SE) up to 84.52%&#x2009;&#xb1;&#x2009;5.93%, with overlap between most risk scores (&#x3c7; [2]&#x2009;&#x2264;&#x2009;2.08). Removing large drusen and pigmentary abnormalities in the fellow eye, intermediate drusen in both eyes, and redefining RPD presence as eye-specific maintained prognostic performance (up to 84.71%&#x2009;&#xb1;&#x2009;4.72%). Assigning one point per retained biomarker, based on similar adjusted risks, improved risk score separability (&#x3c7; [2]&#x2009;&#x2265;&#x2009;3.85, p&#x2009;<&#x2009;0.05) while reducing the number of annual scores from 10 to five.<br><br>CONCLUSIONS: The updated simplified AREDS risk model can be essentially halved without compromising prognostic performance by deriving eye-specific biomarkers and assigning one point per biomarker (large drusen, pigmentary abnormalities, and RPD in the primary eye, and late AMD in the fellow eye). This eye-level risk stratification may improve clinical efficiency and inter-eye study designs when one eye is of particular interest. An example of 3-year risks (scores 0-4) was &#x2248;4%, 8%, 16%, 32%, and 64%.}, }
@article {pmid40610046, year = {2025}, author = {Xu, P and Chotcomwongse, P and Zhang, W and Chen, X and Wu, X and Chung, FHT and Zhang, X and He, M and Shi, D and Ruamviboonsuk, P}, title = {AngioReport: dataset and baseline methods for fundus angiography report generation.}, journal = {The British journal of ophthalmology}, volume = {109}, number = {11}, pages = {1283-1288}, doi = {10.1136/bjo-2024-327006}, pmid = {40610046}, issn = {1468-2079}, mesh = {Humans ; *Fluorescein Angiography/methods ; Retrospective Studies ; Female ; Male ; Fundus Oculi ; Middle Aged ; Aged ; Indocyanine Green/administration &amp; dosage ; Adult ; Aged, 80 and over ; Coloring Agents/administration &amp; dosage ; }, abstract = {PURPOSE: To develop an annotated fundus angiographic dataset, including fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA), and establish baseline methods for automatic report generation.<br><br>METHODS: This retrospective study reviewed patients aged &#x2265;18 years who underwent FFA or ICGA at Rajavithi Hospital, Thailand, between 1 January and 31 December 2019. A total of 55&#x2009;361 de-identified images from 1691 patients (3179 eyes) were annotated by retinal specialists with detailed descriptions of the type, location, shape, size and pattern of abnormal fluorescence. Two baseline methods were developed: (1) a classification-based approach using ResNet101 with class-specific residual attention for multi-label lesion recognition and (2) a language-generation approach using the Bootstrapping Language-Image Pre-training framework, fine-tuned on angiographic images and structured reports. Model performances were evaluated using F1 score and BERTScore.<br><br>RESULTS: The dataset includes 24 diagnostic conditions, with macular neovascularisation (32.5%) being the most prevalent, followed by unremarkable findings (21.8%) and dry age-related macular degeneration (10.2%). Most eyes (81.8%) underwent both FFA and ICGA. Hyperfluorescence was observed in 75.6% of cases, predominantly due to leakage, while hypofluorescence was present in 28.1%. The classification-based method achieved an average score of 7.966, demonstrating superior performance in recognising choroidal neovascularisation, hyperfluorescent and hypofluorescent areas. The language-generation method achieved a comparable average score of 7.947, excelling in impression recognition and the hyperfluorescence identification.<br><br>CONCLUSION: We present the largest annotated fundus angiographic dataset to date, along with two effective baseline methods for automatic report generation, offering a valuable foundation for advancing artificial intelligence applications in ophthalmology.}, }
@article {pmid40611130, year = {2025}, author = {Sekulic, A and Herr, SM and Mulfaul, K and Pompös, IM and Winkler, S and Dietrich, C and Obermayer, B and Mullins, RF and Conrad, T and Zipfel, PF and Sennlaub, F and Skerka, C and Strauß, O}, title = {Factor-H-related protein 1 (FHR1), a promotor of para-inflammation in age-related macular degeneration.}, journal = {Journal of neuroinflammation}, volume = {22}, number = {1}, pages = {173}, pmid = {40611130}, issn = {1742-2094}, mesh = {Animals ; *Macular Degeneration/metabolism/pathology/genetics ; Humans ; Mice ; Retinal Pigment Epithelium/metabolism/pathology ; *Inflammation/metabolism/pathology/genetics ; Mice, Inbred C57BL ; *Complement C3b Inactivator Proteins/metabolism/genetics ; Mice, Knockout ; Disease Models, Animal ; Mice, Transgenic ; }, abstract = {Age-related macular degeneration (AMD), a multifactorial type of retinal degeneration represents the most common cause for blindness in elderly. Polymorphisms in complement factor-H increase, while absence of factor-H-related protein-1 (FHR1) decreases the AMD risk, currently explained by their opposing relationship. Here we identify a FHR1-driven pathway fostering chronic cellular inflammation. FHR1 accumulates below the retinal pigment epithelium (RPE) in AMD donor tissue and similarly the murine homolog, muFHR1 is abundant in three AMD-relevant mouse models. These mouse models express the muFHR1 receptor EGF-like module-containing mucin-like hormone receptor 1 (Emr1) on the RPE and on invading mononuclear phagocytes (MP), where both cells form clusters via muFHR1/Emr1. FHR1 ignited EMR2-dependent Ca[2+]-signals and gene expression in both human RPE cell line and in vivo where muFHR1 affects Emr1[+] cells (RPE and MP) gene expression shown by RNAseq analysis. As muFHR1 deletion in mice revealed significantly reduced MP invasion and neoangiogenesis in laser-induced choroidal neovascularization, we hypothesize that FHR1 accumulates, stabilizes and activates MP in the stage of RPE degeneration.}, }
@article {pmid40612577, year = {2025}, author = {Ye, L and Huang, X and Xu, Y}, title = {Global trends and disparities in burden of blindness and vision loss caused by non-communicable diseases from 1990 to 2021, and forecasts to 2045: a systematic analysis for the global burden of disease study 2021.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1561568}, pmid = {40612577}, issn = {2296-858X}, abstract = {BACKGROUND: Blindness and vision loss (BVL) is a major public health concern. Non-communicable diseases (NCDs), including cataract, glaucoma, age-related macular degeneration, diabetic retinopathy and etc., were the leading causes of vision impairment globally.<br><br>METHODS: We extracted global, regional, national, age-and sex-specific data on the prevalence and years lived with disability (YLDs) of BVL caused by NCDs from the Global Burden of Disease Study 2021 (GBD 2021), and then conducted a secondary comparative analysis based on time, location, age, gender, socioeconomic development index (SDI) and health system level.<br><br>RESULTS: From 1990 to 2021, the global incidence of BVL caused by NCDs continuously increased. In 2021, 1475648.6 thousand BVL cases caused by NCDs occurred globally, and ASR of YLDs reached 371.1 per 100,000 population. Great disparities were found across different genders, ages, and locations. Higher burdens were noted among females, older adult individuals, regions with lower SDI or less advanced health systems.<br><br>CONCLUSION: The burden of BVLs caused by NCDs has increased significantly since 1990 and varies widely across regions. Greater efforts are needed in NCDs control and vision protection, especially in older adult individuals and females, in regions with lower SDI, and in regions with less advanced health systems.}, }
@article {pmid40613237, year = {2025}, author = {Wang, H and Ding, R and Jiang, W and Li, S and Wu, Y and Mao, J and Chen, Y and Sun, P and Shi, M}, title = {Effects of anti‑VEGF on peripapillary retinal nerve fiber layer and papillary/peripapillary blood circulation in retinopathies (Review).}, journal = {International journal of molecular medicine}, volume = {56}, number = {3}, pages = {}, pmid = {40613237}, issn = {1791-244X}, mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Retinal Diseases/drug therapy/pathology ; *Nerve Fibers/drug effects/pathology ; *Angiogenesis Inhibitors/therapeutic use/pharmacology ; }, abstract = {Vascular endothelial growth factor (VEGF) is an endothelial cell‑specific angiogenic factor. VEGF is involved in vasodilatation, nerve protection and retinal development and maturation. Over‑expression of VEGF is closely associated with retinopathies, such as retinal vein occlusion, diabetic retinopathy, age‑related macular degeneration and diabetic macular edema. Intravitreal injections of anti‑VEGFs are widely used in the treatment of retinopathies to reduce the angiogenesis and the macular edema. Hypothetically, repeated anti‑VEGF injections for retinopathies should interfere with the neuroprotective function of VEGF and might induce the vasoconstriction with a subsequent decrease in the ocular perfusion. These two could affect the optic nerve. The peripapillary retinal nerve fiber layer (p‑RNFL) thinning and the decreased papillary/peripapillary blood circulation can show the optic nerve damage earlier. In the present review, the effects of anti‑VEGFs on p‑RNFL and papillary/peripapillary blood circulation in retinopathies were comprehensively summarized and analyzed to explore whether the anti‑VEGFs cause damages to the optic nerve. The present review provided a detailed evaluation and analysis of the changes in p‑RNFL thickness, papillary/peripapillary blood circulation and intraocular pressure and the correlations between these changes with the number and type of anti‑VEGFs in 3,078 affected eyes and 520 fellow eyes with retinopathies. The present review sought to establish a foundation for the intravitreal administration of anti‑VEGFs and efficacy monitoring of the possible side effects on the optic nerve.}, }
@article {pmid40614029, year = {2025}, author = {Wen, M and Xu, Q and Xie, J and Wu, R and Chen, X and Wen, N and Huang, S}, title = {Therapeutic potential of P2X7 receptor in retinal diseases.}, journal = {Purinergic signalling}, volume = {21}, number = {4}, pages = {863-871}, pmid = {40614029}, issn = {1573-9546}, mesh = {Humans ; *Receptors, Purinergic P2X7/metabolism ; *Retinal Diseases/drug therapy/metabolism ; Animals ; *Purinergic P2X Receptor Antagonists/therapeutic use/pharmacology ; }, abstract = {Retinal diseases affect the health of millions of people worldwide and activated P2X7 receptors (P2X7Rs) are associated with the pathophysiology of a variety of retina-related diseases, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Increasing evidence indicated that P2X7R is over-activated in retinopathy and is involved in the occurrence and development of diabetic retinopathy. Purine vasotoxicity caused by over-activation of P2X7R can lead to decreased retinal blood flow and vascular dysfunction and activation of P2X7R can lead to the production of a large number of inflammatory factors, causing local inflammatory cells to infiltrate and form a vascular microenvironment, thus constituting the pathophysiological basis for the occurrence and development of retinopathy. A variety of P2X7R antagonists have been studied in clinical trials as potential treatments for retinal diseases. However, currently no P2X7R antagonists has been approved for retina diseases. In this review, we mainly focus on recent progress on the involvement of P2X7R in retinal diseases and its therapeutic potential in the future.}, }
@article {pmid40614337, year = {2025}, author = {Wang, E and Doig, GS and Ly, A}, title = {An enhanced educational intervention for improving confidence in the eye health benefits of appropriate care for age-related macular degeneration: a randomized controlled trial.}, journal = {Health education research}, volume = {40}, number = {4}, pages = {}, pmid = {40614337}, issn = {1465-3648}, support = {//Australian Government Research Training Program Scholarship/ ; //Commonwealth of Australia/ ; //Novartis Pharmaceuticals Australia/ ; }, mesh = {Humans ; Male ; Female ; Aged ; *Macular Degeneration/therapy/psychology ; Single-Blind Method ; *Patient Education as Topic/methods ; Aged, 80 and over ; Middle Aged ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide. Appropriate care is available for patients, reducing the risk of AMD progression. Unfortunately, patients do not always receive appropriate eye care. Our study aimed to develop and evaluate an enhanced educational intervention focused on the health benefits expected from receiving appropriate eye care for AMD. We conducted a randomized, single-blind, controlled trial between May 2022 and October 2023 at an intermediate-tier not-for-profit clinic, the Centre for Eye Health. We recruited 137 patients previously diagnosed with intermediate or advanced (neovascular, geographic atrophy) AMD. Patients were enrolled and randomized (68 enhanced education, 69 standard care). On the intention-to-treat analysis, there was no significant difference between groups with regards to the primary outcome, confidence in the eye health benefits of AMD-related care at 6 months (P = .25). On a priori-defined subgroup analysis, enhanced education resulted in a clinically meaningful and statistically significant differential improvement in confidence in the eye health benefits of AMD-related care for patients who were diagnosed with AMD less than 5 years ago (Pinteraction = .036). Further study is needed to confirm whether enhanced education can improve confidence in eye health care benefits for newly diagnosed AMD patients. Trial registration: anzctr.org.au Identifier: ACTRN12622000984796.}, }
@article {pmid40614931, year = {2026}, author = {Barikian, A and Kumar, JB and McCullough, AJ and Silva, FQ and Sherman, S and Tanenbaum, K and Moini, H and Singh, RP}, title = {Characteristics and Outcomes of Patients with Neovascular Age-Related Macular Degeneration by Anti-VEGF Exposure in United States Clinical Practice.}, journal = {Ophthalmology. Retina}, volume = {10}, number = {1}, pages = {71-80}, doi = {10.1016/j.oret.2025.06.016}, pmid = {40614931}, issn = {2468-6530}, mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; Male ; Female ; United States/epidemiology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/epidemiology ; *Ranibizumab/administration &amp; dosage ; Treatment Outcome ; Follow-Up Studies ; *Bevacizumab/administration &amp; dosage ; Middle Aged ; Aged, 80 and over ; Dose-Response Relationship, Drug ; Tomography, Optical Coherence ; }, abstract = {OBJECTIVE: To assess 1-year visual outcomes of patients in routine clinical practice treated with ≥7 anti-VEGF injections for neovascular age-related macular degeneration (nAMD), baseline characteristics associated with receiving ≥7 anti-VEGF injections, and impact of treatment exposure on visual outcomes.<br><br>DESIGN: Retrospective analysis.<br><br>PARTICIPANTS: Treatment-naive eyes with baseline best-corrected visual acuity (BCVA) &#x2265;20/400, from patients aged &#x2265;55 years with nAMD diagnosed from January 1, 2013 to December 31, 2019.<br><br>METHODS: This analysis included eyes from the American Academy of Ophthalmology IRIS Registry&#xae; (Intelligent Research in Sight). Visual outcomes were evaluated by treatment exposure (&#x2265;7 or <7 intravitreal anti-VEGF injections) through year 1. Baseline factors associated with &#x2265;7 anti-VEGF injections and impact of treatment exposure on visual outcomes were evaluated by logistic regression.<br><br>MAIN OUTCOME MEASURES: Best-corrected visual acuity change from baseline by treatment exposure, association between baseline factors and treatment exposure, and magnitude of BCVA change by baseline factors and treatment exposure at year 1.<br><br>RESULTS: Of 295&#x2009;561 eligible eyes, 184&#x2009;258 actively treated were analyzed (&#x2265;7 anti-VEGF injections: 109&#x2009;696 eyes [59.5%]; <7 injections: 74&#x2009;562 eyes [40.5%]). At year 1, eyes receiving &#x2265;7 injections achieved greater BCVA gains versus those receiving <7 injections (least squares mean change [95% confidence interval]: +3.4 [3.3-3.5] vs. -0.2 [-0.3 to 0.0] letters). Asian or Black race (vs. White); Hispanic ethnicity (vs. non-Hispanic or Latino); Medicaid insurance (vs. Medicare); and treatment by a nonretina specialist were associated with lower odds of receiving &#x2265;7 injections. For both treatment exposure groups, BCVA <20/200 to 20/400 (vs. 20/100-20/200) was associated with greater visual gains, whereas BCVA >20/80, age &#x2265;85 years (vs. 75-84 years), treatment by a nonretina specialist, and Medicaid insurance were associated with lower BCVA gains.<br><br>CONCLUSIONS: Over one-third of newly diagnosed eyes with nAMD received <7 anti-VEGF injections and experienced worse visual outcomes at year 1 versus eyes receiving &#x2265;7 injections. Race, insurance type, and physician specialty impacted treatment exposure in nAMD management, whereas age, baseline BCVA, and insurance type impacted visual outcomes regardless of treatment exposure.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40617952, year = {2025}, author = {Haas, AM and Kickinger, S and Stattin, M and Ahmed-Balestra, D and Jacob, M and Krepler, K and Ansari-Shahrezaei, S}, title = {Short-term natural history of macular neovascularization in nonexudative age-related macular degeneration using multimodal imaging.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {24070}, pmid = {40617952}, issn = {2045-2322}, mesh = {Humans ; Male ; Female ; Aged ; *Multimodal Imaging/methods ; Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnostic imaging/pathology ; Retrospective Studies ; Aged, 80 and over ; Fluorescein Angiography ; Case-Control Studies ; Middle Aged ; *Choroidal Neovascularization/diagnostic imaging/pathology ; Disease Progression ; }, abstract = {The short-term conversion rate of a non-exudative macular neovascularization (ne-MNV) to an exudative stage in age-related macular degeneration (AMD) was evaluated in a single-center, retrospective case control study and associated imaging characteristics described, using multimodal imaging. A total of 241 Caucasian patients with unilateral, treatment-naive exudative neovascular AMD were screened for the presence of a ne-MNV in the fellow eye between March 2016 and May 2022. Eyes with a confirmed ne-MNV on indocyanine green angiography and/or optical coherence tomography angiography (OCTA) were monitored using structural OCT for signs of exudation. The main outcome was to evaluate multimodal imaging biomarkers to identify predictors of exudative conversion.Among 241 study eyes, 40 (16.6%) showed ne-MNV at baseline, all classified as type 1 MNV. During follow-up, 13 patients (32.5%) progressed to an exudative stage, with a mean time to exudation of 12.6 months (range: 2.6-22.4 months). The presence of a shallow irregular retinal pigment epithelial elevation (SIRE) was the only statistically significant feature associated with an increased risk of conversion to exudation. (p = 0.012) Patients with ne-MNV and a baseline SIRE are at increased risk for exudation. SIRE can be easily identified and followed up with structural OCT, providing a valuable marker for monitoring ne-MNV activation.}, }
@article {pmid40618781, year = {2026}, author = {Ghaseminejad, F and Eden, K and Hopman, WM and Bona, M}, title = {Effectiveness of assistive devices in improving reading performance in vision rehabilitation patients.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {61}, number = {1}, pages = {66-73}, doi = {10.1016/j.jcjo.2025.06.008}, pmid = {40618781}, issn = {1715-3360}, abstract = {OBJECTIVE: To evaluate the effectiveness of assistive devices in improving the reading performance of patients in a vision rehabilitation clinic.<br><br>METHODS: This is a prospective observational cohort study of patients referred to a hospital-based, urban, vision rehabilitation clinic in Southeastern Ontario. Patient demographics, ophthalmic diagnoses, and reading performance were investigated. Median reading speeds in words per minute (wpm) were compared with and without assistive devices, using the Minnesota Reading tool (MNRead). The relationships between improvement in reading speed and MNRead components (i.e., reading acuity, critical print size, and reading accessibility index), visual acuity, age, level of education, and previous exposure to vision rehabilitation were assessed. Subgroup analyses of patients diagnosed with age-related macular degeneration (AMD) and glaucoma were carried out.<br><br>RESULTS: A total of 199 patients were included in this study, with 71.9% over the age of 65. Most self-identified as female (68.8%) and Caucasian (93.0%). The median improvement in reading speed with assistive devices was 39.5 wpm (P < 0.001). Improvement in reading speeds was positively correlated with visual acuity (P&#x202f;=&#x202f;0.005) and inversely correlated with patients' age (P&#x202f;=&#x202f;0.029). Patients with glaucoma experienced a more substantial increase in reading speed (66.2 wpm) with assistive devices compared to AMD (38.0 wpm). Handheld magnifiers were significantly more effective in AMD patients, as compared to glaucoma.<br><br>CONCLUSIONS: This study provides an overview of a group of patients accessing vision rehabilitation interventions. We use the MNRead-based reading speed assessment to demonstrate the varying effectiveness of assistive devices across different patient groups.}, }
@article {pmid40619423, year = {2025}, author = {Lei, S and Liu, Y}, title = {Identifying the important involvement of cuproptosis in the pathophysiology of age-related macular degeneration.}, journal = {European journal of medical research}, volume = {30}, number = {1}, pages = {583}, pmid = {40619423}, issn = {2047-783X}, support = {WX23Z33//The Funding for Scientific Research Projects from Wuhan Municipal Health Commission/ ; WX23Z33//The Funding for Scientific Research Projects from Wuhan Municipal Health Commission/ ; }, mesh = {*Macular Degeneration/genetics/physiopathology/pathology ; Animals ; Mice ; Humans ; Apoptosis/genetics ; Disease Models, Animal ; Gene Expression Profiling ; Retinal Pigment Epithelium/pathology/metabolism ; Transcriptome ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a neurodegenerative disease associated with severe visual impairment in the elders. Despite recent studies and advances, the pathophysiology underlying the development of AMD is still not fully understood, and current therapies remain limited. Programmed cell death (PCD) has been implicated in neurodegenerative diseases. Therefore, the aim of this study is to investigate and identify key types of PCD and PCD-related genes involved in the pathogenesis of age-related macular degeneration (AMD).<br><br>METHODS: This study employs transcriptomic analyses and animal experiments. For bulk tissue transcriptomic analysis, the enrichment scores of PCD forms in AMD samples were calculated using the single-sample gene set enrichment analysis (ssGSEA) algorithm. Single-cell transcriptomic analysis was conducted to examine the expression of PCD-related genes across different cell types. A mouse model was used to evaluate the therapeutic effects of a copper chelator on AMD.<br><br>RESULTS: Enrichment analysis indicated that cuproptosis was the most enriched type of PCD process in both AMD-affected macular and retinal pigment epithelium (RPE) samples. In addition, cuproptosis was associated with the progression of AMD. Single-cell transcriptomic analysis revealed that cuproptosis was highly activated in varies retinal cells from AMD samples when compared to normal ones. Pathway enrichment analysis showed that cuproptosis was associated with angiogenesis, inflammation, and cellular senescence in AMD. Furthermore, the copper chelator demonstrated a protective effect on retinal function in the AMD mouse model.<br><br>CONCLUSIONS: Our findings identified an important role of cuproptosis in the pathophysiology of AMD and suggested the potential of cuproptosis as a therapeutic target for AMD.}, }
@article {pmid40619442, year = {2025}, author = {Mares, V and Reiter, GS and Feitosa, A and Gumpinger, M and Bogunovic, H and Schmidt-Erfurth, U and Nehemy, MB}, title = {Automated fluid monitoring to optimize the follow-up of neovascular age-related macular degeneration patients in the Brazilian population.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {75}, pmid = {40619442}, issn = {2056-9920}, abstract = {OBJECTIVES: To investigate the efficacy of an artificial intelligence (AI)-based fluid monitoring tool in optimizing the monitoring of neovascular age-related macular degeneration (nAMD) patients in a Brazilian cohort.<br><br>METHODS: This is a retrospective real-world study performed in a tertiary center in Brazil, including patients with nAMD. Spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, Germany) images were processed at baseline and over 2 years of follow-up. Demographic and clinical data were collected. A deep learning algorithm (Fluid Monitor, RetInSight, Austria) was used to automatically quantify intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED). A longitudinal panel regression model and Log-Rank test were performed to assess the correlation between fluid volumes and treatment frequency, visual outcomes, macular atrophy (MA) and subretinal fibrosis (SF) development.<br><br>RESULTS: Ninety-nine eyes from 84 patients were included. Fifty-eight eyes were treatment-na&#xef;ve. Higher IRF and PED in the 6&#xa0;mm area were correlated with worse visual outcomes over a 2-year follow-up (p&#x2009;=&#x2009;0.01 and p&#x2009;<&#x2009;0.001, respectively). Higher IRF, SRF and PED were correlated with an increased risk of SF development (p&#x2009;<&#x2009;0.001, p&#x2009;=&#x2009;0.049 and p&#x2009;=&#x2009;0.02 respectively). MA development showed no significant correlation with higher IRF, SRF nor PED in this analysis. Higher SRF volume correlated with a greater number of required intravitreal injections over 2-years.<br><br>CONCLUSION: This study investigates the multifaceted landscape of nAMD in a tertiary center in the Southeast Brazil using an AI-based fluid monitoring tool. Further studies that highlight the significance of using newly validated technologies across diverse populations worldwide will be of interest.}, }
@article {pmid40623726, year = {2025}, author = {Zhang, W and Ji, W and Cheng, M and Xue, H and Peng, C and Li, W and Ma, L and Zhang, W and Ji, X and Zhang, Z}, title = {Nanozymes in the Repair of Fundus Damage.}, journal = {ACS applied materials &amp; interfaces}, volume = {17}, number = {28}, pages = {39880-39899}, doi = {10.1021/acsami.5c07979}, pmid = {40623726}, issn = {1944-8252}, mesh = {Humans ; Animals ; *Nanostructures/chemistry/therapeutic use ; Oxidative Stress/drug effects ; *Fundus Oculi/drug effects ; *Macular Degeneration/drug therapy/metabolism/pathology ; *Diabetic Retinopathy/drug therapy/metabolism/pathology ; Reactive Oxygen Species/metabolism ; *Retinal Neovascularization/drug therapy/metabolism ; }, abstract = {Ocular diseases associated with fundus damage, such as age-related macular degeneration, diabetic retinopathy, and retinal neovascularization, represent significant contributors to severe vision impairment globally. Traditional treatment methods often face challenges, including low drug delivery efficiency, poor bioavailability, and substantial side effects. Nanozymes, a class of enzymatically active nanomaterials, have recently emerged as a promising therapeutic approach to ocular diseases. These nanozymes can effectively alleviate oxidative stress, modulate local immune responses, and inhibit pathological angiogenesis by scavenging reactive oxygen species and regulating inflammasome activation. This review aims to elucidate the mechanisms of action of various types of nanozymes as well as the pathophysiological mechanisms underlying ocular diseases that cause fundus damage. Furthermore, it discusses recent advancements in the use of nanozymes for treating fundus-related ocular disorders. Finally, this review highlights the current limitations and future directions for nanozymes in the treatment of fundus injury-associated diseases.}, }
@article {pmid40623731, year = {2025}, author = {Singh, RP and Weng, CY and Kitchens, JW and Quilantan, J and Schwartz, R and Baumal, CR and Goldberg, RA}, title = {Consideration of patient phenotypes in geographic atrophy due to age-related macular degeneration.}, journal = {BMJ open ophthalmology}, volume = {10}, number = {1}, pages = {}, pmid = {40623731}, issn = {2397-3269}, mesh = {Humans ; *Geographic Atrophy/diagnosis/etiology ; Phenotype ; *Macular Degeneration/complications/diagnosis ; Disease Progression ; Tomography, Optical Coherence/methods ; Risk Factors ; Fluorescein Angiography/methods ; }, abstract = {Geographic atrophy (GA) is a form of advanced age-related macular degeneration (AMD) affecting approximately 1 million people in the USA and 5 million globally. In this review, retinal imaging techniques used for diagnosis and monitoring progression of GA in AMD, and the risk factors associated with the development and progression of GA are summarised. To familiarise clinicians with common phenotypes of patients with GA, the clinical and imaging features that may lead to rapid progression of GA in various phenotypes are highlighted. With the recent US Food and Drug Administration approval of new GA treatments that reduce lesion growth, understanding the risk of progression to GA and factors contributing to GA growth may aid in patient selection and guide patient-level management and treatment.}, }
@article {pmid40624086, year = {2025}, author = {Yanagida, K and Miura, M and Noma, H and Mino, T and Azuma, S and Seesan, T and Makita, S and Yasuno, Y}, title = {Evaluation of retinal pigment epithelium changes in serous pigment epithelial detachment using synthesized multi-contrast polarization-sensitive optical coherence tomography.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {24304}, pmid = {40624086}, issn = {2045-2322}, support = {21K09684//Japan Society for the Promotion of Science/ ; 21H01836//Japan Society for the Promotion of Science/ ; 24K12753//Japan Society for the Promotion of Science/ ; JPMJMI18G8//Japan Science and Technology Agency/ ; JPMJCR2105//Japan Science and Technology Agency/ ; }, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/diagnostic imaging/pathology/metabolism ; Female ; Male ; *Retinal Detachment/diagnostic imaging/pathology ; Aged ; Melanins/metabolism ; Middle Aged ; Macular Degeneration/complications/diagnostic imaging/pathology ; Aged, 80 and over ; }, abstract = {Retinal pigment epithelium (RPE) melanin thickness maps, derived from multi-contrast images-including the degree of polarization uniformity (DOPU), optical coherence tomography (OCT) angiography, and the attenuation coefficient-are obtained using multi-contrast polarization-sensitive OCT (PS-OCT). These maps have demonstrated utility for three-dimensional assessment of changes in melanin within the RPE (RPE-melanin). While both OCT angiography and the attenuation coefficient can be derived from conventional OCT, measuring the DOPU requires PS-OCT, which is not available on standard commercial OCT systems. To overcome this limitation, we utilized a convolutional neural network to generate DOPU-like images from standard OCT images and used these to calculate a synthesized RPE-melanin thickness map. We evaluated 22 eyes from 20 patients with serous pigment epithelial detachment (PED) secondary to age-related macular degeneration. Both original and synthesized RPE-melanin thickness maps were calculated from multi-contrast PS-OCT datasets. Active RPE lesions were defined as areas with RPE-melanin thickness of ≥ 70 μm (originalRPE70 and synRPE70 for the original and synthesized maps, respectively). Both synthesized and original RPE-melanin thickness maps closely resembled near-infrared autofluorescence imaging. Furthermore, both the originalRPE70 area and synRPE70 area were significantly positively correlated with the PED volume. Synthesized RPE-melanin thickness maps may be useful for clinical quantification of RPE-melanin.}, }
@article {pmid40625041, year = {2025}, author = {Kim, MS and Nam, S and Park, SJ and Lee, J and Woo, SJ}, title = {10-Year Change and Projection in Prevalence and Incidence of Exudative Age-Related Macular Degeneration in Korea.}, journal = {Journal of Korean medical science}, volume = {40}, number = {26}, pages = {e128}, pmid = {40625041}, issn = {1598-6357}, support = {RS-2023-00248480/NRF/National Research Foundation of Korea/Korea ; RS-2023-00210974/NRF/National Research Foundation of Korea/Korea ; }, mesh = {Humans ; Republic of Korea/epidemiology ; Male ; Female ; Incidence ; Middle Aged ; Aged ; Prevalence ; *Macular Degeneration/epidemiology/diagnosis ; Aged, 80 and over ; Adult ; Databases, Factual ; }, abstract = {BACKGROUND: Updating the recent epidemiology of exudative age-related macular degeneration (AMD) is crucial for understanding the epidemiological trend of the disease, preparing healthcare strategies, and providing data for global comparisons. This study aimed to estimate the nationwide trend in prevalence and incidence of exudative AMD in Korea.<br><br>METHODS: In this nationwide population-based study using the National Health Insurance Service data, patients who have registration code for exudative AMD and aged 40 years or older were extracted from 2013 to 2022. Cumulative prevalence from 2013 onwards, annual prevalence, and incidence was estimated per 10,000 people. We also calculated age-standardized estimates using the World Health Organization population proportions. Linear regression to test time trend was performed. The annual prevalence and incidence were predicted using time series analysis.<br><br>RESULTS: The crude cumulative prevalence of exudative AMD was 42.7 in 2022, with men having a higher prevalence than women (51.3 vs. 34.6). The annual prevalence rose from 10.7 in 2013 to 22.5 in 2022 (age-standardized, P < 0.001). The incidence consistently increased from 2.8 in 2013 to 4.7 in 2022 (age-standardized, P = 0.001), with higher incidence in men than in women. The prevalence and incidence of exudative AMD were higher in older age groups and showed a faster increase with advancing age. The predicted annual prevalence and incidence of exudative AMD in 2040 are 46.2 and 8.4, respectively. The crude cumulative number of patients was 127,044 in 2022 and is projected to reach 230,899 in 2030 and 374,282 in 2040.<br><br>CONCLUSION: The prevalence and incidence of exudative AMD in Korea has been increased annually, especially in the elderly group. With the Korean and global population aging, there will be a growing burden from visual impairment and medical expenses associated with exudative AMD.}, }
@article {pmid40625502, year = {2025}, author = {Gupta, D and Chawla, S}, title = {Association of Apolipoprotein E (APOE) Gene Polymorphism With Age-Related Macular Degeneration (AMD) in Indian Patients.}, journal = {Cureus}, volume = {17}, number = {6}, pages = {e85441}, pmid = {40625502}, issn = {2168-8184}, abstract = {Background Age-related macular degeneration (AMD or ARMD; Online Mendelian Inheritance in Man (OMIM) #603075) is the degenerative disease of the retina that causes progressive impairment of central vision, leading to irreparable vision loss in older persons. Objective The objective was to investigate the association between apolipoprotein E (APOE) gene polymorphism and AMD in Indian patients. Materials and methods Genotyping for APOEvariants was performed in 121 AMD patients and 100 healthy controls using a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method, followed by sequencing. Genotype and allele were analyzed using the allele counting method. P-value < 0.05 was considered statistically significant. Results The E3/E3 genotype has a frequency of 76/100 (76%) in controls and 97 (80%) in AMD. The frequency of the heterozygous E2/E2 genotype was 19 (19%) in controls and eight (6.6%) in AMD, and the variant E4/E4 genotype was found in one control (1%) and in one AMD case (1%). Some protective effect of the E2/E2 heterozygous genotype is seen (OR = 0.30; P-value = 0.009). Wild allele E3 in controls was 155 (77.5%) in AMD 209 (86.3%), E2 allele 41 (20.5%), and 17 (7%) in controls and AMD. E4 alleles in controls were four (2%) and 16 (6.6%) in AMD. E2 allele showed a protective effect; we did not find any significant association in APOE variant genotypes, and the odds ratios were within a 95% confidence interval (95% CI). As independent risk factors for AMD, logistic regression (LR) analysis was applied using E2, E3, and E4 alleles and their genotypes. Conclusion This study raises the possibility that the APOE gene might not have a significant association with AMD in Indian patients. However, our sample statistics suggest that the APOE E4 allele may be a risk factor for AMD in the Indian population. The study requires verification in a large sample size, across different parts of the country, and among other ethnic groups.}, }
@article {pmid40626613, year = {2026}, author = {Cho, IH and Park, M and Ma, DJ and Hong, IH and Kim, H and Kim, SH}, title = {Continuity of care and risk of vision loss in patients with newly developed macular degeneration.}, journal = {Acta ophthalmologica}, volume = {104}, number = {1}, pages = {e39-e47}, pmid = {40626613}, issn = {1755-3768}, support = {//Soonchunhyang University Research Fund/ ; RS2023-00245657//National Research Foundation of Korea/ ; }, mesh = {Humans ; Female ; Aged ; Male ; Republic of Korea/epidemiology ; *Continuity of Patient Care ; Incidence ; *Visual Acuity ; Risk Factors ; *Wet Macular Degeneration/complications/diagnosis/epidemiology/therapy ; Retrospective Studies ; Middle Aged ; Aged, 80 and over ; Follow-Up Studies ; Risk Assessment/methods ; *Vision Disorders/epidemiology/etiology ; }, abstract = {PURPOSE: Neovascular age-related macular degeneration (AMD) is a major cause of vision loss. Effective treatment requires sustained care, which may be influenced by continuity of care (COC). Understanding this association is crucial for improving patient outcomes. We investigated the association between COC and the risk of visual impairment in patients newly diagnosed with neovascular AMD.<br><br>METHODS: This nationwide cohort study sourced data from the South Korean National Health Insurance Service database (2014-2021). In total, 15&#x2009;563 (6210 females) newly diagnosed patients with neovascular AMD were included. The COC index, based on the frequency of ophthalmology visits over the first 2&#x2009;years post-diagnosis, was assessed; a threshold of 0.75 was used to define good continuity. The primary outcome was visual impairment. Statistical models were used to assess the association between COC and the visual impairment risk, with adjustment for relevant confounding variables.<br><br>RESULTS: Patients with a bad COC index had a significantly higher cumulative incidence (6.86% vs. 4.78%) and a higher incidence rate of visual impairment (909 vs. 704 cases per 100&#x2009;000 person-years; 95% confidence interval, 764.0-1080.4, p&#x2009;<&#x2009;0.001). This elevated risk was especially notable for female patients, patients aged &#x2265;70&#x2009;years, and patients with lower comorbidity burdens.<br><br>CONCLUSIONS: Poor COC is associated with increased visual impairment risk in patients with neovascular AMD. Strategies to improve COC may reduce this risk, particularly among older adults and high-risk groups.}, }
@article {pmid40626807, year = {2025}, author = {Alhelaly, M and Soylu, C and Corradetti, G and Corvi, F and Mahmoudi, A and Abbasgholizadeh, R and Bellisario, G and He, Y and Quarta, A and Nittala, MG and Staurenghi, G and Sadda, SR}, title = {In Vivo Characterization of Bruch's Membrane Breaks in Neovascular Age-Related Macular Degeneration Using High-Resolution Optical Coherence Tomography.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {9}, pages = {19}, pmid = {40626807}, issn = {1552-5783}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Bruch Membrane/pathology ; Female ; Male ; Aged ; Visual Acuity/physiology ; *Wet Macular Degeneration/diagnosis/drug therapy/pathology ; Aged, 80 and over ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Fluorescein Angiography ; *Choroidal Neovascularization/diagnosis ; Middle Aged ; Retrospective Studies ; Follow-Up Studies ; }, abstract = {PURPOSE: The purpose of this study was to investigate the frequency and characteristics of Bruch's membrane (BM) breaks, and their relationship with clinically relevant outcomes in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Forty-seven eyes (39 patients) with nAMD and type 1 macular neovascularization (MNV) were imaged using high-resolution optical coherence tomography (High-Res OCT; Heidelberg). Foveal-centered 20 degrees &#xd7; 20 degrees volume scans (1024 &#xd7; 97, automated real time [ART] = 5-25) were obtained. BM breaks, defined as definite interruptions in the hyper-reflective BM band, were identified within the MNV region. The maximum break extent was measured. Break density, distribution, and eccentricity were also evaluated. BM break parameters were correlated with visual acuity and number of intravitreal injections.<br><br>RESULTS: Thirty eyes were included for quantitative analysis. Multiple breaks were observed in 76.7% of eyes, with a mean of 4.30 &#xb1; 4.15 breaks/eye. Notably, breaks showed a preferential eccentric distribution, tending to be closer to the lesion border (mean eccentricity ratio = 4.33 &#xb1; 3.61). Our model suggested that a higher break count was significantly associated with higher injection number (P = 0.042), whereas a greater break length was associated with fewer injections (P = 0.001). There was a trend for a higher break count to be associated with better BCVA, but this was not statistically significant (P = 0.099).<br><br>CONCLUSIONS: Most MNV lesions demonstrated multiple breaks with a tendency for breaks to be in the lesion periphery. The identification of BM breaks appeared to be of clinical relevance as the number and length of the breaks were associated with the number of intravitreal injections. Larger prospective studies are warranted to confirm these findings.}, }
@article {pmid40626808, year = {2025}, author = {Notomi, S and Wu, G and Nagaoka, T and Yotsumoto, N and Araki, T and Arima, M and Hisatomi, T and Sonoda, KH and Sawada, K}, title = {Intravenous Sodium Iodate Administration Induces Macula-Specific RPE Damage and Rod-Dominant Apoptosis in the Cynomolgus Monkey.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {9}, pages = {18}, pmid = {40626808}, issn = {1552-5783}, mesh = {Animals ; Macaca fascicularis ; Male ; *Retinal Pigment Epithelium/drug effects/pathology/ultrastructure ; *Apoptosis/drug effects ; Tomography, Optical Coherence ; *Iodates/toxicity/administration &amp; dosage ; Fluorescein Angiography ; Disease Models, Animal ; *Retinal Rod Photoreceptor Cells/drug effects/pathology ; Injections, Intravenous ; *Macula Lutea/drug effects/pathology ; Microscopy, Electron, Transmission ; Retinal Degeneration/chemically induced/pathology ; }, abstract = {PURPOSE: Although sodium-iodate (SI)-induced retinal degeneration has been extensively studied in rodent models, its macular pathology and cone/rod vulnerability difference remains elusive. This study aims to characterize SI-induced macular pathology in cynomolgus monkeys.<br><br>METHODS: Intravenous injections of SI were performed on four male cynomolgus monkeys including three young adults (Animal No.&#xa0;1-3; five to six years old) and one juvenile (Animal No.&#xa0;4; two years old) from a breeding colony. To optimize dosing, Animal No.&#xa0;1 received 25 and 37.5&#xa0;mg/kg SI; Animal No.&#xa0;2 received a single SI dose (30&#xa0;mg/kg) to confirm reproducibility. Animal No.&#xa0;3 was used to examine subclinical effects at a lower dose (25&#xa0;mg/kg). Animal No.&#xa0;4 received increasing doses (30, 35, and 40&#xa0;mg/kg). Retinal changes were evaluated using fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT). Histological analysis and transmission electron microscopy (TEM) were also performed.<br><br>RESULTS: In Animal No.&#xa0;1, prominent fluorescein leakage by FA and RPE elevation on OCT was observed in the macula after 37.5&#xa0;mg/kg SI. Histology and TEM revealed that elevated RPE lesion was accompanied by significant RPE migration. Animal No.&#xa0;2 exhibited similar retinal degeneration. Animal No.&#xa0;3 exhibited no RPE barrier disruption but showed outer segment damage and RPE melanolipofuscin accumulation. Animal No.&#xa0;4 showed minimal macular degeneration despite escalating doses. In the peripheral retina, rod apoptosis was evident, whereas macular cone cell death was limited even at high doses.<br><br>CONCLUSION: Systemic SI administration can induce macular degeneration with RPE barrier disruption in young-adult monkeys, supporting a macula- and cell-type-specific vulnerability.}, }
@article {pmid40627958, year = {2025}, author = {Rajendran, N and Runyon, W and Hu, S and Singh, A and Ratnapriya, R and Kumar, R and Csaky, K and Sripathi, SR}, title = {Generation of induced pluripotent stem cell lines (RFSCi003-A, RFSCi004-A) from monozygotic twins discordant for age-related macular degeneration.}, journal = {Stem cell research}, volume = {87}, number = {}, pages = {103768}, doi = {10.1016/j.scr.2025.103768}, pmid = {40627958}, issn = {1876-7753}, mesh = {Humans ; *Induced Pluripotent Stem Cells/metabolism/cytology/pathology ; *Macular Degeneration/pathology/genetics/metabolism ; *Twins, Monozygotic ; Cell Line ; Male ; Female ; Leukocytes, Mononuclear/cytology ; }, abstract = {Age-related macular degeneration (AMD) has significant genetic component, yet monozygotic twins frequently exhibit discordance in disease status, highlighting the role of non-genetic factors. To enable comparative studies of AMD pathogenesis, we generated two induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) of a monozygotic twin pair discordant for AMD. These iPSC lines offer a unique genetically matched resource to investigate molecular differences between affected and unaffected twins, as well as their responses to genetic, epigenetic, and environmental contributors to AMD development.}, }
@article {pmid40628205, year = {2025}, author = {Souied, EH and Couturier, A and Devin, F and Creuzot-Garcher, C and Baillif, S and Weber, M and Ponthieux, A and Kodjikian, L}, title = {Functional and anatomic outcomes of brolucizumab in adults with neovascular age-related macular degeneration - The OCTOPUS cohort study.}, journal = {Journal francais d'ophtalmologie}, volume = {48}, number = {7}, pages = {104583}, doi = {10.1016/j.jfo.2025.104583}, pmid = {40628205}, issn = {1773-0597}, mesh = {Humans ; Female ; Aged ; Male ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use/adverse effects ; Middle Aged ; Treatment Outcome ; Aged, 80 and over ; Visual Acuity/drug effects ; Tomography, Optical Coherence ; *Wet Macular Degeneration/drug therapy/pathology ; Cohort Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage/adverse effects ; Intravitreal Injections ; *Macular Degeneration/drug therapy/pathology ; *Choroidal Neovascularization/drug therapy/pathology ; }, abstract = {PURPOSE: To evaluate the functional and anatomic outcomes of brolucizumab in treatment-naïve adults (≥50years) with neovascular age-related macular degeneration.<br><br>METHODS: This was a single-arm, open-label, multicenter study. Patients (n=210) were treated with brolucizumab 6mg at Weeks (W) 0, 4 and 8, then every 12weeks (q12w) or 8weeks (q8w) depending on disease activity. The primary endpoint was change in the area of the CNV lesion from baseline to Week 12, as measured by OCTA. Functional and anatomic outcomes were evaluated up to Week 48.<br><br>RESULTS: Mean age was 77.8years; 61.4% were female. CNV lesion size decreased from baseline to Week 12 by 79.3% and to W48 by 68.5%. Mean (SD) BCVA increased from baseline to Week 48 by 8.3 (12.0) letters, and disease activity was absent for 77.4% of patients at W48. There was a mean (SD) decrease from baseline in CSFT (&#x3bc;m) of -151&#x3bc;m (&#xb1;134) at Week 48, with most patients (62.3%) having no retinal fluid (23.9% had IRF, 16.4% had SRF, and 11.9% had sub-RPE fluid). Confirmed intraocular inflammation occurred in 24 patients, mostly during loading, and did not compromise gains in BCVA.<br><br>CONCLUSIONS: CNV lesion size as assessed by OCTA decreased with brolucizumab, which also led to vision gains and better anatomic outcomes.}, }
@article {pmid40628339, year = {2025}, author = {El-Mulki, OS and Berni, A and Kastner, J and Shen, M and Cheng, Y and Herrera, G and Beqiri, S and Trivizki, O and Le, VH and Sivathanu Kumar, B and Di Nicola, M and O'Brien, R and Waheed, NK and Gregori, G and Wang, RK and Rosenfeld, PJ}, title = {The Macular Burden of Calcified Drusen and the Onset of Large Choroidal Hypertransmission Defects in Intermediate AMD.}, journal = {American journal of ophthalmology}, volume = {278}, number = {}, pages = {402-412}, doi = {10.1016/j.ajo.2025.07.001}, pmid = {40628339}, issn = {1879-1891}, mesh = {Humans ; Tomography, Optical Coherence/methods ; Female ; Male ; *Retinal Drusen/diagnosis/complications ; Aged ; Prospective Studies ; Fluorescein Angiography/methods ; Follow-Up Studies ; Retrospective Studies ; *Calcinosis/diagnosis/complications ; Aged, 80 and over ; Visual Acuity/physiology ; *Choroid/pathology ; *Choroid Diseases/diagnosis/etiology ; Middle Aged ; Retinal Pigment Epithelium/pathology ; Fundus Oculi ; *Macular Degeneration/diagnosis ; *Macula Lutea/pathology ; }, abstract = {PURPOSE: This study used en face swept-source optical coherence tomography (SS-OCT) imaging to follow eyes with intermediate age-related macular degeneration (iAMD) in the presence and absence of calcified drusen (CaD) to determine if the presence and size of CaD increased the risk of forming large choroidal hypertransmission defects (hyperTDs).<br><br>DESIGN: Post hoc subgroup analysis of a prospective cohort study.<br><br>METHODS: Eyes with iAMD were enrolled in a prospective SS-OCT study, and the onset of large hyperTDs was retrospectively analyzed. Imaging was performed using 6 &#xd7; 6 mm SS-OCT angiography (SS-OCTA) scans at baseline and follow-up. Large hyperTDs were defined as bright lesions &#x2265;250 &#xb5;m in greatest linear dimension (GLD) on en face sub-retinal pigment epithelium (subRPE) slabs positioned 64 to 400 &#xb5;m beneath Bruch's membrane (BM). CaD were identified as drusen with heterogeneous internal reflectivity projecting choroidal hypotransmission defects (hypoTDs) on the same subRPE slabs. CaD were distinguished from hyperreflective foci (HRF) by analyzing corresponding B-scans. Two independent graders used a semiautomated algorithm to refine CaD outlines and reach consensus, with disagreements adjudicated by a senior grader. CaD area, HRF area, and drusen volume were measured within 5-mm fovea-centered circles.<br><br>RESULTS: Median follow-up time for the 171 eyes from 121 patients followed in this study was 59.1 months (95% CI: 52.0-67.8 months), and 82 eyes developed at least one large hyperTD during follow-up. The mean baseline CaD area measurement was 0.037 mm&#xb2; [range: 0-0.567 mm&#xb2;] in eyes that developed hyperTDs, while in eyes that did not, it was 0.008 mm&#xb2; [range: 0-0.360 mm&#xb2;] (P = .01). Drusen volume, HRF area, and CaD area were predictors for hyperTD onset when considered alone, but only HRF area (P < .001) and CaD area (P =.008) remained significant predictors for hyperTD onset when using a multivariable Cox regression analysis. Regardless of area, the presence of any CaD increased the risk of hyperTD formation (P < .001).<br><br>CONCLUSIONS: In a multivariable Cox regression analysis, the area measurements of CaD and HRF in eyes with iAMD were significant predictors of hyperTD onset, and the presence of any CaD increased the risk of hyperTD formation.}, }
@article {pmid40632162, year = {2025}, author = {Çalışkan, B}, title = {Metabolic stress in exudative age-related macular degeneration: potential role of lipid ındex.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {281}, pmid = {40632162}, issn = {1573-2630}, mesh = {Humans ; Female ; Male ; Retrospective Studies ; Aged ; *Lipids/blood ; *Wet Macular Degeneration/blood/diagnosis/metabolism ; Biomarkers/blood ; ROC Curve ; *Triglycerides/blood ; *Stress, Physiological/physiology ; Risk Factors ; Middle Aged ; Blood Glucose/metabolism ; Aged, 80 and over ; }, abstract = {PURPOSE: To evaluate serum lipid profiles with triglyceride-Glucose (TyG) and TG/HDL-c indices in patients with exudative type age-related macular degeneration.<br><br>METHODS: A total of 71 participants were included in the study: 35 with exudative AMD and 36 in the control group. Demographic, clinical, and laboratory data of all patients were analysed retrospectively. Serum lipid profiles and lipid indices were calculated and recorded (total cholesterol, LDL-c, HDL-c and triglycerides, TyG and TG/HDL-c). Statistical analyses, regression analyses, and ROC analysis were performed to compare all results.<br><br>RESULTS: Demographic and systemic comorbidities, including age, gender, hypertension, and history of cardiovascular disease, did not significantly differ between the groups (p&#x2009;>&#x2009;0.05). In comparison to the control group, the exudative AMD group's TyG index was considerably higher (p&#x2009;=&#x2009;0.038). Serum lipid profiles were not significantly different between groups (p&#x2009;>&#x2009;0.05). Logistic regression analysis showed that exudative type was a risk factor for the development of AMD based on the TyG index (OR&#x2009;=&#x2009;0.126, 95% CI: 0.017-0.940, p&#x2009;=&#x2009;0.043). ROC analysis suggested that the TyG index served as a moderate predictor of disease risk.<br><br>CONCLUSION: The TyG index may be substantially associated with the presence of exudative AMD and may serve as a valuable biomarker for clinical application. The relevance of metabolic stress in the development of AMD is emphasized by the lack of association with other lipid parameters. To confirm these findings, further large-scale studies are needed.}, }
@article {pmid40632946, year = {2025}, author = {Alshaikhsalama, AM and Alsoudi, AF and Wai, KM and Koo, E and Mruthyunjaya, P and Rahimy, E}, title = {GOUT AND RISK OF AGE-RELATED MACULAR DEGENERATION.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {12}, pages = {2289-2296}, pmid = {40632946}, issn = {1539-2864}, mesh = {Humans ; *Gout/complications/drug therapy/epidemiology/diagnosis ; Retrospective Studies ; Male ; Female ; Aged ; Risk Factors ; Disease Progression ; Aged, 80 and over ; *Wet Macular Degeneration/epidemiology/diagnosis/etiology ; Middle Aged ; Visual Acuity ; Propensity Score ; Incidence ; Follow-Up Studies ; *Macular Degeneration/epidemiology/etiology/diagnosis ; United States/epidemiology ; }, abstract = {PURPOSE: To examine the association between gout and subsequent development and progression of age-related macular degeneration (AMD).<br><br>METHODS: In this retrospective cohort study, a multicenter health care research network was used to identify patients with an International Classification of Diseases, 10th Revision for idiopathic gout and a prescription for uric acid-lowering agent (Gout cohort) compared with a matched cohort of patients without a diagnosis of gout (Control cohort) for ophthalmic outcomes. Propensity score matching was applied to balance baseline demographics and health status between cohorts.<br><br>RESULTS: Patients with gout had an increased risk of developing dry AMD (relative risk, 2.73, 95% confidence intervals, 2.30-3.25; P < 0.001), advanced dry AMD (relative risk, 2.64, 95% confidence intervals, 1.32-5.28; P < 0.001), wet AMD (relative risk, 2.48, 95% confidence intervals, 1.82-3.38; P < 0.001), and needing subsequent antivascular endothelial growth factor therapy (relative risk, 2.80, 95% confidence intervals, 2.14-3.67; P < 0.001) compared with those without gout at 5 years. Similar trends were observed among patients with early AMD and gout compared with those with early AMD without gout.<br><br>CONCLUSION: In a national multicenter database, an increased risk of AMD development and progression to advanced disease stages was found among patient with gout compared with controls. Additional investigation into the mechanisms and effects of hyperuricemia are necessary to clarify these associations.}, }
@article {pmid40632993, year = {2025}, author = {Sivaprasad, S and Fu, DJ and Faes, L}, title = {Evidence Generation in Intermediate Age-related Macular Degeneration: The 2025 Paul Henkind Memorial Lecture at Macula Society.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {12}, pages = {2219-2223}, doi = {10.1097/IAE.0000000000004603}, pmid = {40632993}, issn = {1539-2864}, }
@article {pmid40634513, year = {2025}, author = {Abbasi, R and Amin, F and Alabrah, A and Choi, GS and Khan, S and Bin Heyat, MB and Iqbal, MS and Chen, H}, title = {Diabetic retinopathy detection using adaptive deep convolutional neural networks on fundus images.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {24647}, pmid = {40634513}, issn = {2045-2322}, mesh = {*Diabetic Retinopathy/diagnostic imaging/diagnosis ; Humans ; *Fundus Oculi ; *Neural Networks, Computer ; *Image Processing, Computer-Assisted/methods ; Retina/diagnostic imaging ; Deep Learning ; *Image Interpretation, Computer-Assisted/methods ; Algorithms ; Convolutional Neural Networks ; }, abstract = {Diabetic retinopathy (DR) is an age-related macular degeneration eye disease problem that causes pathological changes in the retinal neural and vascular system. Recently, fundus imaging is a popular technology and widely used for clinical diagnosis, diabetic retinopathy, etc. It is evident from the literature that image quality changes due to uneven illumination, pigmentation level effect, and camera sensitivity affect clinical performance, particularly in automated image analysis systems. In addition, low-quality retinal images make the subsequent precise segmentation a challenging task for the computer diagnosis of retinal images. Thus, in order to solve this issue, herein, we proposed an adaptive enhancement-based Deep Convolutional Neural Network (DCNN) model for diabetic retinopathy (DR). In our proposed model, we used an adaptive gamma enhancement matrix to optimize the color channels and contrast standardization used in images. The proposed model integrates quantile-based histogram equalization to expand the perceptibility of the fundus image. Our proposed model provides a remarkable improvement in fundus color images and can be used particularly for low-contrast quality images. We performed several experiments, and the efficiency is evaluated using a large public dataset named Messidor's. Our proposed model efficiently classifies a distinct group of retinal images. The average assessment score for the original and enhanced images is 0.1942 (standard deviation: 0.0799), Peak Signal-to-Noise Ratio (PSNR) 28.79, and Structural Similarity Index (SSIM) 0.71. The best classification accuracy is [Formula: see text], indicating that Convolutional Neural Networks (CNNs) and transfer learning are superior to traditional methods. The results show that the proposed model increases the contrast of a particular color image without altering its structural information.}, }
@article {pmid40634735, year = {2025}, author = {Olivieri, C and Tibaldi, T and Berni, A and Eandi, CM and Neri, G and Fai, A and Viggiano, P and Marolo, P and Bandello, F and Reibaldi, M and Borrelli, E}, title = {Quantifying macular atrophy in neovascular AMD using en face structural OCT imaging.}, journal = {Eye (London, England)}, volume = {39}, number = {13}, pages = {2534-2539}, pmid = {40634735}, issn = {1476-5454}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Prospective Studies ; Male ; Female ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; Atrophy ; Aged, 80 and over ; Reproducibility of Results ; Fluorescein Angiography ; *Macula Lutea/pathology ; Angiogenesis Inhibitors/therapeutic use ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Multimodal Imaging ; Visual Acuity ; }, abstract = {PURPOSE: To assess the reliability of en face swept-source OCT (SS-OCT) imaging for quantifying macular atrophy in patients with neovascular age-related macular degeneration (AMD) and evaluate its limitations compared to green autofluorescence (GAF) imaging.<br><br>METHODS: This prospective observational study included 30 patients with macular atrophy associated with neovascular AMD previously treated with anti-VEGF therapy. Multimodal imaging included GAF and en face SS-OCT. Macular atrophy was quantified as regions of hypoautofluorescence on GAF and hypertransmission defects (hyperTDs) on en face SS-OCT. Two masked graders measured atrophy size, followed by qualitative analysis of inter-modality discrepancies. Statistical comparisons were conducted using the Wilcoxon test and Spearman correlation.<br><br>RESULTS: Mean macular atrophy size was 5.96&#x2009;&#xb1;&#x2009;4.48&#x2009;mm&#xb2; on SS-OCT and 7.10&#x2009;&#xb1;&#x2009;5.47&#x2009;mm&#xb2; on GAF, with a significant difference (p&#x2009;<&#x2009;0.001) but strong correlation (&#x3c1;&#x2009;=&#x2009;0.998, p&#x2009;<&#x2009;0.001). Discrepancies arose due to hyperpigmentation obscuring hyperTDs and macular haemorrhages on SS-OCT underestimations of atrophy. Additionally, fibrosis also reduced choroidal hypertransmission, complicating hyperTD detection on SS-OCT. Border delineation inconsistencies were also observed, with diminished autofluorescence on GAF not always corresponding to hyperTDs on SS-OCT.<br><br>CONCLUSIONS: En face SS-OCT is a reliable imaging modality for quantifying macular atrophy in neovascular AMD, with strong correlation to GAF measurements. However, hyperpigmentation, fibrosis, haemorrhages, and variability in border delineation introduce significant challenges. These findings underscore the need for careful interpretation of atrophy metrics and highlight the importance of addressing inter-modality discrepancies in clinical and research applications.}, }
@article {pmid40636510, year = {2025}, author = {Chen, C and Guo, D and Meng, J and Qi, J and Zhang, K and He, W and Tham, YC and Zhu, X}, title = {Grip Strength and Age-Related Ocular Diseases: Insights from Observational, Mendelian Randomization, and Mediation Analyses.}, journal = {Ophthalmology science}, volume = {5}, number = {5}, pages = {100831}, pmid = {40636510}, issn = {2666-9145}, abstract = {OBJECTIVE: We aimed to examine the cross sectional and causal associations of grip strength with cataract, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD) and probe the underlying mechanisms by evaluating the mediating role of metabolomic alterations.<br><br>DESIGN: Cross sectional study.<br><br>SUBJECTS: A total of 307 796 UK Biobank participants with grip strength and covariates data available.<br><br>METHODS: Logistic regression models were used to evaluate the associations between grip strength and age-related ocular diseases. Two-sample Mendelian randomization analyses were conducted to assess the causality. Metabolic biomarkers from plasma samples were measured through nuclear magnetic resonance (n = 152 376), and principal component (PC) analysis was implemented to identify metabolic patterns (PC1-PC8). The mediation effects of both metabolic biomarkers and metabolic patterns were examined.<br><br>MAIN OUTCOME MEASURES: The prevalence of age-related ocular diseases.<br><br>RESULTS: Compared with the highest tertile of grip strength, the lowest tertile had a higher prevalence of cataract (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.24-1.39), glaucoma (OR, 1.23; 95% CI, 1.13-1.33), and DR (OR, 2.80; 95% CI, 2.32-3.38). Genetic-associated elevated grip strength of at least 1 hand was associated with a lower risk of developing cataracts, DR, and AMD. Mediation analyses showed metabolic patterns, characterized by altered lipids and omega-3 polyunsaturated fatty acids (PUFAs) decrement (i.e., PC2 and PC8), significantly mediated the association of grip strength with cataract and DR.<br><br>CONCLUSIONS: Weaker grip strength is associated with cataracts, glaucoma, and DR. Metabolomic alterations, especially disrupted lipid metabolism and omega-3 PUFA decrement, serve to be the critical mediators.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40637952, year = {2025}, author = {Matsumoto, H and Hoshino, J and Numaga, S and Asatori, Y and Akiyama, H}, title = {Loading phase outcomes of intravitreal aflibercept 8 mg for treatment-naïve neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {69}, number = {6}, pages = {911-917}, pmid = {40637952}, issn = {1613-2246}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Intravitreal Injections ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; Follow-Up Studies ; Aged, 80 and over ; Fundus Oculi ; Angiogenesis Inhibitors/administration &amp; dosage ; Dose-Response Relationship, Drug ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Choroid/pathology ; Macula Lutea/pathology ; }, abstract = {PURPOSE: To investigate the efficacy and safety of loading phase treatment with 3 monthly intravitreal injections of aflibercept 8 mg for neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Retrospective, interventional case series.<br><br>METHODS: We retrospectively analyzed 83 consecutive eyes of 80 patients with treatment-na&#xef;ve nAMD who received 3 monthly injections of aflibercept 8 mg as a loading phase treatment. Best-corrected visual acuity (BCVA), foveal thickness, central choroidal thickness (CCT), and dry macula achievement were all assessed every 4 weeks. Moreover, polypoidal lesion regression was evaluated after the loading phase.<br><br>RESULTS: Seventy eyes (84.3%) of 67 patients completed the 3 monthly injections of aflibercept 8 mg. In these cases, BCVA was 0.33&#xb1;0.45 at baseline and showed significant improvement to 0.22&#xb1;0.38 at week 12 (P<0.01). Foveal thickness was 313&#xb1;135&#xb5;m at baseline, decreasing significantly to 171&#xb1;76&#xb5;m at week 12 (P<0.01). CCT was 193&#xb1;98&#xb5;m at baseline, decreasing significantly to 160&#xb1;85&#xb5;m at week 12 (P<0.01). Dry macula had been achieved in 58 (82.9%) of 70 eyes at week 12. Indocyanine green angiography after the loading phase revealed complete polypoidal lesion regression in 16 of 22 eyes (72.7%) with polypoidal lesions. Among the 13 eyes (15.7%) not completing the loading phase treatment, 9 (10.8%) developed non-infectious intraocular inflammation (IOI) associated with retinal vasculitis and aflibercept 8 mg administration was thus discontinued.<br><br>CONCLUSIONS: Loading phase treatment with intravitreal aflibercept 8 mg appears to be effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, careful monitoring is required due to the potential development of IOI associated with retinal vasculitis.}, }
@article {pmid40639430, year = {2026}, author = {Hollaus, M and Baratsits, M and Steiner, I and Weigert, G and Pawloff, M and Mylonas, G and Schmidt-Erfurth, U and Sacu, S}, title = {Long-term effects of drusenoid pigment epithelial detachment on the retina and the choroid.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {61}, number = {1}, pages = {133-141}, doi = {10.1016/j.jcjo.2025.06.010}, pmid = {40639430}, issn = {1715-3360}, abstract = {OBJECTIVE: To analyze the long-term effects of drusenoid pigment epithelial detachment (DPED) on the overlying inner and outer retinal layers and the underlying choroid.<br><br>METHODS: Forty-two eyes from 33 patients with DPED due to intermediate age-related macular degeneration were included in this prospective observational cohort study, which was conducted from December 2017 until July 2023. Patients underwent spectral-domain optical coherence tomography every 6 months. Evaluated parameters included maximum DPED height (=DPED apex) and location of the DPED apex at baseline; furthermore, DPED height, retinal thickness (RT), visibility of retinal layers, presence of hyperreflective foci (HRF), choroidal thickness (CT), and best-corrected visual acuity (BCVA) at baseline and each follow-up visit, as well as development of macular neovascularization or geographic atrophy.<br><br>RESULTS: DPED height, RT, and CT did not change significantly during the observation period (all p values > 0.05). DPED height and RT correlated significantly regardless of visit (estimate&#x202f;=&#x202f;-0.36, 95% CI&#x202f;=&#x202f;-0.4 to -0.32; p < 0.0001), DPED height, and CT did not (p > 0.05). Outer retina (estimate&#x202f;=&#x202f;-2.19, 95% Cl&#x202f;=&#x202f;-2.74 to -1.63; p < 0.0001), location in the central millimeter (estimate&#x202f;=&#x202f;-0.79, 95% Cl&#x202f;=&#x202f;-1.31 to -0.27; p&#x202f;=&#x202f;0.004), and the presence of HRF (estimate&#x202f;=&#x202f;-0.65, 95% Cl&#x202f;=&#x202f;-1.05 to -0.24; p&#x202f;=&#x202f;0.003) were significantly associated with retinal layer visibility regardless of visit, while DPED height was not (p > 0.05). BCVA was not significantly associated with DPED height, RT, CT, or the number of visible outer and inner retinal layers regardless of visit (all p values > 0.05).<br><br>CONCLUSIONS: Our results indicate that increasing DPED height may significantly reduce the thickness of the overlying retina but not of the underlying choroid. Fewer outer retinal layers were visible compared to the inner retina at the DPED apex. Location in the central millimeter of the macula and presence of HRF also reduced the number of visible retinal layers. Impairment of the retinal morphology, which seems to be more pronounced in the outer than the inner retina, need not be accompanied by functional impairment and can recover in case of DPED regression.}, }
@article {pmid40640104, year = {2025}, author = {Wood, AJ and Livingstone, I and Westcott, M and Furniss, D and Wiberg, A}, title = {A review of the role of EFEMP1 in ophthalmic disease.}, journal = {Ophthalmic genetics}, volume = {46}, number = {6}, pages = {523-531}, doi = {10.1080/13816810.2025.2524511}, pmid = {40640104}, issn = {1744-5094}, mesh = {Humans ; *Extracellular Matrix Proteins/genetics ; Genome-Wide Association Study ; Mutation ; *Eye Diseases/genetics ; }, abstract = {EGF-containing fibulin extracellular matrix protein 1 (EFEMP1), or fibulin-3, is an extracellular matrix glycoprotein encoded by the EFEMP1 gene. The role of EFEMP1 in the human eye is incompletely understood, but there are well-reported associations between mutations in the gene and a variety of ophthalmic diseases, such as myopia, juvenile open-angle glaucoma (JOAG), primary open-angle glaucoma (POAG) and familial drusen formation in Malattia Leventinese (ML)/Doyne honeycomb retinal dystrophy (DHRD). Variants which interact with EFEMP1 have also been identified in genome-wide association studies (GWAS) for age-related macular degeneration (AMD). Many of these conditions form a large component of ophthalmology case-load and have incompletely characterized pathogenesis. In this review, we will describe the role of EFEMP1 in ophthalmic disease. We discuss the role of EFEMP1 in Mendelian eye disease, its polygenic contributions to common ophthalmic conditions, and the potential to target EFEMP1 for therapeutic purposes.}, }
@article {pmid40640441, year = {2025}, author = {Balogh, B and Zille, M and Szarka, G and Péntek, L and Futácsi, A and Völgyi, B and Kovács-Öller, T}, title = {Local microglial activation induced and labeled in the retina in a novel subretinal hemorrhage mouse model.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {24804}, pmid = {40640441}, issn = {2045-2322}, mesh = {Animals ; *Microglia/metabolism/pathology ; *Retinal Hemorrhage/pathology/metabolism ; Mice ; Disease Models, Animal ; *Retina/pathology/metabolism ; Mice, Inbred C57BL ; Retinal Pigment Epithelium/pathology/metabolism ; Cholera Toxin/metabolism ; }, abstract = {Subretinal hemorrhage (SRH) is caused by the accumulation of blood between the neurosensory retina and the retinal pigment epithelium or between the retinal pigment epithelium and the choroid. SRH often arises from age-related macular degeneration, traumas, and may occur spontaneously caused by other diseases like hypertension and diabetes. Here, we developed a novel technique - co-injection of blood and a dye-coupled tracer protein, Cholera toxin subunit B (CtB) - to better localize and understand the disease and how it can cause microglial activation, inflammation, and partial vision loss. Our results show that microglia are activated in the inner retinal layers in zones adjacent to blood injection. In contrast, the non-affected zone of the injected eye showed no microglial activation. For the first time, we used phosphate-buffered saline (PBS) injections as a control to assess the specific effects of injected blood. The results demonstrated that blood induced a markedly stronger activation response in the surrounding tissue, whereas PBS elicited a comparatively milder effect. PBS did cause microglial activation, but it was largely confined to the injection site and adjacent regions, and to a lesser extent than that observed with blood. We also observed microglial activation in the inner retina, along with the emergence of microglia and macrophages in the retinal pigment epithelium. Using advanced imaging techniques, we were able to better localize the affected area which comprises not only the immediate retinal area over the blood clot but the neighboring regions as well. These findings will provide the basis for novel therapeutic interventions targeting neuroinflammation in the retina after subretinal hemorrhage and other diseases affecting the eye.}, }
@article {pmid40643526, year = {2025}, author = {Dörschmann, P and von der Weppen, S and Koyama, E and Roider, J and Klettner, A}, title = {Porcine Single-Eye Retinal Pigment Epithelium Cell Culture for Barrier and Polarity Studies.}, journal = {Cells}, volume = {14}, number = {13}, pages = {}, pmid = {40643526}, issn = {2073-4409}, support = {03LW0148//Bundesministerium f&#xfc;r Bildung und Forschung/ ; }, mesh = {*Retinal Pigment Epithelium/cytology/metabolism ; Animals ; Swine ; *Cell Polarity ; Cells, Cultured ; *Cell Culture Techniques/methods ; Electric Impedance ; Bestrophins/metabolism ; }, abstract = {Age-related macular degeneration (AMD) is the main cause of blindness in Western nations. AMD models addressing specific pathological pathways are desired. Through this study, a best-practice protocol for polarized porcine single-eye retinal pigment epithelium (RPE) preparation for AMD-relevant models of RPE barrier and polarity is established. Single-eye porcine primary RPE cells (from one eye for one well) were prepared in 12-well plates including Transwell inserts. Different coatings (laminin (Lam), Poly-ᴅ-Lysine (PDL), fibronectin (Fn) and collagens) and varying serum contents (1%, 5% and 10%) were investigated to determine optimal culture parameters for this model. Success rates of cultures, cell number (trypan-blue exclusion assay), morphology/morphometry (light and fluorescence microscopy), protein secretion/expression (ELISA, Western blot), gene expression (qPCR), transepithelial electric resistance (TEER) and polar location of bestrophin 1 (BEST1) by cryosectioning (IHC-Fr) were assessed. Cells seeded on Lam exhibited the highest level of epithelial cells and confluence properties. Fn resulted in the highest cell number growth. Lam and Fn exhibited the highest culture success rates. TEER values and vascular endothelial growth factor secretion were highest when Lam was used. For the first time, polar (Transwell) porcine single-eye RPE morphometry parameters were determined. RPE on Lam showed bigger cells with a higher variety of cell shapes. CIV displayed the lowest claudin 19 expression. The highest basolateral expression of BEST1 was achieved with Lam coating. The higher the serum, the better the cell number increase and confluence success. A reduction in serum on Lam showed positive results for RPE morphology, while morphometry remained stable. A five percent serum on Lam showed the highest culture success rate and best barrier properties. RPE65 expression was reduced by using 10% serum. Altogether, the most suitable coating of Transwell inserts was Lam, and a reduction in serum to 5% is recommended, as well as a cultivation time of 28 days. A protocol for the use of polar porcine single-eye cultures with validated parameters was established and is provided herein.}, }
@article {pmid40646244, year = {2025}, author = {Negiloni, K and Baskaran, P and Rao, DP and Maitray, A and Savoy, FM and Suresh, S and Mahalingam, M and Vighnesh, MJ and Rajendran, A}, title = {Advancing AMD screening with an offline, AI-powered smartphone-based fundus camera: A prospective, real-world clinical validation.}, journal = {Eye (London, England)}, volume = {39}, number = {13}, pages = {2548-2554}, pmid = {40646244}, issn = {1476-5454}, mesh = {Humans ; Prospective Studies ; *Smartphone/instrumentation ; Middle Aged ; Female ; Male ; Aged ; Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnosis ; Algorithms ; Fundus Oculi ; *Photography/instrumentation ; *Artificial Intelligence ; Sensitivity and Specificity ; Reproducibility of Results ; *Diagnostic Techniques, Ophthalmological/instrumentation ; }, abstract = {OBJECTIVES: This study evaluated a novel offline, AI-driven age-related macular degeneration (AMD) screening algorithm against fundus image-only grading and the standard of care (combined Spectral Domain-Optical Coherence Tomography (SD-OCT) and fundus image grading).<br><br>METHODS: Conducted prospectively at a South Asian tertiary eye hospital, this study utilized a validated smartphone-based non-mydriatic fundus camera to capture macula-centred images. The Medios AI's ability to detect referable AMD was compared to a reference standard image grading, using fundus images from the Zeiss Clarus 700 table-top camera and SD-OCT line scan across fovea. Three retina specialists provided blinded AMD diagnoses based on: (1) Zeiss Clarus 700 fundus images alone, and (2) combined SD-OCT and fundus images (standard of care). Referable AMD was defined as intermediate or advanced AMD.<br><br>RESULTS: Among 984 eyes from 492 patients (mean age 61.8&#x2009;&#xb1;&#x2009;9.9 years), 52% had referable AMD. Inter-grader agreement was strong, with Cohen's Kappa scores of 0.81-0.84. The Medios AI's sensitivity and specificity for detecting referable AMD against fundus-only grading (n&#x2009;=&#x2009;492) were 88.48% (95% CI: 84.04-92.03%) and 87% (95% CI: 81.86-91.11%), respectively. Against combined grading (n&#x2009;=&#x2009;489), AI sensitivity was 90.62% (95% CI: 86.37-93.90%), and specificity was 85.41% (95% CI: 80.21-89.68%). False negatives were primarily intermediate AMD (71%), while 59% of false positives were early AMD.<br><br>CONCLUSION: The novel, automated, offline AMD AI integrated on a smartphone fundus camera demonstrated robust performance in identifying referable forms of AMD, supporting its potential as an affordable and accessible screening solution.}, }
@article {pmid40647687, year = {2025}, author = {Ranetti, AE and Stanca, HT and Munteanu, M and Bievel Radulescu, R and Stanca, S}, title = {Blue Light and Green Light Fundus Autofluorescence, Complementary to Optical Coherence Tomography, in Age-Related Macular Degeneration Evaluation.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {13}, pages = {}, pmid = {40647687}, issn = {2075-4418}, abstract = {Background: Age-related macular degeneration (AMD) is one of the leading causes of permanent vision loss in the elderly, particularly in higher-income countries. Fundus autofluorescence (FAF) imaging is a widely used, non-invasive technique that complements structural imaging in the assessment of retinal pigment epithelium (RPE) integrity. While optical coherence tomography (OCT) remains the gold standard for retinal imaging due to its high-resolution cross-sectional visualization, FAF offers unique metabolic insights. Among the FAF modalities, blue light FAF (B-FAF) is more commonly employed, whereas green light FAF (G-FAF) provides subtly different image characteristics, particularly improved visualization and contrast in the central macula. Despite identical acquisition times and nearly indistinguishable workflows, G-FAF is notably underutilized in clinical practice. Objectives: This narrative review critically compares green and blue FAF in terms of their diagnostic utility relative to OCT, with a focus on lesion detectability, macular pigment interference, and clinical decision-making in retinal disorders. Methods: A comprehensive literature search was performed using the PubMed database for studies published prior to February 2025. The search utilized the keywords fundus autofluorescence and age-related macular degeneration. The primary focus was on short-wavelength FAF and its clinical utility in AMD, considering three aspects: diagnosis, follow-up, and prognosis. The OCT findings served as the reference standard for anatomical correlation and diagnostic accuracy. Results: Both FAF modalities correlated well with OCT in detecting RPE abnormalities. G-FAF demonstrated improved visibility of central lesions due to reduced masking by macular pigment and enhanced contrast in the macula. However, clinical preference remained skewed toward B-FAF, driven more by tradition and device default settings than by evidence-based superiority. G-FAF's diagnostic potential remains underrecognized despite its comparable practicality and subtle imaging advantages specifically for AMD patients. AMD stages were accurately characterized, and relevant images were used to highlight the significance of G-FAF and B-FAF in the examination of AMD patients. Conclusions: While OCT remains the gold standard, FAF provides complementary information that can guide management strategy. Since G-FAF is functionally equivalent in acquisition, it offers slight advantages. Broader awareness and more frequent integration of G-FAF that could optimize multimodal imaging strategies, particularly in the intermediate stage, should be developed.}, }
@article {pmid40648575, year = {2025}, author = {Confalonieri, F and Hertzberg, SNW and Dziedzic, KA and Lumi, X and Lytvynchuk, L and Znaor, L and Petrovski, G and Petrovski, B&#xc9;}, title = {Cost-Effectiveness of Alternative Treatment Strategies of Subretinal Macular Hemorrhage.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {13}, pages = {}, pmid = {40648575}, issn = {2227-9032}, abstract = {Purpose: To evaluate the cost-effectiveness of alternative treatment strategies for subretinal macular hemorrhage (SRMH), a condition often associated with neovascular age-related macular degeneration (AMD) and other retinal vascular disorders, leading to severe visual impairment. Methods: A retrospective cross-sectional study conducted at Oslo University Hospital assessed the cost and utility of various SRMH treatment modalities. These included intravitreal anti-VEGF monotherapy, intravitreal tissue plasminogen activator (tPA) with gas displacement (alone and in combination with anti-VEGF), and pars plana vitrectomy (PPV) with subretinal tPA and gas displacement (with and without anti-VEGF). Costs were analyzed from a healthcare perspective, encompassing direct and indirect costs. Effectiveness was measured using median best-corrected visual acuity (BCVA) improvements. Sensitivity analyses were performed to account for complications and variations in follow-up. Results: Anti-VEGF monotherapy was the most cost-effective treatment, with the lowest cost per unit of BCVA improvement (NOK 44,717) in outpatient settings. Intravitreal tPA with gas displacement emerged as a cost-effective alternative but exhibited higher costs when combined with anti-VEGF or performed as an inpatient procedure. PPV with subretinal tPA and gas displacement, with or without anti-VEGF, was the least cost-effective modality, particularly in inpatient settings. Sensitivity analyses indicated that anti-VEGF therapy remained cost-effective even with increased follow-up requirements and complications, while tPA-based therapies required significant BCVA improvements to match anti-VEGF's cost-utility. Conclusions: Outpatient intravitreal anti-VEGF monotherapy followed by tPA with gas displacement are the most cost-effective strategies for SRMH management. Subretinal tPA-based treatments are associated with higher costs and limited economic viability, highlighting the importance of tailored treatment selection. These findings support strategic resource allocation in managing SRMH while optimizing patient outcomes.}, }
@article {pmid40649894, year = {2025}, author = {Camelo, S}, title = {Repurposing Dimethyl Fumarate Targeting Nrf2 to Slow Down the Growth of Areas of Geographic Atrophy.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40649894}, issn = {1422-0067}, support = {P170919//Programme Hospitaller de Recherche Clinique (PHRC) - 2017 (French Ministry of Health)./ ; }, mesh = {Humans ; *NF-E2-Related Factor 2/metabolism/antagonists &amp; inhibitors ; *Dimethyl Fumarate/therapeutic use/pharmacology ; *Drug Repositioning ; *Geographic Atrophy/drug therapy/metabolism/pathology ; Animals ; Oxidative Stress/drug effects ; Macular Degeneration/drug therapy ; }, abstract = {Recently, marketing authorizations were granted by the Federal Drug Administration (FDA) for pegcetacoplan and avacincaptad pegol, which inhibit C3 and C5 complement components, respectively. These two drugs were demonstrated to slow down the growth of atrophic areas in the retina. These authorizations represent a huge breakthrough for patients suffering from geographic atrophy (GA), the late stage of the dry form of Age-related Macular Degeneration (AMD). Until then, no treatment was available to treat this blinding disease. However, these two new compounds inhibiting the complement system are still not available for patients outside of the United States, and they are not devoid of drawbacks, including a poor effect on vision improvement, an increased risk of occurrence of the neovascular form of AMD and the burden of patients receiving recurrent intravitreal injections. Thus, the important medical need posed by GA remains incompletely answered, and new therapeutic options with alternative modes of action are still required. Oxidative stress and inflammation are two major potential targets to limit the progression of atrophic retinal lesions. Dimethyl fumarate, dimethyl itaconate and other activators of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) display antioxidants and immunomodulatory properties that have shown evidence of efficacy in in vitro and in vivo models of dry AMD. Tecfidera[®], whose active principle is dimethyl fumarate, is already commercialized for the treatment of autoimmune diseases such as multiple sclerosis and psoriasis. The aim of this review is to present the rationale and the design of the clinical trial we initiated to test the effectiveness and safety of repurposing Tecfidera[®], which could represent a new therapeutic alternative in patients with the dry form of AMD.}, }
@article {pmid40649951, year = {2025}, author = {Jiang, F and Ma, J and Lei, C and Zhang, Y and Zhang, M}, title = {Age-Related Macular Degeneration: Cellular and Molecular Signaling Mechanisms.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40649951}, issn = {1422-0067}, support = {2024YFFK0303//Sichuan Provincial Science and Technology Support Project/ ; 82301232//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Macular Degeneration/metabolism/pathology/etiology ; *Signal Transduction ; Retinal Pigment Epithelium/metabolism/pathology ; Oxidative Stress ; Animals ; Choroidal Neovascularization/metabolism/pathology ; }, abstract = {Age-related macular degeneration (AMD) is a progressive retinal disorder and a leading cause of irreversible blindness among elderly individuals, impacting millions of people globally. This review synthesizes the current understanding of the cellular and molecular signaling mechanisms driving AMD, with a focus on the distinct pathophysiological features of dry and wet AMD subtypes. Key mechanisms include oxidative stress, inflammation, lipid metabolism dysregulation, and immune dysregulation, all of which converge on the retinal pigment epithelium (RPE) as a central player in disease initiation and progression. In dry AMD, oxidative damage, mitochondrial dysfunction, and lipofuscin accumulation impair RPE function, contributing to drusen formation and geographic atrophy. In wet AMD, vascular endothelial growth factor-mediated angiogenesis, coupled with inflammation and endothelial metabolic reprogramming, drives choroidal neovascularization. This article integrates findings from multiomics approaches and highlights the potential of artificial intelligence in elucidating AMD pathogenesis and advancing personalized therapies. Future research directions emphasize targeting these molecular pathways to develop innovative treatments, offering hope for improved management of this debilitating condition.}, }
@article {pmid40653260, year = {2025}, author = {Lak, S and Kanavi, MR and Bayat, K and Ahmadieh, H and Soheili, ZS and Suri, F}, title = {Differential expression profiles of MAPT (TAU) gene isoforms in dry age-related macular degeneration.}, journal = {Experimental eye research}, volume = {258}, number = {}, pages = {110517}, doi = {10.1016/j.exer.2025.110517}, pmid = {40653260}, issn = {1096-0007}, mesh = {Humans ; *tau Proteins/genetics/biosynthesis ; Middle Aged ; Male ; Female ; Aged ; Protein Isoforms/genetics ; Real-Time Polymerase Chain Reaction ; RNA, Messenger/genetics ; *Geographic Atrophy/genetics/metabolism ; *Gene Expression Regulation/physiology ; Adult ; Aged, 80 and over ; }, abstract = {Age-related macular degeneration (AMD) is a neurodegenerative retinal disorder that typically emerges later in life and is the primary cause of central visual loss. The microtubule-associated protein Tau (MAPT) gene produces six significant splice variants in neural cells, which are differentiated by the exclusion or inclusion of exon 10, resulting in expression of 3R and 4R isoforms. Changes in Tau expression and the ratio of 4R-3R isoforms have been observed in various neurodegenerative diseases; however, the expression of Tau mRNA in AMD remains unexplored. This study represents the first investigation into the expression of MAPT transcript variants in patients with dry AMD. Human donor eyes were sourced from the Iranian Eye Bank and divided into three categories: Dry-AMD (aged ≥50 years, n = 13), Elderly-Normal (aged ≥50 years, n = 13), and Young-Normal (aged ≤40 years, n = 10). Retinal RNA was isolated, and quantitative real-time PCR (qRT-PCR) was employed to evaluate total Tau, as well as the 3R, and 4R transcript variants using specific primers. Dry-AMD samples showed a mixture of 3R and 4R isoforms, with no significant difference in total Tau levels when compared to both control groups. However, the 4R/3R ratio was significantly higher in Dry-AMD samples compared to both control groups, while no significant difference was observed between elderly and young controls. These findings indicate that changes in the 4R/3R Tau ratio may play a role in the progression of Dry-AMD, potentially triggering pathways that promote disease advancement. Further research is necessary to explore these results across various stages of the disease.}, }
@article {pmid40653498, year = {2025}, author = {Yan, C and Yi, Q and Ge, L and Huang, Y and Yang, C and Lin, B and Jiang, D and Zhou, M}, title = {Metabolomics analysis uncovers metabolic changes and remodeling of anti-VEGF therapy on macular edema.}, journal = {Eye and vision (London, England)}, volume = {12}, number = {1}, pages = {28}, pmid = {40653498}, issn = {2326-0254}, support = {82000909//National Natural Science Foundation of China/ ; 62372331//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Anti-angiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) is currently the first-line treatment for macular edema (ME), but the specific metabolic changes in the aqueous humor (AH) after intravitreal anti-VEGF injections remain poorly understood.<br><br>METHODS: A total of 120 AH samples from 60 ME patients before and after anti-VEGF treatment were collected from the ophthalmology clinic and ward of the Eye Hospital of Wenzhou Medical University. Non-targeted metabolomics analysis of the AH samples was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify metabolite differences before and after anti-VEGF treatment in patients with different ME etiologies.<br><br>RESULTS: Distinct metabolomic profiles were observed between pre- and post-treatment samples. A total of 145 significantly altered metabolites were identified after anti-VEGF treatment, with 84 upregulated metabolites related to carbohydrate and amino acid metabolism, and 61 downregulated metabolites involved in amino acid metabolism. Both common and etiology-specific metabolic alterations were observed. In age-related macular degeneration (AMD)-ME, treatment-induced metabolic changes mainly involved amino acid metabolism, whereas in branch retinal vein occlusion (BRVO)-ME, lipid metabolism was primarily affected. Diabetic macular edema (DME) patients showed more complex metabolic alterations, involving amino acid, lipid and carbohydrate metabolism.<br><br>CONCLUSIONS: Intravitreal anti-VEGF injections significantly alter AH metabolites in ME patients. These findings provide insight into underlying metabolic processes in ME pathogenesis and treatment efficacy.}, }
@article {pmid40653679, year = {2025}, author = {Liu, J and Yi, C and Qi, J and Cui, X and Yuan, X and Deng, W and Chen, M and Xu, H}, title = {Senescence Alters Antimicrobial Peptide Expression and Induces Amyloid-β Production in Retinal Pigment Epithelial Cells.}, journal = {Aging cell}, volume = {24}, number = {9}, pages = {e70161}, pmid = {40653679}, issn = {1474-9726}, support = {2023JJ70047//Hunan Provincial Natural Science Foundation of China/ ; 2025JJ90270//Hunan Provincial Natural Science Foundation of China/ ; AM2201D02//Science Research Foundation of Aier Eye Hospital Group/ ; AMF2401D05//Science Research Foundation of Aier Eye Hospital Group/ ; AEI202304JC01//Science Research Foundation of Aier Eye Institute/ ; KY24002//Philanthropy Foundation of Xiangjiang/ ; KY24008//Philanthropy Foundation of Xiangjiang/ ; AIM2301D02//Clinical Research Foundation of Aier Eye Hospital Group/ ; MR/W004682/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Amyloid beta-Peptides/metabolism/biosynthesis ; *Retinal Pigment Epithelium/metabolism/cytology ; *Cellular Senescence ; *Antimicrobial Peptides/metabolism/genetics ; Amyloid Precursor Protein Secretases/metabolism ; *Epithelial Cells/metabolism ; }, abstract = {Age-related retinal degeneration, such as diabetic retinopathy and age-related macular degeneration, are major causes of blindness in modern society. Recent studies suggest that dysbiosis and intraocular translocation of bacteria from the blood circulation are critically involved in retinal degeneration. We hypothesise that the blood-retinal barrier (BRB) cells can protect the neuroretina from blood-borne pathogens by producing antimicrobial peptides (AMPs). The antimicrobial activity may decline during ageing, putting the retina at risk of low-degree chronic inflammation and degeneration. Here, we found that the retinal pigment epithelial (RPE) cells, which form the outer BRB, express a variety of AMPs/AMP precursors, including APP, RARRES2, FAM3A, HAMP, CAMP, GNLY, and PI3. Senescent RPE cells expressed lower levels of APP and RARRES2 mRNA, accompanied by increased intracellular retention of E. coli in a bactericidal assay. Silencing APP, not RARRES2, with shRNA reduced the antibacterial activity of RPE cells. Senescent RPE cells had lower levels of α-secretase and higher levels of β-secretase (BACE1) and γ-secretase (PS1), accompanied by reduced soluble APPα and increased amyloid beta (Aβ) production, particularly the Aβ42 isoform. Eyes from aged donors showed a higher Aβ accumulation within RPE cells. Our results suggest that while RPE cells possess antimicrobial activity, this ability declines with age and is impaired in senescent cells. The impaired antimicrobial activity and augmented Aβ deposition in senescent RPE cells may contribute to age-related retinal para-inflammation and neurodegeneration.}, }
@article {pmid40655237, year = {2025}, author = {O'Neill, Y and Arrigo, A and Stanga, PE}, title = {Addressing chronic visual hallucination by multimodal retinal imaging: a CBS case.}, journal = {Therapeutic advances in ophthalmology}, volume = {17}, number = {}, pages = {25158414251320032}, pmid = {40655237}, issn = {2515-8414}, abstract = {Charles Bonnet syndrome (CBS) is characterised by visual hallucinations in individuals with significant visual impairment. This literature review and case report focus on the unique presentation of CBS in an 82-year-old woman with age-related macular degeneration, who experienced visual hallucinations for over 10 years. The aim is to raise awareness of CBS among healthcare professionals and the public, addressing the diagnostic challenges that contribute to its underdiagnosis and mismanagement. A literature review was conducted to assess the prevalence and diagnosis of CBS. Databases including Google Scholar and PubMed were searched using the terms 'Charles Bonnet Syndrome', 'Case report' and 'Diagnosis'. The patient reported a range of visual hallucinations, from simple geometric shapes to highly detailed figures. A diagnosis of CBS was made based on her visual impairment and the nature of the hallucinations. No treatment was required, and the patient was reassured that the hallucinations were benign and unrelated to any psychiatric or neurological disorder. This case highlights the diagnostic challenges associated with CBS, which is often misdiagnosed or overlooked due to its rarity and the hesitancy of patients to disclose their symptoms. The long period of unreported hallucinations in this case emphasises the need for greater awareness among healthcare providers, enabling earlier recognition of CBS and differentiation from other conditions. The wide range of hallucination types seen in CBS adds to the complexity of the syndrome. The key takeaway is that increased awareness and recognition of CBS are essential for proper diagnosis, reducing patient anxiety and avoiding unnecessary treatments. This case contributes to the existing literature by illustrating the broad spectrum of CBS presentations and advocating for enhanced education on the condition.}, }
@article {pmid40656517, year = {2025}, author = {Mansour, AM and Lima, LH and Battaglia Parodi, M and Casella, AMB and Cherfan, DG and Arevalo, JF}, title = {Outcomes of and Surgical Technique for Treatment With High-Dose Aflibercept.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251352890}, pmid = {40656517}, issn = {2474-1272}, abstract = {Purpose: To describe an alternate delivery of high-dose aflibercept using previous formulations (ie, prefilled syringe, vial, or compounded). Methods: A prospective pilot study was performed to analyze the short-term safety and visual gain (expressed in logMAR), including increase in intraocular pressure (IOP), resulting from a modified regimen consisting of 0.18 mL paracentesis followed by an intravitreal injection of 0.18 mL aflibercept (prefilled syringe), 0.20 mL aflibercept (vial), or 0.22 mL ziv-aflibercept (compounded). Results: The study comprised 32 eyes (16 naïve; 18 neovascular age-related macular degeneration; 8 retinal vein occlusion). Over a follow-up of 4.1 (± 3.2) months, a mean (± SD) of 1.7 (± 0.9) high-dose injections were administered. The baseline best spectacle-corrected vision was 1.35 ± 0.71 (Snellen VA) and improved to 0.68 ± 0.46 at 1 month (P < .001) and 0.57 ± 0.43 at the final follow-up (P < .001). An increase in IOP of 0.43 ± 4.26 mm Hg was seen 1 minute after injection (P = .58). In 2 eyes (6.3%), reflux as a tiny bleb was noted. Conclusions: When high-dose aflibercept is neither available nor affordable, a patient's readily accessible and cost-effective regimen of aflibercept will allow an exact delivery of high-dose aflibercept, combining minimal drug reflux, minimal immediate increase in IOP, and potential clinical efficacy in the short term.}, }
@article {pmid40656681, year = {2025}, author = {Min, Y and Cuevas-Rios, G and Langmann, T and Neumann, H}, title = {Sialylation as a checkpoint for inflammatory and complement-related retinal diseases.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1623755}, pmid = {40656681}, issn = {1662-5102}, abstract = {Sialylation is a modification process involving the addition of sialic acid residues to the termini of glycoproteins and glycolipids in mammalian cells. Sialylation serves as a crucial checkpoint inhibitor of the complement and immune systems, particularly within the central nervous system (CNS), including the retina. Complement factor H (FH), complement factor properdin (FP), and sialic acid-binding immunoglobulin-like lectin (SIGLEC) receptors of retinal mononuclear phagocytes are key players in regulating the complement and innate immune systems in the retina by recognizing sialic acid (Sia) residues. Intact retinal sialylation prevents any long-lasting and excessive complement or immune activation in the retina. However, sialylated glycolipids are reduced in the CNS with aging, potentially contributing to chronic inflammatory processes in the retina. Particularly, genetically induced hyposialylation in mice leads to age-related, complement factor C3-mediated retinal inflammation and bipolar cell loss. Notably, most of the gene transcript pathways enriched in the mouse retina, following genetically induced hyposialylation, are also involved in age-related macular degeneration (AMD). Interestingly, intravitreal application of polysialic acid (polySia) controlled the innate immune responses in the mouse retina by blocking mononuclear phagocyte reactivity, inhibiting complement activation, and protecting against vascular damage in two different humanized SIGLEC-11 animal models. Accordingly, a polySia polymer conjugate has entered clinical phase II/III testing in patients with geographic atrophy secondary to AMD. Thus, hyposialylation or dysfunctional sialylation should be considered as an age-related contributor to inflammatory retinal diseases, such as AMD. Consequently, sialic acid-based biologics could provide novel therapies for complement-related retinal diseases.}, }
@article {pmid40656874, year = {2025}, author = {Hu, P and He, M and Cai, J and Lin, Z and Zheng, S and Zhuang, Z and Liu, J and Huang, L}, title = {Global burden of smoking-associated age-related macular degeneration: Spatiotemporal trends from 1990 to 2021 and projections to 2040.}, journal = {Tobacco induced diseases}, volume = {23}, number = {}, pages = {}, pmid = {40656874}, issn = {1617-9625}, abstract = {INTRODUCTION: Smoking is a major modifiable risk factor for age-related macular degeneration (AMD); however, the long-term trends and sociodemographic disparities in its global burden remain insufficiently characterized. This study aimed to assess the evolving burden of smoking-associated AMD from 1990 to 2021 and project its trajectory to 2040.<br><br>METHODS: Data from the Global Burden of Disease (GBD) 2021 database were used to extract smoking-associated AMD burden, measured by years lived with disability (YLDs) and age-standardized YLDs rate (ASYLDsR). Trends were stratified by sociodemographic index (SDI) and GBD super-regions, analyzed via estimated annual percentage change (EAPC), and projected using an autoregressive integrated moving average (ARIMA) model.<br><br>RESULTS: In 2021, the global burden of smoking-associated AMD reached 58858 YLDs (a 47.1% increase from 1990), with an ASYLDsR of 2.47 per 100000 population. The burden in males significantly exceeded the female burden (45442 vs 13417 YLDs in 2021), with a widening disparity. YLDs peaked in the age group of 65-69 years (12528 cases), while ASYLDsR increased with age. East Asia had the highest cases (23248 cases, 39.5% of the global total), whereas Central Asia exhibited rising ASYLDsR. ARIMA projections estimated global YLDs to rise to 72574 (95% CI: 61319-83828) by 2040, with ASYLDsR declining to 1.54 per 100000 (95% CI: 0.90-2.17).<br><br>CONCLUSIONS: The burden of smoking-associated AMD demonstrates marked demographic and geographical heterogeneity. Aging populations drive rising absolute case numbers, while disparities in tobacco control policies contribute to regional divergence in ASYLDsR.}, }
@article {pmid40658332, year = {2025}, author = {Iida, T and Gomi, F and Yasukawa, T and Yamashiro, K and Honda, S and Maruko, I and Kataoka, K and , }, title = {Japanese clinical guidelines for neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {69}, number = {4}, pages = {639-660}, pmid = {40658332}, issn = {1613-2246}, mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; *Disease Management ; Fluorescein Angiography/methods ; Japan/epidemiology ; Tomography, Optical Coherence/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/diagnosis/therapy/epidemiology/drug therapy ; }, abstract = {Recent advances in imaging technology and increased options of pharmaceutical therapy require that guidelines on the diagnostic criteria and treatment of neovascular age-related macular degeneration (AMD) be updated at regular intervals. These guidelines aim to standardize the management of neovascular AMD based on the latest understanding of its pathophysiology, advancements in diagnostic imaging modalities, and treatment options. The key updates include: (1) a revision of terminology and stage classification, adopting the AMD classifications of atrophic and neovascular, and adding end-stage AMD to the existing early, intermediate, and late stages; (2) the inclusion of pachychoroid in addition to drusen in the initial pathophysiology and pathogenic background; (3) diagnostic criteria defined by the presence of macular neovascularization based on multimodal imaging, including optical coherence tomography (OCT) and OCT angiography; (4) assessment of disease activity based on OCT; and (5) treatment guidance, including prophylaxis and low vision care as well as loading and maintenance phases by use of anti-vascular endothelial growth factor therapy and adjunctive therapies. We hope that these guidelines will be useful for those working in clinical practice in Japan, in other Asian countries, and in countries outside Asia.}, }
@article {pmid40658846, year = {2025}, author = {Wang, Z and Anderson, DMG and Messinger, JD and Curcio, CA and Schey, KL}, title = {Glycolipids implicated as mediators of clinically visible retinal pigment epithelial migration in age-related macular degeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {29}, pages = {e2503191122}, pmid = {40658846}, issn = {1091-6490}, support = {R01 EY029748//HHS | NIH | National Eye Institute (NEI)/ ; Catalyst Award//Research to Prevent Blindness (RPB)/ ; unrestricted funds//Research to Prevent Blindness (RPB)/ ; unrestricted funds//EyeSight Foundation of Alabama (ESFA)/ ; }, mesh = {*Retinal Pigment Epithelium/metabolism/pathology ; Humans ; *Macular Degeneration/metabolism/pathology ; *Cell Movement ; *Glycolipids/metabolism ; Tomography, Optical Coherence ; Aged ; G(M3) Ganglioside/metabolism ; }, abstract = {The retinal pigment epithelium (RPE) is the metabolic gatekeeper to the photoreceptors, thus playing many essential roles in healthy vision. Under certain conditions, RPE cells may transdifferentiate and migrate from the RPE layer. Ectopic RPE cells are potential signal sources for hyperreflective foci, prominent clinically visible biomarkers in age-related macular degeneration, which causes central vision loss globally. Applying multiple imaging modalities including ex vivo optical coherence tomography, autofluorescence microscopy, and imaging mass spectrometry (IMS) to human retina tissue, we compared lipid profiles in ectopic and orthotopic RPE cells. Our results showed that ectopic RPE cells share some molecular signatures with normal RPE cells as revealed through autofluorescence imaging and IMS. In both orthotopic and ectopic RPE cells, IMS detected phosphatidylglycerol, PG 36:2, and several triacylglycerols containing long-chain fatty acids. GM3 gangliosides (40:1, 42:1, and 42:2) were also detected in ectopic RPE cells with differences in abundance in different populations of ectopic RPE cells. Lactosylceramide (LacCer 44:5) and glucosylceramide (GlcCer 44:5) were found exclusively in ectopic RPE cells. In contrast, ectopic RPE did not exhibit signals of phosphatidylinositols (PI) (PI32:0, PI32:1, PI34:1, and PI34:2) normally detected in RPE cells. Near-single-cell resolution IMS results suggest that RPE transdifferentiation, with loss of normal functions and gain of new functions like migration, may be linked to altered metabolism of glycosphingolipids and PIs.}, }
@article {pmid40659110, year = {2025}, author = {Kim, JY and Kim, S and Cho, J and Lee, JS and Lee, CS and Byeon, SH and Kim, SS and Lee, SW and Kim, YJ}, title = {Exudative AMD Risk Following Blue Light-Filtering IOL Implantation: A Population-Based Study According to Non-Exudative AMD Status.}, journal = {American journal of ophthalmology}, volume = {279}, number = {}, pages = {1-10}, doi = {10.1016/j.ajo.2025.07.007}, pmid = {40659110}, issn = {1879-1891}, mesh = {Humans ; Male ; Female ; Aged ; Incidence ; Republic of Korea/epidemiology ; *Lenses, Intraocular ; *Lens Implantation, Intraocular ; Middle Aged ; Risk Factors ; *Wet Macular Degeneration/epidemiology/etiology/diagnosis/prevention &amp; control ; Retrospective Studies ; Aged, 80 and over ; Follow-Up Studies ; Databases, Factual ; Visual Acuity ; Blue Light ; }, abstract = {PURPOSE: To evaluate whether blue light-filtering (BLF) intraocular lenses (IOLs) reduce the risk of exudative age-related macular degeneration (AMD).<br><br>DESIGN: A nationwide, population-based cohort study using data from the Korean National Health Insurance Sharing Service (NHISS) database.<br><br>PARTICIPANTS: Individuals who underwent cataract surgery and received the same type of IOL (BLF or clear) in both eyes within one year between January 2012 and December 2018.<br><br>METHODS: Participants were categorized into BLF IOL or clear IOL groups, and the risk of exudative AMD was compared between the 2 groups. The 10-year cumulative incidence of exudative AMD was estimated using Kaplan-Meier analysis. Cox proportional hazard models and the Fine-Gray model were applied to calculate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), adjusting for age, sex, socioeconomic status, and systemic diseases. The same analysis was performed in the cohort matched by age, sex, and the calendar year of the index date.<br><br>MAIN OUTCOME MEASURES: 10-year cumulative incidence, incidence rate, and HR for exudative AMD.<br><br>RESULTS: A total of 21,741 individuals with BLF IOLs were compared to 56,357 individuals with clear IOLs. The mean follow-up duration was 7.0 &#xb1; 2.5 years in the BLF IOL group and 6.7 &#xb1; 2.5 years in the clear IOL group (P = .069). The 10-year cumulative incidence of exudative AMD was 1.8% (95% CI, 1.5%-2.0%) in the BLF IOL group and 1.7% (95% CI, 1.5%-1.8%) in the clear IOL group. The incidence rates per 100,000 person-years were 162.8 and 153.9 in the BLF IOL group and clear IOL groups, respectively, with no significant difference in the adjusted Cox model (aHR 1.12; 95% CI, 0.96-1.30; P = .149) and the Fine-Gray model (aHR 1.15; 95% CI, 0.97-1.36; P = .120). Subgroup analyses based on age, sex, and history of nonexudative AMD showed no protective effect of BLF IOLs, with comparable incidence rates across all subgroups. Similar results were observed in the matched cohort analysis.<br><br>CONCLUSIONS: BLF IOL implantation in cataract surgery does not reduce the risk of developing exudative AMD in the South Korean population, regardless of a history of nonexudative AMD.}, }
@article {pmid40661075, year = {2025}, author = {Liu, D and Chen, X and Cai, S}, title = {Inhibition of retinal neovascularization by Dendrobium polysaccharides: a review.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1584553}, pmid = {40661075}, issn = {1663-9812}, abstract = {Retinal neovascularization (RNV) is a critical pathological feature of vision-threatening ocular diseases, such as diabetic retinopathy, retinopathy of prematurity, and wet age-related macular degeneration, presenting a persistent therapeutic conundrum. Current clinical treatments primarily rely on anti-vascular endothelial growth factor (VEGF) drugs and laser therapies, which face limitations including drug resistance, high costs, and potential damage to normal tissues. This underscores the need to develop novel therapeutic targets and cost-effective pharmacological interventions with improved safety profiles. Recent investigations highlight Dendrobium polysaccharides (DP), the primary bioactive components of the traditional medicinal herb Dendrobium, as promising multi-target therapeutic candidates. Studies have shown that Dendrobium polysaccharides significantly inhibits pathological angiogenesis by regulating the VEGF signaling pathway, inhibiting inflammatory response and oxidative stress, protecting the extracellular matrix, and reversing intestinal microecological disorders. This review systematically summarizes the structural and functional properties of DP, explores their mechanism of action and experimental evidence in retinal neovascularization, and analyzes their potential as a new therapeutic strategy for retinal diseases. This review also highlights the main limitations of current research: the uncertain relationship between the structure and activity of DP, the differences between pre-clinical models and human diseases, and the potential for structural optimization and the development of delivery systems.}, }
@article {pmid40661080, year = {2025}, author = {Li, X and Zhang, SQ and Wang, KR and Wu, SN and Wang, MY and Chen, CT and Dong, N}, title = {Chloroquine and hydroxychloroquine-related ocular adverse events in SLE treatment: a real-world disproportionality analysis based on FDA adverse event reporting system (FAERS).}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1498814}, pmid = {40661080}, issn = {1663-9812}, abstract = {OBJECTIVE: This study aimed to evaluate the risk of adverse events associated with chloroquine (CQ) and hydroxychloroquine (HCQ) in patients with systemic lupus erythematosus (SLE), using data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).<br><br>METHODS: Disproportionality analysis was conducted using the Reporting Odds Ratio (ROR) to detect potential safety signals. Sensitivity analyses were performed to validate these signals, and the time to onset for each Preferred Term (PT) was assessed.<br><br>RESULTS: Between 2004 and 2024, a total of 2,575 adverse event reports related to HCQ or CQ use in patients with SLE were identified in the FAERS database, of which 437 involved ocular adverse events. The most frequently reported ocular conditions were cataract, macular degeneration, and glaucoma. Disproportionality analysis demonstrated strong associations between HCQ/CQ use and retinal degeneration (ROR = 28.5, 95%CI: 19.94-40.74), cystoid macular oedema (ROR = 12.46, 95%CI: 8.01-19.37), and optic atrophy (ROR = 6.55, 95%CI: 3.51-12.19). Sensitivity analyses, conducted after excluding SLE cases, indicated that all but one event (vitreous floaters) remained statistically significant, suggesting that these risks are more likely attributable to HCQ/CQ exposure than to the underlying disease. The time-to-onset analysis showed that cataract had the shortest average onset time (125.5&#xa0;days), whereas retinal degeneration had the longest (937.5&#xa0;days).<br><br>CONCLUSION: The extensive clinical use of HCQ and CQ raises significant concerns regarding their ocular safety profile. This study provides real-world pharmacovigilance evidence supporting a substantial risk of ocular adverse events associated with HCQ/CQ use. Further mechanistic and prospective studies are warranted to elucidate the underlying pathophysiological pathways and to confirm these associations.}, }
@article {pmid40661176, year = {2025}, author = {Halev, A and Huang, D and Rezaei, S and Banks, S and McPherson, JD and Shankar, SP and Liu, X and Yiu, G}, title = {Genotype Prediction from Retinal Fundus Images Using Deep Learning in Eyes with Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100836}, pmid = {40661176}, issn = {2666-9145}, abstract = {PURPOSE: To employ deep learning models to predict high-risk genetic variants associated with age-related macular degeneration (AMD) from retinal fundus photographs of patients with this condition.<br><br>DESIGN: Deep learning algorithm development to classify single-nucleotide polymorphism in the complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genes using retinal fundus images.<br><br>PARTICIPANTS: Thirty-one thousand two hundred seventy-one retinal color fundus photographs of 1754 participants from the Age-Related Eye Disease Study.<br><br>METHODS: We trained deep learning models including convolution neural networks and vision transformers (ViTs) to classify patients into high-risk (homozygous high-risk alleles) or low-risk (heterozygous or homozygous low-risk alleles) genotypes for CFH or ARMS2, then evaluated algorithm performance on an independent test set. The complexity of genotype predictions was compared with AMD severity or gender classification tasks using V-usable information. Attribution mapping was performed to identify fundus regions used to predict genotype from phenotype.<br><br>MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC), balanced accuracy, and average precision for predicting high-risk genotypes.<br><br>RESULTS: Our trained ViT models predicted high-risk genotypes in CFH and ARMS2 with an AUROC of 0.719 and 0.741 across all eyes, respectively. For genotype predictions for ARMS2, model performance is improved in eyes with advanced AMD (AUROC 0.867), choroidal neovascularization (AUROC 0.833), and geographic atrophy (AUROC 0.957). Genotype predictions from fundus images appear more difficult than AMD severity or gender classification tasks, although saliency mapping supports biological plausibility by demonstrating attention to the central macula for genotype predictions.<br><br>CONCLUSIONS: Deep learning can predict high-risk genotypes in CFH and ARMS2 from retinal fundus images of patients with AMD. Our findings provide proof of principle for inferring genotype from noninvasive eye imaging and reveal insights into genotype-phenotype relationships in AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40662679, year = {2025}, author = {Chatterjee, S and Ghosh, S and Sin, Z and Babu, VS and Preval, LV and Davis, E and Tran, N and Bammidi, S and Gautam, P and Hose, S and Sergeev, Y and Flores-Bellver, M and Ritter, K and Jessen, HJ and Al Diri, I and Sinha, D and Guha, P}, title = {Age-Dependent Histone Deacetylase 3 Regulation by βA3/A1-Crystallin and Inositol Hexaphosphate in Retinal Pigmented Epithelial Cells Reveals a Novel Pathway in Age-Related Macular Degeneration.}, journal = {Aging cell}, volume = {24}, number = {9}, pages = {e70163}, pmid = {40662679}, issn = {1474-9726}, support = {R16 GM154726/GM/NIGMS NIH HHS/United States ; P20 GM121325/GM/NIGMS NIH HHS/United States ; P30 EY001765/EY/NEI NIH HHS/United States ; K99 EY033421/EY/NEI NIH HHS/United States ; NIH 5P20GM121325 COBRE/NH/NIH HHS/United States ; R01 EY032516/EY/NEI NIH HHS/United States ; R16GM154726/NH/NIH HHS/United States ; NIH 1R01EY032516-01A1/NH/NIH HHS/United States ; R01 EY031594/EY/NEI NIH HHS/United States ; EY001765/EY/NEI NIH HHS/United States ; NIH K99EY033421/NH/NIH HHS/United States ; NIH 1R01EY031594-01A1/NH/NIH HHS/United States ; }, mesh = {*Histone Deacetylases/metabolism/genetics ; Animals ; Humans ; *Macular Degeneration/metabolism/genetics/pathology ; *Retinal Pigment Epithelium/metabolism/pathology ; Mice ; *Phytic Acid/metabolism ; *Aging/metabolism ; Histone Deacetylase 3 ; }, abstract = {Age-related macular degeneration (AMD), a leading cause of vision loss affecting retinal pigment epithelial (RPE) cells, remains largely unexplained by current genome-wide association studies (GWAS) risk variants. Our research on Cryba1, encoding βA3/A1-crystallin protein, reveals its crucial role in RPE cell function via a novel epigenetic mechanism, also evident in human atrophic AMD samples. Loss of Cryba1 in mouse RPE cells triggers epigenetic changes by reducing histone deacetylase 3 (HDAC3) activity through two mechanisms. First, Cryba1 depletion reduces inositol polyphosphate multikinase (IPMK) expression, which potentially reduces inositol hexakisphosphate (InsP6) generation since IPMK's kinase activity is essential for producing InsP4 and InsP5 as precursors to InsP6. Since InsP4, InsP5, or InsP6 is crucial for HDAC3's interaction with the corepressor's DAD domains, reduced IPMK expression in Cryba1-depleted cells likely diminishes the HDAC3-DAD interaction, leading to a reduction in HDAC3's activity. Second, reduced βA3/A1 protein in Cryba1-deficient cells impairs HDAC3's interaction with casein kinase 2 (CK2), resulting in decreased HDAC3 phosphorylation. Collectively, this increases H3K27 acetylation at the RET promoter region, likely enhancing the transcription of RET, a receptor tyrosine kinase critical for cell survival. Although RET is transcriptionally increased, Cryba1 loss disrupts its protein maturation, causing immature RET protein accumulation. This triggers age-dependent endoplasmic reticulum (ER) stress, potentially contributing to the pathogenesis of AMD. Interestingly, although Cryba1 is not identified as an AMD-linked variant in current GWAS, its loss may be linked to AMD mechanisms. These findings underscore the potential of gene-agnostic and epigenetic therapeutic strategies for treating AMD.}, }
@article {pmid40662890, year = {2025}, author = {Du, Y and Feng, L and Tang, J and Qin, X and Bai, B and Liang, L}, title = {C5a-Induced Autophagy Dysfunction Promotes Choroidal Neovascularization Through the ROS-Inflammatory Pathway.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {9}, pages = {44}, pmid = {40662890}, issn = {1552-5783}, mesh = {*Autophagy/drug effects/physiology ; *Choroidal Neovascularization/metabolism/pathology ; *Reactive Oxygen Species/metabolism ; Animals ; Mice, Inbred C57BL ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Humans ; Mice ; Disease Models, Animal ; Blotting, Western ; Cytokines/metabolism ; Enzyme-Linked Immunosorbent Assay ; Mitochondria/metabolism ; Macular Degeneration/metabolism ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness in aging populations. C5a is the primary component of drusen and exerts a pivotal role in AMD, facilitating its progression. In the present research, we explored how C5a exacerbates AMD pathogenesis and its interplay with autophagic pathways, mitochondrial reactive oxygen species (ROS), and proinflammatory cytokines.<br><br>METHODS: Human retinal pigment epithelial (ARPE-19) cells were exposed to recombinant C5a. Autophagy was modulated using rapamycin or 3-MA, and ROS dynamics were perturbed with DPI or rotenone. Autophagy markers (LC3-II, Beclin-1, p62/SQTSM1) were analyzed via Western blot. Mitochondrial ROS levels were quantified using MitoSOX Red, while cytokine secretion (VEGF, MCP-1, IL-6, and IL-8) was measured by ELISA. C57BL/6 mice were utilized to model choroidal neovascularization (CNV), a prevalent subtype of AMD, which was induced by laser photocoagulation.<br><br>RESULTS: C5a stimulation significantly increased LC3-II, Beclin-1, and p62/SQTSM1. The cytokine secretion (VEGF, MCP-1, IL-6, and IL-8), ROS, and the areas in laser-induced CNV were significantly enlarged after C5a treatment. Autophagy activator significantly downregulated the cytokine secretion (VEGF, MCP-1, IL-6, and IL-8), ROS, and the areas in laser-induced CNV. ROS inhibitors can markedly diminish IL-6, IL-8, MCP-1, and VEGF, as well as the progression of CNV.<br><br>CONCLUSIONS: Our results suggest that C5a induced the dysfunction of autophagy and increased the mitochondrial ROS, as well as the mitochondrial ROS-driven cytokine release that fuels CNV formation.}, }
@article {pmid40663469, year = {2025}, author = {Palanker, D and Weiland, JD and Rosin, B and Sahel, JA}, title = {Restoration of Sight with Electronic Retinal Prostheses.}, journal = {Annual review of vision science}, volume = {11}, number = {1}, pages = {125-147}, pmid = {40663469}, issn = {2374-4650}, support = {R01 EY027786/EY/NEI NIH HHS/United States ; R01 EY035227/EY/NEI NIH HHS/United States ; P30 EY026877/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Visual Prosthesis ; *Blindness/rehabilitation/physiopathology ; *Retina ; *Electric Stimulation Therapy/methods ; Macular Degeneration/physiopathology ; Visual Acuity/physiology ; }, abstract = {Retinal prostheses aim at restoring sight to patients blinded by atrophy of photoreceptors using electrical stimulation of the inner retinal neurons. Bipolar cells can be targeted using subretinal implants, and their responses are then relayed to the central visual pathways via the retinal neural network, preserving many features of natural signal processing. Epiretinal implants stimulate the output retinal layer-ganglion cells-and encode visual information directly in spiking patterns.Several companies and academic groups have demonstrated that electrical stimulation of the degenerate retina can elicit visual percepts. However, most failed to consistently and safely achieve an acceptable level of performance. Recent clinical trials demonstrated that subretinal photovoltaic arrays in patients visually impaired by age-related macular degeneration can provide letter acuity matching their 100 μm pixel pitch, corresponding to 20/420 acuity. Electronic zoom enabled patients to read smaller fonts. This review describes the concepts, technologies, and clinical outcomes of current systems and provides an outlook into future developments.}, }
@article {pmid40664371, year = {2025}, author = {Grün, M and Rothaus, K and Lommatzsch, AP and Faatz, H}, title = {Early Outcome of Aflibercept 8 mg for Neovascular AMD in the Real-world Setting.}, journal = {Klinische Monatsblatter fur Augenheilkunde}, volume = {242}, number = {12}, pages = {1224-1232}, doi = {10.1055/a-2655-8854}, pmid = {40664371}, issn = {1439-3999}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Female ; Male ; Treatment Outcome ; Aged ; Retrospective Studies ; Intravitreal Injections ; Visual Acuity/drug effects ; Aged, 80 and over ; *Wet Macular Degeneration/drug therapy/diagnosis ; Tomography, Optical Coherence ; Angiogenesis Inhibitors/administration &amp; dosage ; Middle Aged ; }, abstract = {PURPOSE: To investigate the early outcome of intravitreal aflibercept 8 mg in treating neovascular age-related macular degeneration (nAMD) of eyes that either received prior intravitreal anti-VEGF treatment or were treatment-naïve - under real-world conditions.<br><br>METHODS: This is a retrospective study of a total of 83 eyes with nAMD treated with aflibercept 8&#x2009;mg. 61 of these eyes completed an initial loading phase of 3 monthly intravitreal injections (IVI) and were included in further analyses. Outcome parameters included best-corrected visual acuity (BCVA, logMAR), presence of intraretinal (IRF) and subretinal fluid (SRF), extent of pigment epithelium detachment (PED height, &#xb5;m) and central subfield retinal thickness (CSRT, &#xb5;m) in spectral domain optical coherence tomography (SD-OCT). Patients were assessed at the beginning of aflibercept 8&#x2009;mg treatment and 4 weeks after completing the loading phase. The McNemar test was used to test for changes in distribution of eyes showing IRF and SRF, and the paired t test was performed to test for changes in BCVA, PED height and CSRT.<br><br>RESULTS: 51 eyes had been previously treated with intravitreal anti-VEGF, while 10 eyes were treatment-na&#xef;ve. Mean BCVA after completed loading phase was 0.49&#x2009;&#xb1;&#x2009;0.31&#x2009;logMAR and did not show changes to baseline BCVA, which was 0.49&#x2009;&#xb1;&#x2009;0.32&#x2009;logMAR (p&#x2009;=&#x2009;0.89). A significant reduction was observed in all disease activity parameters in SD-OCT. The proportion of eyes showing IRF and SRF decreased from 54.1% to 26.2% (p&#x2009;<&#x2009;0.001) and 65.6% to 24.6% (p&#x2009;<&#x2009;0.001), respectively. A reduction in PED height from 227.7&#x2009;&#xb1;&#x2009;114.6&#x2009;&#xb5;m at baseline to 191.9&#x2009;&#xb1;&#x2009;111.4&#x2009;&#xb5;m (p&#x2009;<&#x2009;0.001) and a decrease in CSRT from 375.2&#x2009;&#xb1;&#x2009;126.2&#x2009;&#xb5;m to 308.8&#x2009;&#xb1;&#x2009;93.7 (p&#x2009;<&#x2009;0.001) were recorded. Of all eyes (n&#x2009;=&#x2009;83) that had received at least one IVI aflibercept 8&#x2009;mg, 5 eyes (6.0%) developed symptomatic, non-infectious intraocular inflammation (IOI), which resolved completely with topical treatment.<br><br>CONCLUSION: Our results demonstrate good effectiveness of intravitreal aflibercept 8&#x2009;mg in the real-world setting, with significant reduction in disease activity parameters in SD-OCT after the loading phase with 3 monthly injections - while BCVA remained stable. While the PULSAR trial only included treatment-na&#xef;ve eyes, our study underlines the value of aflibercept 8&#x2009;mg, even for pre-treated eyes that responded insufficiently to previous anti-VEGF treatment. Further studies are needed to evaluate long-term outcome in real-world setting, in order to verify the extended IVI intervals shown in the PULSAR trial.}, }
@article {pmid40664762, year = {2025}, author = {Hapeshi, J and Hughes, S and McKibbin, M and Scanlon, PH}, title = {A thematic analysis of patients' experiences of receiving treatment for Neovascular age-related macular degeneration (nAMD).}, journal = {Eye (London, England)}, volume = {39}, number = {13}, pages = {2565-2569}, pmid = {40664762}, issn = {1476-5454}, mesh = {Humans ; *Wet Macular Degeneration/drug therapy/psychology/therapy ; *Patient Satisfaction ; *Angiogenesis Inhibitors/therapeutic use ; Female ; Male ; Aged ; Quality of Health Care ; Surveys and Questionnaires ; Health Services Accessibility ; Aged, 80 and over ; Middle Aged ; Caregivers/psychology ; }, abstract = {BACKGROUND/OBJECTIVES: A positive patient experience is a key element of quality healthcare but data on the patient experience is rarely collected as part of routine care. This study analysed survey and discussion group comments from patients treated for neovascular AMD (nAMD) treatment to identify key elements of the patient experience.<br><br>SUBJECTS/METHODS: Free text comments from an online Macular Society member survey and quotes from subsequent, local, in-person patient discussion groups were reviewed. Thematic analysis was used to code the responses and to identify major themes.<br><br>RESULTS: Analysis include 167 free text comments from Macular Society members and quotes from 2 local discussion groups, with patients and their carers. Key themes, important for the patient experience, included: time and availability of appointments, accessibility and duration of clinic visits, the delivery and quality of care, communication and access to written information and confidence in the healthcare team.<br><br>CONCLUSIONS: Feedback from patients with nAMD and their carers identified a number of key themes that are associated with either a positive or negative patient experience. Construction of an appropriate patient-reported experience measure and collection of data, either locally or nationally, would help identify areas of the care pathway where improvements may be necessary. Improving the patient experience may encourage adherence to and persistence with treatment and the outcomes.}, }
@article {pmid40665980, year = {2025}, author = {Peng, B and Mu, J and Xu, F and Guo, W and Sun, C and Fan, W}, title = {Artificial intelligence in ophthalmology: a bibliometric analysis of the 5-year trends in literature.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1580583}, pmid = {40665980}, issn = {2296-858X}, abstract = {PURPOSE: This study aims to generate and elucidate the latest perspectives on the application of artificial intelligence (AI) in ophthalmology using bibliometric methods. By analyzing literature from the past 5 years (2020-2024), we seek to outline the development trends of this technology, provide guidance for its future directions, and assist clinicians in adapting to these innovations.<br><br>METHODS: We conducted a comprehensive search of all literature related to AI and ophthalmology in the Web of Science Core Collection (WoSCC) using bibliometric methods. The collected data were analyzed and visualized using three widely recognized bibliometric software tools: CiteSpace, VOSviewer, and the R package "Bibliometrix."<br><br>RESULTS: A total of 21,725 documents were included from 134 countries and 7,126 institutions, consisting of 19,978 articles (91.96%) and 1,714 reviews (8.04%), with China and the United States leading the contributions. The number of publications in AI and ophthalmology has increased annually, with the University of California System, the National University of Singapore, and the University of London being the primary research institutions. Ophthalmology and Proc CVPR IEEE are the most co-cited journals and conferences in this field. These papers were authored by 87,695 individuals, with Wang Y, Liu Y, and Zhang Y the most prolific authors. Ting DSW was the most co-cited author. Major research topics include using various models to scan retinal images for diagnosing conditions such as age-related macular degeneration, diabetic retinopathy, and retinal nerve fiber layer thinning caused by glaucoma. The intersection of AI with other subfields of ophthalmology, such as in the diagnosis of ametropia, strabismus, eyelid disease, and orbital tumors, as well as in postoperative follow-up, is also rapidly developing. Key research hot spots are identified by keywords such as "deep learning," "machine learning," "convolutional neural network," "diabetic retinopathy," and "ophthalmology."<br><br>CONCLUSION: Our bibliometric analysis outlines the dynamic evolution and structural relationships within the AI and ophthalmology field. In contrast to previous studies, our research transcends individual domains to offer a more comprehensive insight. Notably, our analysis encompasses literature published beyond the year 2022, a pivotal year marking both the post-pandemic era and the rapid advancement of AI technologies. This temporal scope potentially fills a gap that prior bibliometric studies have not addressed. This information identifies recent research frontiers and hot spot areas, providing valuable reference points for scholars engaging in future AI and ophthalmology studies.}, }
@article {pmid40666342, year = {2025}, author = {Green, DJ and Romero-Bascones, D and Julian, TH and Torchia, S and Joisher, HNV and ,  and Ayala, U and Barrenechea, M and Self, JE and Black, GC and Fitzgerald, T and Birney, E and Cepko, CL and Carroll, J and Sergouniotis, PI}, title = {Genetic insights into foveal morphology and its associations with pigmentation and age-related macular degeneration.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {40666342}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 EY017607/EY/NEI NIH HHS/United States ; R01 EY033580/EY/NEI NIH HHS/United States ; }, abstract = {The fovea is the small depression at the neurosensory retina that underlies high-resolution central vision. It is vulnerable to disease and disruption of its architecture causes visual disability. Foveal morphology varies significantly across individuals. The molecular causes and functional consequences of this anatomical diversity are incompletely understood. Here, we extracted six foveal morphological parameters from Optical Coherence Tomography (OCT) images of 55,604 UK Biobank participants. We found notable variability in foveal morphology, and detected significant links with sex and genetic ancestry. Genome-wide association studies identified 197 lead loci across the six foveal morphological parameters, implicating genes involved in pigmentation (e.g., TYR, TSPAN10, GPR143) and patterning (e.g., FGFR2, PTPRD, CYP1A1). Heritability estimates ranged from 29-43%. Foveal pit volume was associated with future risk of age-related macular degeneration (HR>3.5, p=0.001), a finding supported by Mendelian randomization. These results establish foveal morphology as a highly-heritable trait with substantial influence over retinal disease risk.}, }
@article {pmid40666756, year = {2025}, author = {Bhattacharya, A and Majumdar, S and Ray, MS and Nandi, D and Ghosh, S and Banerjee, D}, title = {A comparative study of retinal vein occlusion and serum 25 hydroxy Vitamin D at a tertiary care centre.}, journal = {Oman journal of ophthalmology}, volume = {18}, number = {2}, pages = {182-186}, pmid = {40666756}, issn = {0974-620X}, abstract = {BACKGROUND: Prevalence of retinal vascular occlusion is second to diabetic retinopathy and age-related macular degeneration. Various age-related local and systemic factors have been associated with retinal vein occlusion (RVO). Hemodynamic changes (venous stasis), degenerative changes of the vessel wall and blood hypercoagulability underlies the pathogenesis. The role of Vitamin D in modulating the inflammatory responses within the arterial wall, the capacity to attenuate the oxidative stress and direct effect of hypovitaminosis D on increased vascular resistance hints at a potential association of Vitamin D levels with disorders of retinal vasculature.<br><br>AIM: To estimate serum 25-hydroxyvitamin D (25 OH Vit D) level in patients of RVO and compare it with matched controls.<br><br>MATERIALS AND METHODS: Fifty patients of RVO as cases and 50 without RVO as controls underwent systemic and ocular examination including the estimation of serum 25 OH Vit D and other biochemical parameters.<br><br>STATISTICAL ANALYSIS: Statistical Package for the Social Sciences (SPSS) software version 25 was used for the analysis. An alpha level of 5% was taken, that is P < 0.05 was considered statistically significant.<br><br>RESULTS: Mean serum 25 OH Vit D level in cases of RVO was 21.82 nanogram/deciliters (ng/dL) compared to 30.71 ng/dL in the control group which was significantly lower in cases compared to control (P < 0.001). The odds ratio calculated for RVO cases versus controls was 1.137; 95% confidence interval (1.074-1.203).<br><br>CONCLUSION: A positive association of low serum 25 OH Vit D levels and RVO was found highlighting the importance of evaluating serum Vitamin D levels in all the cases of RVO. This correlation may have possible implications for prophylaxis and treatment of RVO, even though this part of our country gets abundant sunlight throughout the year.}, }
@article {pmid40667189, year = {2025}, author = {Li, J and Wang, T and Lu, W and Jishkariani, D and Tsourkas, A and Kaja, S and Nair, RM and Dunaief, JL and Mitchell, CH}, title = {Sustained Lysosomal Delivery of Enhanced Cy3-Labeled Acid Nanoparticles Restores Lysosomal pH in Retinal Pigment Epithelial Cells and Astrocytes.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40667189}, issn = {2692-8205}, support = {R01 EY013434/EY/NEI NIH HHS/United States ; R01 EY015537/EY/NEI NIH HHS/United States ; }, abstract = {Lysosomal pH is frequently elevated in age-dependent neurodegenerations like Age-related Macular Degeneration (AMD), Alzheimer's Disease (AD), and Parkinson's Disease (PD). Tools that restore lysosomal pH to an optimal acidic range could enhance enzymatic degradation and reduce waste accumulation. Acidic nanoparticles offer a promising strategy for restoring lysosomal function, but accurate tracking of organelle delivery and long-term retention is needed to optimize dosage. To improve detection and enhance delivery, nanoparticles were synthesized from Poly(D,L-lactide-co-glycolide) (PLGA) polymers covalently linked to the fluorescent Cyanine3 amine (Cy3) probe. Nanoparticle concentration and loading times were optimized to achieve >90% delivery to lysosomes in cultured induced pluripotent stem cell-derived retinal pigment epithelial (iPS-RPE) cells. Uptake was heterogeneous, varying between adjacent cells. Once loaded into lysosomes, the nanoparticles were stably retained, with no detectable changes in concentration, distribution, or size for at least 28 days. iPS-RPE cells internalized more nanoparticles than the ARPE-19 cell line or mouse optic nerve head astrocyte cultures. Functionally, PLGA nanoparticles restored an acidic pH and cathepsin D levels in compromised lysosomes. In summary, Cy3-PLGA nanoparticles enabled improved tracking and long-term delivery to lysosomes, supporting future in vivo applications to restore lysosomal pH in aging and degenerating tissues.}, }
@article {pmid40668050, year = {2025}, author = {Heine, L and Vahldiek, A and Vahldiek, B and Hörst, F and Seibold, C and Lever, M and Pauleikhoff, L and Bechrakis, N and Pauleikhoff, D and Kleesiek, J}, title = {Three-Dimensional Quantification of Macular OCT Alterations Improves the Diagnostic Performance of Artificial Intelligence Models.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {7}, pages = {8}, pmid = {40668050}, issn = {2164-2591}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Artificial Intelligence ; *Imaging, Three-Dimensional/methods ; *Macular Degeneration/diagnostic imaging ; Aged ; *Macula Lutea/diagnostic imaging/pathology ; Female ; Male ; *Wet Macular Degeneration/diagnostic imaging ; }, abstract = {PURPOSE: To evaluate the performance of state-of-the-art semantic segmentation methods on OCT data for age-related macular degeneration (AMD). We measured variability between annotators to quantify differences in ground truth arising from personal bias.<br><br>METHODS: From 94 patients suffering from exudative neovascular AMD (nAMD), 24 volume scans (49 slices each) were selected. Trained members of a reading center for AMD created pixel-wise masks for 12 retinal layers and two pathological labels (fluid, hyperreflective material) to benchmark two-dimensional (2D) and three-dimensional (3D) segmentation models on clinical data. Models were evaluated using fivefold cross-validation, and the best model was used to quantify errors between ground truth and predictions.<br><br>RESULTS: The nnU-Net (3D) achieves the best segmentation performance (mean Dice similarity coefficient [DSC] of 0.907), leaving a theoretical gap of 0.036 DSC to the mean interrater agreement, which is the upper bound of model performances. Comparing the volumes calculated for each structure using the model masks with the ground truth produced an average error of 0.065&#xa0;mm3.<br><br>CONCLUSIONS: Models like nnU-Net can produce high-quality 3D masks, challenging the conventional reliance on 2D slices for optimal performance. Both DSC and low average errors indicate that such a model is fit for the large-scale analysis of cohorts.<br><br>TRANSLATIONAL RELEVANCE: The presented approach can streamline clinical workflows by reducing the time and effort required for manual annotations, ultimately supporting more efficient and accurate monitoring of AMD progression and treatment response. We provide open-source access to the model weights, annotation instructions and sample data.}, }
@article {pmid40668583, year = {2025}, author = {Chen, Q and Keenan, TDL and Agron, E and Allot, A and Guan, E and Duong, B and Elsawy, A and Hou, B and Xue, C and Bhandari, S and Broadhead, G and Cousineau-Krieger, C and Davis, E and Gensheimer, WG and Golshani, CA and Grasic, D and Gupta, S and Haddock, L and Konstantinou, E and Lamba, T and Maiberger, M and Mantopoulos, D and Mehta, MC and Elnahry, AG and Al-Nawaflh, M and Oshinsky, A and Powell, BE and Purt, B and Shin, S and Stiefel, H and Thavikulwat, AT and Wroblewski, KJ and Tham, YC and Cheung, CMG and Cheng, CY and Chew, EY and Hribar, MR and Chiang, MF and Lu, Z}, title = {AI Workflow, External Validation, and Development in Eye Disease Diagnosis.}, journal = {JAMA network open}, volume = {8}, number = {7}, pages = {e2517204}, pmid = {40668583}, issn = {2574-3805}, support = {R00 LM014024/LM/NLM NIH HHS/United States ; }, mesh = {Humans ; *Artificial Intelligence ; *Workflow ; *Macular Degeneration/diagnosis/classification ; Female ; Male ; Aged ; *Eye Diseases/diagnosis ; Reproducibility of Results ; Middle Aged ; }, abstract = {IMPORTANCE: Timely disease diagnosis is challenging due to limited clinical availability and growing burdens. Although artificial intelligence (AI) has shown expert-level diagnostic accuracy, a lack of downstream accountability, including workflow integration, external validation, and further development, continues to hinder its clinical adoption.<br><br>OBJECTIVE: To address gaps in the downstream accountability of medical AI through a case study on age-related macular degeneration (AMD) diagnosis and severity classification.<br><br>This diagnostic study developed and evaluated an AI-assisted diagnostic and classification workflow for AMD. Four rounds of diagnostic assessments (accuracy and time) were conducted with 24 clinicians from 12 institutions. Each round was randomized and alternated between manual (clinician diagnosis) and manual plus AI (clinician assisted by AI diagnosis), with a 1-month washout period. In total, 2880 AMD risk features were evaluated across 960 images from 240 Age-Related Eye Disease Study patient samples, both with and without AI assistance. For further development, the original DeepSeeNet model was enhanced into the DeepSeeNet+&#x2009;model using&#x2009;39 196 additional images from the US population and tested on 3 datasets, including an external set from Singapore.<br><br>EXPOSURE: Age-related macular degeneration risk features.<br><br>MAIN OUTCOMES AND MEASURES: The F1 score for accuracy (Wilcoxon rank sum test) and diagnostic time (linear mixed-effects model) were measured, comparing manual vs manual plus AI. For further development, the F1 score (Wilcoxon rank sum test) was again used.<br><br>RESULTS: Among 240 patients (mean [SD] age, 68.5 [5.0] years; 127 female [53%]), AI assistance significantly improved accuracy for 23 of 24 clinicians, increasing the mean F1 score from 37.71 (95% CI, 27.83-44.17) to 45.52 (95% CI, 39.01-51.61), with some improvements exceeding 50%. Manual diagnosis initially took an estimated 39.8 seconds (95% CI, 34.1-45.6 seconds) per patient, whereas manual plus AI saved 10.3 seconds (95% CI, -15.1 to -5.5 seconds) and remained faster by 6.9 seconds (95% CI, 0.2-13.7 seconds) to 8.6 seconds (95% CI, 1.8-15.3 seconds) in subsequent rounds. However, combining manual and AI did not always yield the highest accuracy or efficiency, underscoring challenges in explainability and trust. The DeepSeeNet+&#x2009;model performed better in 3 test sets, achieving a significantly higher F1 score than the Singapore cohort (52.43 [95% CI, 44.38-61.00] vs 38.95 [95% CI, 30.50-47.45]).<br><br>CONCLUSIONS AND RELEVANCE: In this diagnostic study, AI assistance was associated with improved accuracy and time efficiency for AMD diagnosis. Further development is essential for enhancing AI generalizability across diverse populations. These findings highlight the need for downstream accountability during early-stage clinical evaluations of medical AI.}, }
@article {pmid40669451, year = {2025}, author = {Marques, IP and Almeida, AC and Futterknecht, S and Hatz, K and Cunha-Vaz, J and Scholl, HPN and Lobo, C and Silva, R and Murta, JN and Anders, P and Anders, LM and Santos, AR and Pfau, M}, title = {Association of Localized Retinal Sensitivities with Spectral-Domain Optical Coherence Tomography-Derived Morphologic Data in Macular Subfields in Age-Related Macular Degeneration.}, journal = {Ophthalmic research}, volume = {68}, number = {1}, pages = {389-399}, pmid = {40669451}, issn = {1423-0259}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Cross-Sectional Studies ; Aged ; Male ; Female ; *Macular Degeneration/physiopathology/diagnosis ; Visual Field Tests/methods ; *Visual Fields/physiology ; *Visual Acuity/physiology ; *Macula Lutea/pathology/physiopathology ; Aged, 80 and over ; *Retina/physiopathology ; }, abstract = {INTRODUCTION: This study investigated microperimetry-derived retinal sensitivity and optical coherence tomography (OCT)-based macular morphologic data in eyes with early and intermediate age-related macular degeneration (AMD). The respective metrics were compared between macular subfields and their associations were determined. Detailed knowledge of functional associations with morphology is an asset to future therapeutic trial design.<br><br>METHODS: This is a cross-sectional analysis of microperimetry and spectral-domain OCT baseline data. OCT data were segmented automatically within the HEYEX software (Heidelberg Engineering). Data were assessed for Gaussian normal distribution by the D'Agostino and Pearson tests, and appropriate comparison tests were performed for parametric and nonparametric data. The association of retinal sensitivity metrics with OCT morphologic data was tested with mixed-effects models.<br><br>RESULTS: In total, 19 eyes of 19 participants (75 &#xb1; 6.4 years) with early and intermediate AMD were included in the analysis. Both in mesopic (p < 0.05) and in scotopic red (p < 0.001) microperimetry, retinal sensitivities differed significantly between macular subfields in ANOVA. Nasal and temporal subfields showed the highest retinal sensitivities, also compared to the central subfield. Generally, subfields within the 1 mm-2 mm diameter ring showed higher retinal sensitivities than subfields within the 2 mm-3 mm diameter ring. Superior subfields demonstrated higher retinal sensitivity than inferior subfields in mesopic microperimetry. RPE thickness was mostly negatively associated with retinal sensitivity, which was pronounced in the ETDRS inner ring inferior subfield and for mesopic retinal sensitivity (t value, p value: -3.7, <0.01). In the center position, inner retinal thickness was negatively associated with mesopic retinal sensitivity (t value, p value: -2.2, <0.05).<br><br>CONCLUSION: Retinal layer thicknesses and their associations with retinal sensitivity show localized differences between macular subfields in early and intermediated AMD. An analysis including more subjects is necessary to confirm these trends. This knowledge is of importance since therapeutic trial design requires detailed morphologic but also functional conception in order to detect therapeutic effects and pass regulatory hurdles.}, }
@article {pmid40670757, year = {2025}, author = {Zou, R and Zhang, X and Dai, X and Yuan, Y and Dai, J and Yuan, F}, title = {The SDF-1α/MTDH axis inhibits ferroptosis and promotes the formation of anti-VEGF-resistant choroidal neovascularization by facilitating the nuclear translocation of SREBP1.}, journal = {Cell biology and toxicology}, volume = {41}, number = {1}, pages = {118}, pmid = {40670757}, issn = {1573-6822}, support = {82201181//National Natural Science Foundations of China/ ; 3502Z20227277//Xiamen Municipal Bureau of Science and Technology/ ; 24ZR1411400//Science and Technology Commission of Shanghai Municipality/ ; }, mesh = {*Sterol Regulatory Element Binding Protein 1/metabolism ; Animals ; *Chemokine CXCL12/metabolism ; Mice ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Humans ; *Choroidal Neovascularization/metabolism/drug therapy/pathology ; *Ferroptosis/drug effects ; Ranibizumab/pharmacology ; RNA-Binding Proteins/metabolism ; Mice, Inbred C57BL ; Endoplasmic Reticulum/metabolism ; Membrane Proteins/metabolism ; Macular Degeneration/drug therapy/metabolism ; Golgi Apparatus/metabolism ; Cell Nucleus/metabolism ; }, abstract = {Age-related macular degeneration (AMD) has been well recognized as the first ranked blinding ocular fundus diseases among older individuals, particularly in developed regions, owing to its progressive nature and high prevalence in aging populations. Anti-vascular endothelial growth factor (VEGF) agents injected into patients' vitreous cavity is the preferred treatment regimen for neovascular AMD. However, many patients exhibit resistance to anti-VEGF treatment, which is an urgent clinical problem. In this study, we treated mouse and endothelial cells with anti-VEGF drug Ranibizumab and stromal cell-derived factor-1α (SDF-1α) and found that ferroptosis was induced by Ranibizumab but inhibited by SDF-1α. SDF-1α inhibited ferroptosis by promoting transport of Sterol regulatory element binding protein 1 (SREBP1) from endoplasmic reticulum (ER) to Golgi transportation and SREBP1 maturation. Furthermore, we found that metadherin (MTDH) mediates SREBP1' s movement from the endoplasmic reticulum (ER) to Golgi apparatus by inhibiting SREBP1 binding to INSIG1/INSIG2. Our study revealed the important role of SDF-1α/MTDH/SREBP1 axis in regulating anti-VEGF treatment resistance in patients with AMD.}, }
@article {pmid40671118, year = {2025}, author = {Shippy, DC and Ulland, TK}, title = {Verteporfin attenuates NLRP3 inflammasome activation to alleviate gout arthritis flares.}, journal = {Journal of inflammation (London, England)}, volume = {22}, number = {1}, pages = {28}, pmid = {40671118}, issn = {1476-9255}, support = {R01 AG083883/AG/NIA NIH HHS/United States ; Early-Career Investigator Award//William F. Vilas Trust Estate/ ; R01AG083883/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: Gout arthritis (GA) is an inflammatory disorder characterized by the deposition of monosodium urate (MSU) crystals within synovial joints due to increased urate concentrations in the body. The NLRP3 inflammasome drives a majority of the inflammatory response to MSU crystals; therefore, we hypothesize pharmaceutical agents that attenuate NLRP3 inflammasome activation could be used to treat GA flares.<br><br>RESULTS: We screened a drug library containing 875 FDA-approved drugs and identified five drugs that reduced NLRP3 inflammasome activation without causing cytotoxic effects in bone marrow-derived macrophages (BMDM). The best performing and therefore leading candidate, verteporfin, used to treat macular degeneration and other eye disorders, reduced Nlrp3- and Caspase-1-dependent IL-1&#x3b2; and IL-18 secretion by BMDM. Additionally, verteporfin-treated mice showed a marked reduction in paw swelling and pro-inflammatory cytokine/chemokine induction, including inflammasome markers (IL-1&#x3b2; and IL-18), in a MSU-induced mouse model of GA flares.<br><br>CONCLUSION: Collectively, these data suggest verteporfin is a NLRP3 inflammasome inhibitor that could be repurposed as a treatment for GA.}, }
@article {pmid40671998, year = {2025}, author = {Sato, S and Sakurada, Y and Fukuda, Y and Kotoda, Y and Kashiwagi, K}, title = {Recurrence of Intraocular Inflammation Following an Aflibercept 8-mg Injection in Eyes With a History of Intraocular Inflammation From Faricimab: A Case Report.}, journal = {Cureus}, volume = {17}, number = {6}, pages = {e86113}, pmid = {40671998}, issn = {2168-8184}, abstract = {Vascular endothelial growth factor (VEGF) is critical in various retinal diseases. VEGF inhibitors are a standard treatment for neovascular age-related macular degeneration (AMD). However, intraocular inflammation (IOI) is a major complication after intravitreal administration of second-generation VEGF inhibitors. We report a case of IOI following treatment with aflibercept 8 mg in an eye with a history of IOI due to faricimab. An 83-year-old man was referred to our clinic and diagnosed with type 1 macular neovascularization (MNV), with a previous treatment history of four doses of ranibizumab, 14 doses of aflibercept (2 mg), and two doses of faricimab. The best-corrected visual acuity (BCVA) in the right eye was 0.3 in the decimal format. Treatment was initiated with an as-needed faricimab regimen after three consecutive monthly injections. Thirteen days after the ninth faricimab injection, the patient complained of blurred vision in the right eye. Mild inflammation, with small keratic precipitates (KPs), was observed in the anterior chamber. After topical dexamethasone administration (four times a day), the anterior chamber inflammation resolved one week after treatment. However, exudation recurred 13 weeks after the ninth faricimab administration; therefore, the intravitreal injection was switched to aflibercept 8 mg. Two days after switching to aflibercept 8 mg, the patient complained of pain and blurred vision in the right eye. As with the ninth faricimab injection, mild inflammation was observed in the anterior chamber of the right eye. One week after subtenon triamcinolone acetonide (STTA) and topical dexamethasone, inflammation disappeared in the anterior chamber. In eyes with a history of IOI, careful attention is needed when switching to aflibercept 8 mg from another second-generation VEGF inhibitor, including faricimab.}, }
@article {pmid40672824, year = {2025}, author = {Umair, M and Ahmad, J and Saidani, O and Alshehri, MS and Al Mazroa, A and Hanif, M and Ullah, R and Khan, MS}, title = {OculusNet: Detection of retinal diseases using a tailored web-deployed neural network and saliency maps for explainable AI.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1596726}, pmid = {40672824}, issn = {2296-858X}, abstract = {Retinal diseases are among the leading causes of blindness worldwide, requiring early detection for effective treatment. Manual interpretation of ophthalmic imaging, such as optical coherence tomography (OCT), is traditionally time-consuming, prone to inconsistencies, and requires specialized expertise in ophthalmology. This study introduces OculusNet, an efficient and explainable deep learning (DL) approach for detecting retinal diseases using OCT images. The proposed method is specifically tailored for complex medical image patterns in OCTs to identify retinal disorders, such as choroidal neovascularization (CNV), diabetic macular edema (DME), and age-related macular degeneration characterized by drusen. The model benefits from Saliency Map visualization, an Explainable AI (XAI) technique, to interpret and explain how it reaches conclusions when identifying retinal disorders. Furthermore, the proposed model is deployed on a web page, allowing users to upload retinal OCT images and receive instant detection results. This deployment demonstrates significant potential for integration into ophthalmic departments, enhancing diagnostic accuracy and efficiency. In addition, to ensure an equitable comparison, a transfer learning approach has been applied to four pre-trained models: VGG19, MobileNetV2, VGG16, and DenseNet-121. Extensive evaluation reveals that the proposed OculusNet model achieves a test accuracy of 95.48% and a validation accuracy of 98.59%, outperforming all other models in comparison. Moreover, to assess the proposed model's reliability and generalizability, the Matthews Correlation Coefficient and Cohen's Kappa Coefficient have been computed, validating that the model can be applied in practical clinical settings to unseen data.}, }
@article {pmid40673740, year = {2025}, author = {Curcio, CA and Mullins, RF and Stone, EM and Goerdt, L and Kar, D and Gao, L and McGwin, G and Owsley, C}, title = {Genetic Associations of Rod- and Cone-Mediated Vision in Aging and Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {9}, pages = {50}, pmid = {40673740}, issn = {1552-5783}, support = {UL1 TR003096/TR/NCATS NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; R01 AG004212/AG/NIA NIH HHS/United States ; UL1 TR001417/TR/NCATS NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY026087/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Macular Degeneration/genetics/physiopathology ; Aged ; Male ; Female ; Middle Aged ; *Polymorphism, Single Nucleotide ; Complement Factor H/genetics ; *Dark Adaptation/physiology/genetics ; *Aging/physiology/genetics ; *Retinal Cone Photoreceptor Cells/physiology ; *Retinal Rod Photoreceptor Cells/physiology ; Visual Acuity/physiology ; *Proteins/genetics ; Aged, 80 and over ; }, abstract = {PURPOSE: To compare genetic associations of rod- and cone-driven vision with those previously defined for delayed rod-mediated dark adaptation (RMDA), a functional risk indicator for incident age-related macular degeneration (AMD).<br><br>METHODS: In adults aged &#x2265;60 years with two normal eyes (per the Age-Related Eye Disease Study 9-step scale) or with AMD in one or both eyes, we measured RMDA at 5&#xb0; superior retina, photopic vision (acuity, contrast sensitivity, light sensitivity), and mesopic vision (low luminance acuity and deficit). Vision associations of risk-conferring single-nucleotide polymorphisms in CFH and ARMS2 genes were adjusted for age and smoking and stratified for the presence of subretinal drusenoid deposit (SDD).<br><br>RESULTS: Of 608 participants, 462 had normal maculas and 146 had AMD. Neither ARMS2 nor CFH was significantly associated with AMD stage. Across all eyes, RMDA worsened significantly in association with ARMS2 (P = 0.0005). Associations were stronger in normal eyes than in AMD (P = 0.0012 vs. 0.0580) and in normal eyes lacking SDD (n = 384, P < 0.0024). Across all eyes, RMDA was significantly associated with CFH (P = 0.0023) but not in normal and AMD eyes separately (P = 0.270 vs. 0.0596). RMDA was significantly associated with the number of risk alleles in normal and AMD eyes (P < 0.0001). Low luminance deficit was associated with gene dose for AMD eyes only (P = 0.477).<br><br>CONCLUSIONS: Of six vision tests, only RMDA was consistently associated with major risk alleles, including ARMS2 (not CFH) in normal eyes, with or without SDD. RMDA assesses dynamic retinoid resupply from the circulation, perhaps presaging SDD. Results are interpreted considering localization of key proteins in Bruch's membrane.}, }
@article {pmid40675433, year = {2025}, author = {Tian, Y and Tang, R and Xie, M and Zhan, Y and Guo, Y and Zeng, X and Wang, S and Kuang, H and Yang, S and Gao, Z and Xiong, Z and Zhang, C and Dong, X and Li, X and Lu, W}, title = {SERPINB2 increases endothelial inflammation through augmented fatty acid oxidation to promote choroidal neovascularization.}, journal = {Experimental eye research}, volume = {259}, number = {}, pages = {110524}, doi = {10.1016/j.exer.2025.110524}, pmid = {40675433}, issn = {1096-0007}, mesh = {*Choroidal Neovascularization/metabolism/pathology ; Animals ; Humans ; *Fatty Acids/metabolism ; Oxidation-Reduction ; Disease Models, Animal ; *Inflammation/metabolism/pathology ; Mice, Inbred C57BL ; Mice ; *Plasminogen Activator Inhibitor 2/genetics ; Male ; Cells, Cultured ; Cell Proliferation ; Cell Movement ; *Endothelium, Vascular/metabolism/pathology ; }, abstract = {Neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly population, with choroidal neovascularization (CNV) being its key pathological feature. Endothelial cell (EC) inflammation plays a pivotal role in CNV progression. However, the crucial molecules regulating EC inflammation and the underlying mechanisms remain unclear. In this study, we found that Serine protease inhibitor family B member 2 (SERPINB2) is significantly upregulated in CNV and ECs during inflammation. SERPINB2 depletion by shRNA markedly reduced EC inflammation and neovascularization in a laser-induced CNV model. SERPINB2 knockdown inhibited EC proliferation, migration, and tube formation, as well as the recruitment and transendothelial migration of monocytes. Mechanistically, SERPINB2 depletion reduced the expression of fatty acid oxidation (FAO)-related genes, such as CPT1C, resulting in lipid accumulation and decreased FAO activity in ECs. ETO (an FAO inhibitor) treatment impaired EC functions, whereas supplementation with fatty acid octanoate rescued EC dysfunction caused by SERPINB2 knockdown. Importantly, delivery of AAV-mediated EC-specific shSerpinb2 or ETO treatment markedly inhibited CNV and inflammation in vivo. Collectively, our findings revealed that SERPINB2 promotes CNV by driving EC inflammation through increased FAO. Targeting SERPINB2/FAO may offer a new promising therapeutic strategy for nAMD treatment.}, }
@article {pmid40676038, year = {2025}, author = {Xie, H and Ye, Z and Chan, LLH}, title = {Optimizing electrical stimulation parameters to enhance visual cortex activation in retina degeneration rats.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {25918}, pmid = {40676038}, issn = {2045-2322}, support = {GHP/078/18GD//Innovation Technology Fund, Guangdong-Hong Kong Technology Cooperation Funding Scheme/ ; GHP/078/18GD//Innovation Technology Fund, Guangdong-Hong Kong Technology Cooperation Funding Scheme/ ; GHP/078/18GD//Innovation Technology Fund, Guangdong-Hong Kong Technology Cooperation Funding Scheme/ ; 2022-YF05-01360-SN//Chengdu Municipal Science and Technology Program/ ; 2022-YF05-01360-SN//Chengdu Municipal Science and Technology Program/ ; 11207419//Research Grants Council, University Grants Committee/ ; 11207419//Research Grants Council, University Grants Committee/ ; 7005452//City University of Hong Kong/ ; 7005452//City University of Hong Kong/ ; }, mesh = {Animals ; *Electric Stimulation/methods ; Rats, Long-Evans ; Rats ; *Retinal Degeneration/physiopathology/therapy ; Evoked Potentials, Visual/physiology ; *Visual Cortex/physiopathology ; Visual Prosthesis ; Disease Models, Animal ; Male ; Retina ; }, abstract = {In patients with degenerative retinal diseases such as retinitis pigmentosa and age-related macular degeneration, retinal prostheses offer a promising approach to restoring partial vision. Among these, epiretinal prostheses have shown encouraging preliminary clinical efficacy; however, optimizing stimulation parameters remains essential for improving efficiency and reducing power consumption. In this study, we investigated the effects of key electrical stimulation parameters- phase duration, frequency, and interphase interval (IPI) -on visual cortical electrically evoked potentials (EEPs) in both healthy Long-Evans (LE) rats and retinal degenerated (F1) rats. Our in vivo experiments on both LE and F1 rats revealed that shorter phase durations (500 µs) elicited activation in the primary visual cortex (V1) at lower charge thresholds. Our results also showed that responses to repetitive stimulation were significantly attenuated at high frequencies (10 and 20 Hz) compared to low frequency stimulation (1 Hz). Furthermore, we observed that longer phase durations (1000 and 1500 µs), as well as the inclusion of an IPI, resulted in a more confined spread of cortical activation. These findings suggest that adjusting phase duration can effectively reduce activation thresholds and spatially constrain cortical responses, and application of IPI can limit the extension of cortical responses, offering a potential strategy for enhancing the performance of epiretinal prostheses.}, }
@article {pmid40677744, year = {2025}, author = {Alkhabaz, A and Kim, MY and Pujari, R and Zhang, J and Ren, Y and Leung, LB and Liao, YJ}, title = {Age-related macular degeneration associated with optic disc drusen.}, journal = {Frontiers in ophthalmology}, volume = {5}, number = {}, pages = {1620616}, pmid = {40677744}, issn = {2674-0826}, abstract = {OBJECTIVE: The aim of this study was to investigate the risk of age-related macular degeneration (AMD) in association with optic disc drusen (ODD).<br><br>DESIGN: This was an observational, cross-sectional study.<br><br>PARTICIPANTS: Participants were consecutive patients with and without ODD from the neuro-ophthalmology clinic. Ten patients with concomitant ODD-AMD were sub-analyzed.<br><br>METHODS: The two cohorts were identified from a prospectively recruited dataset between July 2022 and June 2024. Patients received formal diagnoses of ODD and AMD after ophthalmic and imaging assessment. A logistic regression model was utilized in calculating AMD risk to account for demographic differences.<br><br>RESULTS: A total of 94 patients with ODD (median age: 44 [Q1: 20, Q3: 69], 64% women) and 100 patients without ODD (median age: 60 [Q1: 44, Q3: 69], 48% women) were identified. AMD was observed in 9.6% and 3% of the ODD and non-ODD cohorts, respectively. The risk of AMD was higher in the ODD group (OR = 3.93, 95% CI: 0.89-21.85, p = 0.084). Although the association was not statistically significant, a logistic regression model attributed that to the age difference between the two cohorts. Of the 10 patients with ODD-AMD, 70% had a family history of AMD. These patients were all Caucasians and had a median age of 75 years (range: 56-91); 70% were women. Only 30% were smokers. On optic disc imaging, 70% of eyes demonstrated moderate-to-severe ODD.<br><br>CONCLUSION: Patients with ODD might be at a higher risk of AMD compared to patients without ODD, and AMD screening might be warranted. A family history of AMD is often present, indicating shared genetic risk factors.}, }
@article {pmid40682000, year = {2025}, author = {Edarous, DH and Fahim, HI and Momen, M and Shaat, AAE and Manzour, AF}, title = {Epidemiology of age-related macular degeneration among elderly in geriatric homes, East Cairo, Egypt.}, journal = {BMC public health}, volume = {25}, number = {1}, pages = {2495}, pmid = {40682000}, issn = {1471-2458}, abstract = {BACKGROUND: Visual impairment is one of the main causes of years lived with disability among adults 65 and older worldwide, according to the Global Burden of Disease Study (GBD). Both ageing and visual impairment are linked to an increased risk of falling, accounting for 40% of all injury-related deaths among older adults.<br><br>OBJECTIVE: To determine the prevalence of AMD among a sample of elderly residing in geriatric homes, identify associated factors of AMD, and to find out the effect of AMD on fall frequency in the studied group.<br><br>METHODS: A cross-sectional study was conducted on 283 elderly people in thirty geriatric homes in East Cairo. Data was collected using a structured interview questionnaire, and fundus examination for diagnosis.<br><br>RESULTS: The average age of study participants was 73.18&#x2009;&#xb1;&#x2009;7.09 (60&#x2013;96) years. AMD was present in 12.7% of the patients. Early AMD was present in 58.4% of AMD patients, whereas 8.3% and 33.3% of the participants had late dry and late wet AMD, respectively. Bilateral AMD was found in 38.9%, compared to 61.1% who had unilateral AMD. Compared to other age groups, the prevalence of AMD was significantly higher in people aging 75&#x2009;+&#x2009;years. About 47.2% of participants diagnosed with AMD were current smokers. Out of the participants diagnosed with AMD, 72.2% were diabetics and 91.7% were hypertensives. About 52.8% and 36.1% of AMD participants had moderate and high risk of fall according to the Morse Fall scale, respectively, while 52.7% and 30.6% of them had moderate and severe ADL impairment and scored below average in the IADL questionnaire compared to their normal peers.<br><br>CONCLUSION: The prevalence of AMD in Egypt is higher than previously documented. The most common form of AMD was early, and the late wet variety was second. Important non-modifiable risk factors for AMD include advancing age, being a woman, and having a positive family history of the disease. Additionally, smoking, diabetes, and hypertension are important risk factors for AMD. Vitamin A consumption appears to offer some protection against AMD. Compared to older adults without AMD, AMD patients had a higher risk of falls and more impairment in ADL and IADL.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-025-23680-6.}, }
@article {pmid40682461, year = {2026}, author = {Gurubaran, IS and Koskela, A and Heloterä, H and Kaarniranta, K}, title = {Secretory autophagy and epithelial-to-mesenchymal transition in cadaveric AMD samples: Novel pathways in disease progression.}, journal = {Acta ophthalmologica}, volume = {104}, number = {2}, pages = {239-251}, pmid = {40682461}, issn = {1755-3768}, support = {//the Sokeain Yst&#xe4;v&#xe4;t ry - De Blindas V&#xe4;nner sr/ ; //the Finnish Cultural Foundation/ ; //the Eye and Tissue Bank Foundation/ ; //the P&#xe4;ivikki and Sakari Sohlberg Foundation/ ; //the Sigrid Juselius Foundation/ ; //the Finnish Eye Foundation/ ; 5503770//the Kuopio University Hospital VTR grant/ ; 333302//the Academy of Finland/ ; }, mesh = {Humans ; *Epithelial-Mesenchymal Transition/physiology ; *Retinal Pigment Epithelium/pathology/metabolism ; *Autophagy/physiology ; Disease Progression ; Female ; Aged ; Cadaver ; Male ; Aged, 80 and over ; Immunohistochemistry ; Middle Aged ; Biomarkers/metabolism ; *Wet Macular Degeneration/metabolism/pathology ; *Macular Degeneration/metabolism/pathology ; }, abstract = {PURPOSE: To examine the presence of secretory autophagy and epithelial-mesenchymal transition (EMT) in the macular retinal pigment epithelium (RPE) of human cadaver eyes with different forms of age-related macular degeneration (AMD).<br><br>METHODS: Human cadaver macula samples representing dry and wet AMD, as well as age-matched controls, were analyzed using immunohistochemistry. Markers of secretory autophagy, EMT, and inflammation were evaluated in RPE cells.<br><br>RESULTS: Increased expression of proteins associated with secretory autophagy and EMT was detected in the RPE of AMD samples compared to controls. These changes were observed in both dry and wet AMD forms.<br><br>CONCLUSION: Secretory autophagy and EMT are elevated in the macular RPE of AMD-affected eyes. These observations offer novel insight into AMD progression and potential therapeutic approaches.}, }
@article {pmid40682602, year = {2025}, author = {Xie, B and Ding, L and Zhang, Q and Chen, X and Wang, K and Lv, J and Wang, J and Xiang, L and Qu, J and Chen, Q}, title = {Proteomic Signatures of Choroidal Neovascularization via Integrated LC-FAIMS-MS/MS Workflow.}, journal = {Journal of proteome research}, volume = {24}, number = {10}, pages = {5001-5010}, doi = {10.1021/acs.jproteome.5c00363}, pmid = {40682602}, issn = {1535-3907}, mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology/genetics ; *Tandem Mass Spectrometry/methods ; *Proteomics/methods ; Mice ; Chromatography, Liquid/methods ; Disease Models, Animal ; Workflow ; *Proteome/genetics ; Macular Degeneration/metabolism/pathology/genetics ; Protein Interaction Maps ; Retinal Pigment Epithelium/metabolism/pathology/chemistry ; Choroid/metabolism/pathology ; Mice, Inbred C57BL ; }, abstract = {The multicellular retinal pigment epithelium/choroid (RC) tissue is pivotal in maintaining retinal homeostasis and is closely associated with sight-threatening eye diseases. However, the limited sample amount, particularly in mice, poses a great challenge in comprehensively characterizing the functional proteins of the RC in disease models. This study utilized a state-of-the-art FAIMS device coupled with an Orbitrap Fusion Lumos mass spectrometer to systematically optimize the LC, FAIMS, and MS/MS acquisition parameters for in-depth proteomic analysis of the difficultly obtained RC samples. In a mouse model of neovascular age-related macular degeneration (nvAMD), the optimized workflow effectively increased the coverage of the proteome, which enabled the identification of 7047 proteins, compared to 5500 identified by conventional LC-MS/MS. Combined with multiomics data sets across species, differential expression analysis revealed 295 significantly altered proteins in the nvAMD model, including key regulators of extracellular matrix (ECM) remodeling (HTRA1, CCDC80) and immune response (SYK, CTSS). Functional enrichment and protein-protein interaction (PPI) network analysis highlighted critical pathways involved in neutrophil chemotaxis, ECM organization, and PI3K-Akt signaling, uncovering potential crosstalk between immune dysregulation and ECM degradation in choroidal neovascularization (CNV) progression. In conclusion, the optimized LC-FAIMS-MS/MS technique presented in this study offers an enhanced depth of proteomic analysis for the RC tissue, revealing novel insights into the molecular mechanisms of nvAMD and identifying new potential therapeutic targets.}, }
@article {pmid40682747, year = {2025}, author = {Lupidi, M and Iaculli, C and Marco, L and Rossi, S and Sicari, E and Villa, G and Pirani, V}, title = {Faricimab in the Treatment of Exudative Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema in Italy: The FARIT Real World Study.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {9}, pages = {2197-2214}, pmid = {40682747}, issn = {2193-8245}, abstract = {INTRODUCTION: Faricimab is a bispecific antibody that enables greater disease control and extended durability compared with vascular endothelial growth factor (VEGF) inhibition alone in neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). This study aimed to evaluate its effectiveness, durability, and economic and social burden in Italian clinical practice.<br><br>METHODS: FARIT was a retrospective, observational, multicenter cohort study across four Italian sites. Adult patients with nAMD or DME who initiated faricimab from February 2023 and had &#x2265;&#x2009;6&#xa0;months of follow-up were included. Clinical outcomes, treatment patterns, and patient-reported data were collected through chart review and electronic surveys.<br><br>RESULTS: A total of 87 eyes (68 with nAMD, 19 with DME) were followed for a median of 14&#xa0;months. Among them, 33 eyes (24 with nAMD, 9 with DME) were anti-VEGF na&#xef;ve. At 1&#xa0;year, 95.4% and 100% of na&#xef;ve eyes with nAMD and DME, respectively, reached a dosing interval of every 12&#xa0;weeks (Q12W) or longer; 63.6% and 100% received the treatment every 16&#xa0;weeks (Q16W). Among switch eyes, 92.4% (nAMD) and 71.5% (DME) reached &#x2265;&#x2009;Q12W, with 35.9% and 42.9%, respectively, on Q16W dosing. After a full loading phase, the median number of injections administered during the post-loading follow-up period (12&#xa0;months for nAMD, 10&#xa0;months for DME) was three for nAMD and two for DME. The interval extensions were driven by visual acuity stabilization/improvement and fluid resolution. Patients and caregivers reported high satisfaction and reduced burden, with fewer injections and better visual outcomes contributing most to improved quality of life. Economic analysis showed a 12-month direct cost (excluding the drug cost) of 1223.8 &#x20ac;/patient from the healthcare system perspective.<br><br>CONCLUSIONS: Faricimab provided effective disease control and extended treatment intervals in treatment-na&#xef;ve and previously treated eyes with nAMD and DME, showing a fast anatomical response and reduced injection burden.}, }
@article {pmid40683364, year = {2025}, author = {Liu, S and Liu, Y and Wu, X and Wang, H and Jin, Z and Wang, P and Feng, J and Chen, S and Zhou, W}, title = {Efficacy and prognostic factors of anti-VEGF treatment for neovascular age-related macular degeneration: An OCTA imaging-based deep learning analysis.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {55}, number = {}, pages = {104701}, doi = {10.1016/j.pdpdt.2025.104701}, pmid = {40683364}, issn = {1873-1597}, mesh = {Humans ; Female ; Male ; Aged ; Retrospective Studies ; *Deep Learning ; *Tomography, Optical Coherence/methods ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity/drug effects ; Prognosis ; Aged, 80 and over ; *Macular Degeneration/drug therapy/diagnostic imaging ; Middle Aged ; Fluorescein Angiography/methods ; Intravitreal Injections ; }, abstract = {BACKGROUND: Anti-VEGF therapies improve visual acuity and reduce central macular thickness (CMT) in neovascular age-related macular degeneration(nAMD) patients. However, In our study, 35.76 % patients do not respond adequately to the anti-VEGF treatment.. Therefore, this study aimed to investigate imaging biomarkers and forecast the influencing factors of anti-VEGF treatment response in nAMD, aiming to enhance clinical evaluation.<br><br>METHODS: We retrospectively analyzed data from patients treated with anti-VEGF at Tianjin Medical University General Hospital from August 2018 to August 2023, including 165 patients with exudative AMD. We investigated their sex, age, best-corrected visual acuity (BCVA)(LogMAR), number of anti-VEGF treatments, optical coherence tomography angiography (OCTA) results. A deep learning model, the improved LUNet model was used to analyze OCTA images, focusing on retinal features including foveal avascular zone (FAZ), vessel density (VD), vessel diameter index (VDI), vessel dispersion (Vdisp) of retinal layers(deep vascular complex and deep vascular complex) to assess their relationship with treatment response.<br><br>RESULTS: After 6 months of anti-VEGF treatment, the patients' BCVA improved from 0.84 &#xb1; 0.40 to 0.70 &#xb1; 0.40 (t = 2.85, P = 0.005) (corresponds to an improvement from 20/140 to 20/100 on the Snellen scale.), CMT decreased from 300.16 &#xb1; 118.92 &#x3bc;m to 249.53 &#xb1; 84.39 &#x3bc;m (t = 4.46, P < 0.001). FAZ perimeter increased from 2.68 mm (2.29, 3.50) to 3.04 mm (2.57, 3.59) (Z=-2.05, P = 0.040), VDI decreased from 6.09 &#xb1; 0.83 to 5.90 &#xb1; 0.71 (t = 2.33, P = 0.021), central VD decreased (t = 2.21, P = 0.028). Logistic regression showed the Vdisp of macular neovascularization (Vdisp-MNV) (P = 0.007, OR 1.41), Vdisp of deep vascular complex(DVC) (P = 0.006, OR 0.45), neovascular surface area (SA) (P = 0.002, OR 0.26), and pigment epithelial detachment(PED) (P = 0.009, OR 0.29) significantly affected the response to anti-VEGF treatment. There were statistical differences in the association between the base line Vdisp of DVC (b = 0.07, t = 2.50, P = 0.014), base line intraretinal fluid (IRF) (b = 0.17, t = 2.02, P = 0.045) and base line BCVA, shown with multiple linear regression analysis.<br><br>CONCLUSION: This study analyzed factors affecting treatment response. Vdisp in MNV showed positive correlation with anti-VEGF treatment response; SA and PED showed negative correlation with anti-VEGF treatment response. It allowed for making personalized treatment strategy to tailor interventions based on individual risk profiles and vascular characteristics which can enhance patient outcomes.}, }
@article {pmid40683606, year = {2026}, author = {Jin, K and Yu, T and Grzybowski, A}, title = {Multimodal artificial intelligence in ophthalmology: Applications, challenges, and future directions.}, journal = {Survey of ophthalmology}, volume = {71}, number = {1}, pages = {158-167}, doi = {10.1016/j.survophthal.2025.07.003}, pmid = {40683606}, issn = {1879-3304}, mesh = {Humans ; *Artificial Intelligence/trends ; *Diagnostic Techniques, Ophthalmological/trends ; *Eye Diseases/diagnosis ; *Ophthalmology/trends/methods ; }, abstract = {With the rapid development of artificial intelligence (AI) technology, multimodal AI that integrates multiple data modalities has shown tremendous potential in the field of ophthalmology. We systematically evaluate the current applications, technical characteristics, and clinical value of multimodal AI in ophthalmology. We conducted a systematic review following the PRISMA guidelines. We searched relevant literature published from 2018 to 2025 in PubMed, Web of Science, Scopus, and Google Scholar databases. A total of 10 studies were included in the final analysis. The main applications of multimodal AI in ophthalmology include glaucoma, age-related macular degeneration, corneal diseases, ophthalmic emergency triage, cognitive impairment screening, diabetes complication screening, and chatbot-based ophthalmic consultation. Multimodal systems showed superior performance compared to unimodal systems across various application areas, with an Area Under the Curve improvements of 4-5 % and accuracy improvements of 2-7 %. Multimodal AI demonstrates broad application prospects in ophthalmology, providing more comprehensive and accurate diagnostic information. Future research should focus on clinical validation, novel fusion methods, interpretability, and lightweight models to promote the clinical translation of multimodal AI in ophthalmology.}, }
@article {pmid40684053, year = {2025}, author = {Gurudas, S and Marques, I and Girmens, JF and Lechanteur, Y and Parravano, MC and Berger, L and Agostini, H and Barrão, S and Tsiroukis, E and Monés, J and Sararols, L and Silva, R and Scholl, H and Lommatzsch, A and Stanzel, B and Vujosevic, S and Sivaprasad, S and , }, title = {Visual acuity in various phenotypes of intermediate age related macular degeneration (AMD) in a multicentre cohort study in Europe- INTERCEPT-AMD report 1.}, journal = {Eye (London, England)}, volume = {39}, number = {14}, pages = {2655-2663}, pmid = {40684053}, issn = {1476-5454}, mesh = {Humans ; Male ; Female ; Aged ; *Visual Acuity/physiology ; *Macular Degeneration/physiopathology/classification ; Aged, 80 and over ; Europe/epidemiology ; Phenotype ; Retinal Pigment Epithelium/pathology ; Middle Aged ; Tomography, Optical Coherence ; Retinal Drusen/physiopathology ; }, abstract = {BACKGROUND/OBJECTIVES: To study the associations of VA and intermediate age-related macular degeneration (iAMD) subclassifications.<br><br>SUBJECTS/METHODS: This is the analysis of baseline data of a multicentre study on patients with iAMD in at least one eye. The subclassifications of iAMD were classified as: (i) iAMD with no evidence of incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) or subretinal drusenoid deposits (SDD); (ii) iAMD with SDD with no iRORA; (iii) iAMD with iRORA with no SDD and (iv) iAMD with iRORA and SDD.<br><br>RESULTS: 983 eyes from 805 patients with iAMD were analysed. The mean age was 75.8 years (SD 7.9), with 35.0% (282) male. Eyes with iRORA with SDD had lower VA relative to eyes with no iRORA and no SDD (OR&#x2009;=&#x2009;0.98 [95% CI 0.96, 0.998]; P&#x2009;=&#x2009;0.03). The VA in the better seeing eye was significantly higher than in the worse seeing eye. Increased age (sex adjusted OR, 1.07, 95% CI 1.05-1.09; P&#x2009;<&#x2009;0.001) and female gender (age adjusted OR, 0.75, 95% CI 0.56-1.01; P&#x2009;=&#x2009;0.057) were associated with SDD. Eyes with nAMD in the fellow eye had reduced odds of iRORA in the study eye (adjusted OR&#x2009;=&#x2009;0.60, 95% CI 0.40-0.91; P&#x2009;=&#x2009;0.015). Eyes with GA had increased odds of iRORA in the study eye (adjusted OR&#x2009;=&#x2009;3.30, 95% CI 2.00-5.45; P&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: Baseline age, presence of SDD and/or iRORA and fellow eye status need to be considered in future clinical trials evaluating preventive or treatment options for iAMD.}, }
@article {pmid40684142, year = {2025}, author = {Meng, Y and Tan, Z and Liu, Y and Ma, Y and Chen, Z and Jiang, L and Li, T}, title = {Association between life's crucial 9 and major eye diseases among US adults aged 40 years or older.}, journal = {BMC public health}, volume = {25}, number = {1}, pages = {2504}, pmid = {40684142}, issn = {1471-2458}, support = {82070972//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; United States/epidemiology ; Middle Aged ; *Eye Diseases/epidemiology ; Adult ; Nutrition Surveys ; Aged ; *Cardiovascular Diseases/epidemiology ; Risk Factors ; }, abstract = {BACKGROUND: Vision impairment due to eye diseases represents a significant global public health concern. There is an increasing acknowledgment of the relationship between cardiovascular health (CVH) and eye diseases. However, Life's Crucial 9 (LC9), the latest scoring framework for CVH, has yet to be investigated in relation to major eye diseases.<br><br>METHODS: This cross-sectional study included 3830 adults aged 40 years or older from the US National Health and Nutrition Examination Survey 2005-2008. We analyzed the relationship between LC9 scores and major eye diseases, including retinopathy, age-related macular degeneration, cataract, and glaucoma using weighted multivariable logistic regression, restricted cubic spline analysis, and subgroup analyses.<br><br>RESULTS: After adjusting for covariates, the poor CVH group (LC9&#x2009;<&#x2009;50) exhibited significant higher risks of glaucoma (odds ratio [OR]&#x2009;=&#x2009;2.37, 95% confidence interval [CI]: 1.11-5.08), retinopathy (OR&#x2009;=&#x2009;2.92, 95% CI: 1.84-4.63), and any objectively confirmed ocular disease (OR&#x2009;=&#x2009;2.25, 95% CI: 1.45-3.49) compared to the ideal CVH group (LC9&#x2009;&#x2265;&#x2009;80). Restricted cubic spline analysis demonstrated a significant inverse linear association between LC9 scores and the risk of these diseases. Subgroup analyses indicated significant interactions between LC9 score and sex concerning retinopathy and any objectively confirmed ocular disease.<br><br>CONCLUSIONS: Suboptimal CVH correlated with increased odds of several major eye diseases in adults aged 40 years or older, highlighting the potential value of CVH optimization for reducing visual impairment burden in this population. Further investigation on the potential causality is warranted.}, }
@article {pmid40684170, year = {2025}, author = {Yan, C and Figueiredo, CA and Pompös, IM and Ugursu, B and Arribas-Lange, P and Skosyrski, S and Yang, S and Althoff, P and Kociok, N and Joussen, AM and Wolf, SA}, title = {Sex differences on laser-induced choroidal neovascularization and short-chain fatty acid treatment in a mouse model.}, journal = {Journal of neuroinflammation}, volume = {22}, number = {1}, pages = {188}, pmid = {40684170}, issn = {1742-2094}, mesh = {Animals ; *Choroidal Neovascularization/drug therapy/etiology/pathology ; Female ; Mice ; Male ; Disease Models, Animal ; *Sex Characteristics ; Mice, Inbred C57BL ; *Lasers/adverse effects ; Microglia/drug effects/pathology ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness worldwide, with a clinical presentation that varies between sexes. In late-stage AMD, choroidal neovascularization (CNV) triggers retinal inflammation and degeneration, processes that are exacerbated by an overactive response of retinal microglial cells. Short-chain fatty acids (SCFAs) have emerged as potential treatments for AMD due to their anti-inflammatory properties. In this study, we investigate the effects of SCFA treatment in a laser-induced CNV mouse model, focusing on sex-dependent differences in disease progression and microglial response. Our findings demonstrate distinct sex-specific patterns in the development of CNV and associated pathological hallmarks. SCFA treatment resulted in a slight increase in density of Iba1[+] microglial cells in females at 3 days post-laser (3dpl), while it prevented an increase in males at 7 dpl, with both sexes showing enhanced microglial ramification. The dynamics of microglial density were likely linked to protective effects on CNV lesion, leakage size, and inflammation, which occurred earlier in females and later in males. At transcriptional level, SCFA showed mixed effects, mainly targeting inflammation resolution, mitochondrial support, and neuronal repair in a sex-dependent manner. In vitro, SCFAs reduced microglial phagocytosis of retinal debris, suggesting a potential anti-inflammatory action. This study underscores the importance of considering sex-specific responses in the development of AMD treatments, such as SCFAs, and highlights the need for personalized therapeutic strategies.}, }
@article {pmid40684186, year = {2025}, author = {Guan, J and Meng, F and Wang, C and Zhang, B and Chen, J and Han, J}, title = {Recent advances in engineered exosome-based therapies for ocular vascular disease.}, journal = {Journal of nanobiotechnology}, volume = {23}, number = {1}, pages = {526}, pmid = {40684186}, issn = {1477-3155}, support = {20230518//Natural Science Foundation of Liaoning Province/ ; CMU-A-025//China Medical University/ ; }, mesh = {*Exosomes/metabolism/chemistry ; Humans ; Animals ; Macular Degeneration/drug therapy ; Drug Delivery Systems ; *Eye Diseases/therapy ; Angiogenesis Inhibitors/therapeutic use ; Diabetic Retinopathy/drug therapy ; Neovascularization, Pathologic/drug therapy ; }, abstract = {Ocular neovascular diseases (ONDs), including corneal neovascularization (CoNV), age-related macular degeneration (AMD) and diabetic retinopathy (DR), are among the leading causes of visual impairment worldwide. Current therapeutic strategies predominantly involve intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents, which, despite their efficacy, present significant limitations such as drug resistance, frequent intravitreal injections, and insufficient addressing of underlying pathological mechanisms. This review critically examines recent advancements in the application of exosomes as innovative drug delivery platforms for treating ocular neovascular diseases. Exosomes, naturally occurring extracellular vesicles, exhibit superior biocompatibility, low immunogenicity, and intrinsic targeting capabilities, making them ideal carriers for bioactive molecules including proteins, RNAs, and small drugs. We explore the mechanistic roles of exosomes in modulating pathological angiogenesis, inflammation, and tissue repair within the ocular environment. Additionally, this review addresses the current challenges hindering the clinical translation of these exosomes, including large-scale production, regulatory hurdles, and safety concerns. Future perspectives highlight the potential integration of nanoparticles and exosomes with existing therapies, the development of multifunctional and personalized treatment strategies, and the necessity for standardized protocols to facilitate their transition from bench to bedside. By overcoming these challenges, exosomes hold the promise of revolutionizing the therapeutic landscape for ocular neovascular diseases, ultimately enhancing patient outcomes and quality of life.}, }
@article {pmid40684968, year = {2025}, author = {Dhablania, N and Torres, M and Burkemper, B and McKean-Cowdin, R and Jiang, X and Varma, R and , }, title = {Burden and Predictors of Undetected Eye Disease in Adult African Americans: African American Eye Disease Study (AFEDS).}, journal = {American journal of ophthalmology}, volume = {279}, number = {}, pages = {91-99}, pmid = {40684968}, issn = {1879-1891}, support = {U10 EY023575/EY/NEI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Black or African American/statistics &amp; numerical data ; California/epidemiology ; Cross-Sectional Studies ; *Eye Diseases/ethnology/diagnosis ; Prevalence ; Risk Factors ; Surveys and Questionnaires ; *Undiagnosed Diseases ; Visual Acuity/physiology ; }, abstract = {PURPOSE: To estimate the burden of and to evaluate the predictors associated with Undetected Eye Disease (UED) in African American adults.<br><br>DESIGN: Population-based cross-sectional study.<br><br>PARTICIPANTS: Self-identified African American participants 40 years and older (n = 6347) from thirty contiguous census tracts in Inglewood, California.<br><br>METHODS: Participants from the African American Eye Disease Study (AFEDS) underwent a complete ophthalmic examination and an in-home-administered questionnaire to assess predisposing, need, enabling, and health behavior predictors associated with UED, including an assessment of ocular conditions such as age-related macular degeneration (AMD), open-angle glaucoma, diabetic retinopathy (DR), visually-significant cataract, and refractive error. Participants with any eye disease (n = 3434) were included in these analyses. UED was defined as having 1 or more eye diseases (AMD, glaucoma, DR, visually-significant cataract-visual acuity in the cataractous less than 20/40, and refractive error) based on the eye examination and self-reporting no known history of any eye disease. The independent associations with UED were explored using multiple logistic regression analysis.<br><br>MAIN OUTCOMES AND MEASURES: Prevalence of and predisposing, need, enabling, and health behavior predictors of UED.<br><br>RESULTS: Fifty-four percent (3434 of 6347) of the participants had eye disease. Twenty-two percent (766 of 3434) of them had undetected eye disease. The major risk factors for UED included having diabetes mellitus (OR [95% CI], 3.52 [2.92-4.26], P < .0001), never having had an eye examination (OR [95% CI], 1.75 [1.14-2.65], P < .0001), having had an eye examination more than 5 years ago (OR [95% CI], 1.66 [1.19-2.31], P < .0001), having poor or very poor general vision (OR [95% CI], 1.89 [1.58-2.27], P < .0001), and trouble getting glasses (OR [95% CI], 1.57 [1.28-1.94], P < .0001).<br><br>CONCLUSIONS: Our data provides evidence of the significant burden of UED among African American individuals. Interventions that address the modifiable risk factors (e.g., trouble getting glasses, never having had an eye examination) may improve detection of eye disease and decrease the burden of VI in this high-risk minority population.}, }
@article {pmid40686763, year = {2025}, author = {Lam, WZ and Shen, M and Zhang, Q and Le, VH and Singla, K and Fooladi, MI and Jiang, H and Lam, BL and Wang, RK and Gregori, G and Rosenfeld, PJ}, title = {Longitudinal widefield OCT optic nerve thickness measurements in a case of incipient non-arteritic ischemic optic neuropathy.}, journal = {American journal of ophthalmology case reports}, volume = {39}, number = {}, pages = {102367}, pmid = {40686763}, issn = {2451-9936}, abstract = {PURPOSE: Widefield swept-source optical coherence tomography angiography (SS-OCTA) scans were combined with a semi-automated algorithm for the early detection and resolution of optic nerve edema in a case of incipient non-arteritic anterior ischemic optic neuropathy (NAION).<br><br>OBSERVATIONS: An incidental case of incipient NAION was identified in a 71-year-old woman enrolled in an ongoing prospective SS-OCTA imaging study using 12&#xa0;&#xd7;&#xa0;12 mm scans that allowed imaging of both the macular and optic disc regions of patients with age-related macular degeneration (AMD). Early intervention with systemic corticosteroids led to the resolution of optic disc edema without subsequent vision loss. A novel semi-automated algorithm was used to quantify the onset and resolution of optic nerve edema and edema in the surrounding retina.<br><br>CONCLUSIONS AND IMPORTANCE: This use of 12&#xa0;&#xd7;&#xa0;12 mm SS-OCTA scans and a semi-automated algorithm can significantly improve the detection and management of incipient NAION in clinical practice with the possibility that early detection would facilitate earlier intervention and better vision preservation in this condition. The use of widefield OCT imaging in conjunction with this novel algorithm in eyes at risk for optic nerve and macular edema could have broader implications for other retinal diseases in which optic disc and macular edema might arise such as diabetic retinopathy. Integrating this methodology into routine ophthalmic evaluations will enable clinicians to identify the onset of edema prior to vision loss, thereby improving patient outcomes.}, }
@article {pmid40686765, year = {2025}, author = {Micevych, PS and Fleckenstein, M and Bernstein, PS}, title = {Delayed-onset Moraxella nonliquefaciens endophthalmitis following intravitreal injection.}, journal = {American journal of ophthalmology case reports}, volume = {39}, number = {}, pages = {102370}, pmid = {40686765}, issn = {2451-9936}, abstract = {PURPOSE: To report a case of Moraxella nonliquefaciens endophthalmitis presenting one month after intravitreal injection.<br><br>OBSERVATIONS: An 84-year-old man presented to the retina clinic with vision loss, pain, and redness in his right eye 28 days after a routine intravitreal injection of faricimab for exudative age-related macular degeneration. The patient had a remote history of cataract surgery, rhegmatogenous retinal detachment repair, and scleral buckle explant for exposure 3 years prior. The patient was found to have endophthalmitis, characterized by a hypopyon and dense vitritis. Broad-spectrum intravitreal antimicrobials and dexamethasone were administered, and a vitreous tap returned sterile. The patient achieved initial quiescence, but he had two recurrences of inflammation in this eye over the next 4.5 months. The patient ultimately underwent pars plana vitrectomy, vitreous biopsy, intraocular lens explant, capsulectomy and repeat intravitreal antimicrobial injections for definitive treatment. Broad-range PCR testing detected Moraxella nonliquefaciens. Inflammation resolved after surgery without further recurrence in the subsequent 7-month post-operative period.<br><br>CONCLUSIONS AND IMPORTANCE: Moraxella species have been implicated in cases of endophthalmitis associated with glaucoma filtering surgery and trauma, but this report details a delayed-onset Moraxella nonliquefaciens-associated endophthalmitis after intravitreal injection.}, }
@article {pmid40687727, year = {2025}, author = {Shao, Y and Lu, Y and Gu, Y and Chen, Y and Li, C}, title = {Natural active ingredients targeted inflammatory cytokines and major blinding eye diseases: a two-sample Mendelian randomization and molecular docking analysis.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1427144}, pmid = {40687727}, issn = {2296-858X}, abstract = {OBJECTIVES: Previous studies have reported that a few inflammatory cytokines have associations with ocular diseases. The objective of this study is to explore the causal relationship between 41 inflammatory cytokines and five ocular diseases using Mendelian randomization (MR) method and study the interaction between five natural active ingredients and inflammatory cytokines through molecular docking.<br><br>METHODS: The two-sample MR study employed genetic variances related to age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), myopia, and cataract. These variances were sourced from a comprehensive, publicly accessible genome-wide association study (GWAS). Additionally, inflammatory cytokines were derived from a GWAS summary that included 8,293 healthy individuals. The study primarily used the inverse variance weighted (IVW) method to investigate the causality between exposures and outcomes. To further bolster the final results, a variety of methods were concurrently used, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO. A protein-protein interaction (PPI) network was constructed, and corresponding protein interaction relationships were analyzed utilizing the STRING database. Molecular docking served as an evaluation tool, confirming the binding between components and targets. This process was performed using AutoDock and PyMOL software.<br><br>RESULTS: The results indicated that IL-18 (OR: 1.134, 95% CI: 1.009-1.275, P = 0.034) and PDGF-BB (OR: 0.804, 95% CI: 0.678-0.954, P = 0.012) had protective effect on AMD; Genetically predicted RANTES had protective effect on glaucoma (OR: 0.886, 95% CI: 0.810-0.969, P = 0.008); IL-10 had protective effect on DR (OR: 0.871, 95% CI: 0.759-0.999, P = 0.048); GROa may be associated with increased myopia risk (OR: 1.230, 95% CI: 1.046-1.446, P = 0.012); Eotaxin (OR: 1.089, 95% CI: 1.018-1.165, P = 0.013), FGF2 (OR: 1.183, 95% CI: 1.004-1.393, P = 0.045) and GROa (OR: 1.053, 95% CI: 1.000-1.109, P = 0.049) were associated with increased cataract risk, while IL-1RA may be associated with decreased cataract risk. PPI network showed GROa, FGF2, IL-18, IL-1RA, IL-10, and Eotaxin interact closely. Molecular docking simulation showed that most of the compounds have good binding activities with critical targets.<br><br>CONCLUSION: The present study identified inflammatory cytokines with causal relationships to five ocular diseases, revealing potential compounds for treating these diseases, providing a theoretical basis for further clinical practice.}, }
@article {pmid40688783, year = {2025}, author = {Jiang, YX and Gui, SY and Sun, XD}, title = {Associations between organophosphorus pesticides exposure and age-related macular degeneration risk in U.S. adults: analysis from interpretable machine learning approaches.}, journal = {International journal of ophthalmology}, volume = {18}, number = {7}, pages = {1214-1230}, pmid = {40688783}, issn = {2222-3959}, abstract = {AIM: To investigate the associations between urinary dialkyl phosphate (DAP) metabolites of organophosphorus pesticides (OPPs) exposure and age-related macular degeneration (AMD) risk.<br><br>METHODS: Participants were drawn from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2008. Urinary DAP metabolites were used to construct a machine learning (ML) model for AMD prediction. Several interpretability pipelines, including permutation feature importance (PFI), partial dependence plot (PDP), and SHapley Additive exPlanations (SHAP) analyses were employed to analyze the influence from exposure features to prediction outcomes.<br><br>RESULTS: A total of 1845 participants were included and 137 were diagnosed with AMD. Receiver operating characteristic curve (ROC) analysis evaluated Random Forests (RF) as the best ML model with its optimal predictive performance among eleven models. PFI and SHAP analyses illustrated that DAP metabolites were of significant contribution weights in AMD risk prediction, higher than most of the socio-demographic covariates. Shapley values and waterfall plots of randomly selected AMD individuals emphasized the predictive capacity of ML with high accuracy and sensitivity in each case. The relationships and interactions visualized by graphical plots and supported by statistical measures demonstrated the indispensable impacts from six DAP metabolites to the prediction of AMD risk.<br><br>CONCLUSION: Urinary DAP metabolites of OPPs exposure are associated with AMD risk and ML algorithms show the excellent generalizability and differentiability in the course of AMD risk prediction.}, }
@article {pmid40688787, year = {2025}, author = {Yuan, LY and Su, WM and Li, LP and Tian, XF and Zheng, XL and Yuan, XY}, title = {Causal role of oxidative stress in age-related macular degeneration: a bidirectional Mendelian randomization study.}, journal = {International journal of ophthalmology}, volume = {18}, number = {7}, pages = {1307-1316}, pmid = {40688787}, issn = {2222-3959}, abstract = {AIM: To elucidate causal pathways between oxidative biomarkers and age-related macular degeneration (AMD) phenotypes.<br><br>METHODS: A bidirectional Mendelian randomization (MR) analytical protocol was implemented, which utilized genome-wide association study (GWAS) summary statistics derived from the IEU OpenGWAS repositories. The investigation focused on 11 oxidative stress markers and AMD phenotypes, encompassing both wet and dry subtypes. The MR methodology incorporated inverse-variance weighted (IVW) calculations, MR-Egger statistical regression, weighted median approximation, and weighted mode assessments to estimate causative relationships. Sensitivity evaluations were conducted to verify result robustness and identify potential pleiotropy.<br><br>RESULTS: Genetically predicted elevated catalase (CAT) concentrations demonstrated significant associations with heightened risks of overall AMD (IVW OR=1.084, 95%CI: 1.021-1.151, P=0.008) and wet AMD phenotype (IVW OR=1.113, 95%CI: 1.047-1.247, P=0.007). Higher genetically predicted albumin concentrations corresponded with reduced AMD risk (IVW OR=0.827, 95%CI: 0.715-0.957, P=0.013) but increased wet AMD risk (IVW OR=1.229, 95%CI: 1.036-1.458, P=0.018). Reverse MR analysis revealed that genetically predicted dry AMD exhibited significant association with reduced albumin levels (IVW OR=0.987, 95%CI: 0.979-0.996, P=0.004), while wet AMD corresponded with decreased total bilirubin (TBIL) and paraoxonase (PON) activity.<br><br>CONCLUSION: The results offer strong support for a causal link between markers of oxidative stress and the development of AMD, indicating that oxidative processes play a role in driving the disease progression.}, }
@article {pmid40689128, year = {2025}, author = {Motevasseli, T and Seraj, A and Daftarian, N and Kanav, MR and Ahmadieh, H and Sheibani, N}, title = {Intracellular Signaling Pathways and Their Potential Targeting for Treatment of Ocular Posterior Segment Fibrosis.}, journal = {Journal of ophthalmic &amp; vision research}, volume = {20}, number = {}, pages = {}, pmid = {40689128}, issn = {2008-2010}, abstract = {Treatment of posterior segment fibrosis is an unmet challenge in ophthalmology. Fibrotic responses complicate the pathology and treatment of age-related macular degeneration, diabetic retinopathy, retinal detachment, and other retinal diseases resulting in severe visual impairment. There is a lack of clear understanding of the exact mechanisms and different cell types taking part in retinal and preretinal fibrosis. This review discusses the current knowledge regarding various aspects of the intracellular signaling pathways impacting vitreoretinal fibrotic processes, focusing on the cellular and molecular mechanisms, summarizing the results of preclinical and clinical studies, and suggesting strategies for future investigations.}, }
@article {pmid40689254, year = {2025}, author = {Schrittwieser, J and Birner, K and Coulibaly, LM and Schmidt-Erfurth, U and Reiter, GS}, title = {Exploiting Microperimetry as a Functional End Point in Healthy Aging and Different Stages of Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100850}, pmid = {40689254}, issn = {2666-9145}, abstract = {OBJECTIVE: To compare functional parameters between healthy aged eyes and different stages of age-related macular degeneration (AMD) based on functional parameters in microperimetry (MP) in 2 commonly used MP devices.<br><br>DESIGN: A prospective, cross-sectional study.<br><br>SUBJECTS: From 80 eyes from 80 subjects, 14 400 stimuli points were included.<br><br>METHODS: Subjects classified as healthy, intermediate AMD, neovascular AMD (nAMD), or geographic atrophy (GA) secondary to AMD were imaged with Spectralis HRA+OCT (Heidelberg Engineering) and underwent 2 consecutive examinations each, using the MP-3 (NIDEK) under photopic conditions and the MAIA (Centervue) under mesopic conditions. Pointwise sensitivity (PWS), mean sensitivity, range between highest and lowest PWS, fixation stability, and examination duration were compared between all 4 groups in both devices. Group comparison was performed using linear mixed-effects models and a discriminant analysis to find the parameters that best discriminated the respective AMD stage.<br><br>MAIN OUTCOME MEASURES: Pointwise sensitivity, range of the PWS, fixation metrics, and durations of the examinations.<br><br>RESULTS: The groups exhibited significant differences in PWS (P < 0.001) and mean sensitivity (P < 0.001), with healthy eyes showing the highest and late stages of AMD showing the lowest sensitivity values. In addition, GA showed significantly greater fixation stability compared with nAMD in the MP-3 at 2&#xb0; and 4&#xb0; (P = 0.014 and P = 0.008, respectively). The examination duration in healthy patients was significantly shorter compared with patients with GA (P = 0.041) in MP-3. No significant differences in fixation stability and duration between groups were observed with the MAIA device. The range between the highest and lowest PWS was the most effective parameter for discrimination, with a classification accuracy of 52.5% and 50.6% in the MP-3 and MAIA, respectively.<br><br>CONCLUSIONS: Retinal sensitivity declines with disease progression in AMD in both mesopic and photopic background illumination. The lowest retinal sensitivity was observed in patients with GA. Background illumination should be considered when selecting an MP device for a clinical trial.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40689256, year = {2025}, author = {Gabrielle, PH and Creuzot-Garcher, C}, title = {Re: Patel et al: Oral Antithrombotic Medication Is Associated with Improved Visual Acuity Outcomes in Eyes with Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100840}, pmid = {40689256}, issn = {2666-9145}, }
@article {pmid40689257, year = {2025}, author = {Verghese, AP and Lasalle, CC and Ramsey, DJ}, title = {Dark Adaptometry Kinetics Differentiates Age-Related Macular Degeneration from Central Serous Chorioretinopathy.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100835}, pmid = {40689257}, issn = {2666-9145}, abstract = {PURPOSE: To assess the diagnostic utility of dark adaptometry (DA) rod intercept time (RIT) to differentiate age-related macular degeneration (AMD) from central serous chorioretinopathy (CSCR).<br><br>DESIGN: Retrospective consecutive case series.<br><br>PARTICIPANTS: Consecutive patients with a clinical diagnosis of AMD or CSCR who were &#x2265;50 years of age.<br><br>METHODS: The study included patients who had completed a DA study in &#x2265;1 eye measured at 5&#xb0; superior to the fovea on the retina. All patients underwent a comprehensive retina examination, including OCT assessment of the macula.<br><br>MAIN OUTCOME MEASURES: Patients were classified based on their RIT, with an RIT >6.50 minutes considered a delay.<br><br>RESULTS: The study included 67 patients with AMD and 25 with CSCR. Patients with AMD tended to be older (73.8 &#xb1; 8.9 years vs. 65.0 &#xb1; 7.2 years, P < 0.001) and were more likely female (53.7% vs. 28.0%, P = 0.049) compared with their CSCR counterparts. Additionally, patients with AMD tended to exhibit poorer vision in both their better-seeing (logarithm of the minimum angle of resolution 0.14 &#xb1; 0.13 vs. 0.08 &#xb1; 0.13, P = 0.057) and worse-seeing (logarithm of the minimum angle of resolution 0.48 &#xb1; 0.47 vs. 0.26 &#xb1; 0.25, P = 0.028) eyes. Rod intercept times were slower in patients with AMD compared with CSCR, both in the faster-adapting (12.44 &#xb1; 6.96 minutes vs. 4.01 &#xb1; 1.28 minutes, P < 0.001) and slower-adapting (13.06 &#xb1; 6.67 minutes vs. 4.95 &#xb1; 1.78 minutes, P < 0.001) eyes. Using a delayed RIT in the faster-adapting eye to classify patients with AMD versus CSCR showed excellent performance with a sensitivity of 79.1% (95% confidence interval [CI]: 67.4%-88.1%) and perfect specificity of 100.0% (95% CI: 86.3%-100.0%), yielding an accuracy of 97.4% (95% CI: 91.7%-99.6%). After adjusting for age, sex, and visual acuity, RIT in the faster-adapting eye remained an independent predictor of AMD versus CSCR.<br><br>CONCLUSIONS: Prolonged dark adaptation, indicated by a longer RIT, is capable of distinguishing individuals with AMD from CSCR, 2 conditions that share similar fundus features. Future investigations are warranted to assess the effectiveness of this noninvasive technique for AMD screening.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40689376, year = {2025}, author = {Kimura, K and Imai, K and Ueno, M and Sotozono, C}, title = {Assessment of the official national insurance coverage of regenerative medical products for ophthalmic diseases in Japan following regulatory approval.}, journal = {Regenerative therapy}, volume = {30}, number = {}, pages = {384-388}, pmid = {40689376}, issn = {2352-3204}, abstract = {INTRODUCTION: Recently, significant progress has been made in the field of regenerative medicine in Japan for the treatment of ophthalmic diseases, with a notable emphasis placed on clinical research and practical applications, and in 2014, one significant development was the initiation of the world's first clinical research using iPS cells for age-related macular degeneration. In addition, three regenerative medical products for the treatment of limbal stem cell deficiency, a rare and intractable ocular surface disease, have recently been approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) under the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act (PMD Act). In order to expedite the practical implementation of regenerative medicine, the PMD Act presented a new category for regenerative medical products alongside the two categories that currently exist (i.e., 'pharmaceutical products' and 'medical devices'). However, within the current official Japanese national insurance coverage plan, there is no category designated for 'regenerative medical products'. Although the approval system for regenerative medical products differs from country to country (i.e., the United States Food and Drug Administration (U.S. FDA), the European Medicines Agency (EMA), etc.), in Japan, they are approved by the Japanese MHLW and PMDA. When manufacturers seek newly approved regenerative medical products in Japan to be incorporated within those listed in the Japanese national insurance coverage plan, the products are classified as either 'pharmaceutical products' or 'medical devices' and are reviewed by the Central Social Insurance Medical Council ("Chuikyo", in Japanese) of the Japanese MHLW. Although the responsibility for applying for regulatory approval and insurance coverage lies with the manufacturer, as the developer who conducted the clinical study and the investigator-initiated clinical trial for two ophthalmic regenerative medical products (i.e., Sakracy® and Vyznova®), we perceived that the period from regulatory approval to insurance coverage listing for these two products was longer than for other ophthalmic regenerative medical products. These experiences became the research question and the focus was on ophthalmic regenerative medical products, with the rationale behind this submission being that the dissemination of our experience will be of benefit to all clinical researchers and manufacturers. Hence, the purpose of this present study was to investigate the insurance coverage of regenerative medical products for ophthalmic diseases in Japan from the aspect of specific coverage-related categories.<br><br>METHODS: In this study, we investigated newly approved regenerative medical products for ophthalmic diseases in Japan after the Revised Pharmaceutical Affairs Act came into effect in 2014. The insurance coverage categories (i.e., 'pharmaceutical products' or 'medical devices') of each product and the period from regulatory approval to insurance coverage listing were examined based on publicly available materials from the Japanese MHLW.<br><br>RESULTS: As of the end of 2024, five products are included on the insurance coverage list. The period for Luxturna Injection&#xae; (Novartis Pharma), categorized as a pharmaceutical product, to be included was 65 days, which was within the standard administrative processing time for pharmaceutical products, (i.e., 60 days or less, yet no later than 90 days), while the elapsed periods for Nepic&#xae; and Ocural&#xae; (Japan Tissue Engineering), Sakracy&#xae; (CynosBio), and Vyznova&#xae; (Aurion Biotech Japan), which are categorized as medical devices, were 74, 173, 224, and 534 days, respectively. The periods for Sakracy&#xae; and Vyznova&#xae; exceeded the standard administrative processing time for medical devices, which in principle ranges from 5 to 6 months. Moreover, the elapsed period of time from regulatory approval to insurance coverage listing for Vyznova&#xae; was more than twice as long as that which occurred for Sakracy&#xae;.<br><br>CONCLUSIONS: Regenerative medical products categorized as medical devices are required to undergo a review process conducted by the Technical Committee for Insurance Materials on Medical Devices of the Japanese Central Social Insurance Medical Council. Our findings suggest that both manufacturers and regulatory authorities need to revise the Technical Committee's strategy from the aspect of putting regenerative medical products into practical clinical use in Japan.}, }
@article {pmid40689724, year = {2025}, author = {Neri, G and Rebecchi, C and Oakley, JD and Olivieri, C and Ricardi, F and Marolo, P and Russakoff, DB and Reibaldi, M and Borrelli, E}, title = {Deep Learning Model for Automated Classification of Macular Neovascularization Subtypes in AMD.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {9}, pages = {55}, pmid = {40689724}, issn = {1552-5783}, mesh = {Humans ; *Deep Learning ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; Aged ; Male ; Female ; *Wet Macular Degeneration/classification/diagnosis ; ROC Curve ; Aged, 80 and over ; *Choroidal Neovascularization/classification/diagnosis ; Algorithms ; Middle Aged ; *Macula Lutea/pathology ; Sensitivity and Specificity ; }, abstract = {PURPOSE: To develop a deep learning algorithm capable of accurately classifying macular neovascularization (MNV) subtypes in patients with treatment-naïve exudative neovascular age-related macular degeneration (AMD) using structural optical coherence tomography (OCT) images.<br><br>METHODS: In this retrospective cohort study, a total of 193 eyes with treatment-na&#xef;ve neovascular AMD were included. Each case was classified into MNV subtypes (type 1, 2, or 3) based on structural OCT features. Convolutional neural network (CNN)-based deep learning models were trained using cross-validation to classify MNV subtypes. Preprocessing included homogenization of image data to optimize use of layer information for classification. Performance metrics included sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (AUC), with and without homogenization.<br><br>RESULTS: Homogenized OCT data improved classification performance compared to non-homogenized data for all models. The highest reported sensitivity and specificity for type 1 MNV was 96.7% and 84.9%; for type 2, 100.0% and 85.5%; and, for type 3, 84.9% and 87.9%, respectively. The AUCs for type 1, 2, and 3 MNV were 0.95, 0.97, and 0.91, respectively. Occlusion sensitivity analysis revealed critical regions for classification, highlighting distinct anatomical differences among MNV subtypes.<br><br>CONCLUSIONS: The proposed deep learning model demonstrated high accuracy in classifying MNV subtypes on structural OCT, with improved performance following homogenization. This tool could assist clinicians in accurately and efficiently diagnosing MNV subtypes, potentially influencing treatment decisions and patient outcomes in neovascular AMD.}, }
@article {pmid40689796, year = {2025}, author = {Hugi, F and Vollmer, J and Renaud, L and Machacek, M}, title = {A Semimechanistic Ocular Pharmacokinetic Model for ADVM-022 Gene Therapy Describing the Dose-Exposure Relationship in Monkeys and the Scaling to Human.}, journal = {Molecular pharmaceutics}, volume = {22}, number = {8}, pages = {4612-4623}, doi = {10.1021/acs.molpharmaceut.5c00155}, pmid = {40689796}, issn = {1543-8392}, mesh = {Animals ; Humans ; *Genetic Therapy/methods ; *Recombinant Fusion Proteins/pharmacokinetics/genetics/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/genetics/administration &amp; dosage ; *Genetic Vectors/administration &amp; dosage/genetics ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/genetics/antagonists &amp; inhibitors ; Dependovirus/genetics ; Macular Degeneration/therapy/genetics ; *Eye/metabolism ; }, abstract = {Gene therapies are emerging as a new treatment modality. Due to their novelty, general pharmacological properties have yet to be established. For example, the translation from animal models to humans for first-in-human dose selection and the dose-exposure relationship remain poorly characterized. A mechanistic and quantitative framework would improve preclinical program design, enable more robust first-in-human dose predictions, and support more rigorous dose adjustments during clinical development. This study establishes a semimechanistic mathematical model for aflibercept expression and pharmacokinetics (PK) following intravitreal (IVT) ADVM-022 administration in monkeys and humans, drawing on the preclinical and clinical data presently available. ADVM-022 is an AAV2.7m8-based viral vector that delivers the gene encoding aflibercept, an antivascular endothelial growth factor (VEGF) fusion protein. It was developed as a gene therapy for treating wet age-related macular degeneration (wAMD) and is administered through a single IVT injection. The proposed model incorporates established ocular PK for intravitreally administered proteins, along with an expression component that links AAV dose to aflibercept production. Based on pooled PK data from monkey studies, the model suggests that transduction occurs not only in the retina but also in other ocular tissues bordering the vitreous, contributing to the observed intraocular aflibercept levels. Increasing doses within the lower range of preclinical studies (3 × 10[10]-2 × 10[13] vg/eye) lead to increased transduction and expression, plateauing at upper limits of approximately 12.7 μg/day·cm[3] for the retina, and 0.785 μg/day for extra-retinal tissues at higher doses. Assuming similar transduction efficiency between humans and monkeys, with adjustments for anatomical differences, the model provided predictions of ocular aflibercept concentrations that aligned with observations from the two dose groups in the phase 1 OPTIC clinical trial, supporting the utility of this approach.}, }
@article {pmid40690044, year = {2025}, author = {Limoli, C and O'Toole, L and Piccoli, G and Nucci, P and Vujosevic, S}, title = {Patients' awareness and presenting symptoms at the onset of neovascular age-related macular degeneration in two distinct European cohorts.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {304}, pmid = {40690044}, issn = {1573-2630}, mesh = {Humans ; Female ; Aged ; Male ; Aged, 80 and over ; Middle Aged ; Italy/epidemiology ; Surveys and Questionnaires ; Ireland/epidemiology ; *Wet Macular Degeneration/diagnosis/epidemiology/drug therapy/psychology ; *Awareness ; *Visual Acuity ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; Intravitreal Injections ; Fluorescein Angiography/methods ; }, abstract = {PURPOSE: Neovascular age-related macular degeneration (nAMD) is a common ocular condition in the elderly population. If left untreated, it can lead to significant visual impairment. Prompt detection of the disease achieves better therapeutic outcomes. The goal of this study is to ascertain the presenting symptoms of nAMD from two different population groups.<br><br>METHODS: A questionnaire was distributed to two groups of patients with nAMD who attended intravitreal injection services in Milan and Dublin. Four age-subgroups were considered: 60-69, 70-79, 80-89,&#x2009;>&#x2009;90&#xa0;years. Patients completed an interview questionnaire regarding their symptoms at the time of diagnosis with nAMD. The patients were divided into two groups; Group A consisted of Italian patients and group B comprised Irish patients. Symptom differences between the groups were compared using the Chi-square test.<br><br>RESULTS: A total of 237 patients with nAMD were included in the study, with 136 in group A and 101 in group B. The most common age-subgroup was 80-89&#xa0;years (49.8%); the majority 129(54.4%) patients were females. The most frequently reported symptom at the time of nAMD onset was distortion (n&#x2009;=&#x2009;105, 44.3%). Notably, 50 patients (21.1%) were asymptomatic. The Irish patients were less aware of the onset of the symptoms of nAMD compared with their Italian counterparts(p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: This study shows that 21.1% of patients with nAMD were asymptomatic at the onset of their condition. Symptom awareness was higher among the Italian cohort compared to the Irish group. Patients at risk for conversion to nAMD should attend regular OCT monitoring rather than relying on subjective symptoms alone.}, }
@article {pmid40690116, year = {2025}, author = {Kim, CY and Jeong, C and Han, Y and Hwang, C}, title = {Angiopoietin-1 and Tie2-Based Dual Cell Therapy Enhances Antiangiogenic Barrier Function in a Retina-Mimetic Model for Neovascular Retinal Disease.}, journal = {Tissue engineering and regenerative medicine}, volume = {22}, number = {6}, pages = {877-893}, pmid = {40690116}, issn = {2212-5469}, support = {RS-2023-00283544//Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare/ ; 2020IP0041//Asan Institute for Life Sciences, Asan Medical Center/ ; 2024IP0044//Asan Institute for Life Sciences, Asan Medical Center/ ; }, mesh = {Humans ; *Receptor, TIE-2/metabolism ; *Angiopoietin-1/metabolism/pharmacology ; Human Umbilical Vein Endothelial Cells/metabolism ; *Retina/pathology/metabolism ; *Cell- and Tissue-Based Therapy ; Cell Movement/drug effects ; Mesenchymal Stem Cells/metabolism/cytology ; Coculture Techniques ; Animals ; *Angiogenesis Inhibitors/pharmacology ; *Retinal Diseases/therapy/pathology/metabolism ; Retinal Pigment Epithelium ; Choroidal Neovascularization/therapy/pathology/metabolism ; }, abstract = {BACKGROUND: Choroidal neovascularization (CNV) is a major pathological process underlying retinal degenerative diseases such as wet age-related macular degeneration. While anti-VEGF therapies are widely used, limitations in response and vascular instability necessitate new approaches that promote both antiangiogenic effects and barrier restoration.<br><br>METHODS: A dual-cell therapy strategy was developed using human umbilical vein endothelial cells (HUVECs) genetically modified to overexpress Tie2 and mesenchymal stem cells (MSCs) engineered to secrete Angiopoietin-1 (Ang1). Antiangiogenic efficacy was evaluated using scratch assays, Transwell migration, and tube formation under VEGF stimulation. A retina-mimetic 2.5D co-culture system incorporating iPSC-derived RPE cells and mCherry-labeled ECs was used to assess endothelial invasion and epithelial barrier preservation.<br><br>RESULTS: Tie2/Ang1-modified cells significantly suppressed angiogenic behavior. Transwell migration showed OD595 crystal violet absorbance decreased from 3.54&#x2009;&#xb1;&#x2009;0.27 (control HUVEC) to 1.28&#x2009;&#xb1;&#x2009;0.08 (Tie2 overexpressed HUVEC in MSC Ang1 conditioned medium) under VEGF stimulation (p&#x2009;<&#x2009;0.01). Tube formation area cultured in VEGF dropped from 1.25&#x2009;&#xb1;&#x2009;0.05 in control group to 0.74&#x2009;&#xb1;&#x2009;0.07 in Tie2 overexpressed group cultured with MSC-Ang1 conditioned medium (p&#x2009;<&#x2009;0.01). In the retina-mimetic model, EC infiltration to the RPE monolayer across Transwell membrane decreased from 52.2&#x2009;&#xb1;&#x2009;8.5% in control HUVEC to 5.6&#x2009;&#xb1;&#x2009;4.3% with HUVEC-Tie2&#x2009;+&#x2009;Ang1 conditioned medium under VEGF (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: This study demonstrates that co-delivery of Ang1 and Tie2 via engineered ECs and MSCs synergistically inhibits VEGF-induced angiogenesis and choroidal migration while protecting epithelial barrier function. The retina-mimetic co-culture platform further validates the translational relevance of this dual-cell approach as a regenerative and antiangiogenic strategy in retinal vascular disease.}, }
@article {pmid40690698, year = {2025}, author = {Tew, TB and Hsieh, YT and Tsui, MC and Hsia, Y and Lee, CY and Wang, SW and Huang, CJ and Ma, IH and Hung, KC and Lai, TT and Yang, CH and Yang, CM and Ho, TC}, title = {COMPARISON OF CHARACTERISTICS AND TREATMENT OUTCOMES OF TYPE 1 AND TYPE 2 MYOPIC CHOROIDAL NEOVASCULARIZATION AFTER ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {12}, pages = {2279-2288}, pmid = {40690698}, issn = {1539-2864}, mesh = {Humans ; Retrospective Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Female ; Male ; *Visual Acuity/physiology ; Tomography, Optical Coherence/methods ; *Choroidal Neovascularization/drug therapy/diagnosis/etiology ; Intravitreal Injections ; *Myopia, Degenerative/complications/drug therapy/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Fluorescein Angiography/methods ; Aged ; *Bevacizumab/administration &amp; dosage/therapeutic use ; Treatment Outcome ; Follow-Up Studies ; Fundus Oculi ; Adult ; }, abstract = {PURPOSE: This study aims to compare baseline characteristics and treatment outcomes of Type 1 and Type 2 myopic choroidal neovascularization (CNV) after 1 year of antivascular endothelial growth factors therapy and identify clinical factors associated with visual outcomes, recurrence rates, and injection numbers.<br><br>METHODS: In this retrospective study, we reviewed 171 patients with active myopic CNV treated with antivascular endothelial growth factors therapy and followed for at least 1 year. CNV types were classified using optical coherence tomography. Baseline characteristics, including best-corrected visual acuity, myopic maculopathy grade, and optical coherence tomography findings, were compared.<br><br>RESULTS: Type 1 CNVs (19.3% of cases) exhibited worse baseline best-corrected visual acuity and more advanced macular degeneration than Type 2 CNVs. Both types showed significant visual improvement equivalent to 2.2 lines post-therapy, with no difference in recurrence rates or injection numbers. Multivariate analysis revealed that baseline best-corrected visual acuity, severity of myopic macular degeneration, and presence of subretinal hyperreflective exudation were significant predictors of final best-corrected visual acuity, while CNV type was not an independent predictor.<br><br>CONCLUSION: Despite more severe macular degeneration in Type 1 CNV, both types myopic CNVs benefit significantly from antivascular endothelial growth factors therapy. These findings support extending treatment to Type 1 CNVs and highlight the need for individualized management strategies.}, }
@article {pmid40691408, year = {2025}, author = {Torres-Villaros, H and Giocanti-Aurégan, A and Doan, S and Agard, E and Billant, J and Arbousoff, N and Matagrin, B and Fenniri, I and Dot, C}, title = {Continuous versus Intermittent Use of Tear Substitutes in Patients Treated with Anti-VEGF for Neovascular Age-Related Macular Degeneration: The TREDIA Study.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {9}, pages = {2231-2241}, pmid = {40691408}, issn = {2193-8245}, abstract = {INTRODUCTION: The aim of this prospective randomized bicenter study was to compare the effects of continuous versus intermittent use of tear substitutes on the ocular surface and dry eye symptoms in patients receiving repeated and frequent intravitreal injections (IVIs) for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Patients with nAMD treated with anti-vascular endothelial growth factor (anti-VEGF) for more than 1 year at 4-8-week intervals were included. The intermittent treatment group received standard 1.5% povidone artificial tears for three days after each IVI, while the continuous treatment group received an ophthalmic lubricant emulsion with 0.18% sodium hyaluronate four times a day throughout the study. The primary endpoint was the mean change in Ocular Surface Disease Index (OSDI) score between baseline and the day of the fourth IVI. Secondary endpoints included the Schirmer test score, tear break-up time (TBUT), and Oxford staining score.<br><br>RESULTS: Sixty-five patients with mean age of 83.1&#x2009;&#xb1;&#x2009;6.0&#xa0;years who had previously received a mean number of 28.5&#x2009;&#xb1;&#x2009;20.3 IVIs were included. The mean OSDI score change from baseline was -6.6&#x2009;&#xb1;&#x2009;13.5 points in the continuous treatment group versus&#x2009;+0.6&#x2009;&#xb1;&#x2009;13.7 points in the intermittent treatment group (p&#x2009;=&#x2009;0.04). No significant differences in Schirmer test score, TBUT, and Oxford score were found between the groups.<br><br>CONCLUSIONS: Continuous use of tear substitutes in patients with nAMD receiving repeated and frequent IVIs could be beneficial in improving dry eye symptoms, as shown by a significant improvement in OSDI scores in our study, despite no substantial changes in other ocular surface metrics.<br><br>TRIAL REGISTRATION NUMBER: NCT06174181.}, }
@article {pmid40691725, year = {2025}, author = {Beaver, D and Hudson, C}, title = {Are surfers and scuba divers an overlooked at-risk group for age-related macular degeneration?.}, journal = {Eye (London, England)}, volume = {39}, number = {13}, pages = {2495-2496}, pmid = {40691725}, issn = {1476-5454}, }
@article {pmid40691727, year = {2025}, author = {Tang, F and Chandra, S and Grewal, MK and Raza, SA and Wijesingha, N and Faes, L and Fu, DJ and Tsai, WS and Lim, A and Sivaprasad, S}, title = {Determinants of visual functions in patients with early and intermediate age-related macular degeneration: the PEONY study.}, journal = {Eye (London, England)}, volume = {39}, number = {14}, pages = {2686-2693}, pmid = {40691727}, issn = {1476-5454}, support = {1906//Fight for Sight UK/ ; }, mesh = {Humans ; Male ; Female ; *Visual Acuity/physiology ; Tomography, Optical Coherence/methods ; Aged ; Middle Aged ; *Macular Degeneration/physiopathology/diagnosis ; Retinal Drusen/physiopathology ; Geographic Atrophy/physiopathology ; Aged, 80 and over ; Color Vision/physiology ; }, abstract = {BACKGROUND/OBJECTIVES: Although decline in visual functions have been reported in eyes with non-advanced age-related macular degeneration (AMD), it is not known if visual functions in these eyes are influenced by structural changes on optical coherence tomography (OCT). We investigated the association between known OCT changes with photopic and scotopic visual functions.<br><br>SUBJECTS/METHODS: Participants aged 55 years or over with early or intermediate AMD in at least 1 eye, and controls with healthy maculae and were included. Associations between visual functions and retinal structural changes were investigated using linear regression and survival analysis.<br><br>RESULTS: We found that the presence of refractile drusen and nascent geographic atrophy (nGA) and were associated with poorer best-corrected visual acuity (BCVA), low luminance VA (LLVA), and increased low luminance deficit (LLD) (P&#x2009;<&#x2009;0.05). In survival analysis, eyes with thicker subfoveal choroidal thickness (SFCT) had a higher hazard rate of rod intercept, suggesting a decreased rod-intercept time (RIT). Eyes with nGA, drusen, refractile drusen, subretinal drusenoid deposits (SDD) have a significantly lower hazard rate of rod intercept (i.e. increased RIT, P&#x2009;<&#x2009;0.05). Among them, thinner SFCT, drusen, and SDD were identified as independent factors associated with an increased RIT in the final multivariable model (P&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS AND RELEVANCE: Given the associations between visual functions with outer retinal layers thickness and presence of established precursors of progression to advanced AMD, our findings serve as a strong foundation for future investigations into the relationships between retinal phenotypes and functional changes.}, }
@article {pmid40691808, year = {2025}, author = {Hassan, TA and Abouelela, YS and Rizk, H and Tolba, A}, title = {Potential therapeutic applications of stem cells in animal models of ocular affections.}, journal = {Inflammation and regeneration}, volume = {45}, number = {1}, pages = {23}, pmid = {40691808}, issn = {1880-9693}, abstract = {BACKGROUND: Ocular affections are serious damage to the ocular tissue that results in impaired vision or blindness. Cell-based therapies are a potentially effective therapeutic technique that entails using stem-like precursor cells to induce differentiation of specific cell types and implanting the cells to improve vision in the affected tissue area.<br><br>METHODS: Numerous clinical trials were started to investigate the potential benefits of stem cells for treating ocular affections, based on several encouraging findings from the preclinical research. Following our review, data were collected from various databases, "Google Scholar, Springer, Elsevier, Egyptian Knowledge Bank, ProQuest, and PubMed" using different keywords such as corneal ulcer, retinopathy, glaucoma, ocular regeneration, and stem cells to investigate the various methods for regeneration of ocular affections. The data were obtained and analyzed.<br><br>RESULTS: This review includes tables that show all types of stem cells that were used to treat ocular diseases, such as mesenchymal stem cells (MSCs), hematopoietic stem cells, neural stem cells, embryonic stem cells, and induced pluripotent stem cells. The several characteristics of MSCs that aid in the restoration and regeneration of injured ocular tissue are outlined in this paper, along with their potential applications in the management of ocular degenerative diseases, as determined by physical, histological, immunohistochemical, and biochemical evaluations. Finally, our review highlights the most effective regenerative strategies that assist in rapid ocular regeneration in a variety of animal models, including mice, rats, rabbits, and goats.<br><br>CONCLUSION: With the promising results of multiple preclinical studies, stem cell therapy is still a great choice for treating ocular degenerative illnesses. To improve the clinical outcomes, co-transplantation of two or more cell types may be a possibility for future treatment alternatives.}, }
@article {pmid40692491, year = {2025}, author = {Ambresin, A and Quist, SW and Boer, M and Maamari, S and Barthelmes, D}, title = {Cost-minimisation analysis of anti-VEGF therapies in neovascular age-related macular degeneration and diabetic macular oedema in Switzerland.}, journal = {Journal of medical economics}, volume = {28}, number = {1}, pages = {1198-1213}, doi = {10.1080/13696998.2025.2536420}, pmid = {40692491}, issn = {1941-837X}, mesh = {Humans ; Recombinant Fusion Proteins/economics/therapeutic use/administration &amp; dosage ; Switzerland ; *Macular Edema/drug therapy/economics ; Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; Ranibizumab/economics/therapeutic use/administration &amp; dosage ; *Angiogenesis Inhibitors/economics/therapeutic use/administration &amp; dosage ; *Macular Degeneration/drug therapy ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Diabetic Retinopathy/drug therapy ; Biosimilar Pharmaceuticals/economics/therapeutic use/administration &amp; dosage ; Models, Econometric ; Aged ; Male ; Intravitreal Injections ; Female ; }, abstract = {OBJECTIVE: This study compares the direct healthcare costs of anti-VEGF therapies, including treat-and-extend (T&amp;E) and other durable regimens, for unilateral neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO) in Switzerland.<br><br>METHODS: An adapted cost-minimisation model estimated healthcare costs over two years for aflibercept 2&#x2009;mg, aflibercept 8&#x2009;mg, faricimab, ranibizumab, and ranibizumab biosimilars using clinical trial injection frequencies. Break-even analyses identified the medication prices and injection frequencies required for higher-cost therapies to achieve cost parity with the least expensive options. A one-way sensitivity analysis (OWSA) assessed key drivers of cost outcomes.<br><br>RESULTS: Aflibercept 8&#x2009;mg was estimated to be associated with the lowest treatment costs for both indications (CHF 11,814 for nAMD; CHF 11,242 for DMO). Faricimab (CHF 13,737) and aflibercept 2&#x2009;mg (CHF 15,243) followed in nAMD and DMO. Ranibizumab and its biosimilars incurred the highest costs: for nAMD, biosimilars ranged from CHF 16,243 to CHF 17,497 and the reference product reached CHF 18,424; for DMO, biosimilars ranged from CHF 18,187 to CHF 19,596, with the reference product at CHF 20,637. Break-even analyses for nAMD showed that prices would need to drop by -22% (faricimab, CHF 644) to -64% (ranibizumab reference, CHF 218) relative to aflibercept 8&#x2009;mg. For DMO, reductions ranged from -42% (aflibercept 2&#x2009;mg, CHF 493) to -81% (ranibizumab reference, CHF 114). The OWSA highlighted medication price and injection frequency as primary cost drivers.<br><br>CONCLUSIONS: This study estimated that the potentially minimized injection frequency of aflibercept 8&#x2009;mg in a clinical trial regimen may result in the lowest treatment costs for nAMD and DMO, followed by faricimab and aflibercept 2&#x2009;mg, respectively.}, }
@article {pmid40694413, year = {2025}, author = {Power, D and Elstrott, J and Schallek, J}, title = {Photoreceptor loss does not recruit neutrophils despite strong microglial activation.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {40694413}, issn = {2050-084X}, support = {EY028293/EY/NEI NIH HHS/United States ; P30 EY001319/EY/NEI NIH HHS/United States ; Career Advancement Award//Research to Prevent Blindness/ ; Department of Ophthalmology Unrestricted Grant//Research to Prevent Blindness/ ; David Mahoney Neuroimaging Award//Dana Foundation/ ; Collaborative Research Grant//Genentech, Inc./ ; }, mesh = {Animals ; *Microglia/physiology/immunology ; *Neutrophils/immunology/physiology ; Mice ; Ophthalmoscopy/methods ; Tomography, Optical Coherence ; Mice, Inbred C57BL ; Retina/pathology ; *Photoreceptor Cells, Vertebrate/pathology ; }, abstract = {In response to central nervous system (CNS) injury, tissue-resident immune cells such as microglia and circulating systemic neutrophils are often first responders. The degree to which these cells interact in response to CNS damage is poorly understood, and even less so, in the neural retina, which poses a challenge for high-resolution imaging in vivo. In this study, we deploy fluorescence adaptive optics scanning light ophthalmoscopy (AOSLO) to study microglia and neutrophils in mice. We simultaneously track immune cell dynamics using label-free phase-contrast AOSLO at micron-level resolution. Retinal lesions were induced with 488 nm light focused onto photoreceptor (PR) outer segments. These lesions focally ablated PRs, with minimal collateral damage to cells above and below the plane of focus. We used in vivo AOSLO, and optical coherence tomography (OCT) imaging to reveal the natural history of the microglial and neutrophil response from minutes to months after injury. While microglia showed dynamic and progressive immune response with cells migrating into the injury locus within 1 day after injury, neutrophils were not recruited despite close proximity to vessels carrying neutrophils only microns away. Post-mortem confocal microscopy confirmed in vivo findings. This work illustrates that microglial activation does not recruit neutrophils in response to acute, focal loss of PRs, a condition encountered in many retinal diseases.}, }
@article {pmid40694826, year = {2025}, author = {Fineberg, A and Tiosano, A and Golan, N and Yacobi, B and Loebl, N and Smila Perchik, I and Dotan, A and Ehrlich, R and Gal-Or, O}, title = {NEAR-INFRARED REFLECTANCE IMAGING FOR THE ASSESSMENT OF GEOGRAPHIC ATROPHY USING DEEP LEARNING.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {12}, pages = {2311-2318}, doi = {10.1097/IAE.0000000000004614}, pmid = {40694826}, issn = {1539-2864}, mesh = {Humans ; *Geographic Atrophy/diagnosis ; *Deep Learning ; Aged ; Male ; Female ; Middle Aged ; Aged, 80 and over ; *Tomography, Optical Coherence/methods ; Spectroscopy, Near-Infrared/methods ; Retrospective Studies ; Fluorescein Angiography/methods ; Fundus Oculi ; }, abstract = {PURPOSE: Near-infrared reflectance imaging is a widely available but underused modality for assessing geographic atrophy (GA), a late-stage manifestation of dry age-related macular degeneration. The aim of this study was to develop and evaluate a fully automated deep-learning-based approach for detecting GA on near-infrared reflectance imaging.<br><br>METHODS: Near-infrared reflectance images of patients aged 50 years or older with GA, confirmed by two retinal specialists, were analyzed at Rabin Medical Center. The control group included near-infrared reflectance images of patients with healthy-appearing retinas. Models were trained and evaluated based on accuracy, precision, sensitivity, F1 Score, and DICE coefficient.<br><br>RESULTS: A total of 113 GA patients and 119 controls were included. The classification data set contained 330 images, and the localization data set included 659 images. Classification models performed well, with accuracy above 95%, while Vision Transformer B16 achieved the best results (precision = 98.5%, sensitivity = 98.4% and accuracy = 98.5%). For GA localization, YOLOv8-Large achieved 91% sensitivity, 91% precision, IoU of 84%, and DICE coefficient of 88%.<br><br>CONCLUSION: Geographic atrophy can be reliably identified using near-infrared reflectance images. Deep learning models can assist in evaluating GA on this routinely available imaging modality, aiding in the selection of patients who may benefit from emerging therapies.}, }
@article {pmid40696069, year = {2025}, author = {Park, J and Han, K and Kim, B and Lee, K and Jang, HR and Yoon, JM and Lim, DH and Shin, DW}, title = {Risk of age-related macular degeneration according to the chronic kidney disease and proteinuria in Korea: a 10-year nationwide cohort study.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {26595}, pmid = {40696069}, issn = {2045-2322}, support = {HI20C1073//Ministry of Health and Welfare/ ; }, mesh = {Humans ; *Proteinuria/complications/epidemiology ; Male ; Female ; Republic of Korea/epidemiology ; *Renal Insufficiency, Chronic/complications/epidemiology ; Middle Aged ; Aged ; *Macular Degeneration/epidemiology/etiology ; Risk Factors ; Retrospective Studies ; Glomerular Filtration Rate ; Adult ; Proportional Hazards Models ; Cohort Studies ; }, abstract = {The association between chronic kidney disease (CKD) and the risk of age-related macular degeneration (AMD) is unclear. Our study aimed to evaluate this relationship considering the potential impact of proteinuria. This retrospective cohort study used a large representative population sample from the Korean National Health Insurance Service database (2009-2019) of individuals who participated in a national health screening program in 2009. CKD was determined by estimated glomerular filtration rate (eGFR). Proteinuria was assessed using dipstick urinalysis. AMD was identified according to International Classification Disease, Tenth Revision, codes in claims data. The Cox regression hazards model was used to estimate the association between CKD and risk of AMD. Among 4,005,946 participants, 400,189 (10.0%) had CKD. There was no significant association between CKD and AMD, but a positive relationship was identified between proteinuria and AMD. In stratification analysis with age and sex, the risk of AMD was more evident in younger (< 65 years) than older individuals (P-interaction < 0.001) and in men than women (P-interaction < 0.001). A positive association between proteinuria and AMD risk was observed and was prominent in younger males.}, }
@article {pmid40696851, year = {2025}, author = {Wu, S and Zhou, X and Wang, L and Yu, D and Wang, Z and Xu, X}, title = {A Proteomic Study of Different Types of Diabetic Macular Edema.}, journal = {Current eye research}, volume = {50}, number = {10}, pages = {1029-1038}, doi = {10.1080/02713683.2025.2516806}, pmid = {40696851}, issn = {1460-2202}, mesh = {*Macular Edema/metabolism/pathology/therapy ; *Diabetes Complications/metabolism/pathology/therapy ; Proteomics ; Tandem Mass Spectrometry ; Humans ; *Proteins/metabolism ; Biomarkers/metabolism ; Wnt Signaling Pathway ; Up-Regulation ; Down-Regulation ; Male ; Female ; Middle Aged ; Aged ; Apoptosis ; Lipid Metabolism ; Vascular Endothelial Growth Factors/therapeutic use ; }, abstract = {PURPOSE: This study investigates distinct protein markers associated with different morphologic features of diabetic macular edema, focusing on diffuse retinal thickening, cystoid macular edema, and cystoid macular degeneration.<br><br>METHODS: A total of 48 eyes of 33 patients with diabetic macular edema were included in the study and categorized into the aforementioned groups. Preoperative aqueous humor samples were collected from nine diabetic macular edema patients and subjected to tandem mass spectrometry labeling using tandem mass tags quantitative proteomics analysis to compare protein profiles in the aqueous humor among the different morphologic features of diabetic macular edema.<br><br>RESULTS: The analysis revealed that the efficacy of anti-vascular endothelial growth factor treatment was significantly better in the diffuse retinal thickening and cystoid macular edema groups compared to the cystoid macular degeneration group (P&#x2009;<&#x2009;0.05). Differential expression analysis identified 31 upregulated and 43 downregulated proteins in the diffuse retinal thickening group compared to the cystoid macular degeneration group, with upregulated proteins associated with vasoconstriction, apoptotic processes, complement system, and peptidase inhibitors, and downregulated proteins associated with protein kinase and positive regulation of cell cycle regulation. Similarly, the cystoid macular edema group showed 31 upregulated and 32 downregulated proteins compared to the cystoid macular degeneration group, with upregulated proteins associated with the Wnt signaling pathway and extracellular matrix (ECM)-receptor interaction, and downregulated proteins associated with high-density lipoprotein (HDL), cholesterol positive regulation. The screening criteria for differentially expressed proteins were fold change >1.2 or <0.83 and P&#x2009;<&#x2009;0.05.<br><br>CONCLUSION: Associations were found between cystoid macular degeneration formation and factors like the complement system, apoptotic pathway, and lipid metabolizing factors, providing insights for further understanding diabetic macular edema pathogenesis.}, }
@article {pmid40697392, year = {2025}, author = {Jaskoll, S and Shwartz, Y and Kramer, A and Elbaz-Hayoun, S and Rinsky, B and Grunin, M and Tiosano, L and Levy, J and Vofo, BN and Chowers, I}, title = {Genetic Risk and OCT-Based Phenotypic Associations in Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100853}, pmid = {40697392}, issn = {2666-9145}, abstract = {PURPOSE: The risk for developing age-related macular degeneration (AMD) is associated with multiple genetic variants. We aim to evaluate the association of AMD genetic risk variants with specific features of the disease detected by OCT.<br><br>DESIGN: A retrospective cross-sectional study.<br><br>PARTICIPANTS: Subjects diagnosed with AMD and healthy controls (>50 years of age) from a single tertiary referral center.<br><br>METHODS: Genotyping of 52 single nucleotide polymorphisms associated with AMD was analyzed in 578 patients. Weighted genetic risk scores (WGRSs) were calculated for variants in genes encoding proteins involved in the complement cascade, lipid metabolism, and other pathways, respectively. A global WGRS was calculated for all 52 variants. OCT images were annotated for the presence of typical drusen, subretinal drusenoid deposits, hyperreflective foci (HRF), complete retinal pigmented epithelium and outer retinal atrophy (cRORA), and macular neovascularization.<br><br>MAIN OUTCOME MEASURES: Association of WGRS and individual genetic risk variants with specific disease features detected by OCT.<br><br>RESULTS: A positive correlation between the presence of drusen and the lipid WGRS was detected (r = 0.09, P = 0.02). Logistic regression analysis indicated associations between cRORA and the complement score (odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.05-1.50; P = 0.01), as well as the global score (OR = 1.29, 95% CI 1.13-1.46; P < 0.001). Regression also showed an association of HRF with the age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 variant (OR = 1.53, 95% CI 1.03-2.27; P = 0.03), the other pathways score (OR = 1.94, 95% CI 1.20-3.12; P = 0.007), and the global score (OR = 1.16, 95% CI 1.00-1.35; P = 0.04).<br><br>CONCLUSIONS: Weighted genetic risk scores based on risk variants for AMD are associated with specific disease features. Tighter association of the global WGRS compared to pathway-specific scores suggests that several pathways are involved in the development of specific disease features such as cRORA, drusen, and HRF.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40697394, year = {2025}, author = {Guymer, RH and Blair, JPM and De Zanet, S and Apostolopoulos, S and Ciller, C and Wu, Z and , }, title = {Effect of Subthreshold Nanosecond Laser on Loss of OCT Outer Retinal Bands in Age-Related Macular Degeneration: A LEAD Study Report.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100839}, pmid = {40697394}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the effect of subthreshold nanosecond laser (SNL) treatment on the rate of loss of the OCT outer retinal bands in intermediate age-related macular degeneration (AMD).<br><br>DESIGN: Post hoc analysis of the Laser Intervention in the Early Stages of AMD (LEAD) study.<br><br>PARTICIPANTS: A subset of 285 of 292 individuals in the LEAD study with bilateral large drusen without signs of multimodal imaging-defined late AMD at baseline, seen at 1 follow-up visit where neovascular AMD (nAMD) was absent.<br><br>METHODS: Participants were randomized to receive SNL or sham treatment in 1 study eye at 6-monthly intervals and were reviewed for up to 36 months. OCT scans from all visits without nAMD were automatically segmented to examine between-group differences in the rate of change in external limiting membrane (ELM), ellipsoid zone (EZ), and retinal pigment epithelium (RPE) loss in the entire central 5-mm diameter region, or only nondrusen areas in this region.<br><br>MAIN OUTCOME MEASURES: Between-group differences in the rate of ELM, EZ, and RPE loss.<br><br>RESULTS: Overall, there was no significant between-group difference in the rate of change in the loss of all OCT outer retinal band parameters (P &#x2265; 0.206). However, there was evidence of significant treatment effect modification based on the coexistence of reticular pseudodrusen (RPD) in the study eye when evaluating the rate of RPE loss in the entire central 5-mm diameter region, and for the rate of ELM, EZ, and RPE loss when considering only nondrusen areas in this region (P &#x2264; 0.006). In eyes without coexistent RPD, there was a significant slowing of the loss of all OCT outer retinal band parameters with SNL treatment (P &#x2264; 0.038 for all), whereas there was no significant between-group difference in all parameters in eyes with coexistent RPD (P &#x2265; 0.153 for all).<br><br>CONCLUSIONS: Subthreshold nanosecond laser treatment slowed the progressive loss of the OCT outer retinal bands in intermediate AMD in eyes without coexistent RPD. This study also showed for the first time the responsiveness of these novel outcome measures to treatment.<br><br>FINANCIAL DISCLOSURE: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40698098, year = {2025}, author = {Ulusoy, MO and Erseven, C and Erel, B and Çevik, SG and Perente, &#x130;}, title = {The effect of the pandemic on the intravitreal injection treatment for patients with age-related macular degeneration, regardless of lockdown periods.}, journal = {Romanian journal of ophthalmology}, volume = {69}, number = {2}, pages = {164-168}, pmid = {40698098}, issn = {2501-2533}, mesh = {Humans ; Intravitreal Injections ; Male ; *COVID-19/epidemiology ; Female ; *Visual Acuity ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis ; Retrospective Studies ; *SARS-CoV-2 ; *Quarantine ; *Pandemics ; Tomography, Optical Coherence ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; *Macular Degeneration/drug therapy ; }, abstract = {PURPOSE: To evaluate the impact of the pandemic on the intravitreal injection treatment routine for patients with neovascular age-related macular degeneration, regardless of lockdown periods.<br><br>METHODS: We evaluated the data of intravitreal injections between March 2020 and June 1, 2021, which was the last day of official restrictions. We divided into two groups: a regular treatment group and a group that was interrupted for at least 3 months without excuse. The initial visual acuity at the beginning of the pandemic, the last visual acuity, the visual acuity after interruption, the central macular thickness, and the interruption time were recorded.<br><br>RESULTS: A total of 156 patients' data were evaluated. There are forty-eight patients in the regular treatment group, 77 in the interruption group, and 31 in the discontinued group. The visual loss was significantly higher in the interruption group (respectively, -0.11 &#xb1; 0.19 vs. 0.03 &#xb1; 0.16, p<0.001). Central macular thickness changes were higher in the interruption group (respectively, 31.8 &#xb1; 5.7&#xb5;m vs. 13.5 &#xb1; 4.6, p<0.001). The mean interruption time was 6.71 &#xb1; 2.45 months.<br><br>DISCUSSION: Half of the patients in our study interrupted their treatment during the pandemic, and this interruption had a negative impact on their visual acuity and central macular thickness. In addition to COVID-19's own high mortality and morbidity, it also had adverse effects on patients who required regular follow-up and treatment.<br><br>CONCLUSION: Since interruptions in treatment negatively impact the prognosis of AMD, effective protocols that do not require frequent visits are necessary.}, }
@article {pmid40698349, year = {2025}, author = {Okawa, K and Maruyama-Inoue, M and Chin, JY and Inoue, T and Yanagi, Y and Kadonosono, K}, title = {One-Year Outcomes of Intravitreal Faricimab Injection in Treatment-Naïve Patients With Neovascular Age-Related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251352888}, pmid = {40698349}, issn = {2474-1272}, abstract = {Purpose: To investigate the 1-year functional and morphologic outcomes of intravitreal (IVT) faricimab in treatment-naïve Japanese patients with neovascular age-related macular degeneration (nAMD). Methods: A retrospective study was performed to examine the outcomes of patients with nAMD who received IVT faricimab using a treat-and-extend regimen. The best-corrected visual acuity (BCVA), central foveal thickness (CFT), central choroidal thickness, dry macular achievement, and treatment intervals at 48 weeks were evaluated. Furthermore, the presence of polypoidal lesions at 48 weeks, as indicated by indocyanine green angiography, was investigated in patients with polypoidal choroidal vasculopathy (PCV). Results: This study included 48 Japanese treatment-naïve patients with nAMD assessed at 1 year of follow-up. The BCVA was significantly improved 1 year after initial treatment (P < .001). CFT and central choroidal thickness were also significantly decreased after 1 year (P < .001 and P < .001, respectively). Dry macula was achieved in 42 eyes (87.5%), and the mean (±SD) treatment interval at 12 months was 14.5 ± 4.4 weeks. The 1-year polyp regression rate was 76.9% (10/13 eyes). Conclusions: IVT faricimab was well tolerated and appeared to improve both functional and anatomic outcomes in Japanese patients with nAMD. In addition, a high rate of polyp regression was seen in patients with PCV.}, }
@article {pmid40698627, year = {2025}, author = {Beit-Yannai, E}, title = {Exosomes in Ocular Health and Disease.}, journal = {Current eye research}, volume = {50}, number = {12}, pages = {1197-1210}, doi = {10.1080/02713683.2025.2515996}, pmid = {40698627}, issn = {1460-2202}, mesh = {Humans ; *Exosomes/physiology/metabolism ; *Eye Diseases/metabolism ; Biomarkers/metabolism ; Animals ; }, abstract = {PURPOSE: Exosomes, small extracellular vesicles ranging from 30 to 150 nm in diameter, have emerged as crucial mediators of intercellular communication in ocular tissues. This review explores the roles of exosomes in ocular health and disease, focusing on their biogenesis, functions in different eye structures, and potential as diagnostic biomarkers and therapeutic agents.<br><br>METHODS: This comprehensive review synthesizes current research on ocular exosomes, drawing from global studies to present an integrated view of exosome biology in the eye.<br><br>RESULTS: Exosomes play vital roles in maintaining retinal homeostasis, corneal function, and lens transparency. They are implicated in the pathogenesis of major eye diseases, including glaucoma, age-related macular degeneration, and diabetic retinopathy. Recent advances have revealed the potential of exosomes as biomarkers for early disease detection and as vehicles for targeted drug delivery. Emerging technologies, such as microfluidics and nanotechnology, enhance exosome isolation and analysis capabilities.<br><br>CONCLUSIONS: Exosome research in ophthalmology is rapidly advancing, offering promising avenues for novel diagnostic and therapeutic approaches. However, challenges remain in standardization, scalability, and clinical translation. Addressing these issues and ethical considerations will be crucial for realizing the full potential of exosomes in improving ocular health outcomes globally.}, }
@article {pmid40699623, year = {2025}, author = {Zubieta, D and Warden, C and Bhattacharya, S and Brantley, MA}, title = {Tauroursodeoxycholic Acid Confers Protection Against Oxidative Stress via Autophagy Induction in Retinal Pigment Epithelial Cells.}, journal = {Current issues in molecular biology}, volume = {47}, number = {4}, pages = {}, pmid = {40699623}, issn = {1467-3045}, support = {GF02528//International Retinal Research Foundation/ ; }, abstract = {Tauroursodeoxycholic acid (TUDCA) has been shown to protect against oxidative damage in retinal pigment epithelial (RPE) cells. However, the mechanisms by which it mediates these protective effects have not been thoroughly investigated in the context of age-related macular degeneration (AMD) disease onset and progression. We measured LC3-II and p62 expression via Western blot and immunohistochemistry in RPE cells treated with H2O2, TUDCA, or a combination of both to measure autophagy induction. To determine autophagy flux, we measured the expression of LC3-II/LC3-I in RPE cells in the presence of bafilomycin via Western blot. To determine the mechanistic pathways of TUDCA-induced autophagy, we measured the protein expression of autophagy regulators (Atg5, Beclin-1, S6, AMPK, and Akt) via Western blot. We show that TUDCA-mediated autophagy induction confers protection of RPE cells against oxidative damage via mTORC1/mTORC2 independent pathways but depends on Atg5. Our work adds to the overall understanding of RPE cell homeostasis and highlights the role of TUDCA in maintaining RPE health.}, }
@article {pmid40699817, year = {2025}, author = {Harej Hrkać, A and Pelčić, A and Čaljkušić-Mance, T and Mršić-Pelčić, J and Pilipović, K}, title = {The Preventive Power of the Mediterranean Diet Against Blue-Light-Induced Retinal Degeneration: Is the Secret in the Herbs and Spices?.}, journal = {Current issues in molecular biology}, volume = {47}, number = {6}, pages = {}, pmid = {40699817}, issn = {1467-3045}, support = {uniri-iskusni-biomed-23-82//University of Rijeka/ ; }, abstract = {The Mediterranean diet, rich in plant-based foods, healthy fats, and herbs, has long been associated with a range of health benefits, including cardiovascular, neuroprotective, and anti-inflammatory effects. Recent studies suggest that certain components of this diet, particularly spices such as bay laurel, thyme, oregano, sage, and rosemary, may play a critical role in protecting the retina from oxidative damage, a key factor in blue-light-induced retinal degeneration. Blue light, emitted by digital screens and artificial lighting, has been implicated in the development of retinal conditions like age-related macular degeneration by inducing oxidative stress and inflammation. This review explores the potential of the herbs and spices commonly present in the Mediterranean diet to mitigate blue-light-induced retinal damage. These herbs are rich in polyphenols, flavonoids, essential oils, and terpenes, which offer antioxidant, anti-inflammatory, and antimicrobial properties, contributing to retinal health and reducing oxidative damage. By focusing on bioactive compounds such as eucalyptol (1,8-cineole), rosmarinic acid, carnosic acid, eugenol, and thymol, this article investigates how these herbs and spices might act as natural protectants against blue-light-induced stress and retinal degeneration. The findings highlight the promising role of these culinary staples in preventing retinal damage and offer insights into future dietary recommendations for eye health in an increasingly digital world.}, }
@article {pmid40700079, year = {2025}, author = {Trinquet, L and Ajasse, S and Chavane, F and Legras, R and Matonti, F and Sahel, JA and Vignal-Clermont, C and Lorenceau, J}, title = {Uncovering the Characteristics of Pupil Cycle Time (PCT) in Neuropathies and Retinopathies.}, journal = {Vision (Basel, Switzerland)}, volume = {9}, number = {3}, pages = {}, pmid = {40700079}, issn = {2411-5150}, abstract = {Pupil cycle time (PCT) estimates the dynamics of a biofeedback loop established between pupil size and stimulus luminance, size or colour. The PCT is useful for probing the functional integrity of the retinopupillary circuits, and is therefore potentially applicable for assessing the effects of damage due to retinopathies or neuropathies. In previous studies, PCT was measured by manually counting the number of pupil oscillations during a fixed period to calculate the PCT. This method is scarce, requires a good expertise and cannot be used to estimate several PCT parameters, such as the oscillation amplitude or variability. We have developed a computerised setup based on eye-tracking that expands the possibilities of characterising PCT along several dimensions: oscillation frequency and regularity, amplitude and variability, which can be used with a large palette of stimuli (different colours, sizes, shapes or locations), and further allows measuring blinking frequency and eye movements. We used this method to characterise the PCT in young control participants as well as in patients with several pathologies, including age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), Stargardt disease (SD), and Leber hereditary optic neuropathy (LHON). We found that PCT is very regular and stable in young healthy participants, with little inter-individual variability. In contrast, several PCT features are altered in older healthy participants as well as in ocular diseases, including slower dynamics, irregular oscillations, and reduced oscillation amplitude. The distinction between patients and healthy participants based on the calculation of the area under the curve of the receiver operating characteristics (AUC of ROC) were dependent on the pathologies and stimuli (0.7 < AUC < 1). PCT nevertheless provides relevant complementary information to assess the physiopathology of ocular diseases and to probe the functioning of retino-pupillary circuits.}, }
@article {pmid40700658, year = {2025}, author = {Tran, M and Agnihotri, AP and Nagel, ID and Wagner, N and Nudleman, E and Borooah, S}, title = {Rapid progression of maculopathy after Pentosan Polysulfate Sodium cessation.}, journal = {Retinal cases &amp; brief reports}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICB.0000000000001791}, pmid = {40700658}, issn = {1937-1578}, abstract = {PURPOSE: To report a case of pentosan polysulfate sodium (PPS) maculopathy showing rapid progression of retinopathy 4 years after discontinuing PPS.<br><br>METHODS: A 75-year-old woman presenting with gradual vision changes underwent comprehensive examination including multimodal imaging and genetic testing.<br><br>RESULTS: A 75-year-old woman presented with a history of intermediate age-related macular degeneration and progressive blurring of her central vision beginning at 69 years of age. Fundoscopic examination revealed retinal pigment epithelium (RPE) abnormalities and multifocal outer retinal loss. The patient had been first prescribed PPS for interstitial cystitis (IC) aged 63 with a cumulative PPS dose of approximately 1300 grams and ceased PPS at 71 years of age. She was noted to have only minimal retinal changes prior to drug cessation. Four years post-cessation, the patient reported marked night vision and color vision abnormalities and was noted to have severe retinal changes including macular atrophy. Genetic testing revealed the patient to be homozygous for the previously reported risk alleles.<br><br>CONCLUSION: PPS maculopathy is an acquired toxic disease that can significantly impact a patient's quality of life. Our report highlights that marked progression of PPS retinopathy can occur even after drug cessation and that patients need to be carefully monitored and given supportive management.}, }
@article {pmid40700755, year = {2025}, author = {Faes, L and Holekamp, N and Benyamini, G and Nahen, K and Mohan, N and Freund, KB}, title = {Home Optical Coherence Tomography-guided Management of Type 3 Macular Neovascularization.}, journal = {Retinal cases &amp; brief reports}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICB.0000000000001792}, pmid = {40700755}, issn = {1937-1578}, abstract = {PURPOSE: To explore the impact of home optical coherence tomography (OCT)-guided treatment personalization for type 3 macular neovascularization (MNV) in age-related macular degeneration (AMD).<br><br>METHODS: A prospective home OCT trial of a patient with a one-month history of type 3 MNV under anti-angiogenic treatment (two "loading" injections). During the 23.4-week study period, the patient's treatment regimen was managed through regular self-imaging, enabling continuous monitoring of retinal fluid dynamics.<br><br>RESULTS: Over the observation period, the patient performed 143 home OCT measurements (mean 6.1 per week, standard deviation 1), which prompted three in-office visits where three anti-angiogenic injections were delivered at the discretion of the investigator. The mean individualized treatment intervals established through home OCT were 8 weeks, with the patient maintaining stable visual acuity at 20/20 Snellen. Complete resolution of intraretinal fluid was noted between injection. Notably, home OCT revealed unexpected fluctuations in retinal fluid measured as hyporeflective spaces in the absence of treatment. Two out of three injections were administered after the retinal fluid volume had decreased by more than half within two, and eight days following an initial transient spike.<br><br>CONCLUSION: The neovascular subtype as defined by the Consensus Nomenclature for Reporting Neovascular AMD Data (CONAN) may serve as a useful management framework when approaching home OCT guided treatment decisions. In type 3 disease, home OCT-guided management demonstrates significant potential for optimizing treatment. Further research is warranted to elucidate the dynamics of retinal fluid variations in different MNV subtypes.}, }
@article {pmid40701376, year = {2025}, author = {Wu, E and Hasan, N and Vupparaboina, S and Jiang, J and Du, K and DeCicco, J and Sadeghi, E and Zhang, M and Vupparaboina, KK and Bollepalli, SC and Eller, AW and Sahel, JA and Chhablani, J}, title = {Predicting Early Onset of Age-Related Macular Degeneration: A Machine Learning Approach.}, journal = {American journal of ophthalmology}, volume = {279}, number = {}, pages = {156-164}, doi = {10.1016/j.ajo.2025.07.020}, pmid = {40701376}, issn = {1879-1891}, mesh = {Humans ; Retrospective Studies ; Female ; Male ; *Macular Degeneration/diagnosis/epidemiology ; *Machine Learning ; Aged ; Middle Aged ; Case-Control Studies ; ROC Curve ; Age of Onset ; Risk Factors ; United States/epidemiology ; Comorbidity ; Aged, 80 and over ; }, abstract = {PURPOSE: Develop a machine learning model that predicts early-onset AMD based on early patient comorbidities DESIGN: Retrospective case-control study.<br><br>SUBJECTS: This study used 2 datasets: a tertiary eye care center dataset (930 AMD patients, 392 early-onset, 538 late-onset) and the All of Us dataset for validation (560-580 AMD patients early-onset, 560-580 matched controls without AMD).<br><br>METHODS: Health records of AMD patients from a tertiary hospital (1999-2023) and the All of Us Research Program, a nationwide longitudinal cohort of U.S. adults (data collected 6/2016-2/2025) were collected. Unsupervised clustering using Uniform Manifold Approximation and Projection (UMAP) was performed on the tertiary eye care center dataset to identify distinct patient subgroups. Supervised machine learning models, including gradient-boosted decision trees (GBDT), logistic regression, and random forests, were trained to predict early-onset AMD.<br><br>MAIN OUTCOMES MEASURES: Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), while feature importance was assessed using the Gini index for tree-based models and coefficient magnitudes for logistic regression. Additionally, odds ratios for comorbidities associated with early-onset AMD were estimated using 2 &#xd7; 2 contingency tables in the validation dataset (All of Us).<br><br>RESULTS: Clustering identified 2 distinct patient groups, with 1 (93.08% early-onset AMD dominated) showing high rates of inflammatory joint disorders, hypertension, and dyslipidemia. Multiple supervised machine learning models achieved &#x223c;76% accuracy in predicting early-onset AMD from early comorbidities (diagnosed before age of 55). Like clustering, analysis of supervised machine learning models identified inflammatory joint disorders, hypertension, and dyslipidemia as the most predictive features. These comorbidities were validated using the All of Us dataset, with essential hypertension (OR: 5.80, 95% CI: [4.25-7.93], P < .05), rheumatoid arthritis (OR: 4.61, 95% CI: [1.55-13.72], P < .05), and hyperlipidemia (OR: 5.16, 95% CI: [3.76-7.08], P < .05) showing strong associations with early-onset AMD.<br><br>CONCLUSION: Screening hypertension, dyslipidemia, and inflammatory joint disorders in ophthalmologic evaluations may enable earlier AMD detection and intervention.}, }
@article {pmid40701514, year = {2025}, author = {Amatha, S and Das, R and Gautam, MK and Mondal, S}, title = {Biotechnological novel drug delivery systems for age-related macular degeneration.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {100}, number = {9}, pages = {537-548}, doi = {10.1016/j.oftale.2025.07.010}, pmid = {40701514}, issn = {2173-5794}, mesh = {Humans ; *Macular Degeneration/drug therapy/therapy ; *Drug Delivery Systems/methods ; Genetic Therapy/methods ; *Biotechnology ; Precision Medicine ; Cell- and Tissue-Based Therapy/methods ; }, abstract = {Recent years have witnessed remarkable advancements in biotechnological ocular drug delivery systems, introducing novel strategies such as gene therapy, cell-based systems, and targeted carriers. This article focuses specifically on age-related macular degeneration (AMD), the most prevalent ocular condition. While gene therapy holds promise for AMD treatment, it also presents significant challenges, leading to the exploration of cell-based therapy as a complementary or alternative approach. To address these hurdles and ensure successful market translation, new companies often form collaborative expert teams encompassing all relevant fields, including regulatory affairs. As medical science continues to evolve, a comprehensive understanding of gene therapy, cell-based delivery, biocompatibility, safety considerations, regulatory aspects, and ongoing clinical trials is essential to fully grasp the safety and effectiveness of these novel ocular therapies. Consequently, this paper primarily explores these key areas. The successful evolution of biotechnological ocular delivery signals a positive shift towards personalized medicine, which is expected to significantly improve the quality of life for AMD patients in the near future.}, }
@article {pmid40701533, year = {2025}, author = {Zhang, W and Huang, S}, title = {Circadian rhythms in ophthalmic diseases.}, journal = {Experimental eye research}, volume = {259}, number = {}, pages = {110533}, doi = {10.1016/j.exer.2025.110533}, pmid = {40701533}, issn = {1096-0007}, mesh = {Humans ; *Circadian Rhythm/physiology ; *Eye Diseases/physiopathology ; Animals ; }, abstract = {Circadian rhythms, governed by the suprachiasmatic nucleus of the hypothalamus, orchestrate a wide range of physiological processes, including those implicated in ophthalmic diseases. These biological rhythms influence both normal ocular function and disease pathogenesis, with many ophthalmic conditions exhibiting altered circadian rhythmicity in frequency or amplitude. Disruptions to circadian homeostasis may exacerbate disease symptoms and negatively affect treatment outcomes, ultimately impairing patients' quality of life. Emerging evidence supports a strong interplay between circadian rhythm dysregulation and the development of ocular disorders. A comprehensive understanding of these temporal disruptions could deepen insights into disease mechanisms and facilitate the development of circadian-based therapeutic strategies. This review examines circadian alterations in ophthalmic diseases-such as dry eye disease, glaucoma, diabetic retinopathy, age-related macular degeneration, and cataracts-and discusses potential circadian-regulated interventions and directions for future research.}, }
@article {pmid40701607, year = {2025}, author = {Zhang, Z and Zhang, X and Zhang, R and Gao, Y}, title = {Trends and drivers of blindness and vision loss burden attributable to age-related macular degeneration from 1990 to 2021: findings from the Global Burden of Disease Study 2021.}, journal = {BMJ open}, volume = {15}, number = {7}, pages = {e094953}, pmid = {40701607}, issn = {2044-6055}, mesh = {Humans ; *Macular Degeneration/complications/epidemiology ; *Blindness/epidemiology/etiology ; Global Burden of Disease/trends ; Cross-Sectional Studies ; Prevalence ; Aged ; Male ; Female ; Disability-Adjusted Life Years ; Aged, 80 and over ; Global Health ; Middle Aged ; Cost of Illness ; }, abstract = {OBJECTIVES: To investigate the trends and drivers of the burden of blindness and vision loss (BVL) attributable to age-related macular degeneration (AMD) from 1990 to 2021.<br><br>DESIGN: Cross-sectional study.<br><br>SETTING: Studies from the Global Burden of Disease (GBD) Study 2021 database, generated from population-representative data sources identified through a literature review and research collaborations, were included.ParticipantsBVL attributable to AMD participants.<br><br>OUTCOMES: Total numbers and age-standardised rates of prevalence and disability-adjusted life years (DALYs) were the main outcomes. Secondary outcomes consisted of the temporal trends in the BVL burden attributable to AMD at global, regional and national levels, using an age-period-cohort model, and factors influencing changes in BVL burden attributable to AMD, using decomposition analysis.<br><br>RESULTS: Age-standardised prevalence and DALY rates of BVL attributable to AMD showed a decreasing trend, with a global net drift in prevalence of -0.35% (95% CI: -0.38 to -0.32) per year. Globally, we observed unfavourable age effects, subtle period effects and positive cohort effects on prevalence. Over the past three decades, the global increase in prevalence and DALYs of BVL attributable to AMD was primarily due to population growth and ageing.<br><br>CONCLUSIONS: Our research indicates that the population growth and ageing have exacerbated the burden of BVL attributable to AMD over the past 30 years. We identified countries with substantial room for improvement and those with exemplary performance to inspire potential ideas for better managing BVL attributable to AMD.}, }
@article {pmid40703032, year = {2025}, author = {Ho, TC and Tsai, SH and Yeh, SI and Sun, MH and Tsao, YP}, title = {A PEDF-Derived Short Peptide Prevents Sodium Iodate-Induced Retinal Degeneration in Rats by Activating the SLC7A11/GSH/GPX4 Pathway in the RPE Cells.}, journal = {Journal of cellular and molecular medicine}, volume = {29}, number = {14}, pages = {e70693}, pmid = {40703032}, issn = {1582-4934}, support = {MOST 111-2314-B-195-011-MY3//Ministry of Science and Technology/ ; MMH-E-108-006//Mackay Memorial Hospital/ ; }, mesh = {Animals ; *Iodates/toxicity ; *Nerve Growth Factors/chemistry/pharmacology ; *Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; *Eye Proteins/chemistry/pharmacology ; *Glutathione/metabolism ; Rats ; *Serpins/chemistry/pharmacology ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; *Amino Acid Transport System y+/metabolism ; *Retinal Degeneration/chemically induced/metabolism/pathology/prevention &amp; control/drug therapy ; *Signal Transduction/drug effects ; Humans ; Lipid Peroxidation/drug effects ; Oxidative Stress/drug effects ; Male ; Disease Models, Animal ; Cell Line ; Ferroptosis/drug effects ; Antioxidants/pharmacology ; Rats, Sprague-Dawley ; *Peptides/pharmacology ; Pigment Epithelium-Derived Factor ; }, abstract = {Retinal pigment epithelial (RPE) cell damage caused by oxidative stress is a key factor in the pathogenesis of dry age-related macular degeneration (AMD). 6dS peptide is derived from the neuroprotective motif of pigment epithelium-derived factor (PEDF) and has antioxidant effects. This study used the sodium iodate (SI, a chemical oxidant)-induced animal dry AMD model to investigate the 6dS-mediated antioxidant mechanism. 6dS reduced SI-induced cytotoxicity, including ferrous iron accumulation, lipid peroxidation, glutathione (GSH) depletion, and ferroptosis in ARPE-19 cells. SI injection in rats induced cell death and lipid peroxidation in the RPE layer, along with retinal atrophy and electrophysiological dysfunction, recapitulating features of dry AMD that were counteracted by 6dS eye drop treatment. Mechanistically, 6dS induced the expression of SLC7A11 (solute carrier family seven member 11) and glutathione peroxidase 4 (GPX4) to alleviate SI-induced GSH depletion and lipid peroxidation. Inhibitors targeting the PEDF receptor, SLC7A11, and GPX4 abolished the 6dS effect. Our study proposes an antioxidant mechanism through which PEDF receptor signalling links to the SLC7A11/GSH/GPX4 axis to alleviate intracellular redox imbalance. These findings suggest that 6dS eye drops may be a promising treatment for dry AMD.}, }
@article {pmid40705272, year = {2025}, author = {Syed, YY}, title = {SDZ-AFL: An Aflibercept Biosimilar.}, journal = {Clinical drug investigation}, volume = {45}, number = {9}, pages = {677-680}, pmid = {40705272}, issn = {1179-1918}, mesh = {Humans ; *Recombinant Fusion Proteins/therapeutic use/adverse effects/pharmacokinetics/pharmacology/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; *Biosimilar Pharmaceuticals/therapeutic use/adverse effects/pharmacology/pharmacokinetics ; *Angiogenesis Inhibitors/therapeutic use/adverse effects/pharmacology/pharmacokinetics/administration &amp; dosage ; *Macular Degeneration/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; }, abstract = {SDZ-AFL (SOK583A1; Afqlir[®]) is a biosimilar of the reference intravitreal aflibercept, a vascular endothelial growth factor inhibitor. SDZ-AFL has been approved in the EU for the treatment of the same indications in adults as reference aflibercept: neovascular age-related macular degeneration (nAMD), visual impairment due to macular oedema secondary to retinal vein occlusion, visual impairment due to diabetic macular oedema and visual impairment due to myopic choroidal neovascularisation. SDZ-AFL has similar physicochemical and pharmacodynamic properties to those of reference aflibercept, and pharmacokinetic similarity has been demonstrated in patients with nAMD. SDZ-AFL demonstrated clinical efficacy equivalent to that of reference aflibercept in patients with nAMD and was generally well tolerated in this population. The tolerability, safety and immunogenicity profiles of SDZ-AFL were similar to those of reference aflibercept. The role of reference aflibercept in the management of neovascular retinal diseases is well established, and SDZ-AFL provides an effective biosimilar alternative for patients requiring ophthalmic aflibercept therapy.}, }
@article {pmid40707177, year = {2025}, author = {Agostini, HT and Silva, R and Holz, FG and Larsen, M and Altay, L and Souied, EH and Quiering, C and Rose, U and Liakopoulos, S and , }, title = {Impact of retinal thickness fluctuations with ranibizumab versus aflibercept in neovascular age-related macular degeneration (SALT): 12-month results from a multicentre, randomised, phase IV trial.}, journal = {The British journal of ophthalmology}, volume = {110}, number = {1}, pages = {59-66}, pmid = {40707177}, issn = {1468-2079}, mesh = {Humans ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Tomography, Optical Coherence ; Female ; Visual Acuity/physiology ; Male ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Aged ; Prospective Studies ; *Retina/pathology ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Follow-Up Studies ; Fluorescein Angiography ; }, abstract = {BACKGROUND/AIMS: To compare fluctuations of central subfield retinal thickness (CSRT) in patients with neovascular age-related macular degeneration undergoing ranibizumab pro re nata versus aflibercept bimonthly treatment in a prospective 12 month, phase IV, randomised, multicentre study.<br><br>METHODS: Ranibizumab was administered according to best-corrected visual acuity (BCVA) and/or disease activity detected on spectral domain optical coherence tomography. Aflibercept was administered at three initial monthly visits followed by bimonthly treatment. CSRT stability was evaluated between months 3 and 6. CSRT stability was compared between groups and correlated with functional outcomes at month 12.<br><br>RESULTS: Fluctuations of CSRT showed a least-squares (LS) mean (95% CI) difference of -4.12 (-10.22 to 1.98) &#xb5;m between ranibizumab (25.16 (20.09 to 30.24) &#xb5;m) and aflibercept groups (29.28 (24.14 to 34.43) &#xb5;m) (p=0.1850). A predefined analysis of retinal stability, adjusted for baseline CSRT, showed a LS mean (95%&#x2009;CI) difference of -6.53 (-12.47 to -0.58&#x2009;&#xb5;m) in favour of ranibizumab (23.53 (18.58 to 28.49) &#xb5;m) versus aflibercept (30.06 (25.04 to 35.07) &#xb5;m) (p=0.0315). Pearson's correlation coefficient demonstrated no correlation between the mean amplitude of CSRT fluctuation between months 3 and 6, and BCVA at month 12 (r = -0.0888). Adverse event rates were low.<br><br>CONCLUSIONS: Numerical differences in retinal thickness fluctuations between months 3 and 6 were detected between treatment regimens. While the presence of fluctuations has previously been shown to have a negative impact on functional outcomes, our data showed no correlation between the mean amplitude of fluctuations and functional outcomes at month 12.}, }
@article {pmid40707687, year = {2025}, author = {Shin, S and Ryoo, JH}, title = {Combined exposure to three heavy metals and the risk of age-related macular degeneration in the Korean population.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {27016}, pmid = {40707687}, issn = {2045-2322}, support = {RS-2024-00509118//Ministry of Health and Welfare, Ministry of Science and ICT, Ministry of Trade, Industry and Energy, and Korea Disease Control and Prevention Agency/ ; }, mesh = {Humans ; *Macular Degeneration/epidemiology/chemically induced/etiology ; Republic of Korea/epidemiology ; Male ; Female ; Middle Aged ; *Metals, Heavy/toxicity/adverse effects ; Aged ; Risk Factors ; Adult ; Cadmium/toxicity/adverse effects ; *Environmental Exposure/adverse effects ; Mercury/toxicity/adverse effects ; Lead/toxicity/adverse effects ; Nutrition Surveys ; }, abstract = {Toxicological and histological evidence suggests that heavy metals accumulate in the retina, implicating their potential role in the development of age-related macular degeneration (AMD). However, most prior epidemiologic studies have focused on individual metal exposures, overlooking possible joint effects. This study assessed the association between co-exposure to lead (Pb), mercury (Hg), and cadmium (Cd) and AMD risk among Korean adults using 2008-2012 Korea National Health and Nutrition Examination Survey data. A total of 4818 participants aged 40 years or older were included. Logistic regression models evaluated single-metal associations, while quantile g-computation and Bayesian kernel machine regression (BKMR) assessed mixture effects. Participants in the third quartile of Pb had significantly higher odds of AMD (adjusted OR: 1.76, 95% CI: 1.07-2.88) than those in the lowest quartile. Quantile g-computation showed that a one-quartile increase in the metal mixture was associated with elevated AMD risk (adjusted OR: 1.20, 95% CI: 1.02-1.41). BKMR confirmed that the heavy metal mixture increased the risk of AMD, with Pb being the primary contributor in smokers and Cd in non-smokers. Our findings indicate that co-exposure to heavy metals elevates AMD risk and that the predominant contributing metal may differ depending on smoking status.}, }
@article {pmid40709695, year = {2025}, author = {Qi, Z and Qi, J and Zhang, Y and Wang, Y and Feng, Y and Yang, Z and Wang, Y and Shu, W and Guo, D and Kang, C and Zhang, K and Lu, Y and Wan, J and Zhu, X}, title = {Plasma Metabolic Profile with Machine Learning Reveals Distinct Diagnostic and Biological Signatures for Pathologic Myopia.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {39}, pages = {e05861}, pmid = {40709695}, issn = {2198-3844}, support = {2022YFC2502800//National Key Research and Development Program of China/ ; 2024YFE0102200//National Key Research and Development Program of China/ ; 22474040//National Natural Science Foundation of China/ ; 82271069//National Natural Science Foundation of China/ ; 82371040//National Natural Science Foundation of China/ ; 82122017//National Natural Science Foundation of China/ ; 81870642//National Natural Science Foundation of China/ ; 81970780//National Natural Science Foundation of China/ ; 81470613//National Natural Science Foundation of China/ ; 81670835//National Natural Science Foundation of China/ ; 23Y11909800//Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission/ ; 2024ZZ1025//Outstanding Youth Medical Talents of Shanghai "Rising Stars of Medical Talents" Youth Development Program, Shanghai Municipal Health Commission Project/ ; 20244Z0015//Outstanding Youth Medical Talents of Shanghai "Rising Stars of Medical Talents" Youth Development Program, Shanghai Municipal Health Commission Project/ ; //Fundamental Research Funds for the Central Universities/ ; }, mesh = {Humans ; *Machine Learning ; *Biomarkers/blood ; *Myopia, Degenerative/diagnosis/blood/metabolism ; *Metabolome ; Male ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Oxidative Stress ; Female ; Middle Aged ; Metabolomics/methods ; }, abstract = {Pathologic myopia (PM), characterized by serious myopic macular degeneration (MMD), is a detrimental subtype of high myopia (HM) and has become one of the leading causes of blindness worldwide. In this concern, precise and high-throughput molecular diagnosis and further pathologic insights are urgently needed. Here, through the combined strategy of nanoparticle-enhanced laser desorption/ionization mass spectrometry-based rapid metabolic analysis (<30 s) and machine learning, a precise molecular diagnostic approach of PM (HM with MMD grade ≥ 2) is proposed, which achieves areas under the curve of 0.874 and 0.889 for diagnosing PM and early-stage PM, respectively. Further, the biomarkers indicate the PM-associated systemic metabolic reprogramming of amino acid and lipid metabolism, which may mediate dysfunctional oxidative stress, inflammation, hormone/neurotransmitter systems, and energy metabolism. Notably, MMD grade 4, featuring characteristic macula atrophy, exhibits specificity in this metabolic reprogramming. Of these biomarkers, azelaic acid shows a significant protective effect in the ARPE-19 cells under abnormal oxidative stress, which may be involved in PM development as a key antioxidative active metabolite. This work will contribute to PM molecular diagnosis and pathology exploration.}, }
@article {pmid40711396, year = {2025}, author = {Chong, DD and Yue, SC and Raynor, JL and Murray, I and Chuchta, TG and Markle, JC and Shaia, JK and Singh, RP and Talcott, KE}, title = {Estimated Five-year Risk of Systemic Cardiovascular Events With Anti-VEGF Injections in Neovascular Age-related Macular Degeneration.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {56}, number = {10}, pages = {587-592}, doi = {10.3928/23258160-20250702-01}, pmid = {40711396}, issn = {2325-8179}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Intravitreal Injections ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis/complications ; Middle Aged ; *Ranibizumab/administration &amp; dosage/adverse effects ; Aged, 80 and over ; Follow-Up Studies ; *Cardiovascular Diseases/epidemiology/etiology ; Risk Factors ; *Bevacizumab/administration &amp; dosage/adverse effects ; Risk Assessment/methods ; Time Factors ; Incidence ; *Myocardial Infarction/epidemiology ; }, abstract = {BACKGROUND AND OBJECTIVE: To assess 5-year risk for stroke, myocardial infarction (MI), and mortality in patients with neovascular age-related macular degeneration (nAMD) receiving anti-vascular endothelial growth factor (anti-VEGF) injections compared to patients with geographic atrophy (GA).<br><br>PATIENTS AND METHODS: A retrospective cohort study was conducted involving 2,923 patients aged &#x2265; 50 years, diagnosed with nAMD or GA prior to 2019. There were two cohorts: those receiving anti-VEGF for nAMD and those with GA. A 1:1 greedy matching algorithm matched demographics, comorbidities, and medications. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for primary outcomes.<br><br>RESULTS: After matching, there were 1,065 patients in each cohort. No significant differences were observed in risks for ischemic stroke (RR = 1.24, 95% CI [0.91, 1.70]), hemorrhagic stroke (RR = 0.95, [0.52, 1.92]), MI (RR = 0.98, [0.70, 1.39]), or mortality (RR = 1.00, [0.83, 1.19]).<br><br>CONCLUSION: Our findings suggest anti-VEGF therapy for nAMD does not increase the risk of stroke, MI, or mortality compared to patients with GA.}, }
@article {pmid40711662, year = {2025}, author = {Björnestedt, R and Waters, S and Paišytė, A and Furlan, F and Wanner, C}, title = {Evaluation of XSB-001 (Ranibizumab Biosimilar) Physicochemical and Biological Stability in Prepared Syringes for Intravitreal Injection.}, journal = {Advances in therapy}, volume = {42}, number = {9}, pages = {4597-4610}, pmid = {40711662}, issn = {1865-8652}, mesh = {Drug Stability ; Syringes ; *Ranibizumab/chemistry/administration &amp; dosage ; Intravitreal Injections ; *Biosimilar Pharmaceuticals/chemistry/administration &amp; dosage ; Humans ; *Angiogenesis Inhibitors/administration &amp; dosage/chemistry ; Drug Storage ; Chromatography, High Pressure Liquid ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; }, abstract = {INTRODUCTION: Vascular endothelial growth factor A (VEGF-A) is a key driver of neovascularization and vascular permeability in retinal diseases such as neovascular age-related macular degeneration and diabetic macular edema. XSB-001 (Ximluci[®]), a ranibizumab biosimilar has demonstrated equivalent safety, efficacy, and biological activity to reference ranibizumab, supporting its use in these indications.<br><br>METHODS: This study evaluates the extended physicochemical and biological stability of XSB-001 under real-world handling conditions for 30&#xa0;days. XSB-001 was stored at 5&#x2009;&#xb1;&#x2009;3&#xa0;&#xb0;C in vials and prepared into two syringe types. Samples were maintained under monitored conditions for 30&#xa0;days, with a subset exposed to room temperature, humidity and indoor lighting or protected from light for 48&#xa0;h.<br><br>RESULTS: Across all test conditions, XSB-001 maintained expected liquid physical state, clarity, and color within specification limits, besides charge variants. High monomer purity (99.6%), high molecular weight species (0.4%) and low molecular weight species (<&#x2009;0.35%) were observed, satisfying all required criteria. Size exclusion-high-performance liquid chromatography (SE-HPLC) analysis confirmed monomer content at 99.6%, surpassing the&#x2009;&#x2265;&#x2009;99.0% requirement. Reverse-phase high-performance liquid chromatography (RP-HPLC) showed consistent main peak purity of 97.3%, exceeding the&#x2009;&#x2265;&#x2009;97.0% criterion. Strong cation exchange high-performance liquid chromatography (SCX-HPLC) recorded main peak values between 96.5 and 96.6%, meeting the&#x2009;&#x2265;&#x2009;96.5% threshold. Acidic (1.7%) and basic species (1.6-1.7%) were consistently within specification limits (&#x2264;&#x2009;2.5%). Sub-visible particulate analysis indicated particle counts within acceptable limits. Protein concentration was stable across storage conditions, ranging from 9.9 to 10.4&#xa0;mg/ml.<br><br>CONCLUSION: These findings support the extended stability of XBS-001 stored in unopened vials and subsequently prepared syringes (and independent of syringe type), optimizing patient care and treatment management efficiency.}, }
@article {pmid40711716, year = {2025}, author = {Seber, E and Yaylacı, S}, title = {Sustained Drug Delivery Systems for Age-Related Macular Degeneration: Advancements, Challenges, and Future Perspectives.}, journal = {Advances in experimental medicine and biology}, volume = {1499}, number = {}, pages = {71-86}, pmid = {40711716}, issn = {0065-2598}, mesh = {Humans ; *Macular Degeneration/drug therapy/metabolism/pathology ; *Drug Delivery Systems/trends/methods ; Delayed-Action Preparations ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Angiogenesis Inhibitors/administration &amp; dosage ; Animals ; Hydrogels/chemistry ; Intravitreal Injections ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss among the elderly and remains a major public health challenge due to its chronic progression and high recurrence rate. Current standard treatment relies heavily on repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents, which impose significant burdens on patients and healthcare systems. In recent years, sustained-release drug delivery systems (SR-DDS) have emerged as promising alternatives to overcome the limitations of frequent injections and to improve therapeutic outcomes in AMD.This chapter explores the rationale, mechanisms, and current advancements in hydrogel-based platforms and implantable devices designed for the long-term delivery of anti-VEGF agents. We provide a comparative analysis of these two delivery modalities, focusing on their materials, biocompatibility, release kinetics, clinical utility, and translational potential. Furthermore, we discuss the critical role of SR-DDS in supporting personalized medicine through patient-specific dosing strategies and their ability to maintain therapeutic drug levels with minimal invasiveness.Challenges in the development and regulatory approval of SR-DDS, including manufacturing complexity, long-term safety, and economic viability, are also addressed. Finally, we highlight emerging trends in biomaterials science, precision engineering, and combination therapy strategies that may shape the next generation of drug delivery platforms for AMD.Together, these insights underscore the transformative potential of SR-DDS in redefining the clinical management of AMD by offering sustained, localized, and patient-tailored therapeutic delivery.}, }
@article {pmid40712124, year = {2025}, author = {McLaughlin, SA and Davila, N and Shields, C and Bineshfar, N and Banaee, T and Williams, BK}, title = {IMPACT OF GLP-1 RECEPTOR AGONISTS FOR TYPE 2 DIABETES MELLITUS ON THE DEVELOPMENT AND PROGRESSION OF AGE-RELATED MACULAR DEGENERATION.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {12}, pages = {2241-2251}, doi = {10.1097/IAE.0000000000004616}, pmid = {40712124}, issn = {1539-2864}, support = {UL1 TR001439/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2/drug therapy/complications ; Retrospective Studies ; Male ; Female ; *Glucagon-Like Peptide-1 Receptor Agonists ; Disease Progression ; Aged ; *Hypoglycemic Agents/therapeutic use ; Incidence ; Middle Aged ; *Macular Degeneration/epidemiology/prevention &amp; control/etiology ; Follow-Up Studies ; Aged, 80 and over ; }, abstract = {PURPOSE: To evaluate whether GLP-1 receptor agonist (GLP-1RA) therapy reduces the risk of age-related macular degeneration (AMD) in type 2 diabetes mellitus (T2DM) patients.<br><br>METHODS: A retrospective cohort study using a global health research network matched T2DM patients on GLP-1RA versus non-GLP-1RA therapy. AMD incidence was determined over the first 1 to 10 years of treatment. Patients with baseline early or intermediate nonexudative AMD were also matched and assessed for progression to advanced AMD. Measures of association analysis was used to calculate risk, risk difference, and risk ratio.<br><br>RESULTS: Among 600,816 matched patients without a history of AMD, GLP-1RA users had a 15% relative risk reduction in incidence of nonexudative AMD (RR, 0.851; 95% CI, 0.801-0.905; P < 0.0001) versus those who received alternative therapy. These patients also had a 20% relative risk reduction in incidence of exudative AMD (RR, 0.80; 95% CI, 0.808-0.989; P < 0.0001). To assess progression, 4,450 patients with early or intermediate AMD were matched between the cohorts. GLP-1RA use was associated with 29% relative risk reduction in progression to advanced nonexudative AMD (RR, 0.715; 95% CI, 0.529-0.967; P = 0.028) and a 27% relative risk reduction in progression to exudative AMD (RR, 0.729; 95% CI, 0.601-0.883; P = 0.001).<br><br>CONCLUSION: GLP-1RA use may reduce both the risk and progression of AMD and progression of early and intermediate AMD to advanced AMD in adults with T2DM. GLP-1RAs have been shown to promote neuronal survival and reduce inflammation, which may provide a pathophysiological explanation of the potential beneficial role of GLP-1RAs.}, }
@article {pmid40712125, year = {2025}, author = {Heinke, A and Agnihotri, A and Nagel, ID and Kalaw, FGP and Mehta, NN and Sherif Morsy, M and Cheng, L and Uwe-Bartsch, D and Freeman, WR}, title = {OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY ANALYSIS OF COHORT WITH PERIPAPILLARY CHOROIDAL NEOVASCULARIZATION.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {12}, pages = {2297-2302}, doi = {10.1097/IAE.0000000000004626}, pmid = {40712125}, issn = {1539-2864}, support = {R01EY016323/GF/NIH HHS/United States ; 5R01EY033847/GF/NIH HHS/United States ; OT2OD032644/GF/NIH HHS/United States ; }, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Retrospective Studies ; Male ; Female ; Aged ; *Choroidal Neovascularization/drug therapy/diagnosis/etiology ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; Aged, 80 and over ; Follow-Up Studies ; Middle Aged ; Fundus Oculi ; Ranibizumab/therapeutic use/administration &amp; dosage ; *Choroid/blood supply ; Optic Disk ; *Wet Macular Degeneration/drug therapy/complications/diagnosis ; Bevacizumab/therapeutic use ; }, abstract = {PURPOSE: Although many studies have analyzed macular choroidal neovascularization (CNV) using optical coherence tomography angiography, few have focused on peripapillary CNV, which comprises approximately 10% of CNV cases. This study examines optical coherence tomography angiography vessel changes in patients with treated and untreated peripapillary CNV to better understand disease progression.<br><br>METHODS: Nineteen eyes with peripapillary CNV secondary to neovascular age-related macular degeneration were retrospectively analyzed. Treated eyes (n = 13) received anti-VEGF injections after a modified pro re nata regimen, whereas untreated eyes (n = 6) without macular involvement were closely observed. Median follow-up was 11.9 months (treated) and 8 months (untreated). High-quality optical coherence tomography angiography scans centered on the CNV lesions were selected and analyzed using validated software (ImageJ and AngioTool).<br><br>RESULTS: Treated eyes showed significant reductions in CNV lesion size, vessel density, and lacunarity after anti-VEGF therapy (ImageJ: P < 0.001; AngioTool: P = 0.0004). Untreated eyes exhibited significant lesion enlargement (ImageJ: P = 0.0356; AngioTool: P = 0.0013). None of the patients in the untreated group developed macular exudation during the study.<br><br>CONCLUSION: Peripapillary CNV without macular involvement may be considered for short-term observation in selected cases, as these lesions appeared indolent and stable over the limited follow-up period in our cohort. The vessels in optical coherence tomography angiography in the treated group showed regression in size after anti-VEGF therapy. These findings will potentially help clinicians better understand this entity.}, }
@article {pmid40712801, year = {2026}, author = {Carlà, MM and Mottola, F and Cusato, M and Oreste, G and Campaniello, G and Mateo, C and Couturier, A and Philippakis, E and Caporossi, T and Rizzo, S}, title = {Vitreoretinal interface abnormalities in age-related macular degeneration: Prevalence, pathophysiology, and reciprocal influence.}, journal = {Survey of ophthalmology}, volume = {71}, number = {2}, pages = {321-333}, doi = {10.1016/j.survophthal.2025.07.010}, pmid = {40712801}, issn = {1879-3304}, mesh = {Humans ; Prevalence ; *Vitreous Body/pathology/physiopathology ; *Macular Degeneration/physiopathology/epidemiology ; Tomography, Optical Coherence/methods ; *Retina/pathology/physiopathology ; Visual Acuity ; Disease Progression ; }, abstract = {Age-related macular degeneration (AMD) represents a leading cause of vision loss worldwide, while vitreoretinal interface (VRI) abnormalities constitute a dynamic boundary where posterior vitreous interacts with the retinal surface. We explore the intricate relationship between VRI abnormalities and AMD, examining prevalence, underlying pathophysiological mechanisms, and their reciprocal influence on disease development, progression, and treatment outcomes. Evidence suggests a higher prevalence of vitreomacular adhesion in exudative versus nonexudative AMD, while complete posterior vitreous detachment may exert protective effects against AMD progression. Tractional forces, inflammatory mediators, and structural disruption associated with VRI abnormalities may promote AMD progression and confound assessment of anti-vascular endothelial growth factor therapy efficacy. Recent findings underscore that epiretinal membranes might act as physical barriers reducing drug penetration, while VMT/VMA can alter macular morphology, potentially mimicking or obscuring therapeutic response. Surgical management of VRI abnormalities in AMD can achieve anatomical success, though visual outcomes may be limited by underlying macular pathology. Early detection and characterization of VRI abnormalities in AMD patients could improve risk stratification, guide treatment timing, and potentially lead to novel preventive strategies, highlighting the importance of comprehensive evaluation and individualized management approaches for optimizing outcomes in this complex patient population.}, }
@article {pmid40713962, year = {2025}, author = {Liu, X and Liu, G and Zhang, Q}, title = {Re: Brown et al.: MERLIN: Two-year results of brolucizumab in participants with neovascular age-related macular degeneration and persistent retinal fluid. (Ophthalmology. 2025;132:131-140).}, journal = {Ophthalmology}, volume = {132}, number = {10}, pages = {e169}, doi = {10.1016/j.ophtha.2025.06.008}, pmid = {40713962}, issn = {1549-4713}, }
@article {pmid40713972, year = {2025}, author = {Yang, W and Gao, R and Chen, L and Li, S}, title = {CXCR4[+] monocytes promote neovascularization in wet age-related macular degeneration.}, journal = {Experimental eye research}, volume = {259}, number = {}, pages = {110550}, doi = {10.1016/j.exer.2025.110550}, pmid = {40713972}, issn = {1096-0007}, mesh = {*Receptors, CXCR4/metabolism ; *Monocytes/metabolism/pathology ; *Wet Macular Degeneration/metabolism/pathology/genetics ; Humans ; *Choroidal Neovascularization/metabolism/pathology ; Animals ; Mice ; Signal Transduction ; Immunohistochemistry ; Mice, Inbred C57BL ; Disease Models, Animal ; Endothelial Cells/metabolism/pathology ; Cell Differentiation ; Male ; }, abstract = {Wet age-related macular degeneration (wAMD) pathogenesis is primarily driven by choroidal neovascularization (CNV) mediated through intricate angiogenesis-inflammation crosstalk. While chemokine signaling has emerged as a promising therapeutic target, the specific cellular mediators orchestrating this process remain poorly defined. In this study, we employed an integrative approach combining bulk RNA sequencing, single-cell transcriptomics, multiplex immunohistochemistry (mIHC), and in vivo models to systematically elucidate the pivotal role of chemokine signaling in wAMD-associated angiogenesis and identify critical monocyte subsets involved in neovascularization. Our comprehensive analysis revealed MMP2+ endothelial cells (ECs) as a distinct cellular subset demonstrating dual angiogenic and stem-like properties, originating from a dysregulated endothelial differentiation pathway. Furthermore, we identified CXCR4+ monocytes as crucial mediators of pathological angiogenesis, with their activity likely modulated through CXCL12-CXCR4 chemokine axis interactions with MMP2+ ECs. Through transcription factor network analysis, we established RUNX3 as a master regulatory element governing pro-angiogenic monocyte differentiation, providing novel mechanistic insights into monocyte-driven angiogenesis in wAMD pathogenesis. These findings collectively establish MMP2+ ECs and CXCR4+ monocyte signaling as central pathogenic drivers in wAMD. Our results propose that therapeutic targeting of RUNX3-mediated chemokine signaling could synergize effectively with current anti-VEGF treatment paradigms.}, }
@article {pmid40715177, year = {2025}, author = {Lee, H and Jang, H and Chae, JB and Lee, HK and Son, C and Park, CW and Ha, T and Yum, M and Park, S and Hong, SW and Lee, SY and Lyu, J and Lee, S and Lee, DK and Chung, H}, title = {In vivo efficacy of NRL knockdown with cell-penetrating siRNA in retinal degeneration.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {27176}, pmid = {40715177}, issn = {2045-2322}, support = {RS-2024-00453840//National Research Foundation of Korea/ ; NRF-2019M3A9H1030948//National Research Foundation of Korea/ ; }, mesh = {Animals ; Mice ; *RNA, Small Interfering/genetics/administration &amp; dosage ; *Retinal Degeneration/genetics/therapy/pathology ; *Basic-Leucine Zipper Transcription Factors/genetics/metabolism ; Mice, Inbred C57BL ; *Eye Proteins/genetics/metabolism ; Disease Models, Animal ; Retinal Cone Photoreceptor Cells/metabolism/pathology ; Gene Knockdown Techniques ; Retinal Rod Photoreceptor Cells/metabolism/pathology ; Retinitis Pigmentosa/genetics/pathology ; Electroretinography ; Calcium-Binding Proteins ; }, abstract = {Retinal degenerative diseases, such as retinitis pigmentosa (RP) and age‑related macular degeneration (AMD), lead to progressive vision loss through photoreceptor degeneration; RP begins with the gradual loss of peripheral rods, whereas AMD causes central‑vision loss mainly because macular cones and parafoveal rods degenerate. The neural retina leucine zipper (NRL) directs rod photoreceptor differentiation, and its disruption has been linked to upregulated cone-specific markers in rods. This study investigates the therapeutic potential of a cell-penetrating asymmetric small interfering RNA targeting NRL (cp-asiNRL) to induce rod-to-cone conversion and mitigate retinal degeneration. cp-asiNRL was administered intravitreally to C57BL/6J wild-type (WT), neovascular AMD (nAMD), and RP (Rho[P23H/+]) mouse models. Subsequent analyses included cone marker expression levels and electroretinographic evaluations, and single-cell RNA sequencing. Administration of cp-asiNRL suppressed NRL expression, increased cone marker expression, and improved retinal function in both WT and nAMD models. In RP mice, cone marker expression was also elevated, although functional improvements were comparatively modest, likely reflecting the advanced disease stage. Single-cell RNA sequencing revealed a rod-to-cone-like transdifferentiation, suggesting that cp-asiNRL-mediated NRL knockdown partially preserved photoreceptor integrity. cp-asiNRL-mediated NRL silencing shows considerable promise as a therapeutic intervention for retinal degenerative conditions. By promoting rod-to-cone transdifferentiation and supporting photoreceptor survival, this approach may offer a novel strategy for vision preservation.}, }
@article {pmid40716081, year = {2025}, author = {Wang, T and Szczepan, M and Gregg, AT and Wang, X and Smith, LEH and Sun, Y}, title = {TREM2-Mediated Myeloid Cells Protect Against Pathological Choroidal Neovascularization.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {14}, pages = {e70881}, pmid = {40716081}, issn = {1530-6860}, support = {R01 EY029238/EY/NEI NIH HHS/United States ; R01EY017017//HHS | NIH | National Eye Institute (NEI)/ ; R01EY030904//HHS | NIH | National Eye Institute (NEI)/ ; R01 EY030140/EY/NEI NIH HHS/United States ; //Massachusetts Lions Eye Research Fund (MLERF)/ ; R01EY029238//HHS | NIH | National Eye Institute (NEI)/ ; //Knights Templar Eye Foundation (KTEF)/ ; //BrightFocus Foundation (BFF)/ ; R01EY030140//HHS | NIH | National Eye Institute (NEI)/ ; }, mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology/genetics ; *Receptors, Immunologic/metabolism/genetics ; *Membrane Glycoproteins/metabolism/genetics ; Mice ; *Myeloid Cells/metabolism/pathology ; Mice, Inbred C57BL ; Microglia/metabolism/pathology ; Macrophages/metabolism/pathology ; Mice, Knockout ; Male ; }, abstract = {Choroidal neovascularization (CNV) is a hallmark of neovascular age-related macular degeneration, a leading cause of irreversible vision loss in the elderly. While immune dysregulation and myeloid cell activation have been implicated in CNV pathogenesis, the molecular mechanisms by which myeloid subsets influence NV remain incompletely understood. Triggering receptor expressed on myeloid cells 2 (TREM2) is an immunomodulatory receptor enriched in microglia and tissue macrophages, known to play protective roles in retinal and neurodegenerative diseases. However, its function in CNV has not been fully characterized. In this study, we investigated the role of TREM2 in CNV using transcriptomic, genetic, and functional approaches. Single-cell RNA sequencing revealed selective upregulation of Trem2 in activated microglia and macrophages following laser-induced CNV. These findings were validated at the protein level using immunostaining, which confirmed robust TREM2 expression in lesion-associated IBA1[+] myeloid cells. Functionally, Trem2 haploinsufficiency exacerbated CNV lesion size and vascular leakage, indicating a protective role in disease modulation. Transcriptomic profiling demonstrated that Trem2-expressing myeloid cells exhibit distinct angiogenic and inflammasome-related gene signatures, suggesting that TREM2 regulates angiogenesis through modulation of inflammatory pathways. We further examined the functional interaction between TREM2 and suppressor of cytokine signaling 3 (SOCS3), another anti-inflammatory mediator upregulated during CNV. Using compound mutant mice, we showed that Trem2 and SOCS3 function through overlapping but independent anti-angiogenic programs, and their combined deficiency leads to additive worsening of CNV pathology. These findings establish TREM2 as a key regulator of myeloid cell function and angiogenesis in the diseased retina.}, }
@article {pmid40716633, year = {2025}, author = {Xie, J and Xiao, Y and Zhang, Y and Hong, A and Chen, X}, title = {Identification and functional analysis of a novel potent anti-angiogenesis peptide SAIF-B2 derived from shark cartilage.}, journal = {European journal of pharmacology}, volume = {1004}, number = {}, pages = {177961}, doi = {10.1016/j.ejphar.2025.177961}, pmid = {40716633}, issn = {1879-0712}, mesh = {Animals ; Humans ; *Angiogenesis Inhibitors/pharmacology/chemistry/therapeutic use/metabolism ; Zebrafish ; Human Umbilical Vein Endothelial Cells/drug effects ; Sharks ; Cell Proliferation/drug effects ; Cell Movement/drug effects ; Molecular Docking Simulation ; *Peptides/pharmacology/chemistry ; *Cartilage/chemistry ; Neovascularization, Physiologic/drug effects ; Neovascularization, Pathologic/drug therapy ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; Carcinoma, Hepatocellular/drug therapy/pathology ; Signal Transduction/drug effects ; }, abstract = {Marine-derived bioactive molecules represent promising candidates for lead drug development. Structural optimisation of these lead drugs significantly enhances their suitability as drugs, setting the framework for large-scale manufacturing. We previously identified shark-derived angiogenesis inhibition factor (SAIF), a 33 amino acid peptide from shark cartilage, which has anti-angiogenic activity but has inadequate in vivo stability, thereby limiting clinical translation. In this study, we employed a computational molecular docking-guided truncation strategy to optimise and screen SAIF-B2, a truncated 20 amino acid peptide. SAIF-B2 improved plasma proteolytic stability by 67 % while maintaining strong affinity for vascular endothelial growth factor receptor 2 and vascular endothelial growth factor A. Functionally, SAIF-B2 decreased HUVEC proliferation, migration and tube formation in a dose-dependent manner, resulting in G1/S phase cell cycle arrest. SAIF-B2 markedly suppressed neovascularisation in the chick chorioallantoic membrane assay and zebrafish models. Transcriptomic analysis revealed its anti-angiogenic mechanism, which involves the suppression of VEGF, MAPK, and PI3K-AKT signalling pathways. Notably, SAIF-B2 exhibited potent anti-tumour effects in a hepatocellular carcinoma model and effectively inhibited pathological corneal neovascularisation. These findings establish SAIF-B2 as a superior marine-derived anti-angiogenic peptide with enhanced stability (67 % improvement), smaller molecular weight, and lower production costs than those of its parent molecule. This multi-target therapeutic agent shows significant potential for treating angiogenesis-driven pathologies, including malignancies and macular degeneration, thereby warranting further preclinical development.}, }
@article {pmid40716957, year = {2025}, author = {Hunt, A and Hashimoto, Y and Young, S and Arnold, J and Game, J and Hooper, C and Field, A and Barry, R and Barthelmes, D and Gillies, M}, title = {Outcomes After Switching to Faricimab in Neovascular Age-Related Macular Degeneration: Data From the Fight Retinal Blindness! Registry.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {53}, number = {9}, pages = {1156-1167}, pmid = {40716957}, issn = {1442-9071}, support = {NHMRC 2010-1012//National Health and Medical Research Council/ ; 2007-2009//Royal Australian and New Zealand College of Ophthalmologists/ ; }, mesh = {Humans ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Male ; Female ; Visual Acuity ; *Registries ; Intravitreal Injections ; Aged ; Ranibizumab/administration &amp; dosage/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Drug Substitution ; Receptors, Vascular Endothelial Growth Factor ; Aged, 80 and over ; Treatment Outcome ; Tomography, Optical Coherence ; Bevacizumab/administration &amp; dosage/therapeutic use ; Fluorescein Angiography ; Follow-Up Studies ; Antibodies, Bispecific ; }, abstract = {BACKGROUND: We aimed to describe 1-year outcomes of eyes switched to faricimab from first-generation vascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration (nAMD) in routine care.<br><br>METHODS: Multicentre, observational study of 383 eyes tracked in the Fight Retinal Blindness! registry switched to faricimab from aflibercept 2&#x2009;mg, ranibizumab, or bevacizumab between 1st January-1st August 2023 in Australia.<br><br>RESULTS: One-year completion rates were high (335/383 [88%]). The proportion of choroidal neovascular (CNV) lesions graded as inactive increased from 39% at switch to 63% at 12&#x2009;months (p&#x2009;<&#x2009;0.01). Mean visual acuity (95% Confidence Interval) decreased from 70.0 (68.6, 71.5) to 68.4 (66.7, 70.1) logarithm of the minimum angle of resolution letters (both approx. 6/12). Mean treatment intervals increased from 7.2 to 10.5&#x2009;weeks (p&#x2009;<&#x2009;0.01). Eyes with active CNV at switch maintained mean VA -0.5 (-1.7, +0.7) letters; 50% were inactivated at 12&#x2009;months. Eyes with inactive CNV at switch lost -3.5 (-5.0, -1.9) letters; 15% had reactivation at 12&#x2009;months. Switchback occurred in 64/383 eyes (17%), predominantly to aflibercept 2&#x2009;mg, that lost -1.9 letters without interval change at 12&#x2009;months. Adverse outcomes were in keeping with previous reports, with no cases of occlusive retinal vasculitis.<br><br>CONCLUSIONS: We found that faricimab inactivated a significant proportion of CNV lesions that had been active using 1st generation VEGF inhibitors, with a significant extension of the treatment interval. A small reduction in VA occurred in switchers and eyes not switched through the same period.}, }
@article {pmid40717982, year = {2025}, author = {Lv, XM and Li, N and Chen, LW and Sun, C}, title = {A comprehensive and systematic review on resveratrol supplementation as a promising candidate for the retinal disease: a focus on mechanisms of action from preclinical studies.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1615910}, pmid = {40717982}, issn = {1663-9812}, abstract = {BACKGROUND: Resveratrol is a natural polyphenolic compound that shows great potential in neuroprotection, anti-inflammation,and antioxidation. Previous studies have demonstrated that resveratrol can effectively treat various animal models of retinal diseases.<br><br>PURPOSE: The aim of the research was to use an animal experimental model to assess the effectiveness of resveratrol in treating retinal-related diseases in various animal models of retinal diseases such as ischemia-reperfusion injury, diabetic retinopathy, glaucoma, chronic ocular hypertension, optic neuritis, age-related macular degeneration, and retinopathy of prematurity. Furthermore, this study aims to reveal the underlying mechanisms of resveratrol related to the treatment of retina-related diseases.<br><br>METHODS: A search was conducted across several databases, including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and OVID. The search time was from the establishment of the database to October 2024 to collect studies on resveratrol intervention in animal models of retinal diseases. The studies included in this paper adopted the SYRCLE's risk of bias tool. Stata 16.0 and RevMan 5.4 software were used to analyze and visualize the results.<br><br>RESULTS: Our meta-analysis comprises 26 studies and 365 animals demonstrates the following effects of resveratrol compared to the control group: a significant increase in the number of retinal ganglion cells (SMD = 3.91, 95% Cl = [2.97, 4.86], p < 0.00001) and superoxide dismutase activity (SMD = 3.14, 95% Cl = [0.96, 5.33], p = 0.005). Moreover, a decrease in malondialdehyde (SMD = -9.29,95% Cl = [-12.84, -5.74], p < 0.00001), reactive oxygen species level (SMD = -4.29,95% Cl = [-6.25, -2.32], p < 0.0001), cyclooxygenase-2 (SMD = -2.66, 95% Cl = [-4.01, -1.30], p =0.0001), tumour necrosis factor-&#x3b1;(SMD = -3.96,95% Cl = [-6.27, -1.65], p = 0.0008) and interleukin-6 (SMD = -3.32,95% Cl = [-4.20, -2.44], p < 0.00001) was observed. The A-wave amplitude and B-wave amplitude showed an increase respectively (MD = 105.92,95% Cl = [58.99, 152.84], p < 0.00001); (MD = 158.00,95% Cl = [86.35, 229.65], p < 0.0001), along with an increase in inner retinal thickness (SMD = 6.33, 95% CI = [5.10, 7.56], p < 0.00001) and total retinal thickness (SMD = 2.70, 95%Cl = [0.77, 4.83], p = 0.01). Subgroup analysis showed that different doses of resveratrol were associated with an increase in the number of RGCs (p < 0.05). Resveratrol improves retinal diseases through multiple mechanisms: i) Neuroprotection: it activates the SIRT1/NF-&#x3ba;B and Nrf2 pathways, inhibits Caspase-3 expression, and promotes the survival of RGCs and ii) Antioxidation: it upregulates SOD activity, reduces the levels of MDA and ROS, and alleviates oxidative damage and iii) Anti-inflammation: it inhibits the COX-2, TNF-&#x3b1;, IL-6, and NF-&#x3ba;B pathways, alleviating the inflammatory response. These mechanisms resulted in enhanced amplitude of A/B waves, improved retinal thickness and visual function.<br><br>CONCLUSION: Resveratrol has neuroprotective, anti-inflammatory and antioxidant effects through multiple mechanisms, thereby reducing retinal damage and maintaining the structure and function of the retina. This provides preclinical support for its possible therapeutic uses in the management of retinal diseases.<br><br>https://www.crd.york.ac.uk/PROSPERO/myprospero.}, }
@article {pmid40718639, year = {2025}, author = {Lin, X and Zhou, Y and Lv, K and Wu, W and Chen, C}, title = {Nanomedicine-Based Ophthalmic Drug Delivery Systems for the Treatment of Ocular Diseases.}, journal = {International journal of nanomedicine}, volume = {20}, number = {}, pages = {9221-9249}, pmid = {40718639}, issn = {1178-2013}, mesh = {Humans ; *Nanomedicine/methods ; *Eye Diseases/drug therapy ; *Drug Delivery Systems/methods ; Administration, Ophthalmic ; Animals ; *Ophthalmic Solutions/administration &amp; dosage ; Biological Availability ; Liposomes/chemistry ; }, abstract = {Ocular diseases affect over 2.2 billion people globally, imposing a significant socioeconomic burden, with annual productivity losses estimated at US$411 billion. Conventional drug delivery methods-topical, local injection, and systemic administration-face challenges such as low bioavailability (<5%), rapid clearance, and physiological barriers like the cornea and blood-retinal barrier (BRB). Nanomedicine offers promising solutions by enhancing drug bioavailability, prolonging release, and enabling targeted delivery. This review explores nanomedicine-based ophthalmic drug delivery systems, including organic nanomaterials (eg, liposomes, polymer micelles, dendrimers), inorganic nanomaterials (eg, metal nanoparticles, quantum dots), and biological components (eg, exosomes). These systems improve drug penetration, reduce administration frequency, and minimize toxicity, addressing conditions like dry eye disease, keratitis, glaucoma, uveitis, age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vascular occlusion (RVO). For instance, Ocular Therapeutix (OTX)-TP, a sustained-release intracanalicular implant combining poly (ethylene glycol)-based hydrogel with travoprost-loaded poly (lactic acid) microspheres, has shown therapeutic efficacy lasting up to three months in the management of glaucoma and ocular hypertension in Phase III clinical trial. Additionally, a liposomal formulation of verteporfin, approved for the treatment of neovascular AMD, administered intravenously and activated by laser photodynamic therapy, demonstrates a durable response, with a marked reduction in treatment frequency from an average of 3.5 sessions in the first year to only 0.1 by the fifth year post-diagnosis. Despite these advantages, challenges such as manufacturing costs, potential toxicity, and limited clinical translation persist. Future advancements in nanomedicine hold potential for personalized, non-invasive ocular therapies, revolutionizing ophthalmology.}, }
@article {pmid40719090, year = {2025}, author = {Beckers, D and Kretz, F and Glandorf, K and Abdassalam, S and Höhn, F and Amer, M and Breyer, DRH and Beckers, L}, title = {AREDS2 Under Scrutiny: Advocating Unified Regulations.}, journal = {Klinische Monatsblatter fur Augenheilkunde}, volume = {242}, number = {7}, pages = {735-740}, doi = {10.1055/a-2611-2310}, pmid = {40719090}, issn = {1439-3999}, mesh = {Germany ; *Macular Degeneration/diet therapy ; Humans ; *Dietary Supplements/standards/analysis ; Ascorbic Acid/analysis ; *Drug Labeling/legislation &amp; jurisprudence/standards ; *Nonprescription Drugs/standards ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is one of the leading causes of blindness in older adults. Dietary supplements based on the AREDS2 formulation are considered an evidence-based intervention to slow disease progression in intermediate AMD.<br><br>OBJECTIVE: This study aimed to systematically compare the composition of over-the-counter dietary supplements marketed for AMD support with the original AREDS2 formula and to quantify any deviations.<br><br>METHODS: As part of a market analysis, products available in Germany claiming a supportive effect in AMD were identified. The ingredients and dosages declared on the packaging were compared with the reference values used in the AREDS2 study.<br><br>RESULTS: The majority of analysed supplements exhibited substantial deviations from the AREDS2 formulation. On average, the concentrations of vitamin C were 52.3% lower, vitamin E 61.2% lower, and zinc 40.1% lower than the recommended amounts. Only a minority of products matched the reference formulation in both composition and dosage.<br><br>CONCLUSION: There are significant discrepancies in the composition of commercially available AREDS2-based supplements. The implementation of standardised labelling requirements and regulatory guidelines appears necessary to enhance comparability and support evidence-based use in clinical practice.}, }
@article {pmid40719538, year = {2025}, author = {Sadeghi, E and Valsecchi, N and Du, K and Davis, E and Schulman, A and DeCicco, JA and Ibrahim, MN and Singh, SR and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Chhablani, J}, title = {Three-Dimensional Choroidal Vessel Analysis in Asymmetric Bilateral Age-Related Macular Degeneration: A Comparison of Active Neovascular AMD and Dry AMD Fellow Eyes.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {9}, pages = {64}, pmid = {40719538}, issn = {1552-5783}, support = {P30 EY008098/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Retrospective Studies ; Aged ; Male ; Cross-Sectional Studies ; *Choroid/blood supply ; Female ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/diagnosis/physiopathology ; Visual Acuity/physiology ; Aged, 80 and over ; *Geographic Atrophy/diagnosis/physiopathology ; *Imaging, Three-Dimensional/methods ; Fluorescein Angiography/methods ; *Choroidal Neovascularization ; Algorithms ; }, abstract = {PURPOSE: To assess choroidal vasculature in bilateral age-related macular degeneration (AMD) patients, with neovascular AMD in one eye and dry AMD in the other, using an innovative three-dimensional (3D) algorithm.<br><br>METHODS: This retrospective cross-sectional study included 30 patients with asymmetric bilateral AMD. All patients underwent clinical exams and swept-source optical coherence tomography using PlexElite-9000 (Carl Zeiss Meditec, Dublin, CA) scans centered on the fovea. The 3D choroidal vasculature was segmented using our validated deep learning algorithm. These 3D maps were divided into five sectors, with the three largest vessels in each sector selected for mean choroidal vessel diameter and inter-vessel distance (IVD) measurements. Volumetric choroidal thickness (ChT) and choroidal vascularity index (CVI) were calculated. Analysis was performed using a linear mixed model.<br><br>RESULTS: This study analyzed 60 eyes from 30 patients, with a mean age of 78.63 &#xb1; 8.01 years. Neovascular AMD eyes had significantly higher mean LogMar visual acuity (0.63 &#xb1; 0.60 vs. 0.20 &#xb1; 0.18, P < 0.001). Neovascular eyes had higher average vessel diameter (253.711 &#xb1; 20.777 vs. 232.641 &#xb1; 28.249 micrometers, P < 0.001), significant in central, temporal, and superior sectors (P < 0.05). IVD was lower in neovascular AMD (209.563 &#xb1; 21.074 vs. 213.867 &#xb1; 30.684&#xa0;&#xb5;m, P = 0.515). Average ChT was lower in neovascular AMD (193.939 &#xb1; 49.627 vs. 198.245 &#xb1; 53.786 &#xb5;m, P = 0.809), significant in the inferior sector (P = 0.011). Additionally, CVI was higher in neovascular AMD (0.365 &#xb1; 0.033 vs. 0.353 &#xb1; 0.035, P = 0.031), particularly in inferior, superior, and central sectors (P < 0.05).<br><br>CONCLUSIONS: Eyes with neovascular AMD demonstrated higher choroidal vessel diameter, ChT, and CVI and decreased IVD compared to dry AMD eyes, possibly related to vessel congestion and inflammation in eyes with active choroidal neovascularization.}, }
@article {pmid40721821, year = {2025}, author = {Tan, JM and Fei, Y and Wang, L and Otero-Marquez, O and Bhuiyan, TR and Arevalo, JF and Lema, GMC and Smith, RT}, title = {Age-related macular degeneration, subretinal drusenoid deposits, and cuticular and calcified drusen in black and hispanic subjects.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {85}, pmid = {40721821}, issn = {2056-9920}, abstract = {BACKGROUND: Subretinal drusenoid deposits (SDDs), cuticular drusen, and calcified drusen have been linked to rapid progression of age-related macular degeneration (AMD). SDDs have also been linked to high-risk vascular diseases (HRVDs). However, SDDs, cuticular drusen, and calcified drusen have not been reported in Black and Hispanic populations. We report that these drusen phenotypes occur in Black and Hispanic AMD patients.<br><br>METHODS: Twenty-three Black and Hispanic AMD subjects were identified in a published cross-sectional study of 200 AMD subjects. Spectral-domain optical coherence tomography, near-infrared reflectance imaging, and lipid profiles were obtained in the parent study. Masked readers assigned subjects into 2 groups: SDDs, present with or without drusen, and drusen only, as in the parent study. Calcified and cuticular drusen were independently identified. Subjects were assigned by health history questionnaires into those with or without HRVDs, defined as: cardiac valve defect (i.e., aortic stenosis), myocardial defect (i.e., myocardial infarction), and stroke/transient ischemic attack.<br><br>RESULTS: 10/23 subjects were in the SDD group (3 Black and 7 Hispanic subjects), 13 of 23 were in the drusen only group. 4/23 subjects were identified with cuticular drusen (1 Black and 3 Hispanic subjects) and 4/23 subjects were identified with calcified drusen (2 Black and 2 Hispanic Subjects). All subjects had respective phenotypes indistinguishable from that of White subjects. 3/10 SDD subjects had HRVDs.<br><br>CONCLUSIONS: We report, for the first time to our knowledge, that subretinal drusenoid deposits, calcified drusen, and cuticular drusen are present in some AMD patients who identify as Black or Hispanic. A strong association of SDDs with HRVDs was discovered in the parent study. These diseases are known to be over-represented in these under-served populations. SDDs, calcified drusen, and cuticular drusen also confer high risk for progression to advanced AMD. A diligent search for these drusen phenotypes in minority patients with AMD or with HRVDs is thus warranted. Further studies of larger cohorts of Black and Hispanic AMD subjects are needed to better assess associations of these drusen subtypes with life threatening diseases.}, }
@article {pmid40722563, year = {2025}, author = {Ehlers, JP and Yordi, S and Cetin, H and Amine, R and Matar, K and Indurkar, A and Talcott, KE and Kaiser, PK and Khanani, AM and Hu, J and Srivastava, SK}, title = {Differential Visual Outcomes in Neovascular AMD Based on Ellipsoid Zone Integrity and Fluid Presence: Insights from a Phase III Trial.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {14}, pages = {}, pmid = {40722563}, issn = {2075-4418}, support = {n/a//Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA/ ; }, abstract = {Background/Objectives: To investigate the effect of ellipsoid zone (EZ) integrity and retinal fluid on best-corrected visual acuity (BCVA) in neovascular, age-related macular degeneration. Methods: This was a post hoc treatment-agnostic analysis of the phase 3 HAWK trial. Intraretinal fluid (IRF), subretinal fluid (SRF), and ellipsoid zone (EZ) integrity were quantified over 48 weeks. EZ integrity maintenance was defined as EZ-RPE central subfield thickness (CST) >20 µm; partial EZ attenuation was EZ-RPE CST >0 and ≤20 µm; total EZ attenuation was EZ-RPE CST = 0 µm. Results: During treatment, BCVA in eyes with no fluid (66.5 to 70.2 letters) was greater than in eyes with IRF (59.5 to 62.4 letters) but comparable to BCVA in eyes with SRF (64.9 to 68.8 letters). In eyes with no fluid, BCVA was consistently greater in eyes with EZ integrity maintained (73.4 to 78.4 letters) than in eyes with EZ partial attenuation (65.3 to 66.5 letters) or with EZ total attenuation (55.8 to 59.8 letters). Conclusions: Eyes without fluid with EZ preservation achieved the highest overall BCVA, especially when compared to eyes without fluid and a lack of EZ preservation and to eyes with SRF. Achieving a "dry" status with preservation of EZ integrity is important in optimizing visual outcomes.}, }
@article {pmid40722572, year = {2025}, author = {Ardelean, AI and Ardelean, ER and Marginean, A}, title = {Can YOLO Detect Retinal Pathologies? A Step Towards Automated OCT Analysis.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {14}, pages = {}, pmid = {40722572}, issn = {2075-4418}, support = {MySMIS: 334906, and contract number: 390012/28.02.2025//"HUB Rom&#xe2;n de Inteligent&#x103; Artificial&#x103; - HRIA"/ ; }, abstract = {Background: Optical Coherence Tomography has become a common imaging technique that enables a non-invasive and detailed visualization of the retina and allows for the identification of various diseases. Through the advancement of technology, the volume and complexity of OCT data have rendered manual analysis infeasible, creating the need for automated means of detection. Methods: This study investigates the ability of state-of-the-art object detection models, including the latest YOLO versions (from v8 to v12), YOLO-World, YOLOE, and RT-DETR, to accurately detect pathological biomarkers in two retinal OCT datasets. The AROI dataset focuses on fluid detection in Age-related Macular Degeneration, while the OCT5k dataset contains a wide range of retinal pathologies. Results: The experiments performed show that YOLOv12 offers the best balance between detection accuracy and computational efficiency, while YOLOE manages to consistently outperform all other models across both datasets and most classes, particularly in detecting pathologies that cover a smaller area. Conclusions: This work provides a comprehensive benchmark of the capabilities of state-of-the-art object detection for medical applications, specifically for identifying retinal pathologies from OCT scans, offering insights and a starting point for the development of future automated solutions for analysis in a clinical setting.}, }
@article {pmid40722794, year = {2025}, author = {Siqueira, RC and Brandão, CC}, title = {The Role of Cytokines in Degenerative Retinal Diseases: A Comprehensive Review.}, journal = {Biomedicines}, volume = {13}, number = {7}, pages = {}, pmid = {40722794}, issn = {2227-9059}, abstract = {Degenerative retinal diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP), are the leading causes of vision loss worldwide. Inflammation plays a crucial role in the pathogenesis of these diseases, with cytokines acting as key mediators of neuroinflammation, vascular dysfunction, and cellular degeneration. This review explores the complex role of cytokines in degenerative retinal diseases, highlighting their involvement in disease progression, cellular interactions, and potential therapeutic strategies. Understanding the cytokine network within the retina may provide novel insights into targeted interventions for these debilitating conditions.}, }
@article {pmid40723297, year = {2025}, author = {D'Esposito, F and Cappellani, F and Visalli, F and Capobianco, M and Rapisarda, L and Avitabile, A and Cannizzaro, L and Malaguarnera, R and Gagliano, G and Maniaci, A and Lentini, M and Montalbano, G and Zaouali, MA and H'mida, D and Giurdanella, G and Gagliano, C}, title = {Pericytes as Key Players in Retinal Diseases: A Comprehensive Narrative Review.}, journal = {Biology}, volume = {14}, number = {7}, pages = {}, pmid = {40723297}, issn = {2079-7737}, abstract = {Pericytes, specialized mural cells surrounding microvessels, play a crucial role in maintaining vascular homeostasis and function across various organs, including the eye. These versatile cells regulate blood flow, support the integrity of the blood-retinal barrier, and contribute to angiogenesis. Recent advancements in molecular and cellular biology have revealed the heterogeneity of pericytes and their critical involvement in ocular physiology and pathology. This review provides a comprehensive analysis of pericyte functions in ocular health and their implications in diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, and retinal vein occlusion. Pericyte dysfunction is implicated in vascular instability, neurovascular coupling failure, inflammation, and pathological neovascularization, contributing to vision-threatening disorders. The review further explores recent findings on pericyte-targeted therapies, including pharmacological agents, gene therapy, and cell-based approaches, aiming to restore pericyte function and preserve ocular health.}, }
@article {pmid40725253, year = {2025}, author = {Dayma, K and Rajanala, K and Upadhyay, A}, title = {Stargardt's Disease: Molecular Pathogenesis and Current Therapeutic Landscape.}, journal = {International journal of molecular sciences}, volume = {26}, number = {14}, pages = {}, pmid = {40725253}, issn = {1422-0067}, mesh = {Humans ; *Stargardt Disease/therapy/genetics/pathology/metabolism ; Genetic Therapy/methods ; ATP-Binding Cassette Transporters/genetics/metabolism ; Mutation ; Animals ; Oxidative Stress ; }, abstract = {Stargardt's disease (STGD1) is an autosomal recessive juvenile macular degeneration caused by mutations in the ABCA4 gene, impairing clearance of toxic retinoid byproducts in the retinal pigment epithelium (RPE). This leads to lipofuscin accumulation, oxidative stress, photoreceptor degeneration, and central vision loss. Over 1200 pathogenic/likely pathogenic ABCA4 variants highlight the genetic heterogeneity of STGD1, which manifests as progressive central vision loss, with phenotype influenced by deep intronic variants, modifier genes, and environmental factors like light exposure. ABCA4 variants also show variable penetrance and geographical prevalence. With no approved treatment, investigational therapies target different aspects of disease pathology. Small-molecule therapies target vitamin A dimerization (e.g., ALK-001), inhibit lipofuscin accumulation (e.g., soraprazan), or modulate the visual cycle (e.g., emixustat hydrochloride). Gene therapy trials explore ABCA4 supplementation including strategies like RNA exon editing (ACDN-01) and bioengineered ambient light-activated OPSIN. RORA gene therapy (Phase 2/3) addresses oxidative stress, inflammation, lipid metabolism, and complement system dysregulation. Trials like DRAGON (Phase 3, tinlarebant), STARLIGHT (phase 2, bioengineered OPSIN) show promise, but optimizing efficacy remains challenging. With the key problem of establishing genotype-phenotype correlations, the future of STGD1 therapy may rely on approaches targeting oxidative stress, lipid metabolism, inflammation, complement regulation, and genetic repair.}, }
@article {pmid40725453, year = {2025}, author = {Yoneyama, S and Sakurada, Y and Shijo, T and Fukuda, Y and Kotoda, Y and Kikushima, W and Mabuchi, F and Kashiwagi, K}, title = {Genetic Factors Associated with Intraocular Inflammation After Brolucizumab Administration in Patients with Exudative Age-Related Macular Degeneration.}, journal = {Genes}, volume = {16}, number = {7}, pages = {}, pmid = {40725453}, issn = {2073-4425}, mesh = {Humans ; Male ; Female ; Aged ; *Antibodies, Monoclonal, Humanized/adverse effects/administration &amp; dosage/therapeutic use ; Polymorphism, Single Nucleotide ; *Macular Degeneration/drug therapy/genetics ; Cholesterol Ester Transfer Proteins/genetics ; Aged, 80 and over ; *Inflammation/genetics/chemically induced ; Complement Factor H/genetics ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/genetics ; Genotype ; Genetic Predisposition to Disease ; }, abstract = {Purpose: We aimed to investigate whether genetic variants susceptible to age-related macular degeneration (AMD) are associated with intraocular inflammation after brolucizumab administration in eyes that have exudative AMD. Methods: A total of 206 eyes from 206 patients (156 men/50 women, 74.0 ± 8.4 years; treatment-naïve, 128 [62.1%]; switching, 78 [37.9%]) were included in this study. All patients were treated with intravitreal brolucizumab at least once. The genotyping of ARMS2 A69S (rs10490924), CFH I62V (rs800292), CFH (rs1329428), SKIV2L (rs429608), C3 (rs2241394), cholesteryl ester transfer protein (CETP) (rs3764261), and ADAMTS9 (rs6795375) was performed using TaqMan technology. Results: Out of the 206 patients who were included, 21 eyes from 21 patients (10.2%) exhibited intraocular inflammation (IOI). Four (19.0%) exhibited severe IOI, including retinal vasculitis and/or retinal vascular occlusion, and 17 (81.0%) showed mild IOI. The frequency of the T allele of the CETP gene was significantly lower in patients who developed IOI compared to patients who did not develop IOI (T allele frequency: 9.5% vs. 23.5%, p = 0.036). After adjusting for confounding factors, the T allele remained significantly associated with protection against IOI (p = 0.028, 95% confidence interval: 0.098-0.88). Conclusions: The T allele of the CETP gene, a risk allele for AMD and the protective allele for atherosclerosis, may be associated with protection against IOI after brolucizumab administration in eyes that have exudative AMD.}, }
@article {pmid40725503, year = {2025}, author = {AlEissa, MM and Alhawsawi, AA and Alonazi, R and Magharbil, E and Aljahdali, A and AlBalawi, HB and Alali, NM and Hameed, S and Abu-Amero, KK and Magliyah, MS}, title = {Advances in Precision Therapeutics and Gene Therapy Applications for Retinal Diseases: Impact and Future Directions.}, journal = {Genes}, volume = {16}, number = {7}, pages = {}, pmid = {40725503}, issn = {2073-4425}, support = {N/A//Internal funding from the Research Department, King Khaled Eye Specialist Hospital, Riyadh and the Department of Surgery, Faculty of Medicine, University of Tabuk, Tabuk supported this work./ ; }, mesh = {Humans ; *Genetic Therapy/methods/trends ; *Retinal Diseases/therapy/genetics ; *Precision Medicine/methods/trends ; Macular Degeneration/therapy/genetics ; cis-trans-Isomerases/genetics ; Retinoid Isomerohydrolase ; }, abstract = {Gene therapy has emerged as a promising treatment for several eye diseases since it may restore vision and stop blindness. Many eye diseases, including retinitis pigmentosa and macular degeneration, have historically been rather difficult to treat and usually cause permanent vision loss. However, thanks to advances in gene therapy, many disorders can now be effectively targeted and genetically changed, providing a safer, more direct, maybe even curative approach. By introducing, altering, or repairing specific genes inside the eye, gene therapy seeks to fix the defective genes causing these disorders, thereby improving general eye health and visual ability. Voretigene neparvovec is one FDA- and EMA-approved treatment for RPE65 mutations. Retinitis pigmentosa, age-related macular degeneration, X-linked retinoschisis, choroideremia, and Stargardt disease are among the several eye disorders still under clinical trials, and experimental treatment is in progress. As research on gene therapy develops, it opens the path for groundbreaking treatments that could fundamentally change the ophthalmic care scene.}, }
@article {pmid40725517, year = {2025}, author = {Hara, C and Fujimoto, S and Fukushima, Y and Sayanagi, K and Nishida, K and Maruyama, K and Sato, S and Maeno, T and Nishida, K}, title = {Initial Response After Switching to Aflibercept 8 mg for Neovascular Age-Related Macular Degeneration.}, journal = {Journal of clinical medicine}, volume = {14}, number = {14}, pages = {}, pmid = {40725517}, issn = {2077-0383}, abstract = {Objectives: This study aimed to assess the initial anatomical and functional outcomes of switching to aflibercept 8 mg in patients with neovascular age-related macular degeneration (nAMD) previously treated with anti-vascular endothelial growth factor (VEGF) therapy. Methods: Patients with nAMD previously treated with anti-VEGF drugs were switched to aflibercept 8 mg. Patients with any exudative changes (subretinal fluid [SRF], intraretinal fluid [IRF] or serous pigment epithelial detachment [sPED]) at the time of the first aflibercept 8 mg injection and whose dosing interval before and after switching did not differ by more than ±7 days were included. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), and the presence of SRF, IRF, and sPED were evaluated before and after switching to aflibercept 8 mg. Results: A total of 102 eyes from 98 patients were included in the analysis. The drugs used prior to switching were faricimab in five eyes, brolucizumab in six eyes, and aflibercept 2 mg in 91 eyes, with a mean interval of 63.7 ± 20.0 days from the last pre-switch injection and 64.9 ± 20.1 days to the first post-switch visit. The CFT was significantly reduced from 272 ± 85 µm to 246 ± 79 µm (p < 0.0001). The BCVA remained unchanged at 0.27 ± 0.35 logMAR. During switching, SRF, IRF, and sPED were observed in 70, 24, and 38 eyes, respectively. At the post-switch visit, complete resolution of exudative changes was observed in 44% of eyes with SRF, 55% with IRF, and 29% with sPED. No ocular or systemic adverse effects were observed. Conclusions: As an initial response to switching to aflibercept 8 mg in a real-world setting, SRF and IRF completely resolved in approximately half of the patients, and sPED resolved in about 30% of cases.}, }
@article {pmid40725593, year = {2025}, author = {Palm, C and Zweifel, SA and Gabathuler, F and Cozzi, M and Fasler, K}, title = {Efficacy of Aflibercept 8 mg in Pretreated Age-Related Macular Degeneration.}, journal = {Journal of clinical medicine}, volume = {14}, number = {14}, pages = {}, pmid = {40725593}, issn = {2077-0383}, abstract = {This study aims to evaluate the real-world efficacy and safety of aflibercept 8 mg intravitreal injections (IVTs) in pretreated patients with neovascular age-related macular degeneration (nAMD) throughout the first three IVTs. Background: Established anti-vascular-endothelial-growth-factor (anti-VEGF) therapies positively impact the progression of nAMD but require frequent administration, thus burdening patients and the healthcare system. Pivotal trials of the recently approved aflibercept 8 mg have demonstrated extended dosing intervals with comparable safety to standard treatments. However, real-world data is still scarce. Methods: A retrospective, single-center single-arm analysis was conducted on 22 eyes from 18 pretreated nAMD patients. Eyes were switched from other anti-VEGF agents to aflibercept 8 mg injections continuing a treat-and-extend regimen (no loading dose after switching). Treatment intervals and structural (central subfield thickness (CST); disease activity) and functional (best corrected visual acuity (BCVA)) outcomes were assessed at baseline (date of first aflibercept 8 mg injection) and at follow-up examinations until follow-up 3. Safety data, including intraocular pressure changes, were recorded. Results: Over a median follow-up of 16.6 weeks (IQR 15.1-27.0), patients switched to aflibercept 8 mg showed prolonged intervals between injections (5.5 weeks vs. 7 weeks, p < 0.001, Wilcoxon signed-rank test), reduced disease activity, stable CST, and stable BCVA. One patient experienced transient intraocular pressure elevation, which resolved without intervention. No other adverse events were observed. Conclusions: Treatment with aflibercept 8 mg appears to provide effective disease control with prolonged treatment intervals in switched nAMD patients in routine clinical practice. These findings further indicate the potential for reducing treatment burden.}, }
@article {pmid40725833, year = {2025}, author = {Kamao, H and Goto, K and Mizukawa, K and Hiraki, R and Miki, A and Kimura, S}, title = {Punctate Hyperfluorescence as a Favorable Predictive Factor for Treatment Response Following a Switch to Brolucizumab for Patients with Aflibercept-Refractory Neovascular Age-Related Macular Degeneration.}, journal = {Journal of clinical medicine}, volume = {14}, number = {14}, pages = {}, pmid = {40725833}, issn = {2077-0383}, abstract = {Background/Objectives: To identify the predictive biomarkers of treatment response following a switch to brolucizumab in patients with aflibercept-refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 47 eyes of 44 patients with nAMD who were switched to brolucizumab; a two-year follow-up was completed for 37 eyes of 34 patients after the switch. The patients were classified into two groups based on the presence (fluid group) or absence (dry group) of retinal fluid at one and two years after switching, and their visual acuity, central retinal thickness, subfoveal choroidal thickness, injection interval, and dry macular rate were evaluated. Results: A dry macula was achieved for approximately 80% of patients at two years after the switch (p < 0.001), and the mean injection interval was significantly extended from 6.4 ± 1.8 weeks to 10.5 ± 2.6 weeks during the same period (p < 0.001). Both the mean central retinal thickness and subfoveal choroidal thickness showed a significant decrease at two years after the switch (p < 0.001 for both). A significantly higher proportion of patients in the Dry group exhibited punctate hyperfluorescence in the fellow eye (p < 0.001), and all patients in the dry group achieved a dry macula at two years. Conclusions: Switching to brolucizumab may be an effective treatment option for patients with aflibercept-refractory nAMD. Punctate hyperfluorescence may serve as a favorable prognostic factor following a switch to brolucizumab.}, }
@article {pmid40727801, year = {2025}, author = {Lee, KH and Park, B and Jeong, EH and Yoo, GS and Kim, YS and Jin, L and Samadi, AF and Seong, HW and Ryu, JM and Jung, J and Ahn, GH and Kim, JS and Choo, DW and Stewart, JM and Jee, DH and Jahng, WJ}, title = {Phenotypic Drug Discovery Platform by Quantitative High-Throughput Screening Identifies Antiapoptotic Molecules in a Zebrafish Model of Age-Related Macular Degeneration.}, journal = {ACS omega}, volume = {10}, number = {28}, pages = {30467-30488}, pmid = {40727801}, issn = {2470-1343}, abstract = {Age-related macular degeneration (AMD) is a progressive, late-onset, genetic (CFH, HTRA), and environmental (smoking, aging) ocular disease that is a leading cause of blindness affecting more than 200 million people worldwide. New treatments are required for fibrosis, autophagy, and microglia-driven pathologies in AMD patients for personalized medicine approaches, considering that only 10% of AMD patients are treated using the current medicine. The current study examined ninety-one compounds using a phenotypic drug discovery platform in vitro and in vivo to find potential drug candidates that include a new chemical entity (NCE) and extracts from plants such as Diospyros kaki, Achyranthes japonica, and Glycyrrhiza uralensis. The phenotypic drug discovery platform determined mitochondrial function quantitatively by measuring the oxygen consumption rate (OCR) and reactive oxygen species (ROS) of drug-treated cells under oxidative stress in addition to the neuroprotective efficacy test of each candidate. In vitro screening using ARPE-19 cells under oxidative stress identified 18 compounds with significant cytoprotective effects. Among these, JK-14, JK-18, JK-52, and JK-65 demonstrated dose-dependent restoration of cell viability and mitochondrial function, showing a recovered oxygen consumption rate, including basal respiration, ATP-linked respiration, and maximal respiration. In vivo studies used a zebrafish (Danio rerio) model of dry AMD induced by intense blue light exposure. Treatment with natural product candidates, including JK-502, JK-504, JK-505, JK-508, JK-509, JK-514, and JK-520, significantly increased the outer nuclear layer (ONL) thickness, showing a 37% increase compared to blue light-exposed controls, and improved inner retinal layer integrity, including the inner nuclear layer (INL) and inner plexiform layer (IPL). Moreover, the recovery of ganglion cell layer (GCL) nuclei counts further supported the neuroprotective efficacy of these treatments. The current data demonstrate that synthetic small-molecule and natural-product-based formulations can effectively mitigate oxidative stress-induced retinal degeneration. These promising neuroprotectants warrant further investigation as potential therapeutic agents for AMD.}, }
@article {pmid40729132, year = {2025}, author = {, }, title = {Correction: Interpretable multimodal classification for age-related macular degeneration diagnosis.}, journal = {PloS one}, volume = {20}, number = {7}, pages = {e0329294}, pmid = {40729132}, issn = {1932-6203}, abstract = {[This corrects the article DOI: 10.1371/journal.pone.0311811.].}, }
@article {pmid40729288, year = {2024}, author = {Bhat, SP and Shipchandler, A and Tokunaga, C}, title = {Social Isolation as a Precipitating Factor for Charles Bonnet Syndrome in a Patient with Mild Visual Deterioration.}, journal = {Reports (MDPI)}, volume = {7}, number = {3}, pages = {}, pmid = {40729288}, issn = {2571-841X}, abstract = {Charles Bonnet Syndrome (CBS) is characterized by complex visual hallucinations in individuals with acute vision loss, typically affecting older adults. Most CBS cases are observed in patients with sudden severe visual impairment; however, there are limited reports of CBS occurring in individuals with mild visual deterioration, particularly when confounded by sensory deprivation and social isolation. Here, we report a case of CBS in a female in her early 80s, who experienced vivid visual hallucinations during a period of prolonged social isolation following a hip surgery. Although symptomatology initially presented as delirium and psychosis, the diagnosis of CBS was confirmed after a neuropsychiatric evaluation and ophthalmologic exam, which showed mild deterioration in the patient's macular degeneration, combined with a social history of reduced independence and increased isolation. The case highlights the lesser-known role of sudden lifestyle changes and reduced cognitive engagement in CBS development in cases of mild visual impairment. It also suggests that cognitive and social stimulation may play a crucial role in CBS management, which has limited reports in the current literature.}, }
@article {pmid40729752, year = {2026}, author = {Chen, TL and Tsai, HR and Chang, WC and Lu, JW and Chen, YJ and Lee, YC and Wu, CY}, title = {RISK OF AGE-RELATED MACULAR DEGENERATION IN LATE-ONSET ATOPIC DERMATITIS: A Multidatabase Cohort Analysis.}, journal = {Retina (Philadelphia, Pa.)}, volume = {46}, number = {1}, pages = {136-145}, doi = {10.1097/IAE.0000000000004634}, pmid = {40729752}, issn = {1539-2864}, support = {MOST 111-2314-B-075- 012-MY3//Ministry of Science and Technology, Taiwan/ ; }, mesh = {Humans ; Male ; Female ; Retrospective Studies ; *Dermatitis, Atopic/complications/epidemiology/diagnosis ; Middle Aged ; Aged ; Incidence ; Risk Factors ; Taiwan/epidemiology ; Databases, Factual ; United States/epidemiology ; Aged, 80 and over ; *Macular Degeneration/epidemiology/etiology/diagnosis ; Follow-Up Studies ; Risk Assessment/methods ; Age of Onset ; }, abstract = {PURPOSE: To explore the relationship between atopic dermatitis (AD) and the risk of developing age-related macular degeneration (AMD).<br><br>METHODS: This retrospective cohort study used data from two large databases: the US-based TriNetX Research Network (46,018 patients with AD aged &#x2265;50 years, spanning 2005-2021) and Taiwan's National Health Insurance Research Database (9,513 patients with AD aged &#x2265;50 years, spanning 2003-2017). The main outcome was the incidence of AMD. The Cox regression analysis was used to calculate hazard ratios (HRs) for AMD. Additional analyses examined the risk of dry and wet AMD, with stratified assessments based on age, sex, ethnicity, race, and AD activity.<br><br>RESULTS: Adults with AD exhibited a significantly elevated risk of developing AMD in both the TriNetX cohort (HR 1.97; 95% CI: 1.78-2.19) and the National Health Insurance Research Database cohort (HR 1.25; 95% CI: 1.11-1.41). Individual outcome analyses confirmed a heightened risk for both dry and wet AMD associated with AD. This increased risk was consistent across various groups stratified by demographic factors and AD activity.<br><br>CONCLUSION: AD in adulthood is linked to a greater likelihood of developing AMD. These findings underscore the importance of regular funduscopic evaluations and proactive management of AMD in patients with AD.}, }
@article {pmid40729928, year = {2025}, author = {Vienne-Jumeau, A and Bousquet, E and Behar-Cohen, F}, title = {Complement system modulation in age-related macular degeneration: navigating failures, building future successes.}, journal = {Current opinion in immunology}, volume = {96}, number = {}, pages = {102616}, doi = {10.1016/j.coi.2025.102616}, pmid = {40729928}, issn = {1879-0372}, mesh = {Humans ; *Macular Degeneration/therapy/immunology/etiology ; *Complement System Proteins/immunology/metabolism ; Animals ; Complement Activation/drug effects ; Biomarkers ; Precision Medicine ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in elderly populations across developed countries. Complement system dysregulation has been implicated in AMD onset and evolution. Complement inhibition therapies have been authorized in the USA as the primary treatment for geographic atrophy, the dry form of AMD. They have shown moderate efficacy in slowing geographic atrophy lesion growth but have not demonstrated improvements in visual function. Challenges remain, including the optimal timing of intervention, delivery routes, safety concerns, the lack of sensitive biomarkers to assess efficacy and guide patient selection, and variability in therapeutic response. Complement modulation represents a promising yet complex therapeutic avenue in AMD. Future success will require earlier intervention, precision medicine approaches integrating genetic and imaging biomarkers, and the exploration of combination or gene-based therapies.}, }
@article {pmid40729957, year = {2025}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {Unveiling the P2X7 receptor: Exploring its mechanisms, pathogenic role in ocular diseases, and emerging therapeutic potential.}, journal = {Molecular aspects of medicine}, volume = {105}, number = {}, pages = {101389}, doi = {10.1016/j.mam.2025.101389}, pmid = {40729957}, issn = {1872-9452}, mesh = {Humans ; *Receptors, Purinergic P2X7/metabolism/genetics ; Animals ; *Eye Diseases/metabolism/drug therapy/pathology/etiology ; Purinergic P2X Receptor Antagonists/therapeutic use/pharmacology ; Signal Transduction ; Macular Degeneration/metabolism ; *Retinal Diseases/metabolism ; }, abstract = {Purinergic signaling, mediated by extracellular ATP (eATP) and P2 receptors, plays a vital role in physiological and pathological processes. The P2X7 receptor (P2X7R), a ligand-gated cation channel, is crucial in inflammation, cell death, and immune responses. Widely expressed in retinal cells, P2X7R contributes to visual function regulation and retinal degeneration. This review explores P2X7R involvement in retinal diseases, including age-related macular degeneration (AMD), Behçet's disease (BD), diabetic retinopathy (DR), glaucoma, retinitis pigmentosa (RP), uveitis, Stargardt's disease (STGD), and toxoplasmosis. P2X7R activation drives inflammation, oxidative stress, apoptosis, and immune dysregulation. For instance, it contributes to RPE degeneration in AMD, vascular proliferation in DR, neuroinflammation in glaucoma, and photoreceptor loss in RP. In uveitis, P2X7R enhances Th1 and Th17 responses. Targeting P2X7R with antagonists or modulators holds therapeutic potential, offering strategies to preserve retinal function and prevent vision loss in these debilitating diseases.}, }
@article {pmid40730279, year = {2025}, author = {Nguyen, VP and Lee, Y and Park, S and Zheng, M and Wei, Z and Zhang, J and Tran, K and Chen, YE and Yang, D and Paulus, YM}, title = {Multimodal retinal imaging evaluation of macular degeneration persistent disease activity animal model in Watanabe heritable hyperlipidemic rabbits.}, journal = {Experimental eye research}, volume = {259}, number = {}, pages = {110552}, pmid = {40730279}, issn = {1096-0007}, support = {P30 EY001765/EY/NEI NIH HHS/United States ; R01 EY033000/EY/NEI NIH HHS/United States ; R01 EY034325/EY/NEI NIH HHS/United States ; R42 EY035582/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Rabbits ; Disease Models, Animal ; Tomography, Optical Coherence/methods ; *Multimodal Imaging/methods ; Fluorescein Angiography/methods ; *Choroidal Neovascularization/diagnosis/drug therapy ; *Macular Degeneration/diagnosis/diagnostic imaging ; Angiogenesis Inhibitors/therapeutic use ; *Retina/pathology ; Bevacizumab/therapeutic use ; Photoacoustic Techniques ; *Hyperlipoproteinemia Type II/complications ; *Hyperlipidemias ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Male ; }, abstract = {The Watanabe Heritable Hyperlipidemic (WHHL) rabbit, a model for familial hypercholesterolemia, offers a unique opportunity to study lipid metabolism disorders and their ocular effects. This study employed multimodal imaging, including color fundus photography, fluorescein angiography, indocyanine green angiography, photoacoustic microscopy (PAM), and optical coherence tomography (OCT), to longitudinally assess WHHL rabbit eyes over one year. Given its relevance to persistent disease activity (PDA) in age-related macular degeneration (AMD), WHHL rabbits were evaluated as a potential model for PDA-associated AMD. Choroidal neovascularization (CNV) was induced in WHHL rabbits via subretinal injection of VEGF and Matrigel, followed by bevacizumab (Bev) treatment. A progressive lipid layer developed in the cornea by month 7. Histological analysis revealed significant outer nuclear layer cell loss in WHHL rabbits compared to wild-type (WT) controls. OCT imaging demonstrated increased CNV thickness in WHHL rabbits, consistent with PDA. Bev treatment reduced CNV leakage by 90.13 % in WT rabbits but only 16 % in WHHL rabbits, indicating treatment resistance. PAM at 780 nm effectively distinguished CNV from surrounding microvasculature, while OCT provided detailed retinal imaging. Although rabbits lack a fovea, the WHHL model demonstrates key features of wet AMD, including PDA and reduced anti-VEGF response. Our findings support WHHL rabbits as a promising preclinical model for studying lipid-related retinal diseases, AMD pathophysiology, and treatment resistance, advancing research into novel therapeutic strategies.}, }
@article {pmid40731132, year = {2025}, author = {Zhang, A and Wei, TT and Yin, H and Tan, CY and Han, C and Yao, Y and Zhu, L}, title = {Endoplasmic reticulum-mitochondria coupling prompts ZBP1-mediated RPE cell PANoptosis in age-related macular degeneration.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {1118}, pmid = {40731132}, issn = {2399-3642}, mesh = {*Endoplasmic Reticulum/metabolism ; *Mitochondria/metabolism ; *Macular Degeneration/metabolism/pathology ; Inflammation/metabolism ; Apoptosis ; Retinal Pigment Epithelium/metabolism/pathology ; *RNA-Binding Proteins/genetics/metabolism ; Humans ; Animals ; Mice ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; DNA, Mitochondrial/metabolism ; Calcium/metabolism ; Homeostasis ; Multiprotein Complexes/metabolism ; HSP70 Heat-Shock Proteins/metabolism ; Mitochondrial Proteins/metabolism ; Acetylglucosamine/metabolism ; Ubiquitination ; Disease Progression ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of central vision impairment among the elderly. Geographic atrophy is a defining characteristic of AMD, but the detailed mechanism for massive loss of retinal pigment epithelium (RPE) cells is not fully understood. In this study, we found that Z-DNA binding protein 1 (ZBP1), a sensor for dsDNA, is able to induce RPE cell PANoptosis. Silencing ZBP1 efficiently alleviates RPE degeneration and AMD symptoms. Mechanistically, mitochondrial permeability transition pore (mPTP) opening stimulated by Ca[2+] overload can trigger the releasing of mtDNA, which leads to ZBP1 activation and PANoptosis. Importantly, our findings reveal a significant role of aberrant formation of mitochondria-associated ER membranes (MAMs) in AMD. MAMs act as conduits for transferring Ca[2+] from the ER to mitochondria through the VDAC1/GRP75/IP3R1 complex. Furthermore, our results indicate that GRP75 O-GlcNAcylation is involved in MAM formation. Genetic suppression of GRP75 attenuates PANoptosis and AMD progression. In summary, our study sheds light on the intricate organelle interplay underlying AMD and presents insights into potential avenues for AMD intervention.}, }
@article {pmid40732620, year = {2025}, author = {Zedadra, A and Salah-Salah, MY and Zedadra, O and Guerrieri, A}, title = {Multi-Modal AI for Multi-Label Retinal Disease Prediction Using OCT and Fundus Images: A Hybrid Approach.}, journal = {Sensors (Basel, Switzerland)}, volume = {25}, number = {14}, pages = {}, pmid = {40732620}, issn = {1424-8220}, support = {Prot. IR0000013429 - Avviso n. 3264 del 28/12/2021.//European Union - NextGenerationEU427 - National Recovery and Resilience Plan (Piano Nazionale di Ripresa e Resilienza, PNRR) - Project:428 "SoBigData.it - Strengthening the Italian RI for Social Mining and Big Data Analytics"/ ; }, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Fundus Oculi ; Neural Networks, Computer ; *Retinal Diseases/diagnostic imaging/diagnosis ; Diabetic Retinopathy/diagnostic imaging ; Retina/diagnostic imaging ; Macular Degeneration/diagnostic imaging ; }, abstract = {Ocular diseases can significantly affect vision and overall quality of life, with diagnosis often being time-consuming and dependent on expert interpretation. While previous computer-aided diagnostic systems have focused primarily on medical imaging, this paper proposes VisionTrack, a multi-modal AI system for predicting multiple retinal diseases, including Diabetic Retinopathy (DR), Age-related Macular Degeneration (AMD), Diabetic Macular Edema (DME), drusen, Central Serous Retinopathy (CSR), and Macular Hole (MH), as well as normal cases. The proposed framework integrates a Convolutional Neural Network (CNN) for image-based feature extraction, a Graph Neural Network (GNN) to model complex relationships among clinical risk factors, and a Large Language Model (LLM) to process patient medical reports. By leveraging diverse data sources, VisionTrack improves prediction accuracy and offers a more comprehensive assessment of retinal health. Experimental results demonstrate the effectiveness of this hybrid system, highlighting its potential for early detection, risk assessment, and personalized ophthalmic care. Experiments were conducted using two publicly available datasets, RetinalOCT and RFMID, which provide diverse retinal imaging modalities: OCT images and fundus images, respectively. The proposed multi-modal AI system demonstrated strong performance in multi-label disease prediction. On the RetinalOCT dataset, the model achieved an accuracy of 0.980, F1-score of 0.979, recall of 0.978, and precision of 0.979. Similarly, on the RFMID dataset, it reached an accuracy of 0.989, F1-score of 0.881, recall of 0.866, and precision of 0.897. These results confirm the robustness, reliability, and generalization capability of the proposed approach across different imaging modalities.}, }
@article {pmid40733018, year = {2025}, author = {Abo Horan, I and Loftsson, T and Sigurdsson, HH}, title = {The Chemical Stability Characterization and Kinetics of Statins in Aqueous Cyclodextrin Ocular Preparations: A Formulation Perspective.}, journal = {Pharmaceutics}, volume = {17}, number = {7}, pages = {}, pmid = {40733018}, issn = {1999-4923}, support = {813440/ERC_/European Research Council/International ; 2410737051//Icelandic Research council/ ; }, abstract = {Background: Topical statin therapy holds promise for ocular diseases, such as age-related macular degeneration, but the effective delivery to the posterior segment is limited by poor aqueous solubility, chemical instability, and ocular barriers. Cyclodextrins (CDs) can enhance statin solubility and stability; however, the behavior of CD-statin complexes in aqueous eye drops-particularly their influence on the equilibrium between the inactive lactone (ring closed) and active hydroxyacid forms (ring open)-remains unclear. This study aimed to (i) investigate how 5% and 10% (w/v) concentrations of selected CDs affect the lactone/acid equilibrium of simvastatin and atorvastatin and (ii) define formulation parameters (statin form, CD type and concentration, and pH range) for stable eye drop development. Methods: Simvastatin or atorvastatin was added to buffered solutions (pH 2.0 to pH 9.5) of RMβCD, HPβCD, γ-CD, or SBEβCD at 0%, 5%, and 10% (w/v), incubated at 23 ± 1 °C, and sampled over time for UPLC quantification of lactone and hydroxyacid forms, and rate constants for the forward and reverse reaction were calculated. Phase solubility studies were also conducted to further characterize equilibrium behavior in aqueous CD systems. Results: The lactone form was most stable at a pH of 4.5, while the hydroxyacid form prevailed at a pH ≥ 7. γ-CD and HPβCD accelerated lactone hydrolysis for both statins, whereas RMβCD exerted a stabilizing effect. Increasing the CD concentration from 5% to 10% provided minimal additional stabilization. Conclusions: These findings highlight that the precise control of the pH, an appropriate cyclodextrin choice, and the selection of the statin form are critical to developing chemically stable eye drops.}, }
@article {pmid40735363, year = {2025}, author = {Guo, J and Jiang, Y and Xu, X and Wang, J and Yao, X and Wang, X and Yang, H and Li, MJ and Yan, H}, title = {Deciphering gene-smoking interactions in age-related macular degeneration through cross-biobank genomic integration.}, journal = {Tobacco induced diseases}, volume = {23}, number = {}, pages = {}, pmid = {40735363}, issn = {1617-9625}, abstract = {INTRODUCTION: This study aims to identify genetic loci associated with age-related macular degeneration (AMD) and assess the interaction between genetic susceptibility and smoking history.<br><br>METHODS: A meta-analysis of discovery genome-wide association studies (GWASs), involving a total of 42542 AMD patients and 920322 controls from four large-scale European cohorts, was conducted using METAL, a software tool commonly used for meta-analysis of GWAS. A polygenic risk score (PRS) was derived from the meta-analysis results for 331281 UK Biobank participants. Cox proportional hazards models evaluated interactions between genetic predisposition and smoking history at both PRS and variant levels. Logistic regression models examined plasma complement protein profiles across AMD PRS and smoking status groups.<br><br>RESULTS: We identified two novel risk loci, OCA2 melanosomal transmembrane protein (OCA2) and nitric oxide associated 1 (NOA1). Incorporating the PRS significantly enhanced AMD risk prediction in 331281 UK Biobank participants, with the area under the curve (AUC) increasing from 0.74 to 0.76 (p=2&#xd7;10[-16]). During a mean follow-up of 13.6 years, Cox models revealed significant additive (relative excess risk due to interaction, RERI=0.13; 95% CI: 0.06-0.19; attributable proportion, AP=0.08; 95% CI: 0.04-0.13; synergy index, SI=1.33; 95% CI: 1.13-1.56) and multiplicative interactions (hazard ratio, HR=1.08; 95% CI: 1.03-1.14, p=2.65&#xd7;10[-3]) between PRS and smoking history. Variant-level interactions were prominent at complement factor H (CFH) and complement factor I (CFI) loci. Individuals who have ever smoked and high PRS exhibited dysregulated plasma proteins in the alternative, classical and lectin complement pathways.<br><br>CONCLUSIONS: This study revealed the genetic architecture of AMD and highlighted the synergistic effects of smoking and genetic risk, emphasizing the potential need to integrate genetic assessments into prevention strategies.}, }
@article {pmid40735939, year = {2025}, author = {Hulleman, JD and Jeon, S and Bali, S and DiCesare, SM and Abbas, A and Daniel, S and Ortega, AJ and Collier, GE and Yang, J and Bhattacharyaa, A and McCoy, MK and Joachimiak, LA and Posner, BA}, title = {Select Azo Compounds Post-translationally Modulate HTRA1 Abundance and Activity Potentially through Interactions at the Trimer Interface.}, journal = {ACS chemical biology}, volume = {20}, number = {8}, pages = {1849-1862}, doi = {10.1021/acschembio.4c00818}, pmid = {40735939}, issn = {1554-8937}, mesh = {*High-Temperature Requirement A Serine Peptidase 1/metabolism/genetics/chemistry ; Humans ; *Azo Compounds/pharmacology/chemistry ; *Protein Processing, Post-Translational/drug effects ; Macular Degeneration/genetics ; Retinal Pigment Epithelium/metabolism ; CRISPR-Cas Systems ; }, abstract = {High-temperature requirement protein A1 (HTRA1) is a secreted serine protease with diverse substrates, including extracellular matrix proteins, proteins involved in amyloid deposition, and growth factors. Accordingly, HTRA1 has been implicated in a variety of neurodegenerative diseases including a leading cause of blindness in the elderly, age-related macular degeneration (AMD). In fact, genomewide association studies have identified that the 10q26 locus that contains HTRA1 confers the strongest genetic risk factor for AMD. A recent study has suggested that AMD-associated risk alleles located in the HTRA1 gene correlate with a significant age-related defect in HTRA1 synthesis in the retinal pigmented epithelium (RPE) within the eye, possibly accounting for AMD susceptibility. Thus, we sought to identify small molecule enhancers of HTRA1 transcription and/or protein abundance using an unbiased high-throughput screening approach. To accomplish this goal, we used CRISPR/Sp.Cas9 engineering to introduce an 11-amino-acid luminescent peptide tag (HiBiT) onto the C-terminus of HTRA1 in immortalized ARPE-19 cells. Editing was very efficient (∼88%), verified by genomic DNA analysis, short interfering RNA (siRNA), and HiBiT blotting. A total of 1920 compounds from two libraries were screened. An azo compound with reported antiamyloidogenic and cardioprotective activity, Chicago Sky Blue 6B (CSB), was identified as an enhancer of endogenous HTRA1 secretion (2.0 ± 0.3 fold) and intracellular levels (1.7 ± 0.2 fold). These results were counter-screened using HiBiT complement factor H (CFH) edited ARPE-19 cells, verified using HiBiT blotting, and were not due to HTRA1 transcriptional changes. Importantly, serine hydrolase activity-based protein profiling (SH-ABPP) demonstrated that CSB does not affect HTRA1's specific activity. However, interestingly, in follow-up studies, Congo Red, another azo compound structurally similar to CSB, also substantially increased intracellular HTRA1 levels (up to 3.6 ± 0.3 fold) but was found to significantly impair HTRA1 enzymatic reactivity (0.45 ± 0.07 fold). Computational modeling of potential azo dye interaction with HTRA1 suggests that CSB and Congo Red can bind to the noncatalytic face of the trimer interface but with different orientation tolerances and interaction energies. These studies identify select azo dyes as HTRA1 chemical probes that may serve as starting points for future HTRA1-centered small molecule therapeutics.}, }
@article {pmid40736870, year = {2025}, author = {Li, J and Hao, J and Zhu, R and Zhang, J and Wang, Y and Zhang, W and Zhang, Y and Gu, X and Yin, Q and Wu, Z and Yang, L}, title = {Prevalence and Clinical Characteristics of Dark Without Pressure Retinal Changes in a Chinese Hospital-Based Population.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {10}, pages = {2375-2393}, pmid = {40736870}, issn = {2193-8245}, support = {82371064//National Natural Science Foundation of China/ ; 82171059//National Natural Science Foundation of China/ ; BMU2020JI006//Peking University Health Science Center-Michigan Medicine Joint Institute for Translational and Clinical Research Discovery Awards/ ; }, abstract = {INTRODUCTION: This study investigates the clinical characteristics and prevalence of dark without pressure (DWP) retinal changes in a hospital-based Chinese population and evaluates its association with common fundus diseases.<br><br>METHODS: This cross-sectional study analyzed data from 6787 eligible patients recruited from the Ophthalmology Department of Peking University First Hospital between April and July 2023. All participants underwent ultra-wide-field color fundus photography (UWF CFP) for the detection of DWP. Patients were screened by excluding those without UWF CFP images, with blurred images, or who had undergone intraocular surgery, while consolidating duplicate visits. Participants were categorized into diseased (n&#x2009;=&#x2009;3741) and control (n&#x2009;=&#x2009;3046) groups. Prevalence rates were compared between the control group and various disease subgroups (including age-related macular degeneration [AMD], diabetic retinopathy, high myopia, uveitis, retinal hole [RH], retinal detachment [RD], and retinal vein occlusion), as well as across demographic strata, using chi-square tests.<br><br>RESULTS: The overall prevalence of DWP was 21.84% (1481/6787), with a prevalence of 18.55% (565/3046) in the control group. Patients with RH showed the highest prevalence (35.33%, 59/167), whereas those with AMD exhibited the lowest (19.50%, 86/441). There were significant differences in prevalence between the control group and most disease subgroups (all P&#x2009;<&#x2009;0.05), except for AMD (P&#x2009;=&#x2009;0.632). Additionally, DWP prevalence was inversely associated with age (P&#x2009;<&#x2009;0.05) but did not differ by gender (P&#x2009;>&#x2009;0.05). Longitudinal observation revealed diverse DWP patterns, including complete progression, gradual reduction, and bidirectional progression-regression.<br><br>CONCLUSIONS: DWP is highly prevalent in Chinese populations, particularly among younger individuals and patients with retinal disorders. These findings underscore the need for individualized retinal monitoring to prevent unnecessary interventions. Moreover, the dynamic progression of DWP may represent a potential biomarker for retinal disease activity, meriting further mechanistic studies.}, }
@article {pmid40737361, year = {2026}, author = {Davis, CN and Carnes, K and Richardson, G and Brandon, W}, title = {Prevalence of Vision-Threatening Ocular Disease Among North Carolina Veterans.}, journal = {Military medicine}, volume = {191}, number = {1-2}, pages = {e380-e387}, doi = {10.1093/milmed/usaf381}, pmid = {40737361}, issn = {1930-613X}, mesh = {Humans ; North Carolina/epidemiology ; Male ; Female ; Prevalence ; *Veterans/statistics &amp; numerical data ; Retrospective Studies ; Aged ; Middle Aged ; *Eye Diseases/epidemiology ; Aged, 80 and over ; United States Department of Veterans Affairs/organization &amp; administration/statistics &amp; numerical data ; Adult ; United States ; Vision Disorders/epidemiology ; }, abstract = {INTRODUCTION: Prevalence studies on ocular diseases among veterans are limited and underreported. In this retrospective study, we examined the prevalence of vision-threatening ocular diseases among North Carolina veterans. We assessed the prevalence of 6 serious ocular conditions among veterans receiving primary care at the Salisbury Veterans Affairs Health Care System (SVAHCS) in North Carolina to better understand ocular disease prevalence among veterans. Glaucoma, the most common ocular disease in this population, underscores the need for targeted interventions to mitigate vision loss.<br><br>MATERIALS AND METHODS: A retrospective review of medical records from 34,530 veterans enrolled in SVAHCS primary care was conducted. Data collected included demographics such as age, gender, and race. The study focused on 6 vision-threatening diseases: glaucoma, vision-threatening diabetic retinopathy (VTDR), exudative age-related macular degeneration (AMD), retinal vein occlusions (RVO), retinal artery occlusions (RAO), and non-arteritic anterior ischemic optic neuropathy (NAION). Structured Query Language extracted disease frequency, and statistical analysis revealed prevalence rates and socio-demographic patterns.<br><br>RESULTS: The average age of veterans was 69.5 years, with 94% male and 66% White. The most prevalent ocular condition was glaucoma (9%), followed by VTDR (1.3%), exudative AMD (0.9%), RVO (0.8%), RAO (0.4%), and NAION (0.4%). Older male veterans had a disproportionate burden of most ocular conditions. Racial disparities in disease prevalence highlight areas for focused healthcare strategies.<br><br>CONCLUSIONS: This study reveals the significant burden of vision-threatening ocular diseases among North Carolina veterans, with glaucoma being the most prevalent. The findings emphasize the need for targeted screening and personalized interventions to prevent vision loss and address disparities. Further research should explore systemic and behavioral contributors to these trends, guiding evidence-based strategies to improve veterans' ocular health outcomes.}, }
@article {pmid40737650, year = {2025}, author = {Xu, ZJ and Liu, WW and Xu, F}, title = {THE EFFICACY OF RANIBIZUMAB COMBINED WITH SUBSCLERAL TRABECULAR SURGERY IN THE TREATMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.}, journal = {Georgian medical news}, volume = {}, number = {362}, pages = {68-72}, pmid = {40737650}, issn = {1512-0112}, mesh = {Humans ; *Ranibizumab/therapeutic use/administration &amp; dosage ; Male ; Female ; Aged ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Prospective Studies ; Middle Aged ; *Macular Degeneration/surgery/drug therapy ; Visual Acuity/drug effects ; Intraocular Pressure/drug effects ; Treatment Outcome ; Combined Modality Therapy ; *Trabeculectomy/methods ; Sclera/surgery ; }, abstract = {OBJECTIVE: To investigate the clinical effect of subscleral trabecular surgery combined with intravitreal injection of ranibizumab in the treatment of neovascular age-related macular degeneration (NVG).<br><br>METHODS: 132 patients (132 eyes) with NVG admitted to Jiaozhou Center Hospital of Qingdao from November 2018 to June 2021 were selected. All patients were diagnosed by laboratory examination. The patients were divided into operation group and combined group by clinical randomized prospective study, with 66 cases (66 eyes) in each group. The NVG patients in the operation group were treated with subscleral trabecular surgery, and the combined group was treated with intravitreal injection of ranibizumab on the basis of the operation group.<br><br>RESULTS: The BCAV and intraocular pressure of the two groups were evidently reduced, and the above laboratory indexes of the patients in the combined group were markedly reduced (P<0.05). The overall clinical efficacy of the two groups was better than that of the operation group (P<0.05). The surgical complication rate of the combined group was 9.09% compared with 16.67% of the surgical group (P>0.05).<br><br>CONCLUSION: The clinical effect of subscleral trabecular surgery combined with intravitreal injection of ranibizumab in the treatment of NVG patients is positive, which can more effectively correct the visual acuity and intraocular pressure of patients.}, }
@article {pmid40738331, year = {2025}, author = {Acharya, B and Momenaei, B and Zhang, Q and Hyman, L and Haller, JA and , }, title = {Disparities in Presentation and Anti-VEGF Therapy Initiation for Neovascular Age-Related Macular Degeneration: An Analysis of the Academy IRIS® Registry (Intelligent Research in Sight).}, journal = {Ophthalmology}, volume = {132}, number = {12}, pages = {1411-1421}, doi = {10.1016/j.ophtha.2025.07.024}, pmid = {40738331}, issn = {1549-4713}, mesh = {Humans ; Male ; Female ; Retrospective Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Registries ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged ; *Visual Acuity/physiology ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology/ethnology ; Middle Aged ; Aged, 80 and over ; *Healthcare Disparities/statistics &amp; numerical data ; *Ranibizumab/administration &amp; dosage/therapeutic use ; United States/epidemiology ; *Bevacizumab/administration &amp; dosage/therapeutic use ; Academies and Institutes ; Receptors, Vascular Endothelial Growth Factor ; }, abstract = {PURPOSE: To investigate disparities in presentation and initiation of anti-VEGF therapy among patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Patients with nAMD newly diagnosed between October 2016 and October 2021 from the American Academy of Ophthalmology IRIS&#xae; Registry (Intelligent Research in Sight).<br><br>METHODS: Associations between demographic characteristics, presenting visual acuity (VA), and the initiation of anti-VEGF treatment were assessed using multivariable Poisson regression models.<br><br>MAIN OUTCOME MEASURES: Treatment initiation with &#x2265; 1 anti-VEGF injections within 12 months after first presentation with nAMD.<br><br>RESULTS: Among the 918 759 patients with nAMD (61.5% female, 82.3% White), male, Black, and Hispanic patients demonstrated nAMD at younger ages (P < 0.001). Of these, 719 204 patients (78.3%) initiated anti-VEGF treatment within 1 year, with 71.1% of patients (653 340/918 759) receiving the first injection within 1 month. In multivariable regression analysis, Black patients (rate ratio [RR], 0.91; 95% confidence interval [CI], 0.89-0.93; P < 0.001) and Asian patients (RR, 0.95; CI, 0.93-0.97; P < 0.001) were less likely to initiate treatment compared with White patients. Hispanic patients were 4% less likely to initiate treatment than non-Hispanic patients (RR, 0.96; 95% CI, 0.95-0.98; P < 0.001). Patients older than 60 years (vs. those 50-59 years of age) were more likely to initiate treatment (P < 0.001 for all age group comparisons), as were patients from the West (vs. South) region (P < 0.001). Among 701 309 patients with VA data, patients with VA of worse than 20/40 to 20/200 were more likely to initiate treatment (RR, 1.14; 95% CI, 1.12-1.15) than those with 20/20 or better VA, whereas those with hand movements VA (RR, 0.72; 95% CI, 0.69-0.75) and light perception or worse VA (RR, 0.49; 95% CI, 0.44-0.54; all P < 0.001) were less likely to initiate treatment.<br><br>CONCLUSIONS: Over 20% of patients with nAMD did not initiate treatment within 1 year of presentation. Results suggest that lower treatment initiation rates are associated with Black and Asian race, Hispanic ethnicity, age younger than 60 years, and low-vision status. Efforts to improve treatment uptake might prioritize groups with lower initiation rates.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40738389, year = {2025}, author = {Wang, K and Xie, Y and Lin, Y and Zhu, R and Gao, T and Han, Z and Yang, Z and Jiang, X and Chen, H and Wu, Z and Cai, Y and Zeng, J}, title = {Unveiling the link: aging and its impact on ocular diseases.}, journal = {Experimental eye research}, volume = {259}, number = {}, pages = {110551}, doi = {10.1016/j.exer.2025.110551}, pmid = {40738389}, issn = {1096-0007}, mesh = {Humans ; *Aging/physiology ; *Eye Diseases/physiopathology/metabolism ; }, abstract = {Aging is a process of structural and functional decline that occurs in the body with increasing age. As aging progresses, it weakens the cellular system, leading to dysfunction and metabolic imbalance (mitochondrial metabolism, glucose metabolism, lipid metabolism, and blood and fluid flow changes), which can result in disease. Due to its unique immune and barrier systems, extensive cellular senescence can lead to various eye diseases such as cataracts, glaucoma, age-related macular degeneration (AMD), presbyopia, dry eye disease (DED), corneal disease, vitreous opacity, and diabetic retinopathy (DR). This review discusses the relationship between ocular diseases and aging by analyzing the biological mechanisms of aging and anatomical changes in eye structure and function. Furthermore, we highlight therapeutic advancements for age-related eye diseases, emphasizing pharmacological interventions and innovative delivery systems. Oral antioxidants and anti-VEGF therapies combat oxidative damage and abnormal blood vessel growth, respectively. Lutein provides retinal protection, while lifestyle modifications, including smoking cessation and balanced nutrition, are crucial for mitigating aging effects. Nanoparticle-based therapies offer targeted drug delivery and controlled release, showing promise in treating conditions like AMD. Gene therapy advancements focus on improving mitochondrial function and addressing lipid metabolism disorders. Early screening and timely intervention are essential for effective management. Future research should optimize these therapies for long-term efficacy and safety.}, }
@article {pmid40740189, year = {2025}, author = {Niu, J and Jin, L and Hu, Y and Wang, Y and Hao, X and Geng, W and Ma, R}, title = {Identification and validation of integrated stress-response-related genes as biomarkers for age-related macular degeneration.}, journal = {Frontiers in molecular biosciences}, volume = {12}, number = {}, pages = {1583237}, pmid = {40740189}, issn = {2296-889X}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a prevalent ocular condition associated with aging, serving as a significant contributor to vision loss among middle-aged and older individuals. Studies have shown that AMD and integrated stress response (ISR) are associated with oxidative stress, but no specific molecular mechanisms have been identified. Therefore, this study aimed to identify potential biomarkers for AMD through bioinformatics analysis based on the transcriptome database and integrated stress response related genes (ISR-RGs).<br><br>METHODS: Transcriptomic data GSE76237, GSE247168, and ISR-RGs were sourced from public databases and related literature. The biomarkers associated with AMD were identified by differentially expressed gene (DEG) analysis, intersection of common DEGs, and ISR-RGs machine algorithm. After that, nomograms, GSEA, and immune infiltration analysis were performed for the biomarkers. The effects of transcription factors (TFs) and miRNAs on biomarkers were then explored by constructing a TF-biomarker-miRNA regulatory network. In addition, potential effective drugs of the biomarkers were explored by constructing a biomarker-effective drug interaction network. Finally, we verified the gene expression of the biomarkers by RT-qPCR.<br><br>RESULTS: We obtained 2,567 and 1,454 DEGs in GSE76237 and GSE247168, respectively. The up- and downregulated genes shared in both datasets were intersected with ISR-RGs taken to obtain eight candidate genes. SLFN11 and GRIN1 were identified as common biomarkers for AMD. An analysis of the nomogram model of biomarkers revealed good diagnostic predictive abilities (AUC > 0.7). SLFN11 and GRIN1 were mainly enriched in pathways such as proteasome, lysosome, and neuroactive ligand receptor interaction. In addition, the disease group's monocyte expression was significantly higher than that of the control group in GSE76237 (p < 0.01). We obtained thirteen relevant miRNAs and 27 TFs by prediction, with three shared TFs, and seventeen potentially effective drugs were predicted. RT-qPCR validation showed in AMD patients, and SLFN11 and GRIN1 expression was significantly higher than controls (p < 0.05). Only SLFN11 expression was consistent with the bioinformatics analysis.<br><br>CONCLUSION: SLFN11 and GRIN1 were identified as AMD biomarkers, exhibiting robust diagnostic performance and providing new insights into the condition.}, }
@article {pmid40742431, year = {2025}, author = {Eckardt, F and Hafner, M and Lorger, A and Liesenhoff, C and Schiefelbein, J and Herold, TR and Luft, N and Klaas, JE and Schworm, B and Priglinger, SG and Siedlecki, J}, title = {Efficacy of switching treatment to faricimab in recalcitrant neovascular age related macular degeneration - 6 month results after completion of the loading phase.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {263}, number = {11}, pages = {3053-3063}, pmid = {40742431}, issn = {1435-702X}, mesh = {Humans ; *Visual Acuity ; Male ; Female ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence/methods ; Aged ; Treatment Outcome ; Fluorescein Angiography/methods ; *Drug Substitution ; Follow-Up Studies ; Time Factors ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Choroid/pathology ; Retrospective Studies ; Recombinant Fusion Proteins/administration &amp; dosage ; Prospective Studies ; Dose-Response Relationship, Drug ; *Macula Lutea/pathology ; Middle Aged ; Receptors, Vascular Endothelial Growth Factor/antagonists &amp; inhibitors ; Ranibizumab/administration &amp; dosage ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To report the efficacy and durability of switching treatment to faricimab in recalcitrant neovascular age-related macular degeneration (nAMD) at six months after completion of the loading phase (nine months after switching).<br><br>METHODS: Recalcitrant nAMD was defined as persistent fluid despite monthly injections (q4w) or inability to extend treatment intervals beyond six weeks (q6w). The study included patients on a treat &amp; extend regimen for six months after three monthly injections. Primary outcomes were changes in central subfield thickness (CST), subfoveal choroidal thickness (SFCT), visual acuity, and injection interval.<br><br>RESULTS: Nine month-data was available for 56 eyes initially switched to faricimab. At nine months, 51 eyes (91.1%) of 49 patients were maintained on faricimab, while five eyes (8.9%) had been switched back to their older agent. At nine months after switching, median CST was significantly reduced as compared to baseline at switching (332,00 (Q1:295,00; Q3:394,00) to 303,00 (Q1:269,00; Q3:366,00) &#xb5;m; p&#x2009;<&#x2009;0.001). Median SFCT also decreased from 158,00 (Q1:116,00; Q3:219,00) &#xb5;m to 127,00 (Q1:95,00; Q3:196,00) &#xb5;m (p&#x2009;<&#x2009;0.001). The average injection interval was significantly extended from 37.0&#x2009;&#xb1;&#x2009;9.5 days prior to switching to 56.1&#x2009;&#xb1;&#x2009;30.4 days at nine months (p&#x2009;=&#x2009;0.002). Visual acuity was maintained (0.30 (Q1:0.10 Q3:0.50) vs. 0.30 (Q1:0.10 Q3:0.50) logMAR; p&#x2009;=&#x2009;0.07).<br><br>CONCLUSION: In recalcitrant nAMD, faricimab can improve CST and SFCT while maintaining visual acuity. Furthermore, greater durability could be achieved with faricimab at nine months as compared to ranibizumab or aflibercept. Further prospective randomized trials are warranted.}, }
@article {pmid40742530, year = {2025}, author = {Barth, T and Arnds, J and Mohr, S and Schreiner, L and Helbig, H}, title = {[Smoking and eye diseases].}, journal = {Die Ophthalmologie}, volume = {122}, number = {9}, pages = {753-762}, pmid = {40742530}, issn = {2731-7218}, mesh = {Humans ; *Eye Diseases/etiology/epidemiology/prevention &amp; control ; *Smoking/adverse effects/epidemiology ; Risk Factors ; }, abstract = {Smoking represents a substantial risk factor for various eye diseases due to a variety of harmful mechanisms. Nicotine and other harmful substances in tobacco impair the microcirculation, promote oxidative stress and inflammatory processes. Studies have shown that nicotine abuse increases the risk of cataract development and has an unfavorable effect on the course of glaucoma. Other entities associated with smoking are age-related macular degeneration and ocular vascular occlusions. In addition, nicotine abuse exacerbates ocular surface disorders and has a substantial negative influence on the course of an endocrine orbitopathy. In summary, smoking is an important modifiable risk factor for numerous eye diseases and early prevention and smoking cessation can contribute to reducing these risks.}, }
@article {pmid40744710, year = {2025}, author = {Takeuchi, K and Ueda, T and Imai, M and Fujisaki, M and Tsujimura, M and Tokunaga, Y and Kofuku, Y and Shimada, I}, title = {Two-step target recognition for the competitive inhibition activity of an anti-VEGF aptamer.}, journal = {RNA (New York, N.Y.)}, volume = {31}, number = {10}, pages = {1368-1378}, pmid = {40744710}, issn = {1469-9001}, mesh = {*Aptamers, Nucleotide/chemistry/pharmacology/metabolism/genetics ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/chemistry/metabolism/genetics ; Humans ; Heparin/metabolism/chemistry ; Protein Binding ; Binding, Competitive ; Calcium/metabolism/chemistry ; Binding Sites ; Nucleic Acid Conformation ; *Angiogenesis Inhibitors/pharmacology/chemistry ; }, abstract = {The anti-vascular endothelial growth factor (VEGF) aptamer, t44.27, is a 27-mer RNA that functions as the active component of pegaptanib, an antiangiogenic medicine for neovascular age-related macular degeneration. The t44.27 aptamer is extensively 2'-modified and tightly binds to the heparin-binding domain (HDB) of VEGF165 in a Ca[2+]-dependent manner. However, the molecular mechanism by which the aptamer selectively recognizes VEGF HDB to antagonize its function is poorly understood. We found that t44.27 binds to VEGF HBD in a two-step manner using a different region in the molecule: a transient interaction using a structured region of t44.27 followed by a tight complex formation with a larger interaction surface. Ca[2+] binding stabilizes t44.27 base-pair formation suitable for the initial transient interaction. Meanwhile, the tight complex formation was essential for t44.27 to exert a competitive inhibition of heparin binding to VEGF HBD. These results provide structural insight into how the RNA aptamer specifically interacts with its target molecule to inhibit its activity.}, }
@article {pmid40745254, year = {2025}, author = {Cakan-Akdogan, G and Erez, O and Ozer, C and Onal, E and Mert, O and Gullu, S and Arslan, M and Avci, ME and Inan, M and Kalyoncu, S}, title = {Novel anti-VEGF scFv antibodies with superior in vitro and in vivo activities.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {28009}, pmid = {40745254}, issn = {2045-2322}, support = {IBG002//VSY Biotechnology/ ; IBG002//VSY Biotechnology/ ; IBG002//VSY Biotechnology/ ; IBG002//VSY Biotechnology/ ; IBG002//VSY Biotechnology/ ; IBG002//VSY Biotechnology/ ; RareBoost Project #952346//European Commission/ ; 119Z161//T&#xfc;rkiye Bilimsel ve Teknolojik Ara&#x15f;t&#x131;rma Kurumu/ ; 119Z161//T&#xfc;rkiye Bilimsel ve Teknolojik Ara&#x15f;t&#x131;rma Kurumu/ ; 119Z161//T&#xfc;rkiye Bilimsel ve Teknolojik Ara&#x15f;t&#x131;rma Kurumu/ ; }, mesh = {*Single-Chain Antibodies/pharmacology/genetics/immunology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/immunology ; Animals ; Humans ; Zebrafish ; Human Umbilical Vein Endothelial Cells/drug effects ; Ranibizumab/pharmacology ; *Angiogenesis Inhibitors/pharmacology ; Bevacizumab/pharmacology ; Cell Proliferation/drug effects ; Pichia/genetics/metabolism ; Macular Degeneration/drug therapy ; }, abstract = {Vascular Endothelial Growth Factor (VEGF) plays important roles in the pathogenesis of age-related macular degeneration (AMD), the most common cause of vision loss in the elderly. Intravitreal anti-VEGF injection is the gold standard for AMD treatment. Here three novel anti-VEGF single chain variable fragments (scFvs) produced in Pichia pastoris system are reported. First, an scFv was designed based on the variable chain sequence of ranibizumab, then rational mutations were introduced to find the best variant(s). Mutagenesis of two residues that normally reside at the Fab VL- CL resulted in three mutant scFv variants (scFv1, 2, 3) with high affinity to VEGF and good thermal stability. scFv1 and scFv2 outperformed ranibizumab at the HUVEC proliferation inhibition test. The activities of the variants were compared to bevacizumab, ranibizumab and brolucizumab with VEGF bioassay. scFv1 and scFv2 together with brolucizumab performed best, which was seconded by scFv3 and ranibizumab, while all variants performed better than bevacizumab. scFv1 was selected as the lead molecule based on its improved in vivo activity in zebrafish angiogenesis and leaky retinal vasculature models. scFv1 inhibits in vitro angiogenesis and binds selectively to all VEGFA isoforms. The engineered anti-VEGF scFv1, is a promising therapeutic candidate for AMD treatment.}, }
@article {pmid40745591, year = {2025}, author = {Quiroz-Reyes, MA and Quiroz-Gonzalez, EA and Quiroz-Gonzalez, MA and Lima-Gomez, V}, title = {Comparative efficacy of photodynamic therapy (PDT), ranibizumab, aflibercept monotherapy, and combination therapies for polypoidal choroidal vasculopathy: a network meta-analysis of randomized controlled trials.}, journal = {BMC ophthalmology}, volume = {25}, number = {1}, pages = {440}, pmid = {40745591}, issn = {1471-2415}, mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Choroid/blood supply ; *Choroid Diseases/drug therapy ; *Choroidal Neovascularization/drug therapy ; Drug Therapy, Combination ; Intravitreal Injections ; *Photochemotherapy/methods ; Photosensitizing Agents/therapeutic use ; Polypoidal Choroidal Vasculopathy ; *Polyps/drug therapy/diagnosis ; Randomized Controlled Trials as Topic ; *Ranibizumab/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; *Recombinant Fusion Proteins/therapeutic use ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; }, abstract = {PURPOSE: Polypoidal choroidal vasculopathy (PCV) is recognized as a distinct clinical condition characterized by persistent serous leakage, bleeding, and the presence of polypoidal lesions beneath the retinal pigment epithelium (RPE). This systematic review and meta-analysis aimed to evaluate the effectiveness of combination treatments that include antivascular endothelial growth factor (anti-VEGF) agents, such as ranibizumab and aflibercept, along with photodynamic therapy (PDT), in comparison to monotherapy options for managing PCV.<br><br>METHODS: A comprehensive literature search was performed in PubMed, Web of Science, and the Cochrane Library, following the PRISMA guidelines. Eligible studies consisted of treatment-na&#xef;ve patients with PCV receiving anti-VEGF monotherapy, PDT monotherapy, or combination therapies. The key outcomes analyzed included changes in best-corrected visual acuity (BCVA), reduction in central subfield thickness (CSFT), rate of polyp regression, incidence of adverse events, and treatment burden. Statistical analyses were conducted via a random-effects model, and heterogeneity was assessed via the I&#xb2; statistic.<br><br>RESULTS: Fourteen randomized controlled trials (RCTs) involving 1,426 eyes were included. Compared with monotherapies, combination therapies, especially anti-VEGF in conjunction with PDT, showed superior efficacy in improving the BCVA (mean difference [MD]&#x2009;=&#x2009;0.07, 95% CI: 0.06-0.08) and reducing the CSFT (MD = -42.09&#xa0;&#x3bc;m, 95% CI: -59.93 -24.24). The regression rates of polyps were highest in the combination groups, with up to 77.8% achieving complete regression, and fewer anti-VEGF injections were required than monotherapies. Adverse event rates, such as subretinal hemorrhage, remained low across all treatment groups.<br><br>CONCLUSION: Compared with monotherapy, combination therapies using anti-VEGF agents and PDT provide significant visual and anatomical advantages in managing PCV. These treatments are associated with improved efficacy and a reduced treatment burden while maintaining favorable safety profiles. However, further standardization of protocols and evaluation of long-term cost-effectiveness are crucial for improving clinical practice applications.<br><br>TRIAL REGISTRATION: Retrospectively registered.}, }
@article {pmid40745881, year = {2025}, author = {Ndife, TI and Momoh, AJ and Eze, UA and Nwaogwugwu, JO}, title = {Functional Low Vision and Patient Barriers to the Uptake of a Multidisciplinary Low Vision Rehabilitation Service: A Case Study.}, journal = {The Nigerian postgraduate medical journal}, volume = {32}, number = {3}, pages = {233-239}, doi = {10.4103/npmj.npmj_89_25}, pmid = {40745881}, issn = {1117-1936}, mesh = {Humans ; *Vision, Low/rehabilitation/epidemiology/etiology ; Male ; Female ; Cross-Sectional Studies ; Adult ; Middle Aged ; Retrospective Studies ; Aged ; *Health Services Accessibility ; Prevalence ; Visual Acuity ; Young Adult ; *Patient Acceptance of Health Care/statistics &amp; numerical data ; Glaucoma/complications ; }, abstract = {AIMS: To estimate the prevalence, describe causes and prescription needs of functional low vision (FLV) patients, and highlight the barriers these patients encounter to the uptake of multidisciplinary low vision rehabilitation (LVR) service.<br><br>MATERIALS AND METHODS: A mixed study design was adopted. Quantitative analysis consisted of a retrospective and cross-sectional review of 241 (FLV) patients managed at the National Eye Centre, Kaduna. Relevant data extracted from patient records were age, sex, occupation, best-corrected visual acuity, cause of low vision and low vision aids or rehabilitation prescribed. Qualitatively, 45 FLV patients were selected by systematic random sampling. Patient barriers to the uptake of LVR services were elicited through one-on-one interviews.<br><br>RESULTS: The prevalence of FLV was 1.02% (95% confidence interval: 0.98-1.06). The mean age was 44.45 &#xb1; 20 years. One hundred and forty two (59%) were above 40 years old and 60.5% were unemployed. Major causes of FLV were glaucoma (31%), age-related macular degeneration (24%) and retinitis pigmentosa (12%). Prescription needs were magnifiers (29%), non-optical (23%) low vision aids, telescopes (17%), multiple aids (15%) and visual rehabilitation (28%). The uptake of LVRs was 67%. The most common barriers to LVR uptake were the cost of the device (97%), lack of family support (90%) and hesitancy using the device (84%).<br><br>CONCLUSION: FLV was caused by progressively worsening diseases like glaucoma. The major patient barrier to assessing a multidisciplinary LVR service was financial constraint.}, }
@article {pmid40746855, year = {2025}, author = {Duan, MM and Tu, X}, title = {Deep learning-based classification of multiple fundus diseases using ultra-widefield images.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1630667}, pmid = {40746855}, issn = {2296-634X}, abstract = {PURPOSE: This study aimed to develop a hybrid deep learning model for classifying multiple fundus diseases using ultra-widefield (UWF) images, thereby improving diagnostic efficiency and accuracy while providing an auxiliary tool for clinical decision-making.<br><br>METHODS: In this retrospective study, 10,612 UWF fundus images were collected from the JiuJiang No. 1 People's Hospital and the Seventh Affiliated Hospital, Sun Yat-sen University between 2020 and 2025, covering 16 fundus diseases, including normal fundus, nine common eye diseases, and six rare retinal conditions. The model employed DenseNet121 as a feature extractor combined with an XGBoost classifier. Gradient-weighted Class Activation Mapping (Grad-CAM) was used to visualize the model's decision-making process. Performance was evaluated on validation and external test sets using accuracy, recall, precision, F1 score, and AUC-ROC. The model's diagnostic accuracy was also compared with that of junior and intermediate ophthalmologists.<br><br>RESULTS: The model demonstrated exceptional diagnostic performance. For common diseases such as retinal vein occlusion, age-related macular degeneration, and diabetic retinopathy, AUC values exceeded 0.975, with accuracy rates above 0.980. For rare diseases, AUC values were above 0.970, and accuracy rates surpassed 0.998. Grad-CAM visualizations confirmed that the model's focus areas aligned with clinical pathological features. Compared to ophthalmologists, the model achieved significantly higher accuracy across all diagnostic tasks.<br><br>CONCLUSION: The proposed deep learning model can automatically identify and classify multiple ophthalmic diseases using UWF images. It holds promise for enhancing clinical diagnostic efficiency, assisting ophthalmologists in optimizing workflows, and improving patient care quality.}, }
@article {pmid40749832, year = {2025}, author = {Widjaja-Adhi, MAK and Swigris, J and Plau, J and Chung, C and Walczak-Szeffer, A and Jastrzebska, B and Blaner, WS and Golczak, M}, title = {Inactivation of cellular retinol-binding protein 1 protects against bis-retinoid accumulation and light-induced retinal degeneration in mice.}, journal = {The Journal of biological chemistry}, volume = {301}, number = {9}, pages = {110538}, pmid = {40749832}, issn = {1083-351X}, support = {P30 EY011373/EY/NEI NIH HHS/United States ; R01 DK122071/DK/NIDDK NIH HHS/United States ; R01 EY023948/EY/NEI NIH HHS/United States ; R01 EY032874/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Mice ; Mice, Knockout ; *Retinal Degeneration/metabolism/genetics/pathology/etiology ; *Light/adverse effects ; *Retinoids/metabolism ; *Retinol-Binding Proteins, Cellular/genetics/metabolism/antagonists &amp; inhibitors ; *Macular Degeneration/metabolism/genetics/pathology ; ATP-Binding Cassette Transporters/genetics/metabolism ; *Retinaldehyde/metabolism ; Humans ; Stargardt Disease ; Alcohol Oxidoreductases/genetics/metabolism ; Disease Models, Animal ; }, abstract = {Delayed clearance of all-trans-retinal (at-RAL) in photoreceptors is linked to prevalent retinal diseases such as Stargardt disease, rod-cone dystrophies, and age-related macular degeneration. Pharmacological modulation of retinoid metabolism in the eye presents a promising therapeutic strategy, with cellular retinol-binding protein 1 (RBP1) emerging as a potential target. However, it lacks genetic validation as a therapeutic target in an animal model of human disease. Thus, we investigated the effect of the Rbp1 gene inactivation on the phenotype of the Abca4[-/-]/Rdh8[-/-] model of Stargardt disease. Triple knockout (Abca4[-/-]/Rdh8[-/-]/Rbp1[-/-]) mice were protected against light-induced retinal degeneration. RBP1 deficiency also slowed bis-retinoid accumulation in aged animals. Furthermore, pharmacological inhibition of RBP1 alleviated the retinal degeneration phenotype. These findings provide both genetic and pharmacological evidence supporting RBP1 as a promising therapeutic target for retinal degenerative diseases associated with impaired all-trans-retinal clearance.}, }
@article {pmid40749905, year = {2025}, author = {Cheruvu, SS and Merugu, S and Malani, M and Kulkarni, O and Nirmal, J}, title = {Hyaluronic acid based light responsive long acting hydrogel for the intraocular delivery of spironolactone.}, journal = {International journal of biological macromolecules}, volume = {321}, number = {Pt 4}, pages = {146451}, doi = {10.1016/j.ijbiomac.2025.146451}, pmid = {40749905}, issn = {1879-0003}, mesh = {*Hyaluronic Acid/chemistry ; *Spironolactone/chemistry/administration &amp; dosage/pharmacology/pharmacokinetics ; Animals ; *Hydrogels/chemistry ; *Light ; Drug Liberation ; *Drug Delivery Systems ; Humans ; Delayed-Action Preparations/chemistry ; Drug Carriers/chemistry ; }, abstract = {Chorio-retinal diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR), are responsible for irreversible vision loss worldwide. Non-VEGF pathways, such as the renin-angiotensin-aldosterone system (RAAS), show promise as therapeutic targets for retinal diseases to address the increasing non-responder population to anti-VEGF therapy for DR. Elevated renin levels in DR are linked to retinal angiogenesis and inflammation. Spironolactone (SPL) has demonstrated the potential to reduce angiogenesis. A sustained delivery approach could be beneficial for chronic ocular disorders by delivering the therapeutic dose over a longer duration, thus reducing the frequency of intravitreal administration. Hence, a light responsive methacrylated hyaluronic acid (MEHA) polymer was synthesised and used to develop an in situ gelling depot that provides sustained release of SPL upon UV crosslinking. The in vitro release of SPL from the light responsive in situ depot was seen over 90 days. Furthermore, the in vivo ocular residence studies have demonstrated the depot remaining for >60 days. The SPL-loaded light responsive hydrogel demonstrated in vivo safety and efficacy against DR, further supporting its potential as a long acting drug delivery platform for intravitreally injected drugs with reduced frequency of administration.}, }
@article {pmid40750914, year = {2025}, author = {Enoch, J and Matthews, D and Ghulakhszian, A and Sekhon, M and Callaghan, T and Crabb, D and Dinah, C and Taylor, D}, title = {Implementing patient and public involvement (PPI) in eye research: reflections from developing a research study on Geographic Atrophy treatment acceptability.}, journal = {Research involvement and engagement}, volume = {11}, number = {1}, pages = {90}, pmid = {40750914}, issn = {2056-7529}, support = {AMR-000001//Apellis Pharmaceuticals/ ; AMR-000001//Apellis Pharmaceuticals/ ; AMR-000001//Apellis Pharmaceuticals/ ; AMR-000001//Apellis Pharmaceuticals/ ; AMR-000001//Apellis Pharmaceuticals/ ; AMR-000001//Apellis Pharmaceuticals/ ; EIF 397//National Institute for Health and Care Research/ ; EIF 397//National Institute for Health and Care Research/ ; EIF 397//National Institute for Health and Care Research/ ; EIF 397//National Institute for Health and Care Research/ ; EIF 397//National Institute for Health and Care Research/ ; EIF 397//National Institute for Health and Care Research/ ; HEIF//City, University of London/ ; HEIF//City, University of London/ ; HEIF//City, University of London/ ; HEIF//City, University of London/ ; HEIF//City, University of London/ ; HEIF//City, University of London/ ; }, abstract = {BACKGROUND: Awareness of the importance of patient and public involvement (PPI) in ophthalmology research is growing, ensuring studies align with patient priorities and experiences. However, there is limited literature exploring the practicalities and details of how PPI may be conducted within this field. In this case study of PPI within an ophthalmological research project, we aim to provide a transparent, in-depth illustration of how PPI was implemented and helped to shape the Acceptability of Geographic Atrophy INjections (AGAIN) study. The AGAIN study is focused on patients' perspectives regarding the acceptability of new intravitreal (eye) injection treatments for Geographic Atrophy, an advanced form of age-related macular degeneration.<br><br>MAIN TEXT: This commentary explores how PPI was undertaken to shape the design of the two work packages of the AGAIN study. In work package 1, the AGAIN pilot, we worked with a group of patient advisors to design materials for a mixed-methods questionnaire. This questionnaire consisted of Likert-type scale questions, semi-structured interview questions, and an elicitation task considering different hypothetical treatment scenarios. Eight patient advisors provided their input into the design of this questionnaire, and we discuss examples of the concrete changes to the research materials based on the advisors' feedback. In work package 2, we carried out several rounds of consultation with patient advisors to develop a pre-validated quantitative questionnaire on Geographic Atrophy treatment acceptability. This involved using 'think-aloud' techniques to explore the questionnaire's validity, clarity, and comprehensibility. We discuss some of the challenges that may arise when taking on board divergent points of view, and how to maximise comprehensibility without compromising fidelity to a validated questionnaire.<br><br>CONCLUSIONS: Our experience attests to the importance of listening to the insights of patients and those with lived experience in the early stages of designing research, while also ensuring that PPI remains continually integrated throughout the study lifecycle. Our PPI approach evolved in an ad-hoc fashion, and we suggest that given its beneficial impact for our study, PPI should be carefully planned for and adequately resourced in patient-centred ophthalmological research programmes.}, }
@article {pmid40752687, year = {2025}, author = {Sahu, A and Patel, AR and Shetty, KH and Shah, DO and Willcox, MD and Maulvi, FA and Desai, DT}, title = {Revolutionizing age-related macular degeneration treatment: Advances and future directions in non-invasive retinal drug delivery systems.}, journal = {International journal of pharmaceutics}, volume = {683}, number = {}, pages = {126009}, doi = {10.1016/j.ijpharm.2025.126009}, pmid = {40752687}, issn = {1873-3476}, mesh = {Humans ; *Macular Degeneration/drug therapy ; *Drug Delivery Systems/methods ; Animals ; Retina/metabolism/drug effects ; Nanoparticles ; }, abstract = {Age-related macular degeneration (AMD) remains a leading cause of vision loss worldwide. While anti-VEGF therapies are effective, they rely heavily on invasive intravitreal injections, which carry risks such as infection, retinal detachment, and poor patient compliance. Recent advances in nanotechnology and biomaterials have catalyzed the development of non-invasive drug delivery systems capable of targeting the retina through topical administration. This review explores the complex anatomical and physiological barriers to ocular drug delivery and highlights cutting-edge strategies-such as liposomes, solid lipid nanoparticles, polymeric carriers, micelles, and nanoemulsions-designed to overcome these challenges. Emerging technologies, including drug-eluting contact lenses, microneedle arrays, iontophoretic systems, and hydrogel-based platforms, offer promising avenues for sustained, patient-friendly retinal therapy. However, clinical translation faces significant hurdles related to drug bioavailability, barrier penetration, long-term safety, and regulatory validation. Future perspectives underscore the need for personalized, stimuli-responsive delivery systems and multidisciplinary collaboration to bridge the gap between laboratory innovation and clinical application. By integrating advances in nanomedicine, biomaterials science, and ophthalmology, the next generation of topical ocular therapies is poised to redefine the management of retinal diseases, offering safer, more sustainable, and widely accessible alternatives to intravitreal injections.}, }
@article {pmid40752732, year = {2025}, author = {Uemura, S and Miki, A and Kishimoto-Kishi, M and Chubachi-Kamimura, A and Nakamura, M}, title = {Two-year treatment outcome of photodynamic therapy combined with anti-vascular endothelial growth factor therapy for pachychoroid neovasculopathy.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {55}, number = {}, pages = {104746}, doi = {10.1016/j.pdpdt.2025.104746}, pmid = {40752732}, issn = {1873-1597}, mesh = {Humans ; *Photochemotherapy/methods ; Female ; Male ; Middle Aged ; Retrospective Studies ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Choroidal Neovascularization/drug therapy ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Photosensitizing Agents/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity/drug effects ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Intravitreal Injections ; Combined Modality Therapy ; Treatment Outcome ; Verteporfin ; }, abstract = {OBJECTIVE: To investigate the two-year treatment outcomes of photodynamic therapy (PDT) combined with intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with pachychoroid neurovasculopathy (PNV).<br><br>METHODS: A retrospective study was conducted on 22 eyes of 22 treatment-na&#xef;ve patients diagnosed with PNV who underwent combination therapy with PDT and intravitreal anti-VEGF agents (ranibizumab or aflibercept). Patients were followed for at least two years after treatment and evaluated for visual acuity (VA), central retinal thickness (CRT), subfoveal choroidal thickness (SCT), presence of recurrent exudative changes, time to recurrence, and additional treatments.<br><br>RESULTS: The study involved 12 male and 10 female patients with a mean age of 64.1 &#xb1; 11.5 years. Baseline VA (0.16&#xb1;0.26) improved significantly at 6 months (0.05 &#xb1; 0.23; P < 0.01), which was maintained until 24 months (0.04 &#xb1; 0.22; P < 0.01). Baseline CRT and SCT (303.1 &#xb1; 105.0 &#x3bc;m and 362.5 &#xb1; 83.8 &#x3bc;m, respectively) showed significant reductions at one month after treatment (184.5 &#xb1; 56.9 &#x3bc;m and 307.7 &#xb1; 94.6 &#x3bc;m; both P < 0.001), which were maintained until 24 months (170.8 &#xb1; 42.9 &#x3bc;m and 286.2 &#xb1; 99.1 &#x3bc;m; both P < 0.001). Recurrence was observed in five eyes (22.7 %) at a mean recurrence interval of 8.5 &#xb1; 3.9 months. The mean number of additional PDT and anti- VEGF treatments was 0.2 &#xb1; 0.4 and 1.9 &#xb1; 4.5, respectively.<br><br>CONCLUSIONS: Combination therapy with PDT and intravitreal anti-VEGF may be effective in improving visual acuity and anatomy in patients with PNV.}, }
@article {pmid40754855, year = {2025}, author = {Del Fabbro, S and Jimenez, B and Bianco, L and Antropoli, A and Nunziata, A and Stimola, C and Sarasso, E and Agosta, F and Filippi, M and Arrigo, A and Bandello, F and Battaglia Parodi, M}, title = {Neurovisual rehabilitation of patients with geographic atrophy secondary to age-related macular degeneration with AvDesk system.}, journal = {European journal of ophthalmology}, volume = {35}, number = {6}, pages = {2017-2025}, doi = {10.1177/11206721251349039}, pmid = {40754855}, issn = {1724-6016}, mesh = {Humans ; *Geographic Atrophy/rehabilitation/etiology/physiopathology ; Prospective Studies ; Visual Acuity/physiology ; Male ; Female ; Aged ; Visual Fields/physiology ; *Macular Degeneration/complications/physiopathology ; Aged, 80 and over ; Visual Field Tests ; Tomography, Optical Coherence ; Middle Aged ; Surveys and Questionnaires ; Quality of Life ; }, abstract = {PurposeThe aim of this study is to evaluate the efficacy of neurovisual rehabilitation using the AvDesk training system (Linari Medical, Pisa, Italy) in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD) in their eye with better visual acuity.MethodsThis study employed a prospective, observational, single-centre case series design. All patients underwent neurovisual rehabilitation using an AvDesk device. The protocol included sessions twice a week for a duration of 3 consecutive weeks. Before and at the end of the protocol, all patients underwent a standardized ophthalmic examination. MAIA microperimeter was used to assess fixation parameters, using bivariate contour ellipse area (BCEA) at both 63% and 95% confidence intervals, and macular sensitivity (MS). Additionally, the NEI-VFQ 25 questionnaire was administered to evaluate the clinical response.Results17 eyes from 17 patients were included in the study. The mean (SD) best-corrected visual acuity (BCVA) at baseline was 0.55 (0.28), improving to 0.39 (0.26) LogMAR (p = 0.0002), after completing the training. The mean (SD) MS did not change, ranging from 8.81 (6.08) dß to 8.60 (5.99) dß (p = 0.30). Following training, both BCEA 63% and 95% values exhibited a modest reduction, although these changes did not reach statistical significance (p > 0.05). Absolute scotomas remained stable (24.41 before treatment vs. 24.65 after treatment; p = 0.83). The NEI-VFQ 25 overall score improved from 55.05 to 62.18 post-treatment (p < 0.01).ConclusionsThe AvDesk training system is an effective tool for neurovisual rehabilitation in AMD patients with GA, yielding improvements in BCVA, fixation stability and quality of life.}, }
@article {pmid40754859, year = {2025}, author = {Teo, KYC and Ponsioen, TL and Lan, S and OToole, L and Arruabarrena Sanchez, C and Barry, R and Morros, HB and Chung, C and Invernizzi, A and Cheung, GCM and Barthelmes, D and Gillies, MC}, title = {Progression of Loss of Vision From Centre-Involving Macular Atrophy in Eyes Treated for nAMD.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {53}, number = {8}, pages = {925-935}, doi = {10.1111/ceo.14587}, pmid = {40754859}, issn = {1442-9071}, support = {//Australian and New Zealand Eye Foundation/ ; //National Health and Medical Research Council, Australia/ ; //Macula Disease Foundation, Australia/ ; //Walter and Gertrud Siegenthaler Foundation/ ; /SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {Humans ; *Visual Acuity/physiology ; Female ; Male ; Aged ; Disease Progression ; Case-Control Studies ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Angiogenesis Inhibitors/therapeutic use ; Follow-Up Studies ; Tomography, Optical Coherence ; Aged, 80 and over ; Registries ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Macula Lutea/pathology ; Ranibizumab/therapeutic use ; Fluorescein Angiography ; Retrospective Studies ; Middle Aged ; *Blindness/physiopathology/diagnosis ; Incidence ; Atrophy ; }, abstract = {BACKGROUND: This study aimed to characterise visual acuity (VA) changes in eyes without baseline macular atrophy (MA) that subsequently developed MA during treatment for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: A case-control analysis was performed using data from a multicentre real-world AMD registry. We compared VA outcomes in 1998 treatment-na&#xef;ve eyes without MA at baseline and &#x2265;&#x2009;5&#x2009;years of follow-up. Two matched groups (999 eyes each) were analysed: eyes that developed incident MA and those that never did.<br><br>RESULTS: Comparisons were made between two matched groups of 999 eyes each with incident MA and those that never developed it with at least 5&#x2009;years of follow-up. Final VA was best in eyes that never developed MA, followed by eyes that developed extrafoveal and sub-foveal MA (68.9&#x2009;&#xb1;&#x2009;16.7, 67.0&#x2009;&#xb1;&#x2009;16.9 and 52.1&#x2009;&#xb1;&#x2009;23.6 letters, p&#x2009;<&#x2009;0.01). Eyes with incident MA had more inactive disease visits compared to those that never developed MA. Features associated with poor final VA included the presence of sub-foveal MA (odds ratio [OR] [95% confidence interval (CI)] -16.63 [-18.7 to 14.56], p&#x2009;<&#x2009;0.01) and a higher proportion of active visits (per 10%) (OR [95% CI] -0.73 [-1.12 to 0.34], p&#x2009;<&#x2009;0.01). The mean time to lose five letters of vision from first grading of sub-foveal MA was 17.3&#x2009;&#xb1;&#x2009;4.6&#x2009;months.<br><br>CONCLUSION: It is important to achieve disease inactivity in nAMD despite its association with incident MA, as neovascular complications play a significant role in VA loss. The long duration between the incidence of MA and clinically significant loss of vision offers an opportunity for potential interventions against atrophy.}, }
@article {pmid40754930, year = {2025}, author = {Dong, Y and Li, Y and Zhou, X and Huang, W and Yang, S and Lin, H and Wei, K and Yao, J and Zuo, H and Zuo, C}, title = {Synergistic Suppression of Choroidal Neovascularization by Cavtratin and Aflibercept via Inhibition of the eNOS Pathway.}, journal = {Current eye research}, volume = {50}, number = {10}, pages = {1054-1063}, doi = {10.1080/02713683.2025.2523916}, pmid = {40754930}, issn = {1460-2202}, mesh = {*Choroidal Neovascularization/drug therapy/metabolism ; Animals ; *Nitric Oxide Synthase Type III/antagonists &amp; inhibitors/metabolism ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Mice ; Humans ; Disease Models, Animal ; Human Umbilical Vein Endothelial Cells ; Mice, Inbred C57BL ; Intravitreal Injections ; *Caveolin 1/metabolism ; Fluorescein Angiography ; Blotting, Western ; Angiogenesis Inhibitors/therapeutic use ; Male ; Signal Transduction ; Cells, Cultured ; Drug Synergism ; }, abstract = {PURPOSE: Choroidal neovascularization (CNV) is a key pathological feature of exudative age-related macular degeneration (AMD), leading to severe vision loss. Despite anti-vascular endothelial growth factor (anti-VEGF) therapies being the first-line treatment for neovascularization, their long-term application faces challenges including treatment insensitivity and drug resistance. This study aims to investigate the role of Caveolin-1 (Cav-1) in CNV pathogenesis and evaluate the therapeutic potential of Cavtratin, a Cav-1 scaffolding domain-targeting peptide, alone and in combination with Aflibercept.<br><br>METHODS: A laser-induced CNV model in aged mice and VEGF-stimulated human umbilical vein endothelial cells (HUVECs) were used to assess Cav-1 expression dynamics and its interaction with endothelial nitric oxide synthase (eNOS). The effects of Cavtratin on angiogenesis were evaluated using tube formation assays, choroidal sprouting assays, and fluorescein angiography. Western blot and immunofluorescence staining were employed to analyze changes in molecular expression, localization, and inflammatory responses. The efficacy of Cavtratin-Aflibercept combination therapy was examined.<br><br>RESULTS: Cav-1 and eNOS were significantly upregulated during CNV progression (p&#x2009;<&#x2009;0.001). Cavtratin effectively inhibited tube formation in HUVECs, suppressed choroidal sprouting ex vivo, and reduced CNV leakage in vivo (p&#x2009;<&#x2009;0.01). Mechanistically, Cavtratin suppressed eNOS phosphorylation and enhanced the anti-angiogenic effects of Aflibercept (p&#x2009;<&#x2009;0.001). The combination therapy led to greater CNV inhibition, reduced inflammation, and allowed for a lower Aflibercept dosage while maintaining therapeutic efficacy.<br><br>CONCLUSION: Cavtratin combined with Aflibercept can effectively enhance anti-angiogenic efficacy and reduce inflammatory responses. Targeting the Cav-1/eNOS axis with Cavtratin provides a novel strategy to complement the limitations of anti-VEGF therapy. The synergistic effects of Cavtratin and Aflibercept suggest a promising approach to overcoming treatment resistance and improving clinical outcomes in CNV management.}, }
@article {pmid40755970, year = {2025}, author = {Nguyen, MD and Fekrat, R and Gee, C and Demirci, AN and Kharabaf, S and Le, D and Tadros, M and Nguyen, VQ and Patel, S and Truong, T and Ahdoot, R and Kurtz, IB and Kerr, M and Massoud, A and Hanna, R}, title = {Intravitreal vascular endothelial growth factor inhibitor systemic and renal toxicity registry.}, journal = {Clinical kidney journal}, volume = {18}, number = {8}, pages = {sfaf206}, pmid = {40755970}, issn = {2048-8505}, abstract = {BACKGROUND: Intravitreal vascular endothelial growth factor inhibitors (IVEGFi) are used in the treatment of diabetic retinopathy, age-related macular degeneration (AMD) and central retinal vein obstruction. As we have previously reported, there are an increasing number of cases documenting IVEGFi with renal injury and increased concentrations in the serum. To assess this claim, we have developed a novel reporting system through an electronic registry for cases of suspected VEGFi injury.<br><br>METHODS: A website with multiple data protection sets was created to educate, promote awareness and capture patient cases of suspected IVEGFi toxicity. The website displays the molecular biology of VEGF signaling, the process of absorption into the bloodstream, and study reports showing risks on case, cohort and epidemiologic levels. A Health Insurance Portability and Accountability Act (HIPAA)-compliant patient intake form was designed to collect renal, cardiovascular, cerebrovascular, renal biopsy and function data along with drug type, indication and frequency of administration.<br><br>RESULTS: In our updated cohort we added 16 total cases from the literature showing signs of renal injury from the patient population receiving VEGFi. In current literature, 46 cases of VEGFi-related renal injury have been documented. To them, we add our 16 cases for a total of 62 cases.<br><br>CONCLUSION: The current database for VEGFi-related nephrotoxicity constitutes the largest case series presented for this condition. This study opens the door for future studies to evaluate what subgroups experience acute kidney injury, proteinuria and hypertension exacerbations. Additionally, we may expand on our database to include timeline markers for symptomatic-correlative VEGFi usage and, in time, predictive measures on a larger scale to correlate comorbidity/drug use with drug effect and mechanism of action.}, }
@article {pmid40757768, year = {2025}, author = {Chen, H and Xu, N and Rao, H}, title = {Serum Uric Acid and Intermediate Age-Related Macular Degeneration: A Nationally Representative Study in the United States.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {8}, pages = {6}, pmid = {40757768}, issn = {2164-2591}, mesh = {Humans ; *Uric Acid/blood ; Male ; Female ; United States/epidemiology ; Middle Aged ; Aged ; *Macular Degeneration/blood/epidemiology ; Nutrition Surveys ; *Hyperuricemia/blood/epidemiology ; Risk Factors ; Cross-Sectional Studies ; }, abstract = {PURPOSE: The purpose of this study was to investigate the associations between serum uric acid (SUA) levels and intermediate age-related macular degeneration (iAMD) in the United States population.<br><br>METHODS: This study included data from the 2005 to 2008 National Health and Nutrition Examination Survey. Weighted logistic regression models (crude, partially adjusted, and fully adjusted) were used to assess linear associations between SUA levels and iAMD. Restricted cubic spline (RCS) analysis tested nonlinear associations. Subgroup analyses stratified by age, sex, and race/ethnicity further explored potential effect modifiers.<br><br>RESULTS: Among 3208 participants aged &#x2265;50 years, 420 (11.2%) had iAMD and 766 (22.3%) exhibited hyperuricemia (HUA). Logistic regression models showed no significant associations between SUA levels and the odds of developing iAMD across all three models. In the fully adjusted model, the odds ratio (OR) comparing the highest to the lowest SUA quintile was 0.95 (95% confidence interval [CI] = 0.53-1.70, P = 0.84). The trend test indicated no significant increase in the odds of iAMD across quintiles of SUA levels (P for trend = 0.60). Similarly, no significant association was found when SUA values were categorized as HUA or non-HUA (P = 0.66). RCS analysis did not demonstrate a nonlinear relationship between SUA levels and iAMD risk. Subgroup analyses showed no significant differences across age, sex, and race/ethnicity stratifications.<br><br>CONCLUSIONS: Elevated SUA levels were not associated with increased iAMD risk in this large, nationally representative sample.<br><br>TRANSLATIONAL RELEVANCE: Our study provides insights into the relationship between SUA levels and iAMD, challenging "hyperuricemic AMD" and offering valuable implications for clinical risk assessment.}, }
@article {pmid40758327, year = {2025}, author = {Grosso, F and Zanetti, D and Sanna, S}, title = {Causal relationships between gut microbiome and hundreds of age-related traits: evidence of a replicable effect on ApoM protein levels.}, journal = {Aging}, volume = {17}, number = {8}, pages = {1966-1987}, pmid = {40758327}, issn = {1945-4589}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Apolipoproteins M/metabolism/genetics/blood ; *Aging/genetics ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Male ; Aged ; Female ; }, abstract = {In the past 20 years, the involvement of gut microbiome in human health has received particular attention, but its contribution to age-related diseases remains unclear. To address this, we performed a comprehensive two-sample Mendelian Randomization investigation, testing 55130 potential causal relationships between 37 traits representing gut microbiome composition and function and age-related phenotypes, including 1472 inflammatory and cardiometabolic circulating plasma proteins from UK Biobank Pharma Proteomic Project and 18 complex traits. A total of 91 causal relationships remained significant after multiple testing correction (false discovery rate p-value <0.05) and sensitivity analyses, notably two with the risk of developing age-related macular degeneration and 89 with plasma proteins. The link between purine nucleotides degradation II aerobic pathway and apolipoprotein M was further replicated using independent genome-wide association study data. Finally, by taking advantage of previously reported biological function of Faecalibacterium prausnitzii we found evidence of regulation of six proteins by its function as mucosal-A antigen utilization. These results support the role of gut microbiome as modulator of the inflammatory and cardiometabolic circuits, that may contribute to the onset of age-related diseases, albeit future studies are needed to investigate the underlying biological mechanisms.}, }
@article {pmid40760090, year = {2025}, author = {Su, B and Sun, Y and Yu, W and Wang, C and Xia, Q and Zhu, Y}, title = {Exploring the causal relationship between 16 eye diseases and stroke and their subtypes from a genome-wide perspective.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {28357}, pmid = {40760090}, issn = {2045-2322}, mesh = {Humans ; *Genome-Wide Association Study ; *Eye Diseases/genetics/complications ; *Stroke/genetics/complications/epidemiology ; Mendelian Randomization Analysis ; Genetic Predisposition to Disease ; Risk Factors ; Polymorphism, Single Nucleotide ; }, abstract = {There is increasing evidence that eye diseases and stroke frequently co-occur, but the causal relationships remain elusive. Therefore, Mendelian randomization was used to investigate possible causal relationships between eye diseases and stroke (including its subtypes). This study utilized large-scale genome-wide association study pooled genetic data from two major databases: the IEU OpenGWAS project and the FinnGen databases. We then screened for instrumental variables that met the following three conditions: showing strong associations with the exposure factors, being independent of each other and independent of any confounders, and excluding instrumental variables to ensure that the F-value was greater than 10, and used the Inverse Variance Weighted (IVW) method to conduct causal analyses using the weighted median method, MR-Egger method, MR- PRESSO test and leave-one-out sensitivity test to test the robustness, heterogeneity and horizontal pleiotropy of the results. In order to control for the false positive rate in multiple hypothesis testing, a False Discovery Rate (FDR) correction was also performed. A total of 16 eye diseases and strokes and their subtypes were investigated in this study. In the IVW model, the MR study showed a total of 20 IVWs with p-values less than 0.05. We excluded 6 results with heterogeneity or pleiotropy by sensitivity analysis, and finally the following reliable results were left: (1) patients with age-related macular degeneration had a 5%, 2%, and 7% lower risk of subarachnoid hemorrhage, ischemic stroke, and small-vessel stroke; (2) patients with keratitis had a 12% higher risk of cardioembolic; (3) patients with optic atrophy had a 3% higher risk of stroke; (4) patients with amblyopia had a 3% higher risk of stroke; and (5) patients with other inflammation of eyelid had a small-vessel had a 20% elevated risk; (6) patients with ptosis of the eye had a 17% elevated risk of cardioembolic; (7) patients with strabismus have a 23% elevated risk of small-vessel; (8) patients with stroke had a refractive error by 17%; (9) patients with intracerebral hemorrhage had a 15% increased risk of uveitis; (10) patients with IS had an 11% increased risk of diabetic retinopathy; (11) patients with large-artery atherosclerosis had a 2% increased risk of glaucoma; (12) patients with cardioembolic had a 24% increased risk of amblyopia. From a genetic standpoint, keratitis, amblyopia, other eyelid inflammations, ptosis and strabismus are associated with increased risks of the risk of stroke or its subtypes. Conversely, age-related macular degeneration is associated with reduced risks of the risk of stroke or its subtypes. Furthermore, stroke or its subtypes increase the risks of refractive error, uveitis, diabetic retinopathy, glaucoma, and amblyopia. Nevertheless, it is imperative that these causal relationships be subjected to further verification through fundamental research and Randomized Controlled Trial (RCT).}, }
@article {pmid40761529, year = {2025}, author = {Sheth, JU and Bhopalka, AK and Meshram, B and Karande, S}, title = {Quantitative Assessment of En‑face OCT‑Derived Minimum Intensity Fluid Changes Following Ranibizumab Biosimilar Therapy in Macular Neovascularization Secondary to nAMD and PCV.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {2505-2512}, pmid = {40761529}, issn = {1177-5467}, abstract = {PURPOSE: This retrospective study aimed to evaluate the efficacy of a new regulatory approved ranibizumab biosimilar (RzB), Oceva[®] (Sun Pharmaceutical Industries Limited, Mumbai, India), in treating macular neovascularization secondary to neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), using Minimum-Intensity based changes observed on en-face optical coherence tomography (OCT) (en-face MI OCT).<br><br>PATIENTS AND METHODS: Thirty-six eyes with treatment-na&#xef;ve MNV underwent three loading doses of RzB. Best-corrected visual acuity (BCVA) and the proportions of eyes with subretinal fluid (SRF), intraretinal fluid (IRF), and subretinal hyperreflective material (SHRM) were assessed. En-face MI OCT-based analysis was conducted to quantify changes in fluid area and perimeter.<br><br>RESULTS: At 12&#xa0;weeks, there was a statistically significant improvement in BCVA from 0.94 {&#x2248;20/174} (&#xb1; 0.59) logMAR to 0.84 {&#x2248;20/138} (&#xb1; 0.61) logMAR (P=0.04). En-face MI OCT revealed a significant reduction in the median area of fluid from 0.9 mm&#xb2; (IQR 0.62-4.56) to 0.32 mm&#xb2; (IQR 0.1-0.64) (P=0.007), and in the median perimeter of fluid from 10.95 mm (IQR 7.26-25.67) to 6.02 mm (IQR 1.76-7.93) (P=0.0005). The proportion of eyes with SRF, IRF, and SHRM decreased from baseline (83.33%, 66.67%, and 58.33% respectively) to 12&#xa0;weeks (58.33% [P=0.015], 38.89% [P=0.013], and 13.89% [P<0.001]). No adverse events were reported.<br><br>CONCLUSION: Treatment with the novel RzB showed promising outcomes in improving visual parameters and reducing fluid accumulation in patients with MNV secondary to nAMD and PCV. Minimum Intensity-based analysis provided detailed insights into fluid dynamics, demonstrating its utility in evaluating treatment responses in MNV. This study contributes to the initial assessment of RzB in clinical practice, highlighting its potential efficacy in managing MNV.}, }
@article {pmid40762815, year = {2025}, author = {Alsakran, WA and Alsadoon, AA and Alsayed, B and Magliyah, MS and ALBalawi, HB}, title = {Clinical features and classification framework of polypoidal choroidal vasculopathy in Saudi populations.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {323}, pmid = {40762815}, issn = {1573-2630}, mesh = {Humans ; Saudi Arabia/epidemiology ; Retrospective Studies ; Male ; Female ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; *Visual Acuity ; Aged ; *Polyps/diagnosis/classification/epidemiology ; Fundus Oculi ; Middle Aged ; *Choroid/blood supply ; *Choroidal Neovascularization/diagnosis/classification/epidemiology/therapy ; Photochemotherapy/methods ; Angiogenesis Inhibitors/therapeutic use ; Follow-Up Studies ; Polypoidal Choroidal Vasculopathy ; }, abstract = {INTRODUCTION: The Changes in visual acuity(VA) can be caused by polypoidal choroidal vasculopathy(PCV), a subtype of macular neovascularization which is characterized by the formation of polyp-like structures under the retinal pigment epithelium. PCV has been commonly found concurrent with the neovascular age-related macular degeneration (nAMD), which has led to the debate regarding whether, it should be viewed as an independent entity or as a subset of nAMD. The insight into the clinical features of PCV and its therapeutic response such as understanding the prognosis of this disease is very crucial for management and better outcomes. This study aims to differentiate the different types of PCV, and assess its clinical features, disease progression, and treatment options available for Saudi patients and also examine the effectiveness of different treatment modalities.<br><br>MATERIALS AND METHODS: A retrospective study was conducted in Saudi Arabia among 39 PCV diagnosed patients, using multimodal imaging technique for assessment such as fundus imaging, OCT and ICGA. Patients were classified into three subtypes: age-related macular degeneration-associated PCV(PCV-AMD, Type A), a group with posterior-capsule-vitreous neovascularization-associated PCV (PCV-BVN, Type B), and idiopathic PCV (Type C). The treatment options available were photodynamic therapy(PDT), thermal laser therapy and anti-vascular endothelial growth factor (anti-VEGF) therapy. The clinical&#x2002;and visual outcomes were evaluated at the end of 1&#xa0;year. SPSS version 23 was used to conduct statistical analysis, including chi-square, ANOVA and Kruskal-Wallis&#x2002;tests (p&#x2009;<&#x2009;0.05).<br><br>RESULTS: PCV-AMD was the most common subtype(75.7%), followed by PCV-BVN (13.5%) and idiopathic PCV (10.8%). The median age was 68&#xa0;years, with idiopathic PCV patients being significantly younger (p&#x2009;=&#x2009;0.012). Most lesions were macular (94.6%) with peaked/dome-shaped RPE elevations (94.6%). Anti-VEGF therapy was administered in 94.6% of cases, with aflibercept usage differing significantly across subtypes (p&#x2009;=&#x2009;0.018). Complete lesion resolution was achieved in 45.9%, with PCV-BVN showing the highest resolution rate (80%) and idiopathic PCV the lowest at(0%).<br><br>CONCLUSION: PCV is predominantly presents as a variant of nAMD, with significant differences in subtype characteristics and treatment response. While anti-VEGF therapy remains the mainstay of treatment, idiopathic PCV appears more refractory, necessitating the individualized therapeutic strategies. Additional future studies are required to enhance management strategies for this condition.}, }
@article {pmid40762817, year = {2025}, author = {Stark, KJ and Zimmermann, ME and Helbig, H and Heid, IM and Brandl, C}, title = {Central retinal volume derived from optical coherence tomography as a potential predictor of mortality in the old-aged population- results from the German AugUR study.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {263}, number = {10}, pages = {2737-2746}, pmid = {40762817}, issn = {1435-702X}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; Aged, 80 and over ; Germany/epidemiology ; Prospective Studies ; *Retina/pathology/diagnostic imaging ; Cause of Death/trends ; Follow-Up Studies ; Organ Size ; *Population Surveillance/methods ; Survival Rate/trends ; Risk Factors ; }, abstract = {PURPOSE: To estimate mortality risk depending on central retinal volume (CRV) from optical coherence tomography (OCT) in a German cohort of the old-aged population.<br><br>METHODS: In the AugUR study, a prospective population-based cohort study in individuals aged 70-95 years at baseline, we conducted multimodal retinal imaging, including spectral-domain OCT. Heidelberg Spectralis-derived CRV measurements from first examinations of 2,166 participants were included in the analyses. Within the observation period (median 5.9-years), 374 participants died. Association between CRV at baseline and mortality was analysed with Kaplan-Meier curves and Cox proportional hazard regression.<br><br>RESULTS: Decrease in CRV was associated with increased all-cause mortality risk. In a full model with age, sex, body weight, body size, OCT scan focus, age-related macular degeneration, smoking, cardiovascular disease, diabetes, and hypertension, hazard ratio per standard deviation lower CRV was 1.17. Cardiovascular death was not associated with CRV in the full model. However, other causes for death except cardiovascular reasons showed association with lower CRV (hazard ratio 1.25). In addition, the association was significant in those who had already exceeded their expected life expectancy (hazard ratio 1.21) but not in women below 83 years and men below 78 years, respectively.<br><br>CONCLUSION: This study indicates that lower CRV, which can be easily and automatically derived from OCT images, is a potential predictor for mortality in the old-aged population. This effect occurs independently of cardiovascular disease.}, }
@article {pmid40763014, year = {2025}, author = {Chen, L and Zhou, X and Huang, C and Zhang, Y and Xin, C and Hong, J and Wang, Y}, title = {Engineered Un1Cas12f1 with boosted gene-editing activity and expanded genomic coverage.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {32}, pages = {e2501292122}, pmid = {40763014}, issn = {1091-6490}, support = {2023YFA0915000//Nation Key Research and Development Program of China/ ; 82273967//National Natural Science Foundation of China/ ; 2021QN020576//Department of Science and Technology of Guangdong Province/ ; 82425015//MOST | NSFC | National Science Fund for Distinguished Young Scholars (NSF for Distinguished Young Scholars)/ ; 82171102//National Natural Science Foundation of China/ ; 82271044//National Natural Science Fundation of China/ ; QWF158001//National Youth talent support program/ ; 22Y21900900//Shanghai Medical Innovation Research Program/ ; 24SG11//(the "Dawn" Program of) Shanghai Municipal Education Commission/ ; 24J22800500//Shanghai Science and Technology Innovation Action Plan for Cell and Gene Therapy/ ; 24CL2900802//Shanghai Science and Technology Innovation Action Plan for Advanced Materials/ ; 20254Z0019//Shanghai Municipal Commission of Health/ ; }, mesh = {Animals ; *Gene Editing/methods ; Mice ; Dependovirus/genetics ; Humans ; CRISPR-Cas Systems/genetics ; Genetic Vectors/genetics ; PTEN Phosphohydrolase/genetics ; RNA, Guide, CRISPR-Cas Systems/genetics ; Genetic Therapy/methods ; HEK293 Cells ; }, abstract = {Compact programmable nucleases provide versatile genome editing tools with therapeutic potential, particularly when delivered via adeno-associated virus (AAV) vectors. However, their limited editing efficacy and stringent protospaceradjacent motif (PAM) requirements impose significant limitations in practical application. Here, we engineered MiniCasUltra, an optimized Un1Cas12f1 variant, through rational mutagenesis. MiniCasUltra exhibits sixfold higher editing activity than Un1Cas12f1, minimal off-target effects (on/off-target ratio > 10), and an expanded PAM preference (5'-WBTR). Using a single AAV vector encoding MiniCasUltra and two single-guide RNAs, we achieved simultaneous editing of two disease-causing genes (Pten and Fah) in mouse liver, with indel rates of 15.82% and 29.39%, respectively- significantly surpassing CasMINI V3.1 (3.45% and 10.98%). Furthermore, AAV delivery of MiniCasUltra targeting a noncanonical 5'-TCTG PAM site in human vascularendothelial growth factor A reduced choroidal neovascularization (CNV) lesions in a laser-induced CNV mouse model of neovascular age-related macular degeneration, a leading global cause of blindness. The broad and effective targeting capabilities of MiniCasUltra, coupled with its compact size, highlight its potential for in vivo genome editing and therapeutic interventions.}, }
@article {pmid40765005, year = {2025}, author = {An, N and Liao, H and Zhang, C and Zeng, B and Liu, Z and Li, D and Huang, J and Liu, D and Qin, B}, title = {Association between dietary theobromine and age-related macular degeneration: results from NHANES 2005-2008 and in vitro experiments.}, journal = {European journal of medical research}, volume = {30}, number = {1}, pages = {714}, pmid = {40765005}, issn = {2047-783X}, mesh = {Humans ; *Macular Degeneration/epidemiology/metabolism ; Male ; *Theobromine/administration &amp; dosage ; Female ; Nutrition Surveys ; Middle Aged ; Reactive Oxygen Species/metabolism ; Heme Oxygenase-1/metabolism ; Aged ; Cell Proliferation/drug effects ; Superoxide Dismutase-1/metabolism ; *Diet ; Adult ; }, abstract = {OBJECTIVE: To investigate the relationship between theobromine and age-related macular degeneration (AMD) using a nationwide representative sample of adults and in vitro experiments.<br><br>METHODS: We analyzed data from the 2005-2008&#xa0;years of the National Health and Nutrition Examination Survey (NHANES), which included 5485 participants with available data on dietary theobromine intake and AMD. Multivariable logistic regression and smoothing curve fitting were used to examine the potential correlations. The inflection point was determined using a two-piecewise linear regression. Interaction tests and subgroup analyses were also conducted. In vitro experiments were conducted to investigate the effects of theobromine on cell proliferation, intracellular reactive oxygen species (ROS) levels, and the expression of heme oxygenase-1 (HO-1) and superoxide dismutase-1 (SOD-1) in a sodium iodate (NaIO3)-induced ARPE-19 cell injury model.<br><br>RESULTS: After controlling for potential confounding variables, the multivariate logistic regression model revealed an odds ratio of 0.73 (95% confidence interval: 0.56-0.98) for the association between dietary theobromine and AMD. The usage of smoothing curve fitting revealed a non-linear relationship, with an inflection point observed at 60&#xa0;mg/d (adjust OR&#x2009;0.31;95% CI 0.14-0.66). The negative correlation remained consistent across various demographic scenarios in subgroup analyses and interaction tests. In the NaIO3-induced ARPE-19 cell injury model, theobromine enhanced cell proliferation, reduced the expression of HO-1, and increased the expression of SOD-1.<br><br>CONCLUSIONS: A non-linear negative correlation between dietary theobromine and AMD was observed, and the antioxidant activity of theobromine was observed in vitro. Our findings suggest a potential association between higher theobromine intake and lower odds of AMD prevalence, which warrants further investigation of its therapeutic implications.}, }
@article {pmid40766039, year = {2025}, author = {DeLucia, PR and Oberfeld, D and Kearney, JK and Cloutier, M and Jilla, AM and Zhou, A and Corona, ST and Cormier, J and Taylor, A and Wykoff, CC and Baurès, R}, title = {Time-to-Collision Estimation With Age-Related Macular Degeneration Using Visual and Auditory Cues: Which Cues are Most Important?.}, journal = {Proceedings of the Human Factors and Ergonomics Society ... Annual Meeting. Human Factors and Ergonomics Society. Annual meeting}, volume = {69}, number = {1}, pages = {1687-1688}, pmid = {40766039}, issn = {1071-1813}, support = {R01 EY030961/EY/NEI NIH HHS/United States ; }, abstract = {We measured time-to-collision (TTC) judgments from participants with age-related macular degeneration (AMD), and normal vision (NV) controls, with an audiovisual virtual reality system that simulated vehicles approaching in a 3D traffic environment. The vehicle was presented visually only, aurally only, or both simultaneously, allowing us to determine the relative importance of visual and auditory cues with psychophysical reverse correlation. Results indicated that TTC judgments were based on both auditory and visual cues in the AMD and NV groups; the AMD group relied, at least in part, on their residual vision. A multimodal advantage was not observed in either group. TTC estimation in the AMD group was surprisingly similar to that in the NV group. However, the AMD group showed a higher relative importance of "heuristic" cues compared to more reliably accurate cues favored by the NV group, suggesting that similar performance may be achieved through different cue-weighting strategies.}, }
@article {pmid40766447, year = {2025}, author = {Johnathon, S and Ke, J and Stephanie A, H and Maya, M and Bonilha, VL}, title = {Metabolic dysfunction promoted by mitochondrial DNA mutation burden drives retinal degeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40766447}, issn = {2692-8205}, support = {F31 EY035133/EY/NEI NIH HHS/United States ; P30 EY025585/EY/NEI NIH HHS/United States ; T32 EY024236/EY/NEI NIH HHS/United States ; }, abstract = {Retinal degenerative diseases, such as age-related macular degeneration (AMD), retinitis pigmentosa, and glaucoma, have been linked to mitochondrial dysfunction. However, the impact of mitochondrial DNA (mtDNA) mutation accumulation in the context of these retinopathies has yet to be thoroughly explored. Our previous studies focused on the retinal phenotype observed in the PolgD257A mutator mice (D257A), revealing the effects of aging and mtDNA mutation accumulation in the retina. We have reported that this model exhibited significant morphological and functional deficits in the retina by 6 months of age, with notable alterations in the retinal pigment epithelium (RPE) occurring as early as 3 months, including changes in the cristae density and reduction in length of mitochondria. This study investigated how mtDNA mutations affect the metabolic interaction between the retina and RPE in young (3 months) and old (12 months) wild-type (WT) and D257A mice. We assessed cellular energy production using freshly dissected retina samples from both groups through Seahorse analysis, immunofluorescence, and Western blot experiments. The analysis of aged D257A retina punches revealed significantly reduced basal and maximal mitochondrial respiration, along with increased mitochondrial reserve capacity compared to WT. However, glycolytic flux, measured as a function of extracellular acidification rate (ECAR), did not differ between WT and D257A mice. Both D257A retina and RPE exhibited decreased expression of essential electron transport proteins involved in oxidative phosphorylation. Additionally, we observed a reduction in the expression of glucose transporter 1 (GLUT-1) and lactate transporter (MCT1) at the apical surface of the RPE. Enzymes associated with glycolysis, including hexokinase II and lactate dehydrogenase A, were significantly lower in the aged D257A retina, while hexokinase I and pyruvate kinase 2 were upregulated in the RPE. These findings indicate that the accumulation of mtDNA mutations leads to impaired metabolism in both the retina and RPE. Furthermore, it suggests that glucose from the choroidal blood supply is being utilized by the RPE rather than being transported to the neural retina. Mitochondrial dysfunction in RPE promotes a glycolytic state in these cells, leading to reduced availability of metabolites and, consequently, diminished overall retinal function. These results are essential for advancing our understanding of the mechanisms underlying retinal degeneration and provide a new perspective on the role of mtDNA mutations in these diseases.}, }
@article {pmid40767440, year = {2025}, author = {Fragiotta, S and Parravano, M and Sacconi, R and Polito, MS and Cioffi, B and Rissotto, F and Beretta, F and Costanzo, E and Romano, E and Capuano, V and Souied, EH and Querques, G}, title = {Progression Patterns in Foveal-Sparing Geographic Atrophy With Double-Layer Sign Due to Neovascularization or Basal Laminar Deposits.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {11}, pages = {16}, pmid = {40767440}, issn = {1552-5783}, mesh = {Humans ; Retrospective Studies ; Male ; Tomography, Optical Coherence/methods ; Female ; *Fovea Centralis/pathology ; Aged ; Fluorescein Angiography/methods ; *Geographic Atrophy/diagnosis/etiology ; Disease Progression ; Aged, 80 and over ; Visual Acuity ; Fundus Oculi ; Middle Aged ; Prognosis ; *Retinal Neovascularization/diagnosis ; *Choroidal Neovascularization/diagnosis ; Follow-Up Studies ; }, abstract = {PURPOSE: The purpose of this study was to analyze the prognostic significance of double-layer sign (DLS) in eyes with foveal-sparing geographic atrophy (GA) secondary to age-related macular degeneration.<br><br>METHODS: This retrospective, observational cohort study analyzed 46 eyes (46 patients) with foveal sparing GA and associated DLS, using fundus autofluorescence (FAF), near-infrared reflectance (NIR), optical coherence tomography (OCT), and OCT angiography (OCTA). DLS was defined based on OCTA findings as either thick basal laminar deposits (BLamD) or non-exudative macular neovascularization (NE-MNV). The area of GA and foveal sparing were estimated on both FAF and NIR at different time points. Centrifugal and centripetal GA growth rates referring to the lesion expansion away from and toward the fovea, respectively, were evaluated using a mathematical formula.<br><br>RESULTS: Of the 46 eyes enrolled, 25 had thick BLamD, whereas 21 had type 1 NE-MNV. The NE-MNV eyes showed significantly thicker DLS than those with BLamD (90.4 &#xb1; 39.8&#xa0;&#xb5;m vs. 57.0 &#xb1; 27&#xa0;&#xb5;m, 95% confidence interval [CI] = 0.34 to 0.78, P < 0.001). GA areas were smaller on FAF than NIR (95% CI = -0.89 to -0.03, P = 0.03) in the BLamD group, whereas no difference was observed in the NE-MNV group (95% CI = -0.37 to 0.64, P = 0.60). Despite similar GA areas, the NE-MNV eyes exhibited larger foveal sparing (95% CI = 0.02 to 1.21, P = 0.04). The foveal sparing area remained stable (F(1.2, 11 = 4.15, P = 0.06,&#xa0;&#x3c9;2 = 0.02) in the NE-MNV group, whereas a significant reduction was observed in the BLamD subgroup (F(1.39, 20.9) = 7.5, P < 0.001,&#xa0;&#x3c9;2 = 0.09).<br><br>CONCLUSIONS: OCTA has provided valuable insights into the pathogenic interpretation of the DLS signature. Our findings confirm that a neovascular DLS protects the retinal pigment epithelium and outer retina, contributing to prolonged foveal preservation.}, }
@article {pmid40767441, year = {2025}, author = {Huang, Z and Chen, C and Meng, J and Liu, S and Zhang, K and Du, Y and Zhu, X}, title = {Associations Among Sleep Duration, Sleep Quality, and Age-Related Ocular Diseases: Insights From Longitudinal and Mediation Analyses.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {11}, pages = {15}, pmid = {40767441}, issn = {1552-5783}, mesh = {Humans ; Female ; Male ; Aged ; Middle Aged ; Prospective Studies ; *Sleep Quality ; *Glaucoma, Open-Angle/epidemiology/physiopathology ; Incidence ; United Kingdom/epidemiology ; *Sleep/physiology ; Risk Factors ; *Diabetic Retinopathy/epidemiology/physiopathology ; *Cataract/epidemiology/physiopathology ; *Macular Degeneration/epidemiology/physiopathology ; Follow-Up Studies ; Time Factors ; Aged, 80 and over ; Proportional Hazards Models ; Sleep Duration ; }, abstract = {PURPOSE: To investigate the associations among sleep duration, sleep quality, and age-related ocular diseases, accounting for interactions with systemic inflammation.<br><br>METHODS: A total of 380,182 participants in the UK Biobank were included in this prospective population-based cohort study. The investigated exposures were sleep duration, sleep quality (quantified through an established algorithm comprised of five sleep traits), and traits including insomnia, daytime dozing, chronotype, and snoring. Outcomes were incidences of cataract, primary open-angle glaucoma (POAG), diabetic retinopathy (DR), and age-related macular degeneration (AMD). Cox proportional hazards models were used to estimate the hazard ratios (HRs), with mediation analysis of systematic inflammatory indicators further performed to explore potential mechanisms.<br><br>RESULTS: During a median follow-up of 12.6 years, 42,971 cataract cases, 5793 POAG cases, 4267 DR cases, and 7775 AMD cases were documented. Sleep duration displayed U-shaped relationships with cataract, POAG, and DR (all P nonlinear < 0.001), identifying 7 hours per day as optimal. Poor sleep quality also elevated the risks of cataract (HR = 1.17; P < 0.001) and POAG (HR = 1.21; P = 0.019), whereas for DR this effect was not significant but suggestive (HR = 1.15; P = 0.082). Sleep behavior traits including insomnia and daytime dozing were found to predict higher risks of these diseases. Mediation analysis indicated significant contributions of inflammatory indicators to the associations of poor sleep quality with cataract and DR.<br><br>CONCLUSIONS: Our findings suggest that sleep patterns might be modifiable risk factors for age-related ocular diseases and highlight the potential value of anti-inflammatory therapies to delay the manifestations of ocular aging.}, }
@article {pmid40768461, year = {2025}, author = {Khan, AA and Ahmad, KM and Shafiq, S and Akram, MU and Shao, J}, title = {ATLASS: An AnaTomicaLly-Aware Self-Supervised Learning Framework for Generalizable Retinal Disease Detection.}, journal = {IEEE journal of biomedical and health informatics}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/JBHI.2025.3595697}, pmid = {40768461}, issn = {2168-2208}, abstract = {Medical imaging, particularly retinal fundus photography, plays a crucial role in early disease detection and treatment for various ocular disorders. However, the development of robust diagnostic systems using deep learning remains constrained by the scarcity of expertly annotated data, which is time-consuming and expensive. Self-Supervised Learning (SSL) has emerged as a promising solution, but existing models fail to effectively incorporate critical domain knowledge specific to retinal anatomy. This potentially limits their clinical relevance and diagnostic capability. We address this issue by introducing an anatomically aware SSL framework that strategically integrates domain expertise through specialized masking of vital retinal structures during pretraining. Our approach leverages vessel and optic disc segmentation maps to guide the SSL process, enabling the development of clinically relevant feature representations without extensive labeled data. The framework combines a Vision Transformer with dual-masking strategies and anatomically informed loss functions to preserve structural integrity during feature learning. Comprehensive evaluation across multiple datasets demonstrates our method's competitive performance in diverse retinal disease classification tasks, including diabetic retinopathy grading, glaucoma detection, age-related macular degeneration identification, and multi-disease classification. The evaluation results establish the effectiveness of anatomically-aware SSL in advancing automated retinal disease diagnosis while addressing the fundamental challenge of limited labeled medical data.}, }
@article {pmid40769491, year = {2026}, author = {Friedman, S and London, N and Hamouz, J and Kerényi, &#xc1; and Papp, A and Pregun, T and Chow, V and Bautista, B and Wang, D and Grachev, G and Franklin, J}, title = {Randomized Trial of Biosimilar ABP 938 Compared with Reference Aflibercept in Adults with Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {10}, number = {2}, pages = {152-164}, doi = {10.1016/j.oret.2025.07.015}, pmid = {40769491}, issn = {2468-6530}, mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage ; Male ; Female ; Double-Blind Method ; Intravitreal Injections ; *Visual Acuity ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; Treatment Outcome ; *Biosimilar Pharmaceuticals/administration &amp; dosage ; Angiogenesis Inhibitors/administration &amp; dosage ; Middle Aged ; Tomography, Optical Coherence/methods ; Aged, 80 and over ; Follow-Up Studies ; Dose-Response Relationship, Drug ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography ; Fundus Oculi ; Macula Lutea/pathology ; }, abstract = {PURPOSE: To evaluate the clinical efficacy, safety, and immunogenicity of biosimilar ABP 938 compared with the aflibercept reference product (RP) in adults with neovascular (wet) age-related macular degeneration (nAMD).<br><br>DESIGN: A randomized, double-masked, active-controlled, multiregional clinical study.<br><br>PARTICIPANTS: A total of 579 patients with active treatment-na&#xef;ve choroidal neovascularization secondary to nAMD were randomized.<br><br>METHODS: Evaluable patients (N = 576) received 2 mg of ABP 938 (n = 288) or aflibercept RP (n = 288) by intravitreal injection every 4 weeks for the first 3 doses, then every 8 weeks through week 48. At week 16, the ABP 938 group continued on ABP 938 (n = 273), whereas the aflibercept RP group was rerandomized to continue on aflibercept RP (n = 136) or transition to ABP 938 (n = 134).<br><br>MAIN OUTCOME MEASURES: The primary efficacy end point was the least squares (LS) mean difference in change in best-corrected visual acuity (BCVA), measured by ETDRS letter score, from baseline to week 8. Secondary efficacy end points, safety, and immunogenicity were analyzed descriptively. In a substudy of patients, serum drug concentration profiles were assessed.<br><br>RESULTS: Demographic and baseline characteristics and exposure to treatment were similar between groups. Among initially randomized patients, the LS mean difference in change from baseline in BCVA at week 8 between ABP 938 and aflibercept RP was 0.1, with a 2-sided 95% confidence interval (CI: -1.3, 1.5) and 90% CI (-1.1, 1.3) falling within prespecified similarity margins (-3.9, 3.9, and -3, 3, respectively); thus, the primary clinical efficacy end point was met. Secondary efficacy end points (parallel-arm and posttransition) were overall similar between groups. No clinically meaningful differences were observed in the incidence of ocular and nonocular adverse events or events of interest. A low and similar incidence of binding antidrug antibodies was observed in all groups. The substudy confirmed low systemic exposure of free drug concentrations of ABP 938 and aflibercept RP.<br><br>CONCLUSIONS: This study supports the conclusion of no clinically meaningful differences in efficacy, safety, and immunogenicity between ABP 938 and aflibercept RP in patients with nAMD. Additionally, transitioning from aflibercept RP to APB 938 at week 16 resulted in comparable efficacy, safety, and immunogenicity between treatment groups.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40771083, year = {2025}, author = {Mentzer, ZT and Park, YC and Zanjani, MB}, title = {Elucidating the Drug Delivery Mechanism in Porous Antibody Implants Using Molecular Simulations and Graph Theory.}, journal = {The journal of physical chemistry. B}, volume = {129}, number = {33}, pages = {8406-8413}, pmid = {40771083}, issn = {1520-5207}, support = {R03 TR004429/TR/NCATS NIH HHS/United States ; }, mesh = {Porosity ; *Molecular Dynamics Simulation ; *Drug Delivery Systems ; *Antibodies/chemistry ; Drug Liberation ; *Drug Implants/chemistry ; }, abstract = {Drug delivery systems (DDSs) are utilized in the treatment of diseases by controlling the release rate of antibodies in a targeted location. One such form of DDSs is biodegradable polymer-based implants to circumvent traditional treatment processes such as antibody injections. In diseases such as macular degeneration, intravitreal injections are administered weekly/biweekly. These injections are painful for patients and prove to be inconvenient for obtaining transportation to and from appointments, as macular degeneration may cause partial blindness. In order to address this challenge, previous efforts have been made to create a biodegradable ocular DDS to administer antibody dosages over longer periods of time. In this work, a computational framework was developed to investigate the fundamental behavior and translocation of antibody agents through a porous membrane by employing molecular dynamics simulations and graph theory. Through this analysis, the results demonstrate that the release behavior of antibodies is highly correlated to the composition and geometric features of the pore network within the membrane. The computational models developed in this work provide insight into the design of long-term DDSs and can pave the way for future experiments that aim to improve the efficiency of polymer-based drug delivery systems.}, }
@article {pmid40771483, year = {2025}, author = {Tian, M and Zhang, B}, title = {Identification of risk factors for the progression of age-related macular degeneration: a systematic review and meta-analysis of cohort studies.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1544765}, pmid = {40771483}, issn = {2296-858X}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a retinal degenerative disease that primarily affects the elderly population and is a leading cause of vision loss in older adults. There is a lack of research comprehensively examining the risk factors for AMD progression. This study aimed to identify the risk factors influencing the development of AMD using a meta-analysis approach.<br><br>METHODS: We systematically searched the PubMed, Embase, and Cochrane Library databases from their inception until November 2024. Summary effect estimates were assigned as odds ratios (ORs) with 95% confidence intervals (CIs) using a random effects model. Further exploratory analyses included sensitivity and sub-group analyses.<br><br>RESULTS: Eighteen cohort studies involving 38,697 individuals were included in the final meta-analysis. We noted male versus female was associated with a reduced risk of AMD (OR: 0.84; 95% CI: 0.72-0.98; p&#x202f;=&#x202f;0.027). The identified risk factors for AMD included per 5-year increment in age (OR: 1.14; 95% CI: 1.09-1.19; p&#x202f;<&#x202f;0.001), current smoking (OR: 1.28; 95% CI: 1.07-1.52; p&#x202f;=&#x202f;0.007), alcohol intake (OR: 1.30; 95% CI: 1.00-1.67; p&#x202f;=&#x202f;0.046), per 1&#x202f;mmol/L increment in high-density lipoprotein (OR: 1.21; 95% CI: 1.08-1.36; p&#x202f;=&#x202f;0.001), total drusen >10% of the grid (OR: 7.85; 95% CI: 4.66-13.23; p&#x202f;<&#x202f;0.001), presence of depigmentation (OR: 6.39; 95% CI: 2.48-16.44; p&#x202f;<&#x202f;0.001), presence of hyperpigmentation (OR: 6.03; 95% CI: 1.94-18.73; p&#x202f;=&#x202f;0.002), and >10 small drusen (OR: 7.21; 95% CI: 2.10-24.72; p&#x202f;=&#x202f;0.002).<br><br>CONCLUSION: This study systematically identified the risk factors for AMD progression, and exploratory analyses were performed to determine the risk factors for early and late AMD. Patients at high risk of AMD should be monitored to improve modifiable risk factors and slow the progression of AMD.<br><br>INPLASY platform (INPLASY2024120036).}, }
@article {pmid40772916, year = {2026}, author = {Pastor-Idoate, S and Redruello-Guerrero, P and de Juan Hernández, L and Benites-Narcizo, G and Rivera-Izquierdo, M and García-Arumí, J and Pastor Jimeno, JC}, title = {Interventions for submacular haemorrhage: A systematic review and network meta-analysis of controversies-On behalf of the Spanish Vitreo-Retinal Society (SERV).}, journal = {Acta ophthalmologica}, volume = {104}, number = {2}, pages = {139-163}, pmid = {40772916}, issn = {1755-3768}, mesh = {Humans ; *Retinal Hemorrhage/therapy/diagnosis ; *Visual Acuity ; *Vitrectomy/methods ; Network Meta-Analysis as Topic ; *Societies, Medical ; Spain ; *Ophthalmology ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; }, abstract = {PURPOSE: This systematic review aims to evaluate and synthesize the existing literature on the interventions used for submacular haemorrhage (SMH), highlighting the controversies and differences in clinical practice.<br><br>METHOD: A systematic review was conducted following the PRISMA guidelines. A comprehensive search was performed across multiple databases, including MEDLINE, EMBASE and Cochrane Library, to identify studies on SMH treatment. Inclusion criteria encompassed randomized controlled trials, cohort studies and case series that focused on different therapeutic interventions. Data on functional outcomes, efficacy and safety of the interventions were extracted and analysed.<br><br>RESULTS: The review included 150 studies, of which 38 were included in the network meta-analysis. The analysis of best corrected visual acuity (BCVA) Included 26 studies, 20 interventions and 2125 eyes. Heterogeneity was moderate (I[2]&#x2009;=&#x2009;28.9%). Non-vitrectomy therapies showed better BCVA outcomes and fewer complications (e.g. retinal detachment, vitreous haemorrhage), while vitrectomy-based treatments achieved better anatomical results. According to P-score ranking, "Observation" had the highest probability of being most effective for BCVA (P-score&#x2009;=&#x2009;0.8051), followed by anti-VEGF monotherapy and non-vitrectomy combinations. However, this result should be interpreted cautiously, as the "Observation" group was based on only two studies (26 eyes) with clinical heterogeneity. No publication bias was detected (Egger's test p&#x2009;=&#x2009;0.582).<br><br>CONCLUSIONS: There is no consensus on a standard evidence-based treatment for SMH. Minimally invasive strategies are promising, but factors such as timing, lesion size and anti-VEGF use remain critical. Further large-scale randomised trials are needed to define optimal management.}, }
@article {pmid40773002, year = {2026}, author = {Hikichi, T and Kurabe, H and Notoya, A and Oguro, Y and Hirano, M and Doi, Y}, title = {Comparison of 1-year outcomes after switching to faricimab in neovascular age-related macular degeneration previously treated with anti-VEGF agents with/without a loading phase.}, journal = {Japanese journal of ophthalmology}, volume = {70}, number = {1}, pages = {157-165}, pmid = {40773002}, issn = {1613-2246}, mesh = {Humans ; Retrospective Studies ; Male ; Intravitreal Injections ; Female ; Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Follow-Up Studies ; Tomography, Optical Coherence ; Treatment Outcome ; *Drug Substitution ; Fluorescein Angiography ; Aged, 80 and over ; Time Factors ; Ranibizumab/administration &amp; dosage ; Fundus Oculi ; Macula Lutea/pathology ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To compare the 1-year outcomes after switching to faricimab with/without a loading phase of three monthly injections followed by a treat-and-extend (TAE) regimen in eyes with neovascular age-related macular degeneration previously treated with anti-VEGF agents.<br><br>STUDY DESIGN: Retrospective consecutive case study.<br><br>METHODS: Eyes with persistent exudative changes despite injection intervals of 10 weeks or less were switched to faricimab between June 2022 and December 2023 and included in this study. All eyes switched to faricimab between June 2022 and June 2023 received a single injection followed by a treat and extend (TAE) regimen (group 1). Thereafter, all eyes switched to faricimab received three consecutive monthly injections followed by a TAE regimen (group 2).<br><br>RESULTS: Of 153 eyes switched to faricimab, 21 eyes (17 in group 1, four in group 2) were excluded because of discontinuation of faricimab due to persistent exudative changes despite bimonthly injections; 132 eyes of 132 patients were analyzed. Faricimab treatment significantly improved the best-corrected visual acuity, anatomic parameters, with extended injection interval 1 year after the switch in 132 eyes and 45 eyes of group 2. That improvement, except the injection interval in 87 eyes of group 1, did not reach significance. The injection interval in group 2 was extended significantly compared with group 1 (P=0.023).<br><br>CONCLUSION: Switching to faricimab with a loading phase followed by a TAE regimen may improve outcomes in previously treated eyes. Further studies are warranted to confirm these findings.}, }
@article {pmid40774393, year = {2026}, author = {Gao, J and Wang, W and Mo, Y}, title = {Retinal degenerative diseases: Complement system-microglia crosstalk.}, journal = {Survey of ophthalmology}, volume = {71}, number = {2}, pages = {346-360}, doi = {10.1016/j.survophthal.2025.08.005}, pmid = {40774393}, issn = {1879-3304}, mesh = {Humans ; *Microglia/physiology/immunology ; *Complement System Proteins/physiology ; *Retinal Degeneration/immunology/metabolism ; Complement Activation/physiology ; Animals ; }, abstract = {Retinal degenerative diseases (RDD) are a group of age-related blinding eye diseases characterized by progressive degeneration and functional impairment of retinal photoreceptors or ganglion cells, for which there are currently no effective treatments. The complement system is an important innate immune system in the human body, activated through 3 pathways (classical pathway, lectin pathway, and alternative pathway) to ultimately form a membrane attack complex that acts on target cells. Microglia are the innate immune cells of the retina, responsible for maintaining retinal homeostasis. Complement system activation and microglial activation have been identified in RDD. Complement activation products C3 and C5 generate anaphylatoxins C3a and C5a, whose receptors C3aR and C5aR1 can activate microglia. Activated microglia can further produce complement C1q to activate the complement system, forming a positive feedback loop that exacerbates retinal damage. In this review, we focus on the crosstalk between the complement system and microglia in age-related macular degeneration, diabetic retinopathy, glaucoma, and pathological myopia-related retinal degeneration, and summarize clinical studies targeting the complement system and microglia for the treatment of RDD.}, }
@article {pmid40775583, year = {2025}, author = {Ding, Y and Dong, Y and Wei, W}, title = {Protective Role of Erzhi Pills in H2O2-Induced Oxidative Stress, Inflammation, and Angiogenesis in ARPE-19 Cells.}, journal = {Biochemical genetics}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10528-025-11214-z}, pmid = {40775583}, issn = {1573-4927}, support = {81774370//National Natural Science Foundation of China (NSFC)/ ; }, abstract = {This research was purposed to explore the role and mechanism of Erzhi pills (EZP) in age-related macular degeneration (AMD). TCSMP, PubChem, SwissTargetPrediction, and TargetNet databases were utilized to identify the active ingredients and targets of EZP, while disease targets were obtained from the DISEASES and DisGeNET databases. All identified targets were standardized using the UniProt platform. Overlapping targets between the drug and disease were determined using the Jvenn tool, and these targets were subsequently imported into the STRING database for network analysis. Enrichment analyses were conducted using the gProfiler web tool. The hub gene network was constructed utilizing Cytoscape software. Molecular docking studies were performed to assess the interactions between key components and their respective targets. A total of 16 active ingredients and 310 targets of EZP were identified, with 46 targets overlapping with disease-related targets, which implicated pathways involving inflammatory response, angiogenesis, and HIF-1α signaling. The top five hub genes identified were KDR, STAT3, mTOR, ESR1, and HIF1A. In vitro experiments, the CCK-8 assay, DCFH-DA staining, ELISA, tube formation assay, RT-qPCR, and Western blot analysis were conducted to evaluate the cellular biological behaviors and protein expression levels. The results showed that EZP could reduce H2O2-induced ROS accumulation, proinflammatory cytokine release, and promote angiogenesis. EZP inactivated HIF-1α pathway. EZP might target HIF-1α pathway to suppress oxidative stress, inflammation, and angiogenesis in H2O2-exposed ARPE-19 cells.}, }
@article {pmid40776277, year = {2025}, author = {Deng, Q and Kishimoto, K and Sugiyama, O and Miyake, M and Tamura, H}, title = {Automatic Extraction of Images for Prognostic Prediction Models in Age-Related Macular Degeneration.}, journal = {Studies in health technology and informatics}, volume = {329}, number = {}, pages = {1878-1879}, doi = {10.3233/SHTI251260}, pmid = {40776277}, issn = {1879-8365}, mesh = {Humans ; *Macular Degeneration/diagnostic imaging/diagnosis ; Prognosis ; *Deep Learning ; *Image Interpretation, Computer-Assisted/methods ; }, abstract = {Age-related macular degeneration, one of the primary causes of blindness, requires effective prediction of mid-term treatment outcomes to support the ongoing administration of the standard therapy. Our previous work relied on specialist interpretation and manual extraction of images, which limits their applicability in broader practical application. To address this limitation, this study aims to develop a deep learning-based framework capable of automatically identifying an optimal "champion" image from a set of candidate images.}, }
@article {pmid40778359, year = {2025}, author = {Liu, X and Yao, L and Hao, H and Wu, J and Jin, K and Gao, Q and Wang, X and Liao, D and Wang, N and Xiang, X and Chen, M and Zhao, Y and Ye, J}, title = {Assessment of Choriocapillaris in Healthy and Diseased Eyes Using 3-Dimensional Topographic Maps Based on OCT Angiography.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100828}, pmid = {40778359}, issn = {2666-9145}, abstract = {PURPOSE: To achieve clear in vivo imaging and systematic quantification of choriocapillaris (CC), enabling the exploration of age-related and disease-related changes of CC within a large sample size.<br><br>DESIGN: Cross-sectional study.<br><br>PARTICIPANTS: A total of 1050 eyes from 727 individuals, comprising 633 healthy eyes, 277 eyes with age-related macular degeneration (AMD), and 140 eyes with high myopia.<br><br>METHODS: The 3-dimensional (3D) topographic maps of CC were obtained by performing image enhancement, depth reconstruction, and 3D rendering on a single OCT angiography enface image. Based on this map, we targeted key quantitative parameters to analyze vessel thickness, vascular complexity, vascular distribution uniformity, and blood perfusion of CC. We statistically analyzed the correlation between CC metrics and age in healthy population, as well as differences in CC metrics between healthy and diseased populations. To further explore the association between changes in CC and choroidal large vessels, we defined a parameter called "arterial zone (AZ) to venous zone (VZ) ratio" to assess the choroidal large-vessel perfusion.<br><br>MAIN OUTCOME MEASURES: The 3D topographic map of CC, 8 parameters of CC, and AZ/VZ.<br><br>RESULTS: The 3D topographic map effectively displayed the morphology of CC while maintaining high image accuracy. Statistical analysis revealed that with aging, the vessel thickness of CC in healthy eyes became thicker, and there was a decrease in vascular complexity, distribution uniformity, and perfusion. Additionally, AZ/VZ exhibited a trend of initial decline followed by an increase. In eyes with increasing severity of AMD, the vessel thickness of CC showed bidirectional changes followed by significant thickening. Complexity and distribution uniformity initially increased, followed by a marked decrease, whereas blood perfusion decreased initially before increasing. However, no significant intergroup differences in AZ/VZ were observed. In highly myopic eyes, compared to healthy eyes, the CC exhibited vessel thickening, reduced complexity and distribution uniformity, decreased perfusion, and a significant reduction in AZ/VZ.<br><br>CONCLUSIONS: This study explores age-related and disease-related CC changes via clear in vivo imaging and quantification. It aids understanding of CC states and may contribute to early disease diagnosis and prognosis.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40778363, year = {2025}, author = {Saeed, A and Guymer, RH and Hadoux, X and Jannaud, M and Dang, D and Hodgson, LAB and Glover, EK and Gee, EE and van Wijngaarden, P and Wu, Z}, title = {Targeted Defect-Mapping Microperimetry in Geographic Atrophy: A Sensitive Functional Outcome Measure for Intervention Trials.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100856}, pmid = {40778363}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the effectiveness of targeted defect-mapping microperimetry (DMP) for capturing progressive visual function loss in eyes with a small extent of geographic atrophy (GA).<br><br>DESIGN: Prospective longitudinal study.<br><br>PARTICIPANTS: Twenty-seven eyes from 25 participants with <0.75 disc areas of GA, seen over 145 visits in total.<br><br>METHODS: All participants underwent high-density targeted DMP testing of a 4&#xb0; radius region-of-interest. Two tests were performed at each visit, and participants were reviewed at 3-monthly intervals up to a 24-month period. Spearman rank correlations were calculated to assess structure-function relationships between the proportion of locations missed (PLM; nonresponse to 10-decibel stimuli) on each test and GA extent in the corresponding region tested. Targeted DMP outcome measures were derived based on evaluating the PLM from all test locations, or only from points adjacent to locations that were repeatably nonresponding on both baseline tests. These DMP outcome measures, and GA extent in the central 8&#xb0; radius region, were compared based on the coefficient of variation (CoV; representing performance for capturing longitudinal changes) and sample size requirements for trials powered to detect a &#x2265;30% treatment effect.<br><br>MAIN OUTCOME MEASURES: Correlation coefficients, CoV, and sample size estimates.<br><br>RESULTS: There was a strong and moderate structure-function correlation between the PLM on targeted DMP and GA extent in the corresponding region tested at the cross section and longitudinally, respectively (correlation coefficient = 0.88 and 0.57, respectively). Evaluating PLM from points &#x2264;0.5&#xb0; adjacent to repeatably nonresponding locations at baseline was the best-performing DMP outcome measure (CoV = 71%), which was comparable with evaluating GA extent in the central 8&#xb0; region (CoV = 80%). Evaluating this DMP outcome measure reduced the sample size of a 24-month trial by 46% compared with evaluating GA extent.<br><br>CONCLUSIONS: Targeted DMP testing can provide a sensitive functional outcome measure for trials that can capture longitudinal changes as effectively as measuring structural changes in eyes with a small extent of GA. The high structure-function correlations observed suggests that beneficial treatment effects on GA growth would likely be accompanied by corresponding evidence of functional benefit captured by targeted DMP testing.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40778701, year = {2025}, author = {Bora, K and Liu, CH and Kushwah, N and Maurya, M and Pavlovich, MC and Solt, LA and Sun, Y and Fu, Z and Akula, JD and Chen, J}, title = {Genetic Loss of RORα Impairs Visual Function With Rod Bipolar Cell Degeneration In Mice.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {11}, pages = {20}, pmid = {40778701}, issn = {1552-5783}, support = {R01 EY029238/EY/NEI NIH HHS/United States ; R01 EY017017/EY/NEI NIH HHS/United States ; R01 EY030140/EY/NEI NIH HHS/United States ; R01 DK135300/DK/NIDDK NIH HHS/United States ; R01 EY028100/EY/NEI NIH HHS/United States ; R01 DK136298/DK/NIDDK NIH HHS/United States ; R01 EY024963/EY/NEI NIH HHS/United States ; R01 EY031765/EY/NEI NIH HHS/United States ; R01 EY032492/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Electroretinography ; Mice ; *Retinal Bipolar Cells/pathology/metabolism ; *Nuclear Receptor Subfamily 1, Group F, Member 1/genetics/biosynthesis ; *Retinal Rod Photoreceptor Cells/pathology/metabolism ; Disease Models, Animal ; *Retinal Degeneration/genetics/physiopathology/metabolism/pathology ; Mice, Inbred C57BL ; Immunohistochemistry ; Mice, Knockout ; }, abstract = {PURPOSE: Retinoic acid receptor-related orphan receptor alpha (RORα) is a ligand-dependent nuclear receptor involved in eye development and diseases. Genetic variations of RORα have been linked with the development of age-related macular degeneration, yet whether RORα regulates visual function is unknown. In this study we investigated the role of RORα in regulating visual function in mice with genetic deficiency of RORα.<br><br>METHODS: ROR&#x3b1; deficient staggerer (Rorasg/sg) and age-matched wild type control mice were assessed for visual function using electroretinography (ERG). Retinal localization of ROR&#x3b1; and rod bipolar cell morphology were assessed using immunohistochemistry. Retinal thickness was measured as well as presence of retinal gliosis, and expression of genes in visual transduction.<br><br>RESULTS: ROR&#x3b1; is expressed in photoreceptors, retinal ganglion cells, and bipolar cells. Genetic deletion of ROR&#x3b1; in Rorasg/sg mice markedly impaired visual function measured by ERG, with substantial attenuation of b-wave amplitude compared with wild type controls, reflective of bipolar cell dysfunction. Rorasg/sg eyes showed significant degeneration of rod bipolar cells and retinal gliosis, both of which progressed upon aging. Moreover, loss of ROR&#x237a; also resulted in significant retinal thinning, including both outer and inner nuclear layers. Expression of genes involved in phototransduction and rod bipolar cell depolarization was upregulated in Rorasg/sg retinas, suggestive of potential compensatory remodeling of visual signaling.<br><br>CONCLUSIONS: Our findings demonstrate that ROR&#x3b1; is indispensable for the structural and functional maintenance of rod bipolar cells and could pose as a potential therapeutic target for mitigating bipolar cell deficits in retinal degenerative diseases.}, }
@article {pmid40779887, year = {2025}, author = {Liu, F and Li, Q and Yang, Y and Lu, F}, title = {Visual cycle and LC3-associated phagocytosis in retina: regulatory mechanisms and therapeutic potential.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {190}, number = {}, pages = {118423}, doi = {10.1016/j.biopha.2025.118423}, pmid = {40779887}, issn = {1950-6007}, mesh = {Humans ; *Phagocytosis/physiology/drug effects ; Animals ; *Retina/metabolism/drug effects/pathology ; *Microtubule-Associated Proteins/metabolism ; *Vision, Ocular/physiology/drug effects ; }, abstract = {The visual cycle plays a pivotal dual role in retina, while it's essential for maintaining vision through continuous regeneration of the light-sensitive 11-cis-retinal chromophore. Its dysregulation contributes significantly to retinal degenerative disorders including age-related macular degeneration (AMD) and Stargardt disease. Recent advances have elucidated multiple therapeutic targets in visual cycle, ranging from inhibition of enzymatic activity of RPE65 and lecithin retinol acyltransferase (LRAT) to modulation of retinoid transport proteins and enhancement of protective LC3-associated phagocytosis. Pharmacological interventions of the visual cycle demonstrate promising results in reducing toxic retinoid accumulation, though clinical application faces challenges including nyctalopia, delayed dark adaptation, and dyschromatopsia. Future research directions emphasize the need for targeted visual cycle modulators that can selectively disrupt pathological processes without compromising essential visual function. This review summarizes the visual cycle and LC3-associated phagocytosis associated with various retinal diseases, highlights recent advances in pharmacological modulation of visual cycle, and aims to provide new insights into therapeutic strategies for retinal degenerative disorders.}, }
@article {pmid40781266, year = {2025}, author = {Liu, S and Zhang, O and Wang, H and Zhou, S and Luo, P}, title = {Association between age-related macular degeneration and osteoporosis in US.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {29045}, pmid = {40781266}, issn = {2045-2322}, support = {GSP2-07//the Subject Fund of High-level Chinese Medicine Hospital of China Academy of Traditional Chinese Medicine/ ; WJZJ-202415//the construction project of high-level traditional Chinese medicine hospital, Wangjing Hospital, China Academy of Chinese Medical Sciences/ ; }, mesh = {Humans ; *Macular Degeneration/epidemiology/complications ; Female ; Male ; *Osteoporosis/epidemiology/complications ; Aged ; United States/epidemiology ; Cross-Sectional Studies ; Middle Aged ; Nutrition Surveys ; Bone Density ; Absorptiometry, Photon ; Risk Factors ; Aged, 80 and over ; }, abstract = {It has been hypothesized that there could be a potential link between low bone mineral density (BMD) and age-related macular degeneration (AMD). This hypothesis has prompted us to conduct a more in-depth exploration of whether an intrinsic association exists between the two. As a result, we undertook a cross-sectional study using the NHANES database to investigate the potential associations between osteoporosis and AMD. A cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008. AMD was determined by a standardized grading system based on the presence of key features of AMD in color photographs of the macula. The BMD of the spine and femur was assessed by dual-energy X-ray absorptiometry (DXA). Multivariate logistic regression analysis was performed to examine the relationship between osteoporosis and AMD after adjustment for potential confounders. To address potential non-linear relationships, restricted cubic spline regression was employed. Multivariate regression analysis revealed that osteoporosis was significantly associated with all types of AMD (early and late: OR, 2.25; P < 0.001), early AMD (OR, 2.05; P = 0.003) and late AMD (OR, 4.25; P = 0.022) in women. In men, osteoporosis was not associated with any type of AMD. In women, the status of osteoporosis in the total femoral, femoral neck, femoral trochanter and spine showed a nonlinear relationship with AMD (P for nonlinear<0.05). Our findings suggest that osteoporosis plays a role in AMD development in women.}, }
@article {pmid40782213, year = {2025}, author = {Terao, R and Obata, R and Okubo, A and Aoki, S and Azuma, K and Inoda, S and Hashimoto, Y and Yoshida, H and Misawa, M and Takahashi, H and Takahashi, H}, title = {Aqueous humor cytokine profile in insufficient responder to aflibercept for neovascular age-related macular degeneration.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {326}, pmid = {40782213}, issn = {1573-2630}, mesh = {Humans ; *Aqueous Humor/metabolism ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; Female ; Male ; Prospective Studies ; *Cytokines/metabolism ; Aged ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/metabolism/diagnosis ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; Follow-Up Studies ; Treatment Outcome ; Visual Acuity ; Tomography, Optical Coherence ; Middle Aged ; Biomarkers/metabolism ; }, abstract = {PURPOSE: To identify cytokines associated with insufficient response to aflibercept against neovascular age-related macular degeneration.<br><br>METHODS: This prospective, comparative control study enrolled 40 eyes of 40 patients with nAMD. Aqueous humor (AH) samples were collected at the baseline before the intravitreal administration of aflibercept. The patients were further classified into responder and non-responder groups based on the clinical course. Patients were classified as "responders" if they required three or fewer additional injections after the three initial monthly loading doses within one year, and as non-responders, if they required four or more injections after the initial three-monthly loading doses or were switched to alternative anti-VEGF agents or treatments such as photodynamic therapy. The concentration of Angiopoietin 1, angiopoietin like 4 (ANGPTL4), interferon gamma-induced protein 10, hepatocyte growth factor, interleukin 10, platelet derived growth factor BB, plasminogen activator inhibitor 1 (PAI1), vascular endothelial growth factor A, angiopoietin 2, monocyte chemotactic protein 1, IL8, IL12, platelet-derived growth factor (PlGF), and vascular cell adhesion molecule 1 in AH samples were analyzed using a multiplex immunoassay, in order to compare between responders and non-responders.<br><br>RESULTS: 21 eyes were defined as responders, and 19 eyes were defined as non-responders. There were no significant differences in baseline characteristics. Multiple variate analysis using logistic regression analysis found that PAI1 (p&#x2009;=&#x2009;0.023, coefficient&#x2009;=&#x2009;0.025), PlGF (p&#x2009;=&#x2009;0.016, coefficient&#x2009;=&#x2009;-&#x2009;1.4), and ANGPTL4 (p&#x2009;=&#x2009;0.032, coefficient&#x2009;=&#x2009;-&#x2009;0.00070) at the baseline were significantly associated with the resistance to aflibercept.<br><br>CONCLUSION: Baseline higher PAI1 and lower PlGF and ANGPTL4 were associated with insufficient response to aflibercept in 1&#xa0;year. These cytokines can potentially predict the treatment effect against nAMD.}, }
@article {pmid40782305, year = {2025}, author = {Doi, Y and Hata, M and Kawashima, Y and Tamiya, R and Ideyama, M and Kido, A and Miyata, M and Ueda-Arakawa, N and Tamura, H and Ooto, S and Ogino, K and Tsujikawa, A}, title = {One-year outcomes of three-monthly and four-monthly loading regimens of faricimab for treatment-naïve neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {263}, number = {11}, pages = {3073-3079}, pmid = {40782305}, issn = {1435-702X}, support = {21H03092//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; Intravitreal Injections ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence ; Aged ; Treatment Outcome ; Follow-Up Studies ; Fluorescein Angiography ; *Macula Lutea/pathology ; Time Factors ; Aged, 80 and over ; Dose-Response Relationship, Drug ; Fundus Oculi ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Choroid/pathology ; Drug Administration Schedule ; Middle Aged ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To compare the efficacy of different loading doses of faricimab by comparing the outcomes following four-monthly and three-monthly loading regimens in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Patients diagnosed with treatment-na&#xef;ve nAMD who received intravitreal injection of faricimab were retrospectively enrolled from clinical database at the Japanese Red Cross Wakayama Medical Center (JRCW) and Kyoto University Hospital (KUHP) between July 1, 2022, and April 31, 2023. Patients at JRCW and KUHP received four-monthly and three-monthly loading regimens, respectively. Changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and dry macula ratio were evaluated before initial treatment, two months after the final injection in the loading phase (Month 2) and one year after the initial treatment (Year 1). Dosing intervals were determined based on disease activity two and three months after the final injection of the loading phase.<br><br>RESULTS: This study included 24 and 25 eyes in the three-dose and four-dose groups, respectively. BCVA, CMT, and SFCT significantly improved in both cohorts at Month 2 (all P&#x2009;<&#x2009;0.01). After the loading phase, the doing intervals was similar between the two groups (P&#x2009;=&#x2009;0.58). These improvements were sustained through Year 1 (all P&#x2009;<&#x2009;0.01), with no significant differences in changes in BCVA, CMT, or SFCT between the groups at Year 1 (P&#x2009;=&#x2009;0.58, 0.50, and 0.41, respectively).<br><br>CONCLUSIONS: Morphological and functional efficacy over one year was comparable between the four- and three-dose faricimab loading regimens.<br><br>KEY MESSAGES: What is known Faricimab, a bispecific antibody targeting both VEGF-A and Ang-2, is emerging as a promising therapeutic for neovascular AMD. Although a four-dose loading regimen was adopted in the pivotal TENAYA and LUCERNE trials, its superiority over the more conventional three-dose protocol remains uncertain in clinical practice. What is new In this study, we directly compared the four- and three-monthly loading regimens and found no significant differences in the dosing intervals and morphological and functional efficacy at 1 year. For both typical age-related macular degeneration and polypoidal choroidal vasculopathy, the dosing intervals and morphological and functional efficacy were comparable between the four- and three-monthly loading regimens.}, }
@article {pmid40785034, year = {2025}, author = {Huang, Y and Zhou, Z and Huan, M and Guo, Q and Zhang, X and Lu, R and Chen, L and Li, X and Yao, J and Jiang, Q and Xu, Y}, title = {Superoxide Activates Ferroptosis via the Haber-Weiss Reaction and Enhances Age-Related Macular Degeneration.}, journal = {Aging cell}, volume = {24}, number = {10}, pages = {e70195}, pmid = {40785034}, issn = {1474-9726}, support = {81972742//National Natural Science Foundation of China/ ; 82271107//National Natural Science Foundation of China/ ; 82471111//National Natural Science Foundation of China/ ; BK20221186//Natural Science Foundation of Jiangsu Province/ ; }, mesh = {*Ferroptosis/drug effects ; *Macular Degeneration/metabolism/pathology ; Animals ; *Superoxides/metabolism ; Mice ; Humans ; Retinal Pigment Epithelium/metabolism/pathology ; Superoxide Dismutase/metabolism ; Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; Superoxide Dismutase 2 ; }, abstract = {Antioxidant decline is crucial to driving age-related macular degeneration (AMD). Ferroptosis, a regulated cell death mediated by iron-dependent hydroxyl radical-catalyzed phospholipid peroxidation through the Fenton reaction, is implicated in various chronic degenerative diseases. Here, we show that superoxide activates ferroptosis in retinal pigment epithelium (RPE) cells via the Haber-Weiss reaction, thereby contributing to dry AMD. We silenced manganese superoxide dismutase (MnSOD/SOD2) in RPE cells and exposed the cells to blue light to induce ferroptosis by increasing superoxide anions. Additionally, MnSOD deficiency triggered the Hsp70-linked ubiquitin-dependent degradation of GPX4, further aggravating ferroptosis. We validated blue light-induced ferroptosis in the RPE layer as a driver of the dry AMD phenotype in Sod2[+/-] mice. Consequently, SOD mimetics efficiently protected RPE against phototoxicity by reducing superoxide-activated ferroptosis. Iron chelators or overexpressing GPX4 sufficiently eradicated ferroptosis. The finding reveals that excessive superoxide contributes to phospholipid peroxidation, providing a promising approach for preventing dry AMD by elevating MnSOD to inhibit RPE cell ferroptosis.}, }
@article {pmid40785250, year = {2025}, author = {Lewis-Luján, LM and Pérez Martínez, CJ and Iloki-Lewis, AP and Guerrero-Magaña, DE and Vargas-Durazo, J and Galvez-Ruiz, JC and Barnet, GF and Trujillo-López, S and Osadchuk, MA and Trushin, MV and Iloki-Assanga, SB}, title = {Role of Polyphenols in the Prevention and Treatment of Age-Related Macular Degeneration.}, journal = {Molecular nutrition &amp; food research}, volume = {69}, number = {21}, pages = {e70199}, doi = {10.1002/mnfr.70199}, pmid = {40785250}, issn = {1613-4133}, mesh = {Humans ; *Polyphenols/pharmacology/therapeutic use ; *Macular Degeneration/prevention &amp; control/drug therapy ; Antioxidants/pharmacology/therapeutic use ; Curcumin/pharmacology/therapeutic use ; Animals ; Oxidative Stress/drug effects ; Resveratrol ; Neuroprotective Agents/pharmacology ; Quercetin/pharmacology/therapeutic use ; Catechin/analogs &amp; derivatives/pharmacology ; Stilbenes/pharmacology/therapeutic use ; Dietary Supplements ; Anti-Inflammatory Agents/pharmacology ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, driven by oxidative stress, inflammation, and mitochondrial dysfunction. Polyphenols-bioactive compounds in fruits, vegetables, tea, and wine-exert antioxidant, antiinflammatory, and neuroprotective effects, modulating key molecular pathways involved in AMD progression. This review highlights the mechanisms by which specific polyphenols such as resveratrol, curcumin, quercetin, and EGCG contribute to retinal protection. Preclinical and clinical studies support the integration of polyphenol-rich diets or supplements as potential strategies in AMD prevention and therapy.}, }
@article {pmid40788856, year = {2025}, author = {Yao, CS and Lue, V and Stinnett, SS and Luhmann, UFO and Lad, EM}, title = {Association of National Eye Institute Visual Function Questionnaire 39 Scores With Visual Function in Age-related Macular Degeneration Over 24 Months.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {56}, number = {9}, pages = {526-533}, doi = {10.3928/23258160-20250717-01}, pmid = {40788856}, issn = {2325-8179}, mesh = {Humans ; *Visual Acuity/physiology ; Male ; Female ; Aged ; Surveys and Questionnaires ; *Macular Degeneration/physiopathology ; National Eye Institute (U.S.) ; United States ; *Sickness Impact Profile ; Aged, 80 and over ; Visual Fields/physiology ; Middle Aged ; Contrast Sensitivity/physiology ; Dark Adaptation/physiology ; Visual Field Tests ; Quality of Life ; Follow-Up Studies ; }, abstract = {BACKGROUND AND OBJECTIVE: The aim of this study was to determine the National Eye Institute Visual Function Questionnaire 39 (NEI-VFQ39) score association with visual function (VF) tests in early (eAMD) and intermediate (iAMD) age-related macular degeneration.<br><br>PATIENTS AND METHODS: Thirty-three eAMD, 47 iAMD, 21 control subjects completed the NEIVFQ39 at baseline and 22 eAMD, 31 iAMD, 17 control subjects at 24 months. Best-corrected visual acuity (BCVA), low luminance visual acuity (LLVA), cone contrast test (CCT), microperimetry (MP) with eye-tracking (MAIA), and dark adaptation (DA) testing were administered during both visits.<br><br>RESULTS: At baseline and 24 months, iAMD patients scored lower NEI-VFQ39 composite scores than eAMD participants and controls (P < 0.05); longitudinal changes showed no differences between groups. Baseline composite scores were associated with LLVA (Spearman-r = 0.33, P < 0.001), percent-reduced threshold (PRT) (r = -0.33, P = 0.001), and absolute threshold (AT) (r = 0.31, P = 0.003) on MP.<br><br>CONCLUSION: Although the NEI-VFQ39 did not detect change over 24 months, these results support the use of NEI-VFQ39 as a cross-sectional tool in iAMD.}, }
@article {pmid40788858, year = {2025}, author = {Montolío-Marzo, S and Pinazo, RG and Palacios-Pozo, E and Dolz-Marco, R}, title = {New Method to Facilitate Tomographic Macular Neovascularization Classification in Age-related Macular Degeneration.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {56}, number = {9}, pages = {540-544}, doi = {10.3928/23258160-20250717-02}, pmid = {40788858}, issn = {2325-8179}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; *Wet Macular Degeneration/classification/diagnosis ; Aged ; Male ; *Choroidal Neovascularization/classification/diagnosis ; *Macular Degeneration/complications/classification/diagnosis ; Fluorescein Angiography ; Aged, 80 and over ; Reproducibility of Results ; }, abstract = {BACKGROUND AND OBJECTIVE: Evaluation of contrast-modified optical coherence tomography (OCT) images as a tool for better macular neovascularization (MNV) classification in age-related macular degeneration (AMD) cases.<br><br>PATIENTS AND METHODS: Twenty-five OCT images obtained with SPECTRALIS (Heidelberg Engineering GmbH) from patients showing MNV (10 type 1, 10 type 2, and 5 type 3) were selected. Two retina specialists (RDM and RGP) classified the MNV lesions and then the same cases were classified by 37 ophthalmologists with different degree of training. A grading tool was designed to classify these cases using standard OCT images (contrast value: 12) followed by reassessment with contrast-modified OCT images (contrast value: 1).<br><br>RESULTS: Thirty-seven ophthalmologists were involved: four 1st-year trainees, four 2nd-year trainees, four 3rd-year trainees, 12 4th-year trainees, and 13 consultants from different subspecialties. Average result for correct classification was 13.16 using standard images alone and 14.22 using contrast-modified images showing a significant improvement (P = 0.01). The accuracy was greater for type 1 lesions when using contrast-modified images, whereas there was no improvement with type 2 and 3 lesions (P = 0.039, P = 0.835, P = 0.193). The average correct answers was greater for type 2 (&#xb5; = 5.08) than type 1 (&#xb5; = 5.08) and type 3 (&#xb5; = 2) (P = 0.046). The graders (n; %) classified the utility of contrast-modified images as essential (1; 2,7%), very useful (29; 78.4%), indifferent (5; 13.5%), not very useful (1; 2.7%) and useless (1; 2.7%).<br><br>CONCLUSIONS: In challenging cases, it might be easier to locate the retinal pigment epithelium (RPE), evaluate RPE integrity, classify MNV, and study subretinal hyperreflective material using contrast enhanced OCT images. The accuracy for MNV classification increases with contrast-modified images in type 1 MNV. It is an accessible tool that could show even better performance as the ophthalmologist gains more experience using it.}, }
@article {pmid40789472, year = {2025}, author = {Cuello-Rodríguez, S and Blanco-Fernández, G and García-Otero, X and Díaz-Tome, V and Otero-Espinar, FJ and Seoane-Viaño, I}, title = {Long acting injectables &amp; implants: advances in intraocular drug delivery.}, journal = {International journal of pharmaceutics}, volume = {683}, number = {}, pages = {126058}, doi = {10.1016/j.ijpharm.2025.126058}, pmid = {40789472}, issn = {1873-3476}, mesh = {Humans ; *Drug Delivery Systems/methods ; Delayed-Action Preparations/administration &amp; dosage ; *Drug Implants/administration &amp; dosage ; Intravitreal Injections ; Animals ; *Eye Diseases/drug therapy ; Drug Liberation ; }, abstract = {The treatment of posterior segment ocular diseases, such as age-related macular degeneration and diabetic retinopathy, poses a significant challenge for ophthalmologists due to the eye's complex anatomy and physiological barriers. To overcome these challenges, intravitreal drug delivery offers a promising solution by enabling direct administration of therapeutic agents into the pathological area through an injection. However, these injections are highly invasive and carry several risks, including infection, retinal detachment, and increased intraocular pressure. As a result, considerable efforts have been directed toward developing drug delivery platforms (implants, nano- and microparticles, and hydrogels) capable of providing sustained drug release over extended periods. These long-acting systems aim to reduce the frequency of injections, thereby improving patient quality of life and decreasing the overall economic burden of treatment. This review provides an overview of intravitreal drug delivery systems, evaluating their clinical applicability and the potential challenges that must be addressed before they can be successfully translated into marketed drug products.}, }
@article {pmid40791802, year = {2025}, author = {Gómez-Benlloch, A and Widmer-Pintos, JN and Arnaldos-López, C}, title = {Reactive Orbital Myositis as a First Manifestation of Renal Cell Carcinoma.}, journal = {Case reports in ophthalmology}, volume = {16}, number = {1}, pages = {551-558}, pmid = {40791802}, issn = {1663-2699}, abstract = {INTRODUCTION: Orbital myositis (OM) is an inflammatory condition of the extraocular muscles, often idiopathic but occasionally associated with systemic diseases or malignancies. Secondary OM due to metastatic disease is rare. We report a case of OM as the initial manifestation of metastatic renal cell carcinoma, emphasizing the need for comprehensive evaluation of atypical ocular presentations.<br><br>CASE PRESENTATION: An 81-year-old male with a history of age-related macular degeneration presented with acute onset of pain and restricted movement in his left eye. Computed tomography imaging revealed an osteolytic lesion in the left sphenoid bone, causing reactive myositis. Further systemic evaluation identified a left renal mass with evidence of pulmonary and skeletal metastases. A core needle biopsy confirmed the diagnosis of metastatic renal cell carcinoma. Given the advanced disease stage, the patient was managed with palliative treatment. Despite medical interventions, he succumbed to the disease 6 months after symptom onset.<br><br>CONCLUSION: This case underscores the significance of considering malignancy in the differential diagnosis of OM, particularly in elderly patients with atypical ocular symptoms. Early recognition and systemic evaluation are crucial for timely diagnosis and management of underlying malignancies presenting with orbital involvement.}, }
@article {pmid40792095, year = {2025}, author = {Arikan, D and Esfandiari, M and Zhang, P and Sommersperger, M and Dehghani, S and Taylor, RH and Ali Nasseri, M and Gehlbach, P and Navab, N and Iordachita, I}, title = {Towards Motion Compensation in Autonomous Robotic Subretinal Injections.}, journal = {... International Symposium on Medical Robotics. International Symposium on Medical Robotics}, volume = {2025}, number = {}, pages = {66-72}, pmid = {40792095}, issn = {2831-3690}, support = {R01 EB023943/EB/NIBIB NIH HHS/United States ; R01 EB025883/EB/NIBIB NIH HHS/United States ; R01 EB034397/EB/NIBIB NIH HHS/United States ; }, abstract = {Exudative (wet) age-related macular degeneration (AMD) is a leading cause of vision loss in older adults, typically treated with intravitreal injections. Emerging therapies, such as subretinal injections of stem cells, gene therapy, small molecules and RPE cells require precise delivery to avoid damaging delicate retinal structures. Robotic systems can potentially offer the necessary precision for these procedures. This paper presents a novel approach for motion compensation in robotic subretinal injections, utilizing real time Optical Coherence Tomography (OCT). The proposed method leverages B[5]-scans, a rapid acquisition of small-volume OCT data, for dynamic tracking of retinal motion along the Z-axis, compensating for physiological movements such as breathing and heartbeat. Validation experiments on ex vivo porcine eyes revealed challenges in maintaining a consistent tool-to-retina distance, with deviations of up to 200 μm for 100 μm amplitude motions and over 80 μm for 25 μm amplitude motions over one minute. Subretinal injections faced additional difficulties, with phase shifts causing the needle to move off-target and inject into the vitreous. These results highlight the need for improved motion prediction and horizontal stability to enhance the accuracy and safety of robotic subretinal procedures.}, }
@article {pmid40798886, year = {2025}, author = {Kim, YC and Kim, S and Kim, TW and Hong, SC and Seo, HJ and Jeong, JH and Lim, HK and Um, YH}, title = {Association Between Eye Diseases and Sleep Duration: A Nationwide Cross-Sectional Study.}, journal = {Psychiatry investigation}, volume = {22}, number = {9}, pages = {1038-1047}, pmid = {40798886}, issn = {1738-3684}, support = {2020R1I1A1A01057792//National Research Foundation of Korea/ ; //Ministry of Science and ICT/ ; }, abstract = {OBJECTIVE: The visual system plays a crucial role in regulating sleep by providing cues that synchronize the circadian rhythm. Consequently, ophthalmic diseases-particularly diabetic retinopathy (DMR), age-related macular degeneration (AMD), epiretinal membrane (EM), and glaucoma-may influence sleep duration through circadian disruption and disease-related psychological stress. However, large-scale studies examining the relationship between these conditions and sleep duration remain limited. This study investigated these associations in a nationwide, population-based sample.<br><br>METHODS: This cross-sectional study analyzed data from the 2019 and 2020 the Korea National Health and Nutrition Examination Survey. Ophthalmic diseases were diagnosed through fundoscopy, and sleep duration on weekdays and weekends was self-reported. The study included 8,395 participants aged 40 years or older who underwent fundoscopy. Statistical models were adjusted for demographic and clinical covariates, including age, sex, body mass index, and comorbidities.<br><br>RESULTS: Patients with DMR and EM had significantly reduced sleep duration, with reductions of 0.3 hours to 0.5 hours on weekdays and weekends compared to individuals without these conditions. No significant differences in sleep duration were observed for AMD or glaucoma. After covariate adjustment, the associations between shorter sleep duration and DMR or EM remained significant.<br><br>CONCLUSION: This nationwide population-based study using fundus photography revealed that DMR and EM are significantly associated with reduced sleep duration, while AMD and glaucoma are not. These findings suggest a differential sleep impact by disease type and support the need for targeted evaluation and management of sleep in patients with ophthalmic diseases. Further research is warranted to clarify underlying mechanisms and guide public health strategies.}, }
@article {pmid40799295, year = {2025}, author = {Ochoa, A and Brinson, J and Chin Loy, K and Yousuf, SJ}, title = {Associations between Electronic Cigarettes, Smokeless Tobacco, and Age-related Macular Degeneration in the 2017 United States National Health Interview Survey.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251362886}, pmid = {40799295}, issn = {2474-1272}, abstract = {Purpose: To investigate the association of cigarette-alternative tobacco products with age-related macular degeneration (AMD). Methods: The 2017 National Health Interview Survey, comprising epidemiologic data from a nationally representative sample of the US adult population, was queried to identify all participants who reported using electronic cigarettes (e-cigarettes) and smokeless tobacco and whether or not they had AMD. Participant characteristics were analyzed and a multivariable regression was performed to determine predictors of AMD, adjusting for age, sex, race/ethnicity, number of packs of cigarettes smoked per day, and body mass index. Results: The final analytic sample included 26 689 survey respondents, representing the US national population of 246 242 859 adults. The weighted prevalence of AMD was 1.9% (95% confidence interval [95% CI], 1.8-2.1%). Compared to those without AMD, adults with AMD were significantly older, more often female, and disproportionately non-Hispanic White (P < .0001). In adjusted models (including adjustment for number of packs of cigarettes smoked per day), the odds ratios for developing AMD were 1.49 (95% CI, 1.02 to 2.18) in adults who used smokeless tobacco products and 1.08 (95% CI, 0.73 to 1.60) in adults who used e-cigarettes, compared to those who had never used these products. Conclusions: This study identified smokeless tobacco use as a novel factor associated with AMD among a nationally representative sample, suggesting its avoidance may reduce the risk of developing AMD. Additional studies are needed to better understand the long-term effects of e-cigarettes on AMD.}, }
@article {pmid40799657, year = {2025}, author = {Hadzijahic, N and Kim, CK and Djulbegovic, MB and Antonietti, M and Taylor Gonzalez, DJ and Uversky, VN and Pulido, JS and Karp, CL}, title = {The effects of retinal disease on intrinsic protein disorder and liquid-liquid‑phase separation.}, journal = {Journal of proteins and proteomics}, volume = {}, number = {}, pages = {}, pmid = {40799657}, issn = {2524-4663}, support = {P30 EY014801/EY/NEI NIH HHS/United States ; }, abstract = {BACKGROUND: The human retina is integral to vision, converting light into neural signals through a complex interplay of specialized neuronal cell types. Recent proteomic studies have revealed significant insights into retinal function, yet much of the retina's proteome remains unexplored. Our research focuses on quantifying and characterizing intrinsically disordered proteins (IDPs) and regions (IDRs) within the retina and other ocular structures. These proteins are critical for cellular processes due to their flexible, structure-less nature, allowing for versatile interactions in signaling and regulatory networks. Furthermore, we investigate the phenomenon of liquid-liquid-phase separation (LLPS), a process vital for cellular organization and implicated in various diseases, within the retina proteome.<br><br>METHODS: In this study, we employed a suite of bioinformatics and deep learning tools to analyze protein intrinsic disorder and the propensity for LLPS in proteomes from both healthy and diseased retinas. We utilized the Human Protein Atlas (HPA) as a baseline control, comparing it against the RetNet protein set and samples afflicted by age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR) with and without gliosis. Protein sequences were sourced from the universal protein resource (UniProt) and analyzed for intrinsic disorder using the rapid intrinsic disorder analysis online (RIDAO) platform. Disorder levels and phase separation tendencies were further examined through statistical analyses, including ANOVA and chi-squared tests, to evaluate differences across proteomes. In addition, we assessed the likelihood of proteins to undergo LLPS using predictive tools, such as PSPredictor and ParSe V2, integrating these findings with intrinsic disorder data to draw comprehensive conclusions about the structural dynamics within these proteomes.<br><br>RESULTS: The HPA control proteome displayed the highest levels of intrinsic disorder, significantly greater than those observed in disease-specific proteomes, including those affected by AMD, glaucoma, and diabetic retinopathy with and without gliosis. CH-CDF plot analysis revealed distinct structural profiles, with a higher proportion of structured proteins in the HPA and molten globular states prevalent in disease states. Our findings highlight a marked disparity in LLPS propensity, with the HPA proteome and the RetNet Protein Set demonstrating the greatest potential, suggesting a disease-specific alteration in protein interaction dynamics and structural organization.<br><br>DISCUSSION: This study revealed significant variations in protein intrinsic disorder and liquid-LLPS across healthy and diseased retinal proteomes. The highest levels of disorder in the HPA proteome suggest a proteomic flexibility that is critical for normal retinal function. In contrast, the AMD and glaucoma proteomes, with their lower disorder and LLPS propensity, may lack this adaptability, potentially contributing to disease progression. These insights underscore the importance of protein dynamics in retinal disorders and point towards targeted therapies that could manipulate these properties to improve or maintain retinal health.}, }
@article {pmid40800169, year = {2025}, author = {Guo, B and Wang, D and Zhang, R and Hou, J and Liu, W and Wu, Y and Yang, X and Zhang, L}, title = {WaveAttention-ResNet: a deep learning-based intelligent diagnostic model for the auxiliary diagnosis of multiple retinal diseases.}, journal = {Frontiers in radiology}, volume = {5}, number = {}, pages = {1608052}, pmid = {40800169}, issn = {2673-8740}, abstract = {OBJECTIVE: This study constructs a deep learning-based combined algorithm named WaveAttention ResNet (WARN) to investigate the classification accuracy for seven common retinal diseases and the feasibility of AI-assisted diagnosis in this field.<br><br>METHODS: First, a deep learning-based classification network is constructed. The network is built upon ResNet18, integrated with the Convolutional Block Attention Module (CBAM) and wavelet convolution modules, forming the WARN method for retinal disease classification. Second, the public OCTDL dataset is used to train WARN, which contains classification data for seven retinal disease types: age-related macular degeneration (AMD), diabetic macular edema (DME), epiretinal membrane (ERM), normal (NO), retinal artery occlusion (RAO), retinal vein occlusion (RVO), and vitreomacular interface disease (VID). During this process, ablation experiments and significance tests are conducted on WARN, and comprehensive analyses of various indicators for WARN, ResNet-18, ResNet-50, Swin Transformer v2, EfficientNet, and Vision Transformer (ViT) are performed in retinal disease classification tasks. Finally, data provided by Shanxi Eye Hospital are used for testing, and classification results are analyzed.<br><br>RESULTS: WARN demonstrates excellent performance on the public OCTDL dataset. Ablation experiments and significance tests confirm the effectiveness of WARN, achieving an accuracy of 90.68%, F1-score of 91.29%, AUC of 97.50%, precision of 93.31%, and recall of 90.68% with relatively short training time. In the dataset from Shanxi Eye Hospital, WARN also performs well, with a recall of 90.85%, precision of 79.94%, and accuracy of 89.18%.<br><br>CONCLUSION: This study fully confirms that the constructed WARN is efficient and feasible for classifying seven common retinal diseases. It further highlights the enormous potential and broad application prospects of AI technology in the field of auxiliary medical diagnosis.}, }
@article {pmid40800716, year = {2025}, author = {Robinson, K and Cooper, SJ and Persaud, S and Frederick, JL and Singh, RP}, title = {Discordance Among Patients and Ophthalmologists Regarding the Burden of Intravitreal Injections.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {2637-2645}, pmid = {40800716}, issn = {1177-5467}, abstract = {PURPOSE: To determine how patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) perceive their disease and its treatment and to assess the degree of alignment between patient and clinician perceptions.<br><br>PATIENTS AND METHODS: In June 2024 a survey of 101 patients (50 with DME and 51 with nAMD) and 100 ophthalmologists who treat these conditions completed surveys.<br><br>RESULTS: Sixty-six percent and 86% of patients with DME and nAMD, respectively, reported receiving intravitreal injections at least once every 8&#xa0;weeks. Eighty-two percent required a caregiver and/or public transportation to get to their appointments. The most significant symptoms for patients with DME were vision loss over time (2.89 out of 4.0) and blurred or double vision (2.76), and for those with nAMD were poor night vision (3.43), seeing in low-light conditions (3.27), and blurred vision (2.96). The proportion of patients who were dissatisfied with the education and counseling they received about their disease was greater for nAMD (31%) compared with DME (11%; P < 0.01). Ophthalmologists overestimated the extent to which patients perceived that injections were necessary (mean Likert scale score 3.41 vs 3.00; P < 0.01) and that patients experienced insurance barriers to receiving treatment (3.00 vs 2.46; P < 0.01). They overestimated the extent to which patients became less nervous with subsequent injections after the first (3.40 vs 2.94; P < 0.01) and underestimated their difficulty of getting to appointments (2.30 vs 2.64; P < 0.01).<br><br>CONCLUSION: This study highlights the significant burden experienced by patients undergoing intravitreal injections and identifies key areas of discordance between patient and clinician perceptions. Targeted education and counseling focused on these differences is indicated to improve patient satisfaction and outcomes.}, }
@article {pmid40801600, year = {2025}, author = {Miller, RD and Mondon, I and Ellis, C and Muir, AM and Turner, S and Keeling, E and Wai, HA and Chatelet, DS and Johnson, DA and Tumbarello, DA and Lotery, AJ and Baralle, D and Ratnayaka, JA}, title = {Whole RNA-Seq Analysis Reveals Longitudinal Proteostasis Network Responses to Photoreceptor Outer Segment Trafficking and Degradation in RPE Cells.}, journal = {Cells}, volume = {14}, number = {15}, pages = {}, pmid = {40801600}, issn = {2073-4409}, support = {1/CX/CSRD VA/United States ; BB/T008768/1 to C.E//The BBSRC South Coast Doctoral Training Partnership/ ; RP-2016-07- 011//National Institute for Health and Care Research Professorship to D.B/ ; }, mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/cytology ; *Proteostasis/genetics ; *Retinal Photoreceptor Cell Outer Segment/metabolism ; *RNA-Seq ; Lysosomes/metabolism ; Cell Line ; Protein Transport ; Proteolysis ; Autophagy/genetics ; RNA, Messenger/genetics/metabolism ; Transcriptome ; Gene Regulatory Networks ; }, abstract = {RNA-seq analysis of the highly differentiated human retinal pigment epithelial (RPE) cell-line ARPE-19, cultured on transwells for ≥4 months, yielded 44,909 genes showing 83.35% alignment with the human reference genome. These included mRNA transcripts of RPE-specific genes and those involved in retinopathies. Monolayers were fed photoreceptor outer segments (POS), designed to be synchronously internalised, mimicking homeostatic RPE activity. Cells were subsequently fixed at 4, 6, 24 and 48 h when POS were previously shown to maximally co-localise with Rab5, Rab7, LAMP/lysosomes and LC3b/autophagic compartments. A comprehensive analysis of differentially expressed genes involved in proteolysis revealed a pattern of gene orchestration consistent with POS breakdown in the autophagy-lysosomal pathway. At 4 h, these included elevated upstream signalling events promoting early stages of cargo transport and endosome maturation compared to RPE without POS exposure. This transcriptional landscape altered from 6 h, transitioning to promoting cargo degradation in autolysosomes by 24-48 h. Longitudinal scrutiny of mRNA transcripts revealed nuanced differences even within linked gene networks. POS exposure also initiated transcriptional upregulation in ubiquitin proteasome and chaperone-mediated systems within 4-6 h, providing evidence of cross-talk with other proteolytic processes. These findings show detailed evidence of transcriptome-level responses to cargo trafficking and processing in RPE cells.}, }
@article {pmid40801672, year = {2025}, author = {Ansari, G and Schärer, N and Pfau, K and Valmaggia, P and Gabrani, C and Zuche, H and Giani, A and Esmaeelpour, M and Yamaguchi, TC and Feltgen, N and Maloca, PM and Schmetterer, L and Scholl, HPN and Pfau, M}, title = {Evaluating the Progression of Retinal Sensitivity Loss in Geographic Atrophy Using Machine-Learning-Based Structure-Function Correlation (OMEGA 2).}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {11}, pages = {34}, pmid = {40801672}, issn = {1552-5783}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Male ; *Geographic Atrophy/physiopathology/diagnosis ; Female ; Aged ; Tomography, Optical Coherence/methods ; *Machine Learning ; *Retina/physiopathology ; Disease Progression ; Visual Field Tests ; *Visual Fields/physiology ; Visual Acuity/physiology ; Middle Aged ; Aged, 80 and over ; Follow-Up Studies ; }, abstract = {PURPOSE: The purpose of this study was to evaluate the effectiveness of different machine-learning models in predicting retinal sensitivity in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and compare the progression of sensitivity loss using observed versus inferred data over time.<br><br>METHODS: Thirty patients with GA (37 eyes) were recruited for the OMEGA study. Participants underwent fundus-controlled perimetry (microperimetry) and spectral-domain optical coherence tomography (SD-OCT) imaging at baseline and follow-up visits at weeks 12, 24, and 48. Retinal layers were segmented using a custom-written deep-learning algorithm. We used various machine-learning models, including random forest, LASSO regression, and multivariate adaptive regression splines (MARS), to predict retinal sensitivity across three scenarios: (1) unknown patients, (2) known patients at later visits, and (3) interpolation within visits. Predictive accuracy was evaluated using the mean absolute error (MAE), and the models' ability to reduce test variability over time was analyzed using linear mixed models.<br><br>RESULTS: The random forest model demonstrated the highest accuracy across all scenarios, with an MAE of 3.67 decibels (dB) for unknown patients, 2.96 dB for known patients at follow-up, and 3.10 dB for within-visit interpolation. The inferred sensitivity data significantly reduced variability compared to the observed data in longitudinal mixed model analysis, with a residual variance of 2.72 dB&#xb2; versus 8.67 dB&#xb2;, respectively.<br><br>CONCLUSIONS: Machine-learning models, particularly the random forest model, effectively predict retinal sensitivity in patients with GA, with patient-specific baseline data improving accuracy for subsequent visits. Inferred sensitivity mapping presents a reliable, functional surrogate endpoint for clinical trials, offering high spatial resolution without extensive psychophysical testing.}, }
@article {pmid40802164, year = {2025}, author = {Khodor, A and Caranfa, JT and Nanda, T and Ruiz-Lozano, RE and Quiroga-Garza, ME and Choi, S and Chehab, A and Ramos-Dávila, EM and Heier, JS and Shah, CP and Witkin, AJ}, title = {Correction: Functional and Anatomical Outcomes of Faricimab in Previously Treated Wet Age-Related Macular Degeneration: Systematic Review and Pooled Analysis.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {10}, pages = {2621}, doi = {10.1007/s40123-025-01224-w}, pmid = {40802164}, issn = {2193-8245}, }
@article {pmid40802977, year = {2026}, author = {Carlà, MM and Scampoli, A and Grieco, G and Governatori, L and Catalani, R and Rizzo, S and Caporossi, T}, title = {MORPHOMETRIC CHANGES IN MACULAR NEOVASCULARIZATION ARCHITECTURE AFTER FARICIMAB TREATMENT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Comparison Between Naive and Switched Eyes.}, journal = {Retina (Philadelphia, Pa.)}, volume = {46}, number = {1}, pages = {125-135}, doi = {10.1097/IAE.0000000000004635}, pmid = {40802977}, issn = {1539-2864}, mesh = {Humans ; Prospective Studies ; Tomography, Optical Coherence/methods ; Male ; Female ; Fluorescein Angiography/methods ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Visual Acuity ; Follow-Up Studies ; *Macula Lutea/pathology ; Aged, 80 and over ; Fundus Oculi ; *Retinal Vessels/pathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To evaluate the morphometric changes in macular neovascularization (MNV) architecture after faricimab treatment in neovascular age-related macular degeneration, comparing treatment-naive and previously treated eyes.<br><br>METHODS: Prospective study analyzing 45 eyes (18 treatment naive, 27 switched) with neovascular age-related macular degeneration undergoing faricimab treatment. Optical coherence tomography angiography images were exported and the quantification of changes in MNV area, vessel area, vessel density, number of junctions, branching index, total vessel length, end points, and lacunarity was performed using AngioTool v0.6a. Follow-ups at baseline (V0), at the end of the loading phase (V1), and at 1 year (V2) were collected.<br><br>RESULTS: Baseline MNV characteristics differed significantly between treatment-naive and switched eyes. Switched eyes exhibited greater MNV area (P < 0.001), vessel area (P < 0.001), junction count (P = 0.004), vessel length (P < 0.001), average vessel length (P = 0.02), end point count (P = 0.002), and lacunarity (P = 0.04). Conversely, naive eyes had higher vessel density (P < 0.001) and branching index (P = 0.007). Posttreatment, MNV area (P < 0.001), vessel area (P < 0.001), junction count (P = 0.001), and total vessel length (P < 0.001) decreased, whereas lacunarity increased (P = 0.001). Greater changes were observed in naive eyes, but the end point count only reduced in switched eyes (P = 0.01), being stable in naive eyes. At V2, switched eyes still had larger MNV area (P = 0.007), vessel area (P = 0.004), junction count (P = 0.002), vessel length (P = 0.004), and end points (P = 0.007).<br><br>CONCLUSION: Faricimab induces significant and sustained remodeling of the MNV network in neovascular age-related macular degeneration, with more pronounced changes in treatment-naive eyes. These changes were primarily driven by the loading phase, but then remained stable toward the 1-year follow-up.}, }
@article {pmid40803555, year = {2026}, author = {Hong, AT and Luu, IY and Keenan, JD and Stewart, JM}, title = {Long-Term Metformin Use and Reduced Risk of Age-Related Macular Degeneration: A Large Database Study.}, journal = {Ophthalmology. Retina}, volume = {10}, number = {2}, pages = {135-141}, doi = {10.1016/j.oret.2025.07.018}, pmid = {40803555}, issn = {2468-6530}, mesh = {Humans ; *Metformin/administration &amp; dosage/therapeutic use ; Retrospective Studies ; Female ; Male ; Hypoglycemic Agents/administration &amp; dosage/therapeutic use ; Aged ; Databases, Factual ; *Macular Degeneration/epidemiology/prevention &amp; control ; Middle Aged ; Follow-Up Studies ; *Diabetes Mellitus, Type 2/drug therapy/complications ; Risk Factors ; Incidence ; Time Factors ; Aged, 80 and over ; Risk Assessment/methods ; Propensity Score ; }, abstract = {OBJECTIVE: To evaluate the association between metformin use and the risk of developing age-related macular degeneration (AMD) among patients with diabetes, with a focus on exposure duration and AMD subtypes.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Patients were identified from the TriNetX network using International Classification of Diseases, 10th Revision, and Current Procedural Terminology codes for diabetes and ophthalmic care. Patients aged &#x2265;60 years with diabetes and no documentation of AMD were included in the cohort.<br><br>METHODS: Patients were required to have no AMD diagnoses at 2 eye care visits &#x2265;1 year apart, with the second visit serving as the index event for analysis. The main exposure was yearly metformin use for &#x2265;5 years, with subanalysis up to 10 years. The outcome was incident AMD. Propensity score matching controlled for potential confounders, including demographics, comorbidities, medications, laboratory values, and health care utilization. The association between metformin and AMD was assessed using survival analysis. Results were reported as hazard ratios (HRs) with 95% confidence intervals (CIs).<br><br>MAIN OUTCOME MEASURES: The primary outcome was a new diagnosis of AMD. Secondary outcomes included a new diagnosis of dry AMD and wet AMD.<br><br>RESULTS: After propensity score matching, the main cohort analysis included 7496 patients, of whom 3748 had &#x2265;5 consecutive years of metformin use. Incident AMD was documented in 122 (3.3%) patients who had been exposed to metformin and 184 (4.9%) who had not (HR, 0.68; 95% CI, 0.54-0.85). The metformin group had lower rates of both dry AMD (HR, 0.69; 95% CI, 0.53-0.90) and wet AMD (HR, 0.84; 95% CI, 0.50-1.39), although the association with wet AMD was not statistically significant. The metformin use for &#x2265;6 consecutive years showed consistent protective effects; 1 to 4 years showed weaker associations.<br><br>CONCLUSIONS: Prolonged metformin use in patients with diabetes was associated with a reduction in AMD risk in this claims database. These findings suggest a potential protective role for metformin, warranting further exploration of its long-term effects on AMD prevention.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40806264, year = {2025}, author = {Hughes, D and Prestle, J and Zippel, N and McFetridge, S and Szczepan, M and Neubauer, H and Xu, H and Chen, M}, title = {Nintedanib Induces Mesenchymal-to-Epithelial Transition and Reduces Subretinal Fibrosis Through Metabolic Reprogramming.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806264}, issn = {1422-0067}, support = {xxxx//Boehringer Ingelheim/ ; }, mesh = {*Epithelial-Mesenchymal Transition/drug effects ; Animals ; Humans ; Fibrosis ; *Indoles/pharmacology ; Mice ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Transforming Growth Factor beta2/pharmacology/metabolism ; Cell Line ; Mice, Inbred C57BL ; Disease Models, Animal ; *Cellular Reprogramming/drug effects ; Metabolic Reprogramming ; }, abstract = {This study aimed to investigate the tyrosine kinase inhibitor Nintedanib and its potential role in reversing epithelial-mesenchymal transition (EMT) induced by transforming growth factor beta 2 (TGF-β2) in retinal pigment epithelial (RPE) cells, along with its therapeutic potential using a mouse model of subretinal fibrosis. We hypothesized that the blockade of angiogenesis promoting and fibrosis inducing signaling using the receptor tyrosine kinase inhibitor Nintedanib (OfevTM) can prevent or reverse EMT both in vitro and in our in vivo model of subretinal fibrosis. Primary human retinal pigment epithelial cells (phRPE) and adult retinal pigment epithelial cell line (ARPE-19) cells were treated with TGF-β210 ng/mL for two days followed by four days of Nintedanib (1 µM) incubation. Epithelial and mesenchymal phenotypes were assessed by morphological examination, quantitative real-time polymerase chain reaction(qPCR) (ZO-1, Acta2, FN, and Vim), and immunocytochemistry (ZO-1, vimentin, fibronectin, and αSMA). Metabolites were measured using luciferase-based assays. Extracellular acidification and oxygen consumption rates were measured using the Seahorse XF system. Metabolic-related genes (GLUT1, HK2, PFKFB3, CS, LDHA, LDHB) were evaluated by qPCR. A model of subretinal fibrosis using the two-stage laser-induced method in C57BL/6J mice assessed Nintedanib's therapeutic potential. Fibro-vascular lesions were examined 10 days later via fluorescence angiography and immunohistochemistry. Both primary and ARPE-19 RPE stimulated with TGF-β2 upregulated expression of fibronectin, αSMA, and vimentin, and downregulation of ZO-1, consistent with morphological changes (i.e., elongation). Glucose consumption, lactate production, and glycolytic reserve were significantly increased in TGF-β2-treated cells, with upregulation of glycolysis-related genes (GLUT1, HK2, PFKFB3, CS). Nintedanib treatment reversed TGF-β2-induced EMT signatures, down-regulated glycolytic-related genes, and normalized glycolysis. Nintedanib intravitreal injection significantly reduced collagen-1+ fibrotic lesion size and Isolectin B4+ neovascularization and reduced vascular leakage in the two-stage laser-induced model of subretinal fibrosis. Nintedanib can induce Mesenchymal-to-Epithelial Transition (MET) in RPE cells and reduce subretinal fibrosis through metabolic reprogramming. Nintedanib can therefore potentially be repurposed to treat retinal fibrosis.}, }
@article {pmid40806482, year = {2025}, author = {Balzamino, BO and Biamonte, F and Micera, A}, title = {Biomolecular Aspects of Reelin in Neurodegenerative Disorders: An Old Candidate for a New Linkage of the Gut-Brain-Eye Axis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806482}, issn = {1422-0067}, mesh = {*Reelin Protein/metabolism ; Humans ; *Neurodegenerative Diseases/metabolism ; Animals ; *Brain/metabolism ; Alzheimer Disease/metabolism ; Gastrointestinal Microbiome ; Macular Degeneration/metabolism ; }, abstract = {Recent findings highlight that Reelin, a glycoprotein involved in neural development, synaptic plasticity, and neuroinflammation, plays some specific roles in neurodegenerative disorders associated with aging, such as age-related macular degeneration (AMD) and Alzheimer's disease (AD). Reelin modulates synaptic function and guarantees homeostasis in neuronal-associated organs/tissues (brain and retina). The expression of Reelin is dysregulated in these neurological disorders, showing common pathways depending on chronic neurogenic inflammation and/or dysregulation of the extracellular matrix in which Reelin plays outstanding roles. Recently, the relationship between AMD and AD has gained increasing attention as they share many common risk factors (aging, genetic/epigenetic background, smoking, and malnutrition) and histopathological lesions, supporting certain pathophysiological crosstalk between these two diseases, especially regarding neuroinflammation, oxidative stress, and vascular complications. Outside the nervous system, Reelin is largely produced at the gastrointestinal epithelial level, in close association with innervated regions. The expression of Reelin receptors inside the gut suggests interesting aspects in the field of the gut-brain-eye axis, as dysregulation of the intestinal microbiota has been frequently described in neurodegenerative and behavioral disorders (AD, autism, and anxiety and/or depression), most probably linked to inflammatory, neurogenic mediators, including Reelin. Herein we examined previous and recent findings on Reelin and neurodegenerative disorders, offering findings on Reelin's potential relation with the gut-brain and gut-brain-eye axes and providing novel attractive hypotheses on the gut-brain-eye link through neuromodulator and microbiota interplay. Neurodegenerative disorders will represent the ground for a future starting point for linking the common neurodegenerative biomarkers (β-amyloid and tau) and the new proteins probably engaged in counteracting neurodegeneration and synaptic loss.}, }
@article {pmid40806731, year = {2025}, author = {Kisswani, D and Carroll, C and Valdes-Mora, F and Rutar, M}, title = {Epigenetic Alterations in Age-Related Macular Degeneration: Mechanisms and Implications.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806731}, issn = {1422-0067}, support = {1165599//National Health and Medical Research Council/ ; }, mesh = {Humans ; *Macular Degeneration/genetics/metabolism/pathology ; *Epigenesis, Genetic ; DNA Methylation ; Proto-Oncogene Mas ; Animals ; RNA, Long Noncoding/genetics ; }, abstract = {Age-related macular degeneration (AMD) is one of the leading causes of irreversible vision loss among the elderly, and is influenced by a combination of genetic and environmental risk factors. While genetic associations in AMD are well-established, the molecular mechanisms underlying disease onset and progression remain poorly understood. A growing body of evidence suggests that epigenetic modifications may serve as a potential missing link regulating gene-environment interactions. This review incorporates recent findings on DNA methylation, including both hypermethylation and hypomethylation patterns affecting genes such as silent mating type information regulation 2 homolog 1 (SIRT1), glutathione S-transferase isoform (GSTM), and SKI proto-oncogene (SKI), which may influence key pathophysiological drivers of AMD. We also examine histone modification patterns, chromatin accessibility, the status of long non-coding RNAs (lncRNAs) in AMD pathogenesis and in regulating pathways pertinent to the pathophysiology of the disease. While the field of ocular epigenetics remains in its infancy, accumulating evidence to date points to a burgeoning role for epigenetic regulation in AMD, pre-clinical studies have yielded promising findings for the prospect of epigenetics as a future therapeutic avenue.}, }
@article {pmid40806887, year = {2025}, author = {Kim, KE and Ahn, SJ}, title = {Visual Field Examinations for Retinal Diseases: A Narrative Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {15}, pages = {}, pmid = {40806887}, issn = {2077-0383}, support = {RS-2025-00561352//National Research Foundation of Korea/ ; }, abstract = {Visual field (VF) testing remains a cornerstone in assessing retinal function by measuring how well different parts of the retina detect light. It is essential for early detection, monitoring, and management of many retinal diseases. By mapping retinal sensitivity, VF exams can reveal functional loss before structural changes become visible. This review summarizes how VF testing is applied across key conditions: hydroxychloroquine (HCQ) retinopathy, age-related macular degeneration (AMD), diabetic retinopathy (DR) and macular edema (DME), and inherited disorders including inherited dystrophies such as retinitis pigmentosa (RP). Traditional methods like the Goldmann kinetic perimetry and simple tools such as the Amsler grid help identify large or central VF defects. Automated perimetry (e.g., Humphrey Field Analyzer) provides detailed, quantitative data critical for detecting subtle paracentral scotomas in HCQ retinopathy and central vision loss in AMD. Frequency-doubling technology (FDT) reveals early neural deficits in DR before blood vessel changes appear. Microperimetry offers precise, localized sensitivity maps for macular diseases. Despite its value, VF testing faces challenges including patient fatigue, variability in responses, and interpretation of unreliable results. Recent advances in artificial intelligence, virtual reality perimetry, and home-based perimetry systems are improving test accuracy, accessibility, and patient engagement. Integrating VF exams with these emerging technologies promises more personalized care, earlier intervention, and better long-term outcomes for patients with retinal disease.}, }
@article {pmid40807033, year = {2025}, author = {Jeong, A and Liang, H and Baek, SC and Sagong, M}, title = {Real-World Efficacy and Durability of Faricimab in Aflibercept-Resistant Neovascular Age-Related Macular Degeneration.}, journal = {Journal of clinical medicine}, volume = {14}, number = {15}, pages = {}, pmid = {40807033}, issn = {2077-0383}, abstract = {Objectives: This study aimed to evaluate the 6-month real-world outcomes of switching to faricimab in patients with aflibercept-resistant neovascular age-related macular degeneration (nAMD). Methods: A retrospective review was conducted on the eyes of 60 patients with aflibercept-resistant nAMD that were switched to faricimab. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, including central subfield thickness (CST), subfoveal choroidal thickness (SFCT), and both the maximum height and width of pigment epithelial detachment (PED), at baseline and 1, 3, and 6 months after switching were evaluated. The type of PED and retinal fluid were also analyzed. Results: The results showed that BCVA remained stable at month 6 (p = 0.150), while CST significantly decreased (p = 0.020), and SFCT remained unchanged (p = 0.072). The maximum PED height significantly decreased (p = 0.030), while the maximum PED width did not change (p = 0.07). The mean injection interval significantly increased from 6.8 ± 2.4 weeks before switching to 11.2 ± 1.7 weeks after switching (p = 0.068). Furthermore, the dry macula rate was 43.3% at month 6. Conclusions: Switching to faricimab in aflibercept-resistant nAMD patients showed stable visual outcomes, significant anatomical improvements, and reduced treatment burden over 6 months in real-world clinical settings.}, }
@article {pmid40808916, year = {2025}, author = {Kayembe-Mulumba, B and Leffondré, K and Merle, BMJ and Korobelnik, JF and Helmer, C and Tzourio, C and Delcourt, C and Cougnard-Grégoire, A and Delyfer, MN}, title = {Long-Term Blood Pressure Variability and Risk of Age-Related Macular Degeneration in Older Adults: The ALIENOR Study.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100878}, pmid = {40808916}, issn = {2666-9145}, abstract = {PURPOSE: Long-term blood pressure variability (BPV) has emerged as a risk factor for various health problems, including eye diseases, independent of blood pressure (BP) levels. Yet, its role in age-related macular degeneration (AMD) progression remains unknown. This study aimed to assess associations between long-term BPV and the risk of AMD.<br><br>DESIGN: Prospective analysis of 14-year data from the ALIENOR (Antioxydants, LIpides Essentiels, Nutrition et maladies OculaiRes) study, a French longitudinal population-based cohort study (2006-2020).<br><br>PARTICIPANTS: The ALIENOR study included 963 participants aged &#x2265;73 years from the Three-City (3C) study in Bordeaux, for an ophthalmic follow-up.<br><br>METHODS: Systolic BPV (SBPV), diastolic BPV (DBPV), and pulse pressure variability (PPV) were determined as the standard deviation of available BP measurements in 3C visits (1999-2017).<br><br>MAIN OUTCOME MEASURES: Age-related macular degeneration was assessed using retinal color photographs and OCT imaging every 2 years from 2006 to 2020. Shared random effects joint models fitted BPV current values and quantified their effect on AMD onset. The implemented Bayesian approach yielded the mean of adjusted posterior hazard ratios of AMD and their 95% credibility intervals (CrIs).<br><br>RESULTS: Of the 692 (median age: 79.0 years; 63.5% female) and 475 (median age: 78.5 years; 61.1% female) at-risk participants, 10% and 36% developed advanced and intermediate AMD, respectively. The hazard of advanced AMD was significantly increased by 54% for a 5-mmHg increase in DBPV (adjusted hazard ratio [aHR]: 1.54, 95% CrI: 1.02-2.44), whereas statistical significance was not reached for a 5-mmHg increase in SBPV (aHR: 1.20, 95% CrI: 0.96-1.51) and PPV (aHR: 1.17, 95% CrI: 0.88-1.54). Conversely, BPV was not significantly associated with intermediate AMD (aHR: 0.96, 95% CrI: 0.83-1.11; aHR: 0.96, 95% CrI: 0.71-1.30; and aHR: 0.92, 95% CrI: 0.77-1.09; for a 5-mmHg increase in SBPV, DBPV, and PPV, respectively).<br><br>CONCLUSIONS: This study suggested that long-term variability in BP may be associated with an increased risk of advanced AMD, particularly for DBP. These findings underscore the need for further research to confirm this association, explore the underlying mechanisms, and propose potential interventions that could mitigate this risk.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40809969, year = {2025}, author = {Liu, Z and Hammer, DX}, title = {Wide-field choriocapillaris mapping with 3.4 MHz adaptive optics-optical coherence tomography angiography.}, journal = {Biomedical optics express}, volume = {16}, number = {8}, pages = {3255-3269}, pmid = {40809969}, issn = {2156-7085}, abstract = {The human choriocapillaris (CC) plays an essential role in supporting the overlying photoreceptor and retinal pigment epithelial cells and in maintaining overall retinal health. Disruption of CC structure and function is implicated in many retinal diseases, including age-related macular degeneration. Despite recent advances in ophthalmic imaging technologies, a full understanding of disease mechanisms remains elusive due to the inability to visualize CC microstructure. Here, we present a 3.4 MHz adaptive optics-optical coherence tomography angiography (AO-OCTA) approach for mapping the human choriocapillaris at high resolution to address the primary limitations of existing methodologies for CC imaging. We optimized our AO-OCTA acquisition protocols and offered guidelines for performing AO-OCTA for vessel imaging. Our approach achieves high resolution and high contrast CC imaging with single volume acquisition that takes <1 second, allowing rapid montaging and quantification over a 34° field of view. The proposed AO-OCTA method offers a more complete view of the outer retinal neurovascular complex, opening tremendous opportunities to investigate chorioretinal diseases.}, }
@article {pmid40810576, year = {2025}, author = {Miao, H and Qu, T and Huang, Y and Fan, S and Yang, Y and Lv, A and Hu, J and Guo, L and Jia, Q and Li, Z and Zhang, S and Li, Y and Shi, W and Chen, Y and Chen, S and Yan, H}, title = {The Impact of Helicobacter pylori Infection on Retinal Nerve Fiber Layer and Macula.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {11}, pages = {35}, pmid = {40810576}, issn = {1552-5783}, mesh = {Humans ; *Helicobacter Infections/complications/diagnosis/microbiology ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; *Helicobacter pylori/isolation &amp; purification ; Tomography, Optical Coherence/methods ; *Nerve Fibers/pathology ; *Retinal Ganglion Cells/pathology ; *Macula Lutea/pathology ; Aged ; Adult ; *Eye Infections, Bacterial/microbiology/diagnosis ; *Macular Degeneration/diagnosis/epidemiology ; Incidence ; }, abstract = {PURPOSE: This study aims to elucidate the effects of Helicobacter pylori infection on the retinal nerve fiber layer (RNFL) and macula.<br><br>METHODS: A cross-sectional study was undertaken at the Health Examination Center of the First Hospital of Handan from 2021 to 2022. Participants who underwent both the 14C-urea breath test and ocular examinations were selected. The RNFL and macula were assessed using a swept-source optical coherence tomography device (Topcon OCT, Tokyo, Japan). Data are presented as mean &#xb1; SD and were analyzed using the Mann-Whitney U-test and t-test, with a significance level set at P < 0.05.<br><br>RESULTS: RNFL analysis of 1693 H. pylori-positive and 1693 negative left eyes revealed significantly thinner inferior temporal RNFL in the H. pylori-positive group (149.79 &#xb1; 29.55&#xa0;&#xb5;m vs. 152.76 &#xb1; 29.15&#xa0;&#xb5;m, P = 0.026). No other regional RNFL differences were found (P > 0.05). In the macula study of 2117 H. pylori-positive and 2117 negative participants, macular degeneration occurred in 74 positive (avgerage age 54.66 &#xb1; 10.08 years) and 67 negative individuals (avgerage age 60.22 &#xb1; 10.50 years). The incidence rates were not significantly different (P > 0.05), but the positive group with lesions was significantly younger (P = 0.002).<br><br>CONCLUSIONS: H. pylori infection may be associated with localized defects in the RNFL, which could serve as early indicators of glaucoma, and it may also be potentially linked to accelerated progression of macular degeneration.}, }
@article {pmid40811806, year = {2026}, author = {Arrigo, A and Aragona, E and Antropoli, A and Bianco, L and Saladino, A and Del Fabbro, S and Bandello, F and Parodi, MB}, title = {AGE-RELATED RETINAL PIGMENT EPITHELIUM DISEASE: Clinical and Differential Features.}, journal = {Retina (Philadelphia, Pa.)}, volume = {46}, number = {1}, pages = {108-114}, pmid = {40811806}, issn = {1539-2864}, mesh = {Humans ; Retrospective Studies ; *Retinal Pigment Epithelium/pathology ; Female ; Male ; *Fluorescein Angiography/methods ; Cross-Sectional Studies ; Aged ; *Tomography, Optical Coherence/methods ; Middle Aged ; Diagnosis, Differential ; Fundus Oculi ; Aged, 80 and over ; *Macular Degeneration/diagnosis ; Visual Acuity ; Multimodal Imaging ; }, abstract = {PURPOSE: We described the clinical characteristics of age-related retinal pigment epithelium disease (ARPED). This looks like an age-related, retinal disease showing a primary RPE involvement, no typical age-related macular degeneration features, and no pachychoroid-related characteristics.<br><br>METHODS: The study was designed as observational, both cross-sectional and retrospective investigation. We collected data from patients affected by ARPED, defined by precise diagnostic criteria. We performed both qualitative and quantitative multimodal retinal imaging investigations. The main outcome measure is the characterization of ARPED, defined by precise diagnostic criteria, about age-related macular degeneration. Secondary outcome is the identification of differential diagnostic features about other retinal diseases.<br><br>RESULTS: We included 31 ARPED eyes (62 patients). Intergraders agreement for detecting ARPED was 0.98 (P < 0.05). Age-related retinal pigment epithelium disease is characterized by the absence of age-related macular degeneration-related findings, such as drusen and pseudodrusen. Moreover, it is characterized by the absence of pachychoroid-related features, as also confirmed by fluorescein angiography and indocyanine green angiography.<br><br>CONCLUSION: Although further studies are warranted to better define ARPED features and if it may be considered a distinct macular disease, the characteristics of this clinical phenotype introduce new intriguing pathophysiologic features and should be carefully considered both in clinical practice and research contexts.}, }
@article {pmid40812794, year = {2026}, author = {Dong, L and Gao, W and Niu, L and Deng, Z and Gong, Z and Li, HY and Fang, LJ and Shao, L and Zhang, RH and Zhou, WD and Ma, L and Wei, WB}, title = {AI-based prediction of best-corrected visual acuity in patients with multiple retinal diseases using multimodal medical imaging.}, journal = {The British journal of ophthalmology}, volume = {110}, number = {2}, pages = {158-165}, pmid = {40812794}, issn = {1468-2079}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Visual Acuity/physiology ; Retrospective Studies ; *Multimodal Imaging/methods ; Male ; Female ; *Retinal Diseases/physiopathology/diagnosis/diagnostic imaging ; *Artificial Intelligence ; Middle Aged ; Algorithms ; Aged ; Adult ; Optic Disk/diagnostic imaging ; Fundus Oculi ; Fluorescein Angiography/methods ; }, abstract = {BACKGROUND/AIMS: This study evaluated the performance of artificial intelligence (AI) algorithms in predicting best-corrected visual acuity (BCVA) for patients with multiple retinal diseases, using multimodal medical imaging including macular optical coherence tomography (OCT), optic disc OCT and fundus images. The goal was to enhance clinical BCVA evaluation efficiency and precision.<br><br>METHODS: A retrospective study used data from 2545 patients (4028 eyes) for training, 896 (1006 eyes) for testing and 196 (200 eyes) for internal validation, with an external prospective dataset of 741 patients (1381 eyes). Single-modality analyses employed different backbone networks and feature fusion methods, while multimodal fusion combined modalities using average aggregation, concatenation/reduction and maximum feature selection. Predictive accuracy was measured by mean absolute error (MAE), root mean squared error (RMSE) and R&#xb2; score.<br><br>RESULTS: Macular OCT achieved better single-modality prediction than optic disc OCT, with MAE of 3.851 vs 4.977 and RMSE of 7.844 vs 10.026. Fundus images showed an MAE of 3.795 and RMSE of 7.954. Multimodal fusion significantly improved accuracy, with the best results using average aggregation, achieving an MAE of 2.865, RMSE of 6.229 and R&#xb2; of 0.935. External validation yielded an MAE of 8.38 and RMSE of 10.62.<br><br>CONCLUSION: Multimodal fusion provided the most accurate BCVA predictions, demonstrating AI's potential to improve clinical evaluation. However, challenges remain regarding disease diversity and applicability in resource-limited settings.}, }
@article {pmid40812795, year = {2025}, author = {Pu, J and Zhuang, X and Li, M and Zhang, X and Ji, Y and Mi, L and Hao, X and He, G and Su, Y and Gan, Y and Zhang, Y and Chen, X and Wen, F}, title = {Association between early lesion response and long-term anti-VEGF injection frequency in nAMD: a 2-year prospective study using 3D volumetric analysis.}, journal = {The British journal of ophthalmology}, volume = {110}, number = {1}, pages = {67-75}, doi = {10.1136/bjo-2025-327339}, pmid = {40812795}, issn = {1468-2079}, mesh = {Humans ; Prospective Studies ; *Angiogenesis Inhibitors/administration &amp; dosage ; Male ; Female ; Intravitreal Injections ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Ranibizumab/administration &amp; dosage ; Follow-Up Studies ; Fluorescein Angiography/methods ; Middle Aged ; *Imaging, Three-Dimensional/methods ; Visual Acuity ; Time Factors ; Subretinal Fluid ; *Bevacizumab/administration &amp; dosage ; Treatment Outcome ; Fundus Oculi ; }, abstract = {PURPOSE: To explore the association between early response of different lesions and the number of anti-vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective study included treatment-na&#xef;ve nAMD eyes with a 2-year follow-up period. Volumetric changes of multiple lesions during the loading phase were documented, including subretinal fluid (SRF), intraretinal fluid (IRF), vascular subretinal hyper-reflective material (vSHRM) and avascular subretinal hyper-reflective material, fibrovascular pigment epithelial detachment and serous pigment epithelial detachment (sPED) and total lesion. Imaging biomarkers associated with treatment frequency were analysed for 1-year and 2-year periods.<br><br>RESULTS: A total of 92 eyes (92 patients) were included, with a mean age of 65.77&#xb1;7.28 years. During the loading phase, all lesions except vSHRM showed significant temporal changes (p<0.05). Multivariate regression revealed that greater SRF changes at month 3 and IRF changes at month 1 were associated with increased injection frequency for both 1-year (&#x3b2;=0.353&#x2009;and 0.360, p=0.025&#x2009;and 0.022) and 2-year periods (&#x3b2;=0.336&#x2009;and 0.293, p=0.004&#x2009;and 0.026). Conversely, greater changes in vSHRM and sPED at month 2 were associated with fewer first-year injections (&#x3b2;=-0.307&#x2009;and -0.697, p=0.023&#x2009;and 0.022), while sPED changes at months 2 and 3 correlated with reduced 2-year requirements (&#x3b2;=-0.845&#x2009;and -0.297, p=0.005&#x2009;and 0.031).<br><br>CONCLUSION: Enhanced absorption of SRF and IRF during early treatment was associated with increased injection frequency, while greater absorption of vSHRM and sPED correlated with reduced treatment requirements.<br><br>TRIAL REGISTRATION NUMBER: ChiCTR2200063428.}, }
@article {pmid40813365, year = {2025}, author = {Schubert, A and Lobo Barbosa da Silva, ME and Ambrock, T and Terosian, O and Malyshkina, A and Padberg, C and Larafa, S and Matschke, J and Fandrey, J and Henning, Y}, title = {Targeting hypoxia-inducible factor-1 in a hypoxidative stress model protects retinal pigment epithelium cells from cell death and metabolic dysregulation.}, journal = {Cell death discovery}, volume = {11}, number = {1}, pages = {380}, pmid = {40813365}, issn = {2058-7716}, abstract = {Oxidative stress and hypoxia lead to dysfunction of retinal pigment epithelium (RPE) cells and are hallmarks of diseases such as age-related macular degeneration (AMD), the most common blinding disease in the elderly population. We have previously shown that a combination of these two risk factors, i.e. hypoxidative stress, exacerbates RPE cell death by ferroptosis. Hypoxia leads to stabilization of hypoxia-inducible factors (HIFs), key regulators of cellular adaptation to hypoxic conditions. In the present study, we have therefore investigated the roles of HIF-1 and HIF-2 in RPE cell death in a human RPE cell line under hypoxidative stress. For this purpose, we conducted siRNA-mediated knockdowns of the α-subunits of HIF-1 and HIF-2. We found that especially iron metabolism, in particular the expression of transferrin receptor 1 (TFR1) was affected by HIF-1α silencing, resulting in decreased intracellular iron levels and ferroptosis susceptibility. We also found that heme oxygenase 1 (HO-1) contributed to cell death by hypoxidative stress. In addition, we also observed that cell metabolism was improved by HIF-1α silencing under hypoxia, most likely contributing to the protective effect. Furthermore, we identified an FDA-approved small molecule inhibitor, Vorinostat, to downregulate HIF-1α, TFR1, and HO-1 and improve cell metabolism, which eventually resulted in a full rescue of RPE cells from hypoxidative stress-induced cell death. In conclusion, this study highlights the importance of considering targeted HIF inhibition as a promising approach to protect RPE cells from degeneration.}, }
@article {pmid40813679, year = {2025}, author = {Gao, S and Guo, D and Huang, P and Yin, N and Jia, H and Li, S and Sun, X and Zhu, X}, title = {Molecular marker discovery and detection for blinding eye disease.}, journal = {Journal of nanobiotechnology}, volume = {23}, number = {1}, pages = {565}, pmid = {40813679}, issn = {1477-3155}, mesh = {Humans ; *Biomarkers/analysis/metabolism ; Aqueous Humor/chemistry/metabolism ; Female ; Male ; *Chemokine CCL2/analysis/metabolism ; Aged ; Middle Aged ; Proteomics/methods ; *Macular Degeneration/diagnosis/metabolism ; Reproducibility of Results ; Adult ; Cataract/diagnosis/metabolism ; }, abstract = {Accurate, sensitive, and specific detection of molecular markers in intraocular fluid will facilitate the early discovery, diagnosis, and intervention of eye diseases. In this study, a total of 168 participants were recruited and divided into two distinct cohorts: discovery and verification. In the discovery phase, proteomic analysis identified MCP-1 in aqueous humor as a potential molecular marker for blinding eye disease. We further developed a molecular detection technology for the marker based on biolayer interference sensing. The technology utilizes a sandwich strategy with one-to-one pairing of two different biorecognition molecules for MCP-1. It also incorporates automation, high throughput, and real-time monitoring, achieving highly selective recognition and accurate analysis of MCP-1. It demonstrates a low detection limit (0.16 pM), good reliability (R[2] = 0.995), and a wide analytical range (0.244-1000 pM) for MCP-1 in human aqueous humor samples. Crucially, in the verification phase with 150 subjects, the technology achieved a high detection rate (95.0%) for patients with age-related macular degeneration and high myopia cataract in under 30 min, and was able to further differentiate between them with a specificity of 86.0%. Therefore, the developed molecular detection technology may provide a robust, convenient, and valuable solution for widespread screening, early discovery, and differential diagnosis of blinding eye diseases.}, }
@article {pmid40814089, year = {2025}, author = {Plasencia, C and Eschle, J and Hatz, K}, title = {Management and safety of same day bilateral intravitreal anti-VEGF injections in a treat-and-extend regimen.}, journal = {BMC ophthalmology}, volume = {25}, number = {1}, pages = {459}, pmid = {40814089}, issn = {1471-2415}, mesh = {Humans ; Intravitreal Injections ; Retrospective Studies ; *Ranibizumab/administration &amp; dosage ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; Female ; *Recombinant Fusion Proteins/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Visual Acuity ; *Macular Edema/drug therapy ; Middle Aged ; Retinal Vein Occlusion/drug therapy ; Aged, 80 and over ; *Wet Macular Degeneration/drug therapy ; }, abstract = {BACKGROUND: Anti-vascular endothelial growth factor (VEGF) intravitreal injection treatment (IVT)s are gold standard for various neovascular retinal diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and macular edema due to retinal vein occlusion (RVO). Same day bilateral IVTs are commonly performed off-label worldwide to reduce patient burden, despite limited safety data. This study evaluates the safety and management of bilateral same day anti-VEGF injections within a treat-and-extend regimen (TER) and proposes a clinical guideline for coordination of bilateral treatment.<br><br>METHODS: This retrospective observational study analysed electronic health records of 428 included patients treated bilaterally with ranibizumab 0.5mg or aflibercept 2mg at the VISTA Augenklinik (Binningen, Switzerland) between 2015 and 2019. Patients included had bilateral macular edema due to nAMD, DME, or RVO and received at least two cycles of same day bilateral anti-VEGF injections within the TER. Treatment coordination followed one of four strategies: Equal TER, Coordinated TER, Mixed TER and pro re nata (PRN), and Asynchronous TER. Unilateral IVTs were also recorded during the same period in the same patient cohort. Ocular and systemic adverse events (AEs) were compared between unilateral and bilateral injections using Fisher's exact test.<br><br>RESULTS: A total of 15,825 anti-VEGF injections were administered: 4,766 bilateral same day injections ([Formula: see text]) and 6,293 unilateral injections. Treatment intervals were synchronised according to visual acuity potential and disease activity. A treatment regime for bilateral IVTs has been established and is provided in the manuscript. The most frequently reported ocular AEs were conjunctival haemorrhage and sicca symptoms. Systemic AEs such as cerebrovascular and cardiovascular events were rare, with no significant difference between bilateral and unilateral injections.<br><br>CONCLUSION: Bilateral same day intravitreal anti-VEGF injections within a TER regimen appear to be safe with no significant increase in ocular or systemic AEs compared to unilateral treatment. Coordinating bilateral IVTs using the clinical guideline presented in this study may reduce treatment visits, ease patient burden and improve compliance. Larger prospective studies are needed to confirm safety and support standardised guidelines for bilateral IVTs.}, }
@article {pmid40814782, year = {2025}, author = {Bond, K and Klokman, G and Xu, Y and Wu, X and Schustak, J and Mandelbaum, J and Twarog, M and Han, H and Aihara, F and Paulina, MK and Coble, M and Hayden, C and Galarneau, JR and Demirs, JT and Qiu, Y and Esterberg, R and Huang, Q and Prasanna, G and Wilson, CW and Saint-Geniez, M and Aranda, J and Bao, Y}, title = {Double-Stranded RNA Induces Retinal Pigment Epithelium Cell Degeneration and Inflammation.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {16}, pages = {e70786}, doi = {10.1096/fj.202402181R}, pmid = {40814782}, issn = {1530-6860}, support = {//Novartis (Novartis AG)/ ; }, mesh = {*Retinal Pigment Epithelium/pathology/metabolism ; *RNA, Double-Stranded/genetics/metabolism ; Animals ; Humans ; Mice ; *Inflammation/metabolism/pathology/genetics ; *Macular Degeneration/pathology/metabolism/genetics ; Mice, Inbred C57BL ; DEAD Box Protein 58/metabolism/genetics ; Signal Transduction ; Geographic Atrophy/metabolism/pathology ; Receptors, Immunologic ; }, abstract = {RIG-I signaling has been previously implicated as a driver of inflammation to the retinal pigment epithelium (RPE) during age-related macular degeneration (AMD). Double-stranded RNA (dsRNA) is known to initiate RIG-I signaling and lead to a type I interferon response. We show through shRNA knockdown that RIG-I is essential for initiating an interferon response in iPS-RPE in response to both synthetic dsRNA-mimetic 3p-hpRNA and the double-stranded retrotransposable element Alu. Analysis of human tissue from patients suffering from AMD show accumulation of dsRNA, peaking at the geographic atrophy (GA) stage. Using a new murine model of 3p-hpRNA subretinal challenge to RPE cells, we confirmed that accumulation of dsRNA initiates a type I interferon response, as well as RPE and photoreceptor degeneration. Although RPE response to synthetic dsRNA was acute, extensive leukocyte migration was observed. The results from this study verify the importance of RIG-I signaling in regulating inflammation in the subretinal space and implicates dsRNA accumulation as a driver of AMD pathogenesis.}, }
@article {pmid40815370, year = {2025}, author = {Li, C and Chen, M and Lu, Y}, title = {An assessment of anti-VEGF drugs safety based on real-world data: from popularity to spontaneous reporting in eudravigilance database.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {263}, number = {11}, pages = {3257-3270}, pmid = {40815370}, issn = {1435-702X}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Databases, Factual ; Aged ; Ranibizumab/adverse effects/administration &amp; dosage ; Intravitreal Injections ; *Adverse Drug Reaction Reporting Systems/statistics &amp; numerical data ; *Wet Macular Degeneration/drug therapy ; Aged, 80 and over ; Middle Aged ; *Pharmacovigilance ; Incidence ; Receptors, Vascular Endothelial Growth Factor ; Recombinant Fusion Proteins/adverse effects ; Bevacizumab/adverse effects/administration &amp; dosage ; *Drug-Related Side Effects and Adverse Reactions/epidemiology ; }, abstract = {PURPOSE: Anti-vascular endothelial growth factor (VEGF) drugs are the first-line treatment for neovascular age-related macular degeneration (nAMD). This study analyzed four commonly used anti-VEGF drugs, preliminarily compared the search query results for these drugs on Google to assess public interest and analyzed the profile of ocular adverse drug reactions (ADRs) for these drugs in the EudraVigilance (EV) database.<br><br>METHODS: A descriptive retrospective study was conducted. We observed four commonly used anti-VEGF drugs for the clinical treatment of nAMD, with ADR reports sourced from the EV database. Data collected included age, gender, regional distribution, and report origins. We analyzed the overall characteristics of these ADR reports and explored the distribution across 27 System Organ Classes (SOCs) for these drugs. Additionally, we compared the off-label use ratios and severe outcomes of these drugs. Subsequently, we used disproportionality analysis (DPA) to compare the relationship between these drugs and ocular ADRs. Lastly, we compared the most common ocular ADRs among different drugs and the similarities and differences in ocular ADRs.<br><br>RESULTS: Google Trends indicated that in 2024, the interest scores for the four drugs ranked from highest to lowest were aflibercept, ranibizumab, faricimab, and brolucizumab. As of October 22, 2024, the total number of Individual Case Safety Reports (ICSRs) for the four drugs uploaded in EV was 32,878, with a higher proportion of ADR reported in brolucizumab-treated cases compared to the other three drugs. The age group of 65-85 years reported the highest incidence, and a higher proportion of ADRs occurred in females. Compared to the European Economic Area (EEA), more cases were reported for these drugs in NON-EEA regions, with reports primarily from healthcare professional (HP). Eye disorders were the most frequently reported among the four drugs. The frequency of ADRs reported for off-label use was highest with faricimab, while ranibizumab had a higher number of cases with severe outcomes. DPA revealed that brolucizumab had a significantly higher reporting rate of ocular ADRs compared to the other three inhibitors.<br><br>CONCLUSION: Anti-VEGF drugs often cause ocular ADRs when treating nAMD, which should be a clinical concern. To reduce the risk of adverse reactions, clinicians should closely monitor patients using these drugs.}, }
@article {pmid40816649, year = {2025}, author = {Lugassy, Y and Berent, E and Tarony, L and Jeries, S and Ziv, T and Savion, N and Eldar-Finkelman, H}, title = {HDAC inhibition protects RPE cells from oxidative stress via enhanced mitochondrial fusion, cytoskeletal repair, and Nrf-2 activation.}, journal = {Free radical biology &amp; medicine}, volume = {240}, number = {}, pages = {59-70}, doi = {10.1016/j.freeradbiomed.2025.08.007}, pmid = {40816649}, issn = {1873-4596}, mesh = {*Oxidative Stress/drug effects ; *Histone Deacetylase Inhibitors/pharmacology ; Humans ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology/cytology ; Hydroxamic Acids/pharmacology ; *Mitochondrial Dynamics/drug effects ; Vorinostat/pharmacology ; *NF-E2-Related Factor 2/metabolism/genetics ; Rotenone/pharmacology/toxicity ; Reactive Oxygen Species/metabolism ; Cytoskeleton/drug effects/metabolism ; Mitochondria/drug effects/metabolism ; *Macular Degeneration/drug therapy/pathology/metabolism/genetics ; Histone Deacetylase 6/antagonists &amp; inhibitors/genetics ; Kelch-Like ECH-Associated Protein 1/genetics/metabolism ; Cell Line ; Cell Survival/drug effects ; Heme Oxygenase-1/genetics/metabolism ; }, abstract = {Oxidative stress is a key driver of retinal pigment epithelium (RPE) damage and the development of age-related macular degeneration (AMD). Here, we demonstrate that the histone deacetylase (HDAC) inhibitors vorinostat and trichostatin A (TSA) elicit a coordinated cytoprotective response in RPE cells exposed to rotenone. Both compounds significantly reduced reactive oxygen species (ROS) levels, enhanced mitochondrial fusion, increased mitochondrial ATP production, and improved cell morphology and cell survival in the rotenone-treated cells. In addition, the compounds activated Nrf-2 as evidenced by Keap1 downregulation, increased p62/SQSTM1 expression, and induction of Nrf-2 targets, including heme oxygenase 1 (HO-1). Proteomic analysis of drug-treated cells revealed a significant enrichment of proteins involved in cytoskeletal organization and dynamics. Consistently, specific staining for actin filaments confirmed that vorinostat and TSA preserved cytoskeletal architecture and increased levels of the tight junction protein TJP3 in cells exposed to rotenone. Finally, inhibition of the vorinostat/TSA target HDAC6, or blockade of α-tubulin acetyltransferase, demonstrated that modulation of α-tubulin acetylation could influence ROS levels. Similarly, enhanced mitochondrial fusion by Mdivi-1 reduced ROS accumulation in the rotenone-treated cells. However, these last two interventions did not fully recapitulate the antioxidant effects observed with vorinostat or TSA. Our results identify a multifaceted protective mechanism triggered by HDAC inhibition in oxidatively stressed RPE cells and support the therapeutic repurposing of vorinostat in oxidative stress-driven RPE or retinal degeneration.}, }
@article {pmid40816663, year = {2025}, author = {Soylu, C and Corradetti, G and Alhelaly, M and Khan, H and Aziz, AA and Khan, H and Ali, H and Sulahria, H and Khanani, AM and Sadda, S}, title = {Real-World Outcomes in Eyes With Neovascular AMD Switched From Brolucizumab to Faricimab: A TRUCKEE Study Analysis.}, journal = {American journal of ophthalmology}, volume = {280}, number = {}, pages = {169-175}, doi = {10.1016/j.ajo.2025.08.018}, pmid = {40816663}, issn = {1879-1891}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Visual Acuity/physiology ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; Treatment Outcome ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence ; Drug Substitution ; Follow-Up Studies ; Fluorescein Angiography ; Middle Aged ; Antibodies, Bispecific ; }, abstract = {OBJECTIVE: To investigate anatomical and functional outcomes in a subset of eyes with neovascular age-related macular degeneration (nAMD) switched from brolucizumab to faricimab in the real-world TRUCKEE study.<br><br>DESIGN: Retrospective, multicentric clinical cohort study.<br><br>SUBJECTS AND PARTICIPANTS: 134 eyes of 108 patients were switched from brolucizumab to faricimab. This study included 56 eyes (49 patients) with complete data after 1 injection of faricimab and 40 eyes (34 patients) with complete data after 3 injections of faricimab.<br><br>METHODS: A multicenter, retrospective chart review was conducted on real-world participants enrolled in the TRUCKEE study switched from brolucizumab to faricimab for the treatment of nAMD. Participants were considered eligible for this post-hoc analysis if they had documented anatomical and functional outcome data following 1 and 3 injections of faricimab after being switched from brolucizumab. A comparative analysis was performed using the Wilcoxon signed-rank test.<br><br>MAIN OUTCOME MEASURES: Change in best corrected visual acuity (BCVA) measured in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, durability - defined as time interval between treatments in days, and central subfield thickness (CST), following 1 and 3 injections of faricimab.<br><br>RESULTS: The mean age of patients who had complete data after 1 injection of faricimab was 81.1 &#xb1; 7.1 years, and 25 were males. After 1 injection of faricimab following the switch, (mean treatment interval of 57.0 &#xb1; 32.9 days) a significant reduction in CST was observed (mean -5.25 &#xb5;m, P = .048). Changes in BCVA and durability were not statistically significant after 1 injection. The mean age of patients who had data after 3 injections was 80.4&#xb1;7.7 years, and 16 were males. The mean CST reduction measured -11.28 &#xb5;m, when comparing post-faricimab with post-brolucizumab values (P = .086). Additionally, after 3 injections of faricimab, a numerical increase in retreatment interval (+5.0 days, P = .769) and improvement in visual acuity (BCVA +1.63 letters, P = .174) were observed, though these were not statistically significant.<br><br>CONCLUSIONS: Switching from brolucizumab to faricimab was associated with numerical improvements in BCVA, CST, and retreatment interval. The apparent benefit in patients already on maximum VEGF suppression with brolucizumab, may suggest the relevance of angiopoetin-2 suppression with faricimab.}, }
@article {pmid40817252, year = {2025}, author = {Schroers, A and Neueder, A and Massoudy, I and Dillinger, AE and Ergün, S and Braunger, BM and Schlecht, A}, title = {Illuminating photoreceptors: TGFβ signaling modulates the severeness of retinal degeneration.}, journal = {Cell death discovery}, volume = {11}, number = {1}, pages = {384}, pmid = {40817252}, issn = {2058-7716}, support = {SCHL2362-2//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; NE 2372/1-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; BR 4957/3-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; BR 4957/4-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, abstract = {In various ocular diseases, retinal degeneration (RD) is a clinical symptom that can lead to irreversible vision loss. These diseases include age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Retinal degeneration describes a process during which the retina deteriorates due to the gradual death of photoreceptor cells. Although extensive research has been pursued to identify the underlying pathomechanisms, the precise molecular mechanisms that leads to photoreceptor death remains unclear. In this study, we combined the mouse model of light-induced photoreceptor degeneration with single-cell RNA sequencing to decipher the transcriptional response of degenerating photoreceptor cells. We additionally performed pseudotime analysis of gene expression changes for both the control and light-damaged photoreceptor clusters to analyze the extent of degeneration following a virtual trajectory of severeness. We found a transcriptional heterogeneity of rod photoreceptors in both control and degenerative conditions, and mapped several rod clusters which strongly differ in their transcriptional profile. We defined one of these clusters as the predominant disease-associated rod cluster, containing the most severely damaged rod cells. Pseudotime analysis demonstrated a strong regulation of TGFβ signaling and the RNA-induced silencing complex (RISC) in light-damaged photoreceptors suggesting a pivotal role of these mediators in retinal degeneration.}, }
@article {pmid40817925, year = {2025}, author = {Sacconi, R and Menna, M and Marra, S and Beretta, F and Bandello, F and Querques, G}, title = {Subthreshold laser treatment does not change choriocapillaris perfusion in patients with intermediate age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {263}, number = {11}, pages = {3091-3096}, doi = {10.1007/s00417-025-06926-2}, pmid = {40817925}, issn = {1435-702X}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/diagnostic imaging ; Fluorescein Angiography/methods ; Male ; Female ; Aged ; Fundus Oculi ; Follow-Up Studies ; *Visual Acuity ; Regional Blood Flow/physiology ; *Laser Coagulation/methods ; Capillaries/diagnostic imaging ; Aged, 80 and over ; *Macular Degeneration/surgery/diagnosis/physiopathology ; Middle Aged ; Treatment Outcome ; Prospective Studies ; *Retinal Vessels/physiopathology/diagnostic imaging ; }, abstract = {PURPOSE: To evaluate the safety of subthreshold laser treatment (SLT) at the level of the choriocapillaris (CC) using optical coherence tomography angiography (OCTA) in patients affected by intermediate age-related macular degeneration (iAMD).<br><br>METHODS: This is an analysis of patients included in the PASCAL clinical trial, including iAMD patients with reticular pseudodrusen (RPD). OCTA imaging was performed at baseline, 1-month, and 3-month follow-ups, focusing on a 3&#x2009;&#xd7;&#x2009;3-mm treated area. The CC slab was segmented and analyzed quantitatively for flow voids using the Phansalkar binarization method. Flow voids in the treated area were compared to no-treated areas and analyzed across time points.<br><br>RESULTS: 20 patients (20 eyes) were included in the study. No significant differences in CC flow voids (%) were observed between treated and no-treated areas at baseline (27.9% vs. 24.6%, p&#x2009;=&#x2009;0.641), nor were significant changes noted over time in treated areas (baseline: 27.9%, 1-month: 28.8%, 3-month: 32.6%, p&#x2009;=&#x2009;0.115). Similarly, no-treated areas exhibited no significant alterations over time (baseline: 24.1%, 1-month: 24.3%, 3-month: 26.8%, p&#x2009;=&#x2009;0.204).<br><br>CONCLUSION: SLT did not induce detectable CC damage or alter perfusion in treated areas, further confirming its safety in managing RPD secondary to dry AMD. These findings support SLT as a viable therapeutic option, warranting further investigation to validate its long-term efficacy and safety.}, }
@article {pmid40818729, year = {2025}, author = {Rajeswaren, V and Trivedi, V and Yoganathan, P}, title = {Macular hole after anti-vascular endothelial growth factor injection: A review.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2025.08.009}, pmid = {40818729}, issn = {1879-3304}, abstract = {Anti-vascular endothelial growth factor (anti-VEGF) injections are a crucial treatment for neovascular age-related macular degeneration (nvAMD); however, each injection carries the risk of complications, including macular hole (MH) formation. A comprehensive literature search of the PubMed, Embase, and Google Scholar databases identified studies reporting MH formation after anti-VEGF injections for nvAMD. Demographic characteristics included age, sex and affected eye. The presence of intraretinal fluid, subretinal fluid (SRF), pigment epithelial detachment (PED), posterior vitreous detachment, epiretinal membrane, vitreomacular adhesion (VMA), vitreomacular traction (VMT), and retinal pigment epithelial (RPE) tears was recorded. This review includes 15 articles, encompassing 50 eyes. Median patient age was 76.0 years, and 54 % were female. Prior to MH formation, SRF and PED were present in 68 % of eyes. VMA or VMT was observed in 36 % of eyes and the median number of injections before MH development was 3, with a median time to diagnosis of 60 days. While anti-VEGF is an essential therapy, clinicians must be aware of the risk of MH Predisposing factors including PEDs, VMT, and significant intra- or subretinal fluid, should be considered. Further research is needed to fully understand the mechanisms and explore preventative strategies.}, }
@article {pmid40819142, year = {2025}, author = {Anjum, F and Maqbool, F and Razzaq, MS and Shehzad, HMF and Ali, S and Shah, D and Tahir, M and Ilyas, M}, title = {Semantic web ontology for structured knowledge representation and clinical decision support in eye diseases.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {29986}, pmid = {40819142}, issn = {2045-2322}, mesh = {Humans ; *Eye Diseases/diagnosis/therapy ; *Semantic Web ; *Biological Ontologies ; *Decision Support Systems, Clinical ; }, abstract = {Vision is a vital sense that allows people to interact with their surroundings and carry out tasks efficiently while maintaining safety and independence. At least 2.2 billion people globally suffer from blindness or vision impairment, of which more than 1 billion cases are avoidable or untreated because they lack access to eye care services. In ophthalmology, there are numerous challenges in knowledge organization and management, mainly due to the complexity of eye diseases. Ontologies are used as excellent tools for organizing and managing complicated information due to their structured representations of domain knowledge and to make data more findable, accessible, interoperable, and reusable. We have developed an ontology, that is, Eye Disease Ontology (EDO), for the most common eye diseases as a resource that helps in data extraction and analysis for the general public and medical professionals. EDO is a comprehensive and systematic knowledge representation system that categorizes and organizes information about commonly occurring eye diseases such as cataracts, glaucoma, age-related macular degeneration, etc, and connects it to vital details such as symptoms, causes, risk factors, diagnostic tests, and treatment options. The significant metrics of EDO include 566 classes, 16 object properties, 12 data properties, and 119 instances. In this study, the ontology of eye diseases has the potential to improve clinical diagnosis, advance research, and enrich medical education, while improving patient care. This ontology was created using the NeOn technique in the Protégé/OWL environment. Several competency questions were created to meet the demands of various stakeholders, and the ontology was validated using SPARQL queries, the Hermit Reasoner, and the OOPS Pitfalls Scanner. In addition, we develop comprehensive documentation for EDO to promote reuse and emphasise the importance of reuse in future applications.}, }
@article {pmid40819748, year = {2025}, author = {Shang, Z and Qin, D and Liu, X and Li, H and Liu, C and Zhang, R and Sun, T and Pan, Z and Feng, W and You, X}, title = {The cGAS-STING pathway in age-related ocular diseases: Mechanisms and therapeutic opportunities.}, journal = {Cellular signalling}, volume = {135}, number = {}, pages = {112069}, doi = {10.1016/j.cellsig.2025.112069}, pmid = {40819748}, issn = {1873-3913}, mesh = {Humans ; *Nucleotidyltransferases/metabolism ; *Membrane Proteins/metabolism ; *Signal Transduction ; *Aging/metabolism ; Animals ; *Macular Degeneration/metabolism/pathology ; *Eye Diseases/metabolism/pathology ; Cellular Senescence ; STING Protein ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; }, abstract = {The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a crucial component of the innate immune system, which senses abnormal double-stranded DNA in the cytoplasm and induces the type I interferon and pro-inflammatory cytokines expression. In cellular senescence, the cGAS-STING signaling pathway triggers the senescence-associated secretory phenotype, thereby exacerbating the senescence phenomenon and leading to age-related ocular diseases, including age-related macular degeneration and diabetic retinopathy. Herein, we outline the structure of cGAS-STING signaling pathway and its association with cellular senescence, and discuss the mechanism of behavior between cGAS-STING and ocular aging-related diseases. Finally, we summarize the relevant inhibitors of the cGAS-STING signaling pathway, thereby offering a novel direction for exploring the mechanism of ocular aging-related inflammatory diseases.}, }
@article {pmid40820046, year = {2025}, author = {Boscia, G and Chauhan, D and Corradetti, G and O'Neill, CP and Samarasinghe, G and Lindenberg, SM and Urrea, A and Mauger, S and Do, G and Gupta, M and Sadda, SR}, title = {The impact of swithching faricimab in the treatment of neovascular age-related macular degeneration: a real-world analysis.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {263}, number = {11}, pages = {3097-3103}, pmid = {40820046}, issn = {1435-702X}, abstract = {BACKGROUND: To report a real-world analysis of switching to faricimab in the setting of neovascular age-related macular degeneration (nAMD), with regards to fluid volumes on optical coherence tomography (OCT), treatment interval, and best corrected visual acuity (BCVA).<br><br>METHODS: We retrospectively collected the OCT scans of all eyes that were being treated with anti-vascular endothelial growth factor (VEGF) therapy and were switched to faricimab in clinical the practices of eight retina specialists at five clinics in three Australian states (CORRNet Study Group; Clinical Ophthalmologists&#x2019; Real-world Research Network). Only those that remained on faricimab are the subject of this report. All OCT scans were analyzed for both the presence and volume of intraretinal fluid (IRF) and subretinal fluid (SRF) using machine learning (ML) algorithms (Macuject Pty Ltd, Melbourne, Australia).&#xa0;Mean interval time between injections and BCVA were recorded at the time of switch and after the switch to faricimab.<br><br>RESULTS: Of the 3082 eyes of 2200 patients treated with intravitreal anti-VEGF injections for nAMD, 473 eyes (84.0% of those switched to faricimab) remained on faricimab and thus met the criteria to be included in the analysis. At the time of switch to faricimab the number of eyes having IRF, either alone or in combination with SRF, was 142 (30.0%) and the number of eyes with SRF, either alone or in combination with IRF, was 223 (47.2%). Following the switch to faricimab, for the 142 eyes with any IRF, 115 eyes (80.9%) had a reduction in IRF volume, and of the 223 eyes with SRF, 190 eyes (85.2%) had a reduction in SRF volume, and 64 of the 69 (92.8%) eyes with both IRF and SRF present had a reduction in both fluid subtypes.&#xa0;The interval distribution shifted from a mean of 5.78&#x2009;&#xb1;&#x2009;1.92 (SD) to 6.91&#x2009;&#xb1;&#x2009;2.26 (SD) weeks over the study period (p&#x2009;<&#x2009;0.001).&#xa0;The mean BCVA improved from 63.91&#x2009;&#xb1;&#x2009;20.03 logMar letters to 69.25&#x2009;&#xb1;&#x2009;17.38 logMar letters (p&#x2009;<&#x2009;0.001) after the switch.<br><br>CONCLUSIONS: Switching to faricimab in eyes with nAMD previously treated with other anti-VEGF agents was associated with anatomical and functional improvements in this selected cohort. Further prospective studies including the comparison with other anti-VEGF agents are warranted to more definitively evaluate the clinical benefits of faricimab in this setting.}, }
@article {pmid40820160, year = {2025}, author = {Ridley, RB and Tischner, BM and Lee, J and Walsh, E and Massengill, MT and Lewin, AS and Ildefonso, CJ}, title = {Modulation of retinal inflammation delays degeneration in a mouse model of geographic atrophy.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {30153}, pmid = {40820160}, issn = {2045-2322}, support = {EY026268//National Eye Institute,United States/ ; S10OD028476/EY/NEI NIH HHS/United States ; M2017126//Bright Focus Foundation/ ; S10 OD028476/OD/NIH HHS/United States ; R01 EY026268/EY/NEI NIH HHS/United States ; T32 EY007132/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Mice ; Disease Models, Animal ; *Geographic Atrophy/pathology/genetics/metabolism ; Dependovirus/genetics ; Transcription Factor RelA/genetics/metabolism/antagonists &amp; inhibitors ; Retina/pathology/metabolism ; *Inflammation/pathology ; Microglia/metabolism ; Oxidative Stress ; Electroretinography ; NF-kappa B/metabolism ; *Retinitis/pathology ; }, abstract = {Geographic atrophy, the advanced form of age-related macular degeneration (AMD), is associated with increased oxidative stress and chronic inflammation. Pro-inflammatory genes, like TNF-α and IL-1β, are under the regulation of the transcription factor p65/RelA. We have previously shown that adeno-associated virus (AAV) delivery of the RelA inhibitory gene M013 blocks retinal inflammation in uveitis models. In this study, we evaluated the effects of RelA inhibition in an oxidative stress-driven geographic atrophy mouse model. We injected Sod2[RPEcKO] mice with rAAV, delivering either secreted GFP (sGFP control) or sGFP fused to a cell-penetrating version of the tagged M013 (sGFP-TatM013v5). Over nine months, we measured retinal function, structure, and morphological changes using electroretinography, optical coherence tomography, and fundoscopy. We quantified changes in inflammatory markers using multiplex ELISA, RT-qPCR, and immunofluorescence staining of the retinal tissue. Finally, we generated an NF-kB-luciferase reporter microglia cell line to study the impact of immune signaling changes on microglia. Mice injected with the rAAV delivering M013 had transient protection of their retinal function at 3 months. Based on ERG evaluations, the intravitreal injection of rAAV delivering sGFP-TatM013v5 significantly delayed the loss of retinal function. Furthermore, the rAAV-mediated expression of the sGFP-TatM013v5 protected photoreceptors' outer and inner segments based on OCT and immunofluorescence analysis. Analysis of postmortem tissues showed decreased migration of immune cells towards the RPE. Retinas injected with the sGFP-M013v5 vector showed increased levels of IL-9, IL10 and LIF. Finally, adding LIF to our NF-kB reporter cell line showed decreased TNF-induced reporter expression and modulation of microglia-specific genes. Our results indicate that modulating retinal inflammation could significantly slow the degeneration associated with geographic atrophy. Specifically, inhibiting the RelA protein in the retina may offer protective effects against retinal degeneration. Additionally, we demonstrated that LIF can counteract the influence of TNF on microglial gene expression. Future research will explore the dynamic interactions between RelA and other transcription factors and the NF-kB signaling pathway in the retina as they relate to retinal diseases.}, }
@article {pmid40820321, year = {2025}, author = {Song, JR and Park, KH and Kang, SW and Chin, HS and Yu, SY and Park, YH and Kim, YC and Lee, JE and Lim, ST and Kim, JG and Kim, CR and Sagong, M and Oh, HS and Lee, CS and Woo, SJ}, title = {Consensus of Expert Recommendations for the Safe Administration of Brolucizumab in Neovascular Age-related Macular Degeneration.}, journal = {Korean journal of ophthalmology : KJO}, volume = {39}, number = {4}, pages = {362-368}, pmid = {40820321}, issn = {2092-9382}, support = {RS-2023-00248480//National Research Foundation of Korea/ ; //Ministry of Science and ICT/ ; }, mesh = {Humans ; Angiogenesis Inhibitors/administration &amp; dosage ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis ; }, abstract = {Brolucizumab offers improved anatomical outcomes and extended dosing intervals compared to aflibercept, reducing treatment burden. However, postmarketing surveillance and real-world studies have highlighted safety concerns, including intraocular inflammation (IOI), retinal vasculitis, and retinal vascular occlusion, necessitating risk management strategies. To address these concerns, a comprehensive review of clinical trials, real-world data, and safety reports were conducted by an expert panel. This consensus report offers practical, evidence-based recommendations to ensure the safe administration of brolucizumab in patients with neovascular age-related macular degeneration (nAMD). The safety management of brolucizumab in patients with nAMD starts with selecting suitable patient profiles through thorough risk assessments. Educating patients about the risk of inflammation and its symptoms is important, as prompt recognition and early medical attention may help improve outcomes. Close monitoring with frequent follow-ups and the use of widefield fundus imaging or peripheral fundus examination are also necessary for early detection and management of complications. Effective management of IOI includes considering discontinuation of brolucizumab, alternative anti-vascular endothelial growth factor therapies, and corticosteroid treatments based on anatomical location and severity of IOI. Differentiating noninfectious IOI from infectious endophthalmitis is essential to ensure appropriate intervention and safeguard vision. In conclusion, this consensus recommendations emphasized the importance of the evidence-based and patient-centered stepwise approaches that should be considered when prescribing brolucizumab to patients with nAMD. This is not an absolute guideline, and the management should be adapted according to the ophthalmic conditions and the patients' opinions after thorough discussions.}, }
@article {pmid40820958, year = {2025}, author = {Medina Arellano, AE and Albert-Garay, JS and Huerta, NF and Hernández, KT and Ruiz-Cruz, M and la Paz, LO}, title = {From Neurotransmission to Retinal Pathophysiology: Unraveling the Role of GABA Receptors in Retinal Disease Progression.}, journal = {Journal of neurochemistry}, volume = {169}, number = {8}, pages = {e70198}, pmid = {40820958}, issn = {1471-4159}, support = {PAPIIT IN221023//Direcci&#xf3;n General de Asuntos del Personal Acad&#xe9;mico, Universidad Nacional Aut&#xf3;noma de M&#xe9;xico/ ; CVU 560536//Secretaria de Ciencia, Humanidades, Tecnologia e Inovaci&#xf3;n/ ; CVU 789988//Secretaria de Ciencia, Humanidades, Tecnologia e Inovaci&#xf3;n/ ; CVU 895582//Secretaria de Ciencia, Humanidades, Tecnologia e Inovaci&#xf3;n/ ; CVU 960540//Secretaria de Ciencia, Humanidades, Tecnologia e Inovaci&#xf3;n/ ; LOP.PTR.22-01//Asociaci&#xf3;n para Evitar la Ceguera en M&#xe9;xico I.A.P. Hospital Dr. Luis S&#xe1;nchez Bulnes/ ; }, mesh = {Humans ; *Receptors, GABA/metabolism/physiology ; Animals ; *Synaptic Transmission/physiology ; *Retinal Diseases/physiopathology/metabolism/pathology ; *Retina/metabolism/physiopathology/pathology ; *Disease Progression ; }, abstract = {Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system (CNS). The biological effects of GABA are mediated by activating its receptors, GABAA or GABAB, which are distributed across various tissues, predominantly in the brain and retina. The retina is a neural tissue responsible for receiving and transducing light stimuli. Within this tissue, GABA receptors (GABARs) primarily mediate lateral inhibition in the retina. In recent years, several studies have focused on elucidating the potential role of GABARs in retinal diseases, such as diabetic retinopathy (DR), retinitis pigmentosa (RP), glaucoma, and age-related macular degeneration (AMD). This review aims to present the most significant findings from recent years regarding the involvement of GABA receptors in retinal pathologies. Additionally, it highlights the potential of GABA receptors as targets for developing precise therapies or adjunctive strategies for treating retinal diseases.}, }
@article {pmid40821904, year = {2025}, author = {Yatsu, T and Nagata, A and Chiba, T and Miyata, Y}, title = {Reduction of Heterogeneous nuclear ribonucleoprotein A1 levels in retinal pigment epithelial cells induces inflammation and inhibits autophagy flux: pathology of age-related macular degeneration.}, journal = {Biochemistry and biophysics reports}, volume = {43}, number = {}, pages = {102195}, pmid = {40821904}, issn = {2405-5808}, abstract = {Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) regulates RNA metabolism and inhibits various aging processes. It has also been reported as an inhibitor of inflammation; however, its role in the retina, particularly in retinal pigment epithelial (RPE) cells-a major source of inflammatory cytokines in the retina-remains unclear. Retinal inflammation is a key factor in the development of dry age-related macular degeneration (AMD), an age-related disease that can lead to blindness and currently lacks an established treatment. Therapeutic strategies are focused on preventing the suppression of autophagy, a precursor to inflammation. However, the factors regulating autophagy in RPE cells are not yet fully understood. In this study, we investigated the role of HNRNPA1 in RPE cells to evaluate its potential as a therapeutic target for dry AMD. HNRNPA1 knockdown experiments were conducted, followed by RNA sequencing (RNA-seq) and Gene Ontology term analyses to elucidate the impact of HNRNPA1 reduction. The results revealed that reduced HNRNPA1 levels induced the increased expression of CXCL8 and IL1B, decreased autolysosome formation, and increased autophagosome formation, showing that HNRNPA1 reduction induces inflammation and suppressed autophagy, demonstrating its essential role in maintaining autophagy and mitigating inflammation under normal conditions. Furthermore, in an NaIO3-induced dryAMD model, RPE degeneration was accompanied by a reduction in HNRNPA1. These findings raise the possibility that decreased HNRNPA1 levels play a role in the onset and progression of dry AMD, and support the rationale for further exploring HNRNPA1 as a potential therapeutic target for this currently untreatable condition.}, }
@article {pmid40822473, year = {2025}, author = {Zhang, Y and Chen, Y and Sun, C and Li, F and Shen, Y}, title = {α-Lipoic acid mitigates age-related macular degeneration via ferroptosis: integrative multi-omics and network pharmacology.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1626907}, pmid = {40822473}, issn = {1663-9812}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the elderly. α-Lipoic acid (ALA), a naturally occurring antioxidant and iron-chelator, has shown potential in modulating ferroptosis, but its mechanism in AMD remains unclear.<br><br>METHODS: Network pharmacology, transcriptomic profiling, and machine learning were used to identify potential molecular targets of ALA in AMD. Core genes were identified through interaction network construction, functional enrichment analysis, and machine learning-based screening. Molecular docking and molecular dynamics simulations were performed to assess the binding affinity and stability between ALA and its predicted targets. In vivo validation was conducted using a sodium iodate (SI)-induced AMD mouse model, with retinal structure, function, oxidative stress, and gene expression evaluated through behavioral tests, histological staining, and qRT-PCR.<br><br>RESULTS: We identified six ferroptosis-related core targets (AHCY, DHODH, MAPK1, MAPK8, NOS2, and HMOX1) of ALA implicated in AMD. Molecular docking revealed strong binding affinities between ALA and these six targets, with dynamic simulations confirming stable interactions, particularly with HMOX1 and MAPK1. In the SI-induced AMD mouse model, ALA significantly preserved retinal structure, maintained visual function, and reduced oxidative stress and iron accumulation. qRT-PCR confirmed that ALA exerted differential effects on the expression of the six genes, demonstrating a context-dependent regulatory mechanism.<br><br>CONCLUSION: This study provides multi-level evidence that ALA protects against AMD by modulating ferroptosis-related pathways and restoring retinal structural integrity and functions. These findings warrant further investigation into the therapeutic potential of ALA in AMD.}, }
@article {pmid40822995, year = {2025}, author = {Khaohoen, A and Chantarasorn, Y}, title = {Clinical Features and Optical Coherence Tomography Angiography in Neovascular Age-Related Macular Degeneration and Pachychoroid Neovasculopathy.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251359847}, pmid = {40822995}, issn = {2474-1272}, abstract = {Purpose: To investigate differences in baseline characteristics, outcomes, and metrics of swept-source optical coherence tomography (SS-OCT) angiography between drusen-associated neovascular age-related macular degeneration (nAMD) vs pachychoroid neovasculopathy. Methods: This prospective cohort study enrolled 1 eye per patient with treatment-naïve nAMD or pachychoroid neovasculopathy who underwent 3 monthly bevacizumab injections followed by a treat-and-extend regimen for 12 months or longer. Eligible patients were classified into 2 groups: those with drusen-associated nAMD and those with pachychoroid neovasculopathy. Drusen-associated nAMD refers to macular neovascularization (MNV) or polypoidal lesions surrounded by subretinal drusenoid deposits or soft drusen 63 μm or larger in diameter. The outcomes were collected at baseline, 6 months, and 12 months. Results: Patients with drusen-bordering MNV (51 cases) were older (69.6 years vs 64.2 years) and had a smaller ratio of low-density to high-density lipoprotein cholesterol (1.85 vs 2.14), longer daily sleep hours (7.03 hours vs 6.07 hours), a smaller proportion of patients with a history of central serous chorioretinopathy (CSCR) (0% vs 12.5%), and smaller baseline central choroidal volume compared with those with pachychoroid neovasculopathy (57 cases). At 12 months, eyes with drusen exhibited a lower choroidal vascularity index, larger foveal thickness (327 µm vs 273 µm), and more antivascular endothelial growth factor injections per year (7.0 vs 5.2) compared with eyes with pachychoroid neovasculopathy. Regarding secondary outcomes, a closed-circuit vascular pattern was associated with persistent retinal fluid at study completion. Conclusions: Patients with pachychoroid neovasculopathy appear to carry some systemic risk factors for CSCR, whereas patients with drusen-related nAMD had inferior responses to bevacizumab monotherapy and greater choriocapillaris hypoperfusion (characterized by thinner choroidal volume and lower choroidal vascularity index values).}, }
@article {pmid40823516, year = {2025}, author = {Mourad, D and Singh, S and Mohamed, F and Zaitoun, A and Al Jayyousi, B}, title = {Prosthetic valve dysfunction post-bevacizumab: a transcatheter aortic valve replacement thrombosis case report.}, journal = {European heart journal. Case reports}, volume = {9}, number = {8}, pages = {ytaf370}, pmid = {40823516}, issn = {2514-2119}, abstract = {BACKGROUND: Transcatheter aortic valve replacement (TAVR) thrombosis is a known complication, but its association with vascular endothelial growth factor (VEGF) inhibitors has not been previously reported.<br><br>CASE SUMMARY: A 69-year-old male with previous TAVR developed new-onset prosthetic valve dysfunction after receiving bevacizumab for age-related macular degeneration. Echocardiography revealed moderate aortic stenosis with significantly elevated gradients compared to baseline. Following discontinuation of bevacizumab and initiation of systemic anticoagulation, valve function normalized at three-month follow-up.<br><br>DISCUSSION: This first reported case of TAVR thrombosis potentially linked to bevacizumab therapy demonstrates a temporal relationship between drug administration and valve dysfunction, with subsequent resolution upon drug discontinuation and anticoagulation. Clinicians should be aware of potential thrombotic complications when prescribing bevacizumab to patients with bioprosthetic valves and maintain regular echocardiographic surveillance. Prompt anticoagulation and medication adjustment may reverse valve dysfunction. Further studies are needed to determine a causal relationship between TAVR thrombosis and VEGF inhibitors.}, }
@article {pmid40827292, year = {2025}, author = {Gnanaraj, R and Palestine, AG and Wagner, BD and Patnaik, JL and de Carlo Forest, TE and Mathias, MT and Manoharan, N and Rajeswaren, V and Mandava, N and Lynch, AM}, title = {Systemic C-reactive protein levels in patients with geographic atrophy stratified by sex.}, journal = {International journal of ophthalmology}, volume = {18}, number = {8}, pages = {1498-1505}, pmid = {40827292}, issn = {2222-3959}, abstract = {AIM: To determine the differences in levels of systemic C-reactive protein (CRP) in patients with geographic atrophy (GA) and sex-based differences in CRP levels.<br><br>METHODS: Blood samples from patients with GA and controls were collected in a prospective age-related macular degeneration (AMD) registry from August 2014 to June 2021. AMD was confirmed using multimodal imaging and the Beckman and Consensus of Atrophy Meeting criteria for GA. High-sensitivity serum CRP levels were measured using an automated nephelometer. A non-parametric (rank-based) linear regression model was fit with an interaction between sex and GA.<br><br>RESULTS: There were 97 GA patients and 139 controls, with females comprising 55% and 66% of each cohort, respectively. There is no difference in CRP between cases and controls, with a median (interquartile range) of 1.2 (0.6-2.6) mg/L in GA patients versus 1.3 (0.8-2.9) mg/L in controls (P=0.52). Although females had higher CRP levels compared to males in both the GA and control groups, this difference did not reach statistical significance after adjustment for multiple comparisons.<br><br>CONCLUSION: There is no significant difference in systemic CRP levels between GA cases and controls.}, }
@article {pmid40827293, year = {2025}, author = {Shi, YM and Xie, X and Wang, WQ and Yuan, XM and Zhang, ZP and Wang, HY and Meng, J and Kong, ZH and Jing, X and Liu, TT}, title = {Quantitative characterization of types 1 and 2 macular neovascularization in neovascular age-related macular degeneration with intravitreal conbercept: an analysis utilizing optical coherence tomography angiography.}, journal = {International journal of ophthalmology}, volume = {18}, number = {8}, pages = {1490-1497}, pmid = {40827293}, issn = {2222-3959}, abstract = {AIM: To quantitatively assess central macular thickness (CMT), macular neovascularization (MNV) area, vascular tortuosity (VT), and vascular dispersion (VDisp) in neovascular age-related macular degeneration (nAMD), type 1 and type 2 MNV, by means of optical coherence tomography (OCT) and OCT angiography (OCTA) techniques.<br><br>METHODS: In this retrospective and observational case series, patients were classified into type 1 or type 2 MNV groups. A comprehensive panel of OCT and OCTA metrics was evaluated, including CMT, MNV area, VT, and VDisp. All subjects underwent a standardized intravitreal conbercept (IVC) regimen [3+pro re nata (PRN)] with a 12-month follow-up. MNV area was obtained by manual measurements with OCTA software, and VT and VDisp were calculated by automated analysis with Image J software.<br><br>RESULTS: A total of 101 participants were included, with 51 patients in the type 1 MNV group (mean age 67.32&#xb1;9.12y) and 50 patients in the type 2 MNV group (mean age 64.74&#xb1;5.21y). The mean number of IVC injections was 3.98&#xb1;1.53 for type 1 MNV and 3.73&#xb1;0.81 for type 2 MNV. Both subtypes exhibited significant improvements in visual acuity, accompanied by marked reductions in CMT and MNV area (P<0.05) at 12mo after treatment. In type 2 MNV, VT significantly decreased (P<0.05), whereas no significant change was observed in VT for type 1 MNV. VDisp did not significantly changed in either sybtypes. Moreover, in type 1 MNV, final best-corrected visual acuity (BCVA) using logMAR correlated positively with both pre- and post-treatment CMT, while in type 2 MNV, a significant positive correlation was found between the number of injections and final CMT.<br><br>CONCLUSION: This study shows that conbercept treatment significantly improves visual acuity and macular structure in both type 1 and type 2 MNV with reductions in CMT and MNV area. The significant reduction in VT in type 2 MNV suggests its potential as a biomarker for disease activity. The findings imply the quantitative assessment useful for the stratification, prognostication, and personalized management of MNV in nAMD.}, }
@article {pmid40827295, year = {2025}, author = {Jing, RH and Zhou, DK and Yang, ZY and Ding, ZD and Deng, JH and Xing, Y and Chen, XF}, title = {Does uveitis increase the risk of age-related wet macular degeneration? A Mendelian randomization study.}, journal = {International journal of ophthalmology}, volume = {18}, number = {8}, pages = {1484-1489}, pmid = {40827295}, issn = {2222-3959}, abstract = {AIM: To use two-sample Mendelian randomization (MR) method to study uveitis causal association with wet age-related macular degeneration (wAMD) risk from the genetic level.<br><br>METHODS: Two-sample MR analysis was used to assess the causal role of uveitis on wAMD risk, using the 8 genetic variants associated strongly with uveitis as instrumental variables. Besides, eight MR methods [inverse variance weighted (IVW), weighted median, MR-Egger regression, weighted mode, simple mode, robust adjusted profile score (RAPS), contamination inverse-variance weighted method, and debiased inverse-variance weighted method] were used to get the whole causal estimate for multiple instrumental single nucleotide polymorphism (SNPs). The MR analysis was based on Europeans.<br><br>RESULTS: Uveitis was related to a higher risk of wAMD [odds ratio (OR): 1.08, 95% confidence interval (CI) 1.03-1.12; P=1.03&#xd7;10[-3]] with the IVW method. No heterogeneity and directional pleiotropy were detected. On the contrary, no significant results were detected in reverse MR analysis.<br><br>CONCLUSION: Uveitis is related to an increased risk of wAMD. Due to the high blindness rate of wAMD, understanding and controlling the risk factors of AMD is of great significance for reducing its incidence and early diagnosis and treatment.}, }
@article {pmid40827631, year = {2025}, author = {Zhao, X and Xia, W and Wang, Y and Zhang, Y and Zhou, Z and Liu, P and Zhang, S and Zheng, Z and Shen, W and Zhang, S and Yao, J and Sun, T and Jiang, C and Zhao, C}, title = {Intravenous Multifunctional Nanotherapy for Treating Dry Age-Related Macular Degeneration.}, journal = {Advanced healthcare materials}, volume = {14}, number = {29}, pages = {e02925}, doi = {10.1002/adhm.202502925}, pmid = {40827631}, issn = {2192-2659}, support = {82301217//National Natural Science Foundation of China/ ; 81730025//National Natural Science Foundation of China/ ; 82020108006//Science and Technology Commission of Shanghai Municipality/ ; }, mesh = {Animals ; *Sirolimus/pharmacology/chemistry/administration &amp; dosage ; Humans ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Oxidative Stress/drug effects ; *Macular Degeneration/drug therapy/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Mice ; Reactive Oxygen Species/metabolism ; Micelles ; Polyethylene Glycols/chemistry ; *Nanoparticles/chemistry ; Iodates ; }, abstract = {Retinal pigment epithelium (RPE) degeneration is the pathological hallmark of multifactorial dry age-related macular degeneration (dAMD). Mounting evidence implicates oxidative stress and aberrant activation of mammalian target of rapamycin (mTOR) as key drivers of this process. Recent studies have shown that simultaneous modulation of these pathways may offer therapeutic benefit. However, clinical trials of rapamycin, an mTOR inhibitor widely employed in retinal research, have demonstrated limited efficacy, potentially due to poor bioavailability and paradoxical effects on RPE and photoreceptors. To overcome these challenges, APMNP@Rapa, a rapamycin-loaded, methionine-based ROS-responsive polymeric micellar system functionalized with an Ab peptide for active targeting of damaged RPE is developed. The micelles self-assemble from poly(ethylene glycol) - poly-methionine copolymers, leveraging methionine's endogenous nature and innate biocompatibility as an innovative ROS-responsive motif. This design yields particles with exceptional circulation stability and enhanced biocompatibility. In the high-ROS microenvironment of diseased RPE, APMNP@Rapa triggers on-demand rapamycin release. In a sodium iodate (NaIO3)-induced RPE oxidative stress model, APMNP@Rapa simultaneously inhibited aberrant mTOR activation, attenuated oxidative damage, and suppressed inflammatory response. These combined effects resulted in a marked preservation of the retina against degradation. Overall, the research establishes a paradigm for intravenous treatment of dAMD using multifunctional nanotherapy.}, }
@article {pmid40828189, year = {2025}, author = {Scampoli, A and Carlà, MM and Grieco, G and Governatori, L and Catalani, R and Rizzo, S and Caporossi, T}, title = {One-year outcomes of faricimab for neovascular age related macular degeneration with OCT angiography: focus on resistant and refractory cases.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {342}, pmid = {40828189}, issn = {1573-2630}, mesh = {Prospective Studies ; Follow-Up Studies ; Treatment Outcome ; *Macular Degeneration/diagnostic imaging/drug therapy/pathology ; Tomography, Optical Coherence/methods ; *Visual Acuity/drug effects ; Biomarkers/analysis ; *Angiogenesis Inhibitors/administration &amp; dosage ; Intravitreal Injections ; *Choroidal Neovascularization/diagnostic imaging/drug therapy/pathology ; Choroid/blood supply/drug effects/pathology ; *Antibodies, Bispecific/administration &amp; dosage ; Fluorescein Angiography/methods ; Macula Lutea/diagnostic imaging/drug effects/pathology ; Humans ; Male ; Female ; Aged ; Aged, 80 and over ; }, abstract = {PURPOSE: To investigate the 12-month effectiveness and safety of intravitreal faricimab (IVF) in patients with neovascular age-related macular degeneration (nAMD) resistant to previous anti-VEGF treatment.<br><br>METHODS: Prospective, monocentric study including consecutive patients with resistant/refractory nAMD switched to IVF between July 2023 and November 2024. Primary endpoints were safety, best corrected visual acuity (BCVA), central subfield thickness (CST), and subfoveal choroidal thickness. Secondary endpoints included changes in optical coherence tomography (OCT) and OCT angiography biomarkers: fluid prevalence, pigment epithelial detachment (PED) height, and vascular densities. All patients received four monthly loading doses of faricimab, with subsequent treat-and-extend regimen.<br><br>RESULTS: The study included 30 eyes of 30 patients. Mean follow-up was 14.2&#x2009;&#xb1;&#x2009;1.9&#xa0;months and no adverse events were reported. BCVA significantly improved from 0.77 to 0.62 LogMAR at the end of the study period (p&#x2009;=&#x2009;0.009), with 67% of eyes showing stable vision. CST significantly decreased from baseline (-57&#xa0;&#x3bc;m on average, p&#x2009;<&#x2009;0.001), along with PED height which showed its main decrease during the loading phase. Forty-seven percent of eyes achieved complete macular dryness at week 16, with significant reduction in terms of subretinal fluid (SRF) and intraretinal fluid (IRF) prevalence. At the end of the study, 90% of patients achieved treatment intervals of at least q8w, with 27% of eyes being on q12w. Finally, no changes in superficial/deep vessel densities were observed.<br><br>CONCLUSION: Faricimab demonstrated efficacy and safety in refractory/resistant nAMD, with significant improvements in structural outcomes and stable/improved visual acuity. Extended treatment intervals suggest a potential reduction in treatment burden.}, }
@article {pmid40828357, year = {2025}, author = {Kong, Q and Jiang, Y and Li, X and Lu, X}, title = {Regulation of toll-like receptor signaling pathways in age-related eye disease: from mechanisms to targeted therapeutics.}, journal = {Inflammopharmacology}, volume = {33}, number = {9}, pages = {5257-5271}, pmid = {40828357}, issn = {1568-5608}, mesh = {Humans ; *Toll-Like Receptors/metabolism/antagonists &amp; inhibitors ; *Signal Transduction/physiology/drug effects ; Animals ; *Aging/metabolism/pathology ; *Eye Diseases/metabolism/drug therapy ; Inflammation/metabolism ; Dry Eye Syndromes ; }, abstract = {Aging is a significant risk factor for various ophthalmic diseases, which can lead to vision loss. With the worldwide elderly population expanding, it is essential for researchers to elucidate the mechanisms underlying the progression of ocular diseases and to ascertain methods for their prevention or deceleration. The five principal age-related eye disorders (AREDs) consist of glaucoma, dry eye syndrome (DES), diabetic retinopathy (DR), cataracts, and age-related macular degeneration (AMD). A sustained subclinical low-grade inflammation has been observed at the ocular surface of elderly individuals who identify as "healthy." In these instances, an imbalance in para-inflammatory processes, which are essential for preserving tissue homeostasis in response to environmental injuries or insults, results in ocular surface system dysfunction, commonly referred to as InflammAging. Corneal and conjunctival epithelial cells express a variety of immune-related recognition receptors, including toll-like receptors (TLRs). At the ocular surface, TLRs play an active role in immunological instruction and innate defense mechanisms. The function of TLRs in AREDs is summarized here. In addition to discussing potential solutions and challenges in the clinical use of TLR inhibitors, future challenges will also be addressed.}, }
@article {pmid40828526, year = {2025}, author = {Yeh, SI and Ho, TC and Chu, TW and Chen, SL and Ou, R and Tsao, YP}, title = {OBM1701 Alleviates Choroidal Neovascularization in Experimental Animals Via Suppressing the Expression of HIF-1α in Retinal Pigment Epithelial Cells.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {8}, pages = {21}, pmid = {40828526}, issn = {2164-2591}, mesh = {Rats, Inbred BN ; Humans ; Male ; Female ; Animals ; Mice ; Rats ; Mice, Inbred C57BL ; Cell Line ; *Choroidal Neovascularization/drug therapy ; *Peptide Fragments/administration &amp; dosage ; *Retinal Pigment Epithelium/drug effects/metabolism ; Epithelial Cells/drug effects/metabolism ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Drug Evaluation, Preclinical ; Administration, Ophthalmic ; Swine ; Primary Cell Culture ; Cell Hypoxia ; Lasers, Solid-State ; Vascular Endothelial Growth Factor A/metabolism ; Eye Proteins ; Nerve Growth Factors ; Serpins ; Pigment Epithelium-Derived Factor ; }, abstract = {PURPOSE: OBM1701, a pigment epithelium-derived factor-derived short peptide, can eliminate corneal neovascularization by blocking endothelial cell angiogenesis. Activation of hypoxia-inducible factor (HIF)-1α in the retinal pigment epithelium (RPE) is critical for the pathogenesis of choroidal neovascularization (CNV), the hallmark of neovascular age-related macular degeneration (nAMD). Here, the potential inhibitory effect of OBM1701 on laser-induced CNV in animals was investigated.<br><br>METHODS: Two days after the laser injury, topical OBM1701 eye drops were applied once daily for 12 days. Subsequently, CNV vascular leakage and CNV area were measured by fluorescein angiography and isolectin GS-IB4 staining on choroidal/RPE flatmounts, respectively. Immunostaining was used to detect the expression of HIF-1&#x3b1; and vascular endothelial growth factor A (VEGFA) in CNV lesions. In vitro, ARPE-19 cells and primary porcine RPE were exposed to hypoxia mimetic condition by adding dimethyloxalylglycine and oxygen&#xa0;deprivation in&#xa0;cultures, respectively. Then the gene and protein expression of HIF-1&#x3b1; and VEGFA were evaluated by real-time PCR and Western blotting.<br><br>RESULTS: OBM1701 effectively reduced vascular leakage and CNV formation. Meanwhile, OBM1701 treatment blocked the overexpression of HIF-1&#x3b1; and VEGFA in RPE cells located within CNV lesions. In culture, OBM1701 pretreatment suppressed hypoxia-induced HIF-1&#x3b1; and VEGFA expressions.<br><br>CONCLUSIONS: Through animal studies, we demonstrate that OBM1701 has the potential to treat CNV. We also suggest RPE as a drug target for OBM1701 to treat CNV, by attenuating the hypoxia-induced HIF-1&#x3b1;/VEGFA signaling.<br><br>TRANSLATIONAL RELEVANCE: OBM1701 in ophthalmic drop shows the potential to be developed into a novel therapy for the treatment of nAMD.}, }
@article {pmid40828709, year = {2025}, author = {Chen, T and Zhang, D and Chen, D and Fu, H and Jin, K and Wang, S and Cohen, LD and Zhao, Y and Yi, Q and Zhang, J}, title = {Neovascularization Segmentation via a Multilateral Interaction-Enhanced Graph Convolutional Network.}, journal = {IEEE transactions on pattern analysis and machine intelligence}, volume = {47}, number = {12}, pages = {11107-11123}, doi = {10.1109/TPAMI.2025.3600335}, pmid = {40828709}, issn = {1939-3539}, mesh = {Humans ; Tomography, Optical Coherence/methods ; *Choroidal Neovascularization/diagnostic imaging ; *Image Interpretation, Computer-Assisted/methods ; Algorithms ; *Neural Networks, Computer ; Databases, Factual ; }, abstract = {Choroidal neovascularization (CNV), a primary characteristic of wet age-related macular degeneration (wet AMD), represents a leading cause of blindness worldwide. In clinical practice, optical coherence tomography angiography (OCTA) is commonly used for studying CNV-related pathological changes, due to its micron-level resolution and non-invasive nature. Thus, accurate segmentation of CNV regions and vessels in OCTA images is crucial for clinical assessment of wet AMD. However, challenges existed due to irregular CNV shapes and imaging limitations like projection artifacts, noises and boundary blurring. Moreover, the lack of publicly available datasets constraints the CNV analysis. To address these challenges, this paper constructs the first publicly accessible CNV dataset (CNVSeg), and proposes a novel multilateral graph convolutional interaction-enhanced CNV segmentation network (MTG-Net). This network integrates both region and vessel morphological information, exploring semantic and geometric duality constraints within the graph domain. Specifically, MTG-Net consists of a multi-task framework and two graph-based cross-task modules: Multilateral Interaction Graph Reasoning (MIGR) and Multilateral Reinforcement Graph Reasoning (MRGR). The multi-task framework encodes rich geometric features of lesion shapes and surfaces, decoupling the image into three task-specific feature maps. MIGR and MRGR iteratively reason about higher-order relationships across tasks through a graph mechanism, enabling complementary optimization for task-specific objectives. Additionally, an uncertainty-weighted loss is proposed to mitigate the impact of artifacts and noise on segmentation accuracy. Experimental results demonstrate that MTG-Net outperforms existing methods, achieving a Dice socre of 87.21% for region segmentation and 88.12% for vessel segmentation.}, }
@article {pmid40829697, year = {2025}, author = {Hussain, ZS and Chauhan, MZ and Muayad, J and Loya, A and Nembhard, W and Sallam, AB}, title = {Potency Matters: The Role of Statin Intensity in Modulating Risk for Age-Related Macular Degeneration.}, journal = {American journal of ophthalmology}, volume = {280}, number = {}, pages = {326-333}, doi = {10.1016/j.ajo.2025.08.024}, pmid = {40829697}, issn = {1879-1891}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Diabetes Mellitus, Type 2/complications ; *Dyslipidemias/drug therapy/complications ; Follow-Up Studies ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration &amp; dosage ; Incidence ; *Macular Degeneration/epidemiology/prevention &amp; control ; Propensity Score ; Retrospective Studies ; Risk Factors ; United States/epidemiology ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of vision loss. Statins, primarily used for cardiovascular disease prevention, may have pleiotropic effects on AMD, but existing evidence is inconclusive. This study investigated the association between statin intensity (high, moderate, low) and the risk of AMD in patients with type 2 diabetes and dyslipidemia.<br><br>DESIGN: A retrospective clinical cohort study using de-identified electronic health records from the US Collaborative Network.<br><br>METHODS: Adults aged 40 years or older with type 2 diabetes, dyslipidemia, and at least 1 ophthalmologic visit were included from 2014 to 2024 Patients with confounding conditions (liver disease, HIV, etc.) and prior AMD diagnoses were excluded. Propensity score matching was used to balance covariates between statin intensity cohorts and a treatment-na&#xef;ve control group. Intensity groups included: high-intensity statin therapy (rosuvastatin 20-40 mg or atorvastatin 40-80 mg), high-intensity-na&#xef;ve, medium-intensity statin therapy (rosuvastatin [5 mg, 10 mg], simvastatin [20 mg, 40 mg], fluvastatin [80 mg], pravastatin [40 mg, 80 mg], lovastatin [40 mg], atorvastatin [10 mg, 20 mg], or pitavastatin [1 mg, 2 mg, 4 mg]), and low-intensity statin therapy (simvastatin 5-10 mg, pravastatin 10-20 mg, lovastatin 10-20 mg, or fluvastatin 20-40 mg).<br><br>MAIN OUTCOME MEASURES: Incidence of combined AMD (nonexudative and exudative), nonexudative AMD, exudative AMD, and all-cause mortality at 6 months, 1 year, 3 years, and 5 years after the index event. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazard regression models.<br><br>RESULTS: After matching, a total of 20 282 patients were included. High-intensity statin use was associated with a reduced risk of combined AMD at 3 and 5 years (HR: 0.74 (95% CI: 0.57-094) and 0.79 (95% CI: 0.62-0.98), respectively). Medium-intensity statin therapy was associated with a significantly lower risk of combined AMD (HR range: 0.49 [95% CI 0.55-0.91] to 0.77 [95% CI: 0.60-0.98]) and exudative AMD (HR range: 0.19 [0.06-0.054] to 0.62 [95% CI: 0.40-0.96]) at all follow-up points. All statin intensities were associated with reduced all-cause mortality.<br><br>CONCLUSIONS: In this study of patients with type 2 diabetes and dyslipidemia, medium- and high-intensity, but not low-intensity, statin therapies were associated with a reduced risk of AMD. Further research is needed to confirm these findings and elucidate the underlying mechanisms.}, }
@article {pmid40830052, year = {2025}, author = {Lylyk, P and Lylyk, I and Lylyk, PN and Bleise, C and Scrivano, E and Lundquist, J and Nella-Castro, R and Perez, N and Franco, J and Calhoun, MW and Wilbur, LR and Rosenfeld, PJ and Saravia, MJ}, title = {Ophthalmic artery angioplasty in a cohort of patients with geographic atrophy secondary to non-exudative age-related macular degeneration.}, journal = {Journal of neurointerventional surgery}, volume = {}, number = {}, pages = {}, doi = {10.1136/jnis-2025-023608}, pmid = {40830052}, issn = {1759-8486}, abstract = {BACKGROUND: There is increasing evidence that vascular disease and chronic perfusion deficits play a role in the progression of age-related macular degeneration (AMD). This controlled clinical study evaluated the safety and feasibility of treating patients with late-stage AMD and associated geographic atrophy (GA). In addition, exploratory endpoints evaluated the potential to disrupt the disease process and initiate functional changes.<br><br>METHODS: A total of 17 subjects with confirmed late-stage AMD with GA, ophthalmic artery stenosis, and systemic stability were enrolled in this prospective multicenter study. Eleven (64.7%) of these subjects were successfully treated with ophthalmic artery angioplasty using an investigational ophthalmic percutaneous transluminal catheter system designed for this novel anatomical target and indication for use. Primary endpoints included procedure-related complications and procedural feasibility. All exploratory analyses were focused on ophthalmic outcomes and assessed for potential efficacy in choroidal thickness, visual acuity, reading ability, and patient-reported outcomes. Treated subjects were followed for 3 months by the interventional neuroradiology site and for 6 months by the ophthalmology site.<br><br>RESULTS: All systemic procedure-related adverse events (AEs) were potentially expected, effectively treated, resolved without sequelae, and included bronchial abrasion and hemoptysis secondary to intubation, urinary tract infection secondary to urinary catheterization, and vascular access site inflammation and hematoma. Procedure-related ocular AEs (eg, suspected retinal microemboli and potential reperfusion injury) were asymptomatic, graded as mild, and resolved without treatment or sequelae. Mean (SD) primary lesion stenoses decreased 59% from 43.7 (14.25)% to 18.2 (12.09)%. At study exit, mean best-corrected visual acuity improved by 6.7 letters (P=0.003) over baseline, and reading ability results improved 3.4%, 5.1%, and 28.5% (P=0.03) over baseline for reading acuity, critical print size, and reading speed, respectively. Patient-reported outcomes showed improvements in mobility and independence and in reading and accessing information.<br><br>CONCLUSIONS: The feasibility of ophthalmic artery angioplasty in this population was demonstrated with the investigational devices, while providing an acceptable safety profile. Efficacy and functional improvement were also seen, providing guidance for future study.}, }
@article {pmid40830152, year = {2025}, author = {Goldbach, F and Gerendas, BS and Leingang, O and Alten, T and Bampoulidis, A and Brugger, J and Bogunovic, H and Sadeghipour, A and Schmidt-Erfurth, U}, title = {Human expert grading versus automated quantification of fluid volumes in nAMD, DME and BRVO.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {30414}, pmid = {40830152}, issn = {2045-2322}, mesh = {Humans ; *Macular Edema/diagnostic imaging/pathology ; *Diabetic Retinopathy/diagnostic imaging/pathology ; Tomography, Optical Coherence/methods ; Deep Learning ; *Subretinal Fluid/diagnostic imaging ; *Retinal Vein Occlusion/diagnostic imaging/pathology ; Female ; Male ; Aged ; Algorithms ; *Macular Degeneration/diagnostic imaging/pathology ; }, abstract = {This study compared an automated deep learning algorithm with certified human graders from the Vienna Reading Center (VRC) in identifying intra- (IRF) and subretinal fluid (SRF) in OCT scans of patients treated for neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME) and branch retinal vein occlusion (BRVO). Multicenter clinical trial data from the VRC imaging database was used for this post hoc analysis. OCT scans were analyzed using a validated algorithm (RetInSight, Vienna, Austria) to compute IRF and SRF volumes. These fluid volumes were compared to fluid presence graded by trained and experienced graders of the VRC. 6898 OCT scans were analyzed for fluid volumes and presence of IRF and SRF. For nAMD/DME /BRVO in the central millimeter: the overall concordance for the detection of IRF and SRF between the algorithm and manual grading reached an AUC of 0.94/0.92/0.98 and 0.89/0.95/0.92, respectively. This deep learning approach showed a high concordance with human expert grading for detection of IRF and SRF and provides precise volumetric information across different retinal fluid-associated diseases. Thus, automated fluid quantification is a feasible tool for standardized treatment decision support and disease monitoring in clinical practice at the highest human expert level.}, }
@article {pmid40830259, year = {2025}, author = {Holland, R and Taylor, TRP and Holmes, C and Riedl, S and Mai, J and Patsiamanidi, M and Mitsopoulou, D and Hager, P and Müller, P and Paetzold, JC and Scholl, HPN and Bogunović, H and Schmidt-Erfurth, U and Rueckert, D and Sivaprasad, S and Lotery, AJ and Menten, MJ and , }, title = {Specialized curricula for training vision language models in retinal image analysis.}, journal = {NPJ digital medicine}, volume = {8}, number = {1}, pages = {532}, pmid = {40830259}, issn = {2398-6352}, support = {/WT_/Wellcome Trust/United Kingdom ; 210572/Z/18/Z//Wellcome Trust Collaborative Award/ ; }, abstract = {Clinicians spend significant time reviewing medical images and transcribing findings. By integrating visual and textual data, foundation models have the potential to reduce workloads and boost efficiency, yet their practical clinical value remains uncertain. In this study, we find that OpenAI's ChatGPT-4o and two medical vision-language models (VLMs) significantly underperform ophthalmologists in key tasks for age-related macular degeneration (AMD). To address this, we developed a dedicated training curriculum, designed by domain specialists, to optimize VLMs for tasks related to clinical decision making. The resulting model, RetinaVLM-Specialist, significantly outperforms foundation medical VLMs and ChatGPT-4o in AMD disease staging (F1: 0.63 vs. 0.33) and referral (0.67 vs. 0.50), achieving performance comparable to junior ophthalmologists. In a reader study, two senior ophthalmologists confirmed that RetinaVLM's reports were substantially more accurate than those written by ChatGPT-4o (64.3% vs. 14.3%). Overall, our curriculum-based approach offers a blueprint for adapting foundation models to real-world medical applications.}, }
@article {pmid40830295, year = {2025}, author = {Liu, F and Li, Q and Yang, Y and Lu, F}, title = {Advances in Stem Cell Therapies for Ocular Diseases: Progress in Clinical Trials and Future Perspectives.}, journal = {Stem cell reviews and reports}, volume = {21}, number = {8}, pages = {2386-2406}, pmid = {40830295}, issn = {2629-3277}, support = {82201210//National Natural Science Foundation of China/ ; 82222030//National Natural Science Foundation of China/ ; 2023NSFSC1660//Sichuan Science and Technology Program/ ; 2024HXBH082//Postdoctor Research Fund of West China Hospital, Sichuan University/ ; 2023YFC3403300//National Key Research and Development Program of China/ ; ZYYC23009//1.3.5 project for disciplines of excellence from West China Hospital of Sichuan University/ ; }, mesh = {Humans ; *Eye Diseases/therapy ; *Stem Cell Transplantation/methods/trends ; Clinical Trials as Topic ; Animals ; Macular Degeneration/therapy ; Cell Differentiation ; }, abstract = {Stem cell-based therapies hold promise for vision-threatening ocular diseases by promoting tissue repair and restoring visual function. Stem cells are classified by differentiation potential into two main types. Pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), possess the capacity to differentiate into somatic cells. Multipotent adult stem cells, such as mesenchymal stem cells (MSCs), are restricted to differentiating into cell types within specific lineages. The therapeutic potential of stem cells is discussed in the context of treating corneal diseases, glaucoma, and retinal disorders such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). This review focuses on the clinical trials of stem cell therapies for ocular diseases and discusses prospects in the field. Despite the considerable promise of these preclinical results in restoring visual function, significant challenges in clinical application remain, such as insufficient long-term cell survival, incomplete functional integration into host tissues, and the potential risk of oncogenic transformation. Future progress will depend on the development of standardized protocols, efficient delivery methods, and interdisciplinary collaboration to effectively translate preclinical advances into clinical applications.}, }
@article {pmid40830492, year = {2025}, author = {Chen, J and Long, Z and Shi, D and Zhang, Q and Peng, H}, title = {Ferroptosis-related hub genes and immune cell dynamics as diagnostic biomarkers in age-related macular degeneration.}, journal = {European journal of medical research}, volume = {30}, number = {1}, pages = {777}, pmid = {40830492}, issn = {2047-783X}, support = {81670881//This study received funding from the National Natural Science Foundation of China/ ; }, mesh = {*Ferroptosis/genetics ; Humans ; *Macular Degeneration/genetics/diagnosis/immunology ; Animals ; Biomarkers/metabolism ; Mice ; Gene Expression Profiling ; Transcriptome ; }, abstract = {BACKGROUND: Age-related Macular Degeneration (AMD) is widely acknowledged as a principal cause of vision loss in the elderly. Currently, the therapeutic interventions available in clinical practice fail to achieve satisfactory outcomes. Therefore, it is imperative that we approach the progress of AMD from novel perspectives in order to explore new therapeutic strategies.<br><br>METHOD: We obtained transcriptomic data from the macular and the peripheral retina from patients with AMD and a control group from the&#xa0;Gene Expression Omnibus (GEO) database. Through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we identified differentially expressed genes&#xa0;(DEGs) that were significantly enriched in functions associated with ferroptosis. Subsequent application of machine learning techniques enabled the identification of key hub genes, whose diagnostic potential was further validated. Additionally, the expression of these hub genes was corroborated in both animal and cellular models. Finally, we performed a functional enrichment analysis of these hub genes.<br><br>RESULTS: In the macula of patients with AMD, 452 DEGs were identified, while in the peripheral retina, 222 DEGs were discovered. Within the macula, 19 genes were associated with ferroptosis, compared to 3 in the peripheral retina. Consequently, the macular was selected as the primary focus of the study. Subsequent screening of these 19 genes using LASSO regression, Support Vector Machine (SVM), and Random Forest algorithms identified four hub genes: FADS1, TFAP2A, AKR1C3, and TTPA. Consequently, we utilized cigarette smoke extract (CSE) to either stimulate retinal pigment epithelial (RPE) cells in vitro or administer it via intravitreal injection, thereby establishing in vitro and in vivo models of AMD. Results from RT-PCR and Western blot analyses revealed an upregulation of FADS1, AKR1C3, and TTPA, while TFAP2A exhibited decreased expression. Finally, we investigated the infiltration of immune cells within the macular and performed a functional enrichment analysis of the hub genes.<br><br>CONCLUSION: We identified four key ferroptosis-related genes (FRGs)-FADS1, AKR1C3, TFAP2A, and TTPA-that possess diagnostic relevance for AMD and correlate with immune cell infiltration. Moreover, significant changes in both mRNA and protein expression levels of these genes have been observed in in vitro experiments and mice models.}, }
@article {pmid40832922, year = {2025}, author = {Katschke, KJ and Truong, T and Pham, V and Xi, H and Tang, W and Gu, X and Teotia, P and Hofmann, JW and Chaney, SY and Kirchhofer, D and van Lookeren Campagne, M and Jeanne, M}, title = {HTRA1-dependent proteolysis induces age-related retinal degeneration and exacerbates choroidal neovascularization.}, journal = {Disease models &amp; mechanisms}, volume = {18}, number = {10}, pages = {}, pmid = {40832922}, issn = {1754-8411}, support = {//Genentech/ ; }, mesh = {Animals ; High-Temperature Requirement A Serine Peptidase 1 ; *Choroidal Neovascularization/pathology/enzymology/complications ; *Retinal Degeneration/pathology/enzymology/complications ; Retinal Pigment Epithelium/pathology/metabolism ; Humans ; *Proteolysis ; *Serine Endopeptidases/metabolism ; *Aging/pathology ; Mice ; Macular Degeneration/pathology ; Mice, Inbred C57BL ; Photoreceptor Cells, Vertebrate/pathology/metabolism ; Photoreceptor Cells/pathology/metabolism ; Inflammation/pathology ; }, abstract = {Polymorphisms in the ARMS2/HTRA1 locus on chromosome 10 enhance the risk of geographic atrophy and macular neovascularization, the advanced forms of age-related macular degeneration (AMD). Although HTRA1 mutations have been associated with microvascular defects in the brain, it remains unclear whether changes in HTRA1 expression contribute to AMD pathophysiology. In this study, we showed that, in AMD donor eyes, HTRA1 protein accumulated around the retinal pigment epithelium (RPE)/photoreceptor lesions. We then demonstrated that overexpression of catalytically active, but not catalytically inactive, HTRA1 in RPE cells in mice induced age-dependent loss of photoreceptors, inflammation and a decline in photoreceptor functional responses. This retinal degeneration was not exacerbated when the mice were exposed to phototoxic stress in the constant light exposure preclinical model. However, mice overexpressing catalytically active HTRA1 had significant exacerbation of laser-induced choroidal neovascularization lesions. Finally, as substrate processing may define the molecular basis for HTRA1-induced retinal degeneration, we initiated a proteomics approach and identified the visual cycle key player RBP3 as a disease-relevant HTRA1 substrate in the retina.}, }
@article {pmid40833323, year = {2025}, author = {Mai, J and Reiter, GS and Riedl, S and Vogl, WD and Sadeghipour, A and McKeown, A and Foos, E and Bogunovic, H and Schmidt-Erfurth, U}, title = {Dynamics of the EZ/RPE Loss Ratio on OCT Over Time During Geographic Atrophy Progression and Treatment With Pegcetacoplan.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {11}, pages = {48}, pmid = {40833323}, issn = {1552-5783}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Geographic Atrophy/drug therapy/diagnosis/etiology ; *Retinal Pigment Epithelium/pathology ; Disease Progression ; Aged ; Male ; Female ; Intravitreal Injections ; Prospective Studies ; Visual Acuity ; *Angiogenesis Inhibitors/therapeutic use ; Follow-Up Studies ; Aged, 80 and over ; Fluorescein Angiography ; Deep Learning ; }, abstract = {PURPOSE: The purpose of this study was to investigate the change of ellipsoid zone (EZ)/retinal pigment epithelium (RPE) loss ratio on optical coherence tomography (OCT) in geographic atrophy (GA) secondary to age-related macular degeneration using deep learning-based analysis.<br><br>METHODS: OCT volumes of patients from the OAKS (NCT03525613) and DERBY (NCT03525600) trials, two phase III prospective randomized trials of GA treated with sham, intravitreal pegcetacoplan monthly (PM) and every other month (PEOM) were included. RPE and EZ loss were measured on OCT using validated deep learning-based algorithms. Pooled study eyes were divided into 4 quartiles determined by EZ/RPE loss ratios on OCT at baseline, month 12, and month 24. The change in ratio with treatment and its association with further disease progression and therapeutic response were analyzed.<br><br>RESULTS: Eight hundred eighty-nine OCT volumes were included. Overall, quartiles shifted downward at 12 and 24 months, representing a moderate decrease in disease activity, particularly in treated eyes. The EZ/RPE loss quartiles at month 12 were prognostic for further disease progression in the sham eyes for RPE and EZ loss. There was a higher likelihood of a quartile decrease in the PM and PEOM groups versus the sham at month 24 (P value quartile shift PM versus sham = 0.14, PEOM versus sham = 0.0053).<br><br>CONCLUSIONS: The change in EZ/RPE loss ratios at month 12 remained to be predictive for disease activity and therapeutic response, providing insights into disease mechanisms and relevant guidance for GA management in clinical practice. The EZ/RPE loss ratio decreased either due to advanced GA or induced by therapy in treated patients versus sham.}, }
@article {pmid40833326, year = {2025}, author = {Roberts, PA and Thomas, CN and Bellamy Plaice, G and Roberts, JA and Jones, MC and Andrews, JW and Hill, LJ}, title = {Mathematical Models of Topically and Intravitreally Applied Ranibizumab.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {11}, pages = {45}, pmid = {40833326}, issn = {1552-5783}, mesh = {Ranibizumab/administration &amp; dosage/pharmacokinetics ; Animals ; Swine ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/pharmacokinetics ; Vascular Endothelial Growth Factor A/metabolism/antagonists &amp; inhibitors ; *Vitreous Body/metabolism ; Administration, Topical ; Aqueous Humor/metabolism ; *Models, Theoretical ; Enzyme-Linked Immunosorbent Assay ; Disease Models, Animal ; Wet Macular Degeneration/drug therapy/metabolism ; }, abstract = {PURPOSE: Wet age-related macular degeneration (AMD) causes vision loss when vascular endothelial growth factor (VEGF) stimulates blood vessel growth into the light-sensitive retina. Anti-VEGF treatments such as ranibizumab are currently administered to treat wet AMD via intravitreal injections, which are unpleasant, expensive, and risk complications. We explored the efficacy of topically administered ranibizumab, with cell-penetrating peptides (CPPs).<br><br>METHODS: Ex vivo pig eyes were divided into three groups and treated with (1) topical or (2) intravitreal ranibizumab and CPP, or (3) intravitreal ranibizumab. ELISAs measured ranibizumab and VEGF concentrations in the aqueous and vitreous at 20&#xa0;min, 40&#xa0;min, 1 h, and 3.5 h (n = 3, per group). An ordinary differential equation&#xa0;model was formulated to describe the evolving concentrations of ranibizumab, VEGF, and their compounds in the tear, aqueous, and vitreal compartments.<br><br>RESULTS: Experimental-Topical: aqueous ranibizumab levels increased significantly, coincident with a significant drop in aqueous VEGF. Vitreal ranibizumab increased significantly, while vitreal VEGF remained constant. Intravitreal (with and without CPP): vitreal ranibizumab reached high concentrations, coincident with a significant drop in vitreal VEGF. Mathematical-topical treatment may provide sustained, moderate suppression of vitreal VEGF levels, while intravitreal treatment provides strong suppression, which lessens between treatments.<br><br>CONCLUSIONS: CPP allows topical ranibizumab to penetrate the cornea. Combined intravitreal/topical treatment presents a promising approach; topical treatment suppresses vitreal VEGF levels between injections and thereby potentially reduces the frequency of injections. Treatment efficacy would be enhanced if ranibizumab's rate of binding to VEGF or tear residence time could be increased.}, }
@article {pmid40833455, year = {2025}, author = {Lupidi, M and Bandello, F and Vujosevic, S and Parravano, M and Bacherini, D and Minnella, AM and Giansanti, F and Ascardi, C and Staurenghi, G}, title = {Multimodal Imaging to Assess Disease Activity and Predict Fluid Resolution in Patients with wAMD Treated with Brolucizumab: The IMAGINE Study.}, journal = {Ophthalmology and therapy}, volume = {14}, number = {10}, pages = {2497-2510}, pmid = {40833455}, issn = {2193-8245}, abstract = {BACKGROUND: This prospective, open-label, single-arm, multicenter phase IV study (NCT04774926) evaluated early imaging parameters as predictors of long-term fluid resolution and assessed the efficacy and safety of brolucizumab in treatment-naïve patients with wet age-related macular degeneration (wAMD) in a real-world Italian setting.<br><br>PATIENTS AND METHODS: A total of 122 patients aged&#x2009;&#x2265;&#x2009;50&#xa0;years with subfoveal macular neovascularization secondary to wAMD were enrolled. All patients were anti-vascular endothelial growth factor (anti-VEGF)- and investigational treatment-na&#xef;ve. Brolucizumab (6&#xa0;mg) was administered intravitreally at baseline and weeks 4 and 8, followed by maintenance dosing every 12&#xa0;weeks (q12w) or 8&#xa0;weeks, on the basis of disease activity. Imaging modalities included spectral-domain optical coherence tomography (OCT), OCT angiography, fluorescein angiography, and indocyanine green angiography. Disease activity was assessed using anatomical and functional parameters.<br><br>RESULTS: No significant predictive anatomical biomarkers for fluid-free status were identified. At week 48, 22.5% of patients achieved q12w fluid-free status. Significant reductions in central subfield thickness were observed, with a median change of -143.0&#xa0;&#xb5;m (p&#x2009;<&#x2009;0.0001). Median best-corrected visual acuity improved by 5.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline (p&#x2009;<&#x2009;0.0001). Ocular adverse events were consistent with the known safety profile of brolucizumab.<br><br>CONCLUSIONS: Brolucizumab demonstrated effectiveness and safety in a real-world wAMD cohort, aligning with findings from randomized trials. Although no predictive biomarkers were identified, results emphasize the role of multimodal imaging in guiding individualized treatment strategies and highlight variability in patient responses.<br><br>GOV ID: NCT04774926.}, }
@article {pmid40835159, year = {2025}, author = {Dettoraki, M and Vandorou, KT and Tsoukalas, D and Basagianni, E and Chatziralli, I and Theodossiadis, P and Loukides, S and Toumpanakis, D}, title = {Ocular manifestations in COPD patients. An underrecognized comorbidity.}, journal = {Respiratory medicine}, volume = {247}, number = {}, pages = {108313}, doi = {10.1016/j.rmed.2025.108313}, pmid = {40835159}, issn = {1532-3064}, mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/complications/epidemiology/physiopathology ; *Eye Diseases/epidemiology/etiology ; Comorbidity ; Cardiovascular Diseases/epidemiology ; Quality of Life ; }, abstract = {Chronic obstructive pulmonary disease (COPD) is characterized by the presence of comorbidities, such as cardiovascular diseases, that significantly impact symptoms, quality of life and prognosis. Indeed, it is shown that patients with COPD may present with diseases of aging, earlier in life, including eye disorders, such as macular degeneration and cataract. Although underrecognized, cumulative evidence over the last years suggests that COPD is associated with ocular abnormalities, mainly in the posterior segment of the eye, affecting both the microvascular network of the retina and the optic nerve, while structural abnormalities of the choroid and cornea have also been described. Thus, the aim of this review is to provide a comprehensive description of the evidence for ocular findings in patients with COPD that is an underrecognized entity and co-morbidity. A secondary aim of this review is to introduce pulmonologists to current ophthalmological techniques that may foster both clinical practice and research, especially through the assessment of the ocular microvascular network that is closely related to cardiovascular comorbidities.}, }
@article {pmid40835392, year = {2025}, author = {Shao, Z and Li, A and Lv, J and Yu, C and Pan, L and Pei, P and Yang, L and Chen, Y and Li, Y and Schmidt, D and Barnard, M and Lam, H and Bragg, F and Chen, J and Chen, Z and Li, L and Du, H and Sun, D and , }, title = {Patterns and correlates of visual impairment and ocular hypertension among older adults in the general Chinese population: results from the CKB Biobank.}, journal = {The British journal of ophthalmology}, volume = {110}, number = {1}, pages = {107-116}, pmid = {40835392}, issn = {1468-2079}, support = {088158/WT_/Wellcome Trust/United Kingdom ; 104085/WT_/Wellcome Trust/United Kingdom ; 202922/WT_/Wellcome Trust/United Kingdom ; 212946/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Biological Specimen Banks/statistics &amp; numerical data ; China/epidemiology ; Cross-Sectional Studies ; Intraocular Pressure/physiology ; *Ocular Hypertension/epidemiology/physiopathology ; *Persons with Visual Disabilities/statistics &amp; numerical data ; Prevalence ; Risk Factors ; Rural Population/statistics &amp; numerical data ; Tonometry, Ocular ; *Vision Disorders/epidemiology/physiopathology ; *Visual Acuity/physiology ; }, abstract = {BACKGROUND: While numerous ophthalmology-specific cohort studies have been conducted in China, there is a significant lack of comprehensive, population-based study on the potential determinants of visual impairment and ocular hypertension (OHT) in the general Chinese population.<br><br>METHODS: In the 2020-2021 resurvey of the China Kadoorie Biobank study, ~25 000 randomly selected participants from 10 diverse localities (5 urban and 5 rural) were surveyed. Presenting visual acuity (PVA) was measured using the Random E eye chart and intraocular pressure (IOP) was measured using a handheld Icare (ic100) tonometer. Associations of sociodemographic and other factors with risks of visual impairment and OHT were examined using multivariable logistic regression.<br><br>RESULTS: Among the 24 613 (aged 45-95 years, 64.4%&#x2009;women) participants, 21.8% had visual impairment (PVA <0.50) and 18.4% had OHT (IOP >18.6&#x2009;mm Hg). The prevalence rate of visual impairment increased dramatically with age (49.3% in those &#x2265;75 years vs 8.9% in those <55 years), but an opposite trend was observed for OHT. Risks of these two eye conditions were both inversely associated with household income and fish consumption but positively with systolic blood pressure and blood glucose. Higher education was associated with a higher OHT risk but not with visual impairment. Body mass index was inversely associated with visual impairment but positively with OHT. Age-related macular degeneration and glaucoma were most strongly associated with risk of visual impairment, followed by cataract.<br><br>CONCLUSION: The relatively high prevalence rates of poor vision and OHT in China suggest that well-targeted public health interventions should be developed.}, }
@article {pmid40836128, year = {2025}, author = {Jin, E and Chan, AC and Thomas, GN}, title = {Efficacy of faricimab secondary to anti-vascular endothelial growth factor agents in patients with neovascular age-related macular degeneration: a systematic review and meta-analysis.}, journal = {Eye (London, England)}, volume = {39}, number = {15}, pages = {2738-2751}, pmid = {40836128}, issn = {1476-5454}, mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Ranibizumab/therapeutic use ; Treatment Outcome ; Tomography, Optical Coherence ; Antibodies, Bispecific ; }, abstract = {This study examines the efficacy and safety of faricimab as a secondary treatment for neovascular age-related macular degeneration (nAMD) patients previously treated with anti-vascular endothelial growth factors (anti-VEGF) agents. A literature search was performed on PubMed, EMBASE, and Cochrane Library up to 24 October 2024. Cohort and observational studies reporting functional and anatomical outcomes in nAMD patients switched to faricimab were included. Meta analysis with common and random-effect model was performed using "metagen" package in R version 3.2.1. 446 studies were identified on our preliminary search, of which 20 studies (1007 eyes) with a baseline central macular thickness (CMT) of 342.07 (± 110.14) um were included in the final analysis. Switching to faricimab led to significant reductions in CMT at 3 months (Mean difference = -47.08 um, 95% Confidence Interval (CI)= (-66.01, -28.15), p = 0.009) and 6 months post-switch (Mean difference =-44.68 um, 95% CI= (-67.17, -22.20), p = 0.002). Pigment epithelium detachment (PED) height was also reduced at 3 months (Mean difference = -31.71um, 95% CI= (-45.12, -18.30), p = 0.036) and 6 months post-switch (Mean difference = -34.85 um, 95% CI= (-50.19, -19.51), p = 0.011). However, no significant improvements in best corrected visual acuity (BCVA) were observed at 3 months (p = 0.407), 6 months (p = 0.920) or ≥12 months (p = 0.261) post-switch. Treatment intervals were significantly extended (Mean difference=1.87 weeks, 95% CI = (0.41, 33.3), p = 0.019), with a low incidence of serious adverse events. In conclusion, faricimab demonstrates favorable structural benefits, stable functional outcomes and extended treatment intervals as a second-line treatment for nAMD in patients with prior anti-VEGF therapy.}, }
@article {pmid40836983, year = {2024}, author = {Dandamudi, M and McLoughlin, P and Behl, G and Coffey, L and Chauhan, A and Kent, D and Rani, S and Fitzhenry, L}, title = {Investigation of novel combination therapy for age-related macular degeneration on ARPE-19 cells.}, journal = {Frontiers in drug delivery}, volume = {4}, number = {}, pages = {1337686}, pmid = {40836983}, issn = {2674-0850}, abstract = {Age-related macular degeneration (AMD) is a multifactorial degenerative disease characterised by the gradual loss of central vision in individuals aged more than 50 years. There is currently no cure for this disease, but treatment can delay its progression. Consequently, there is an urgent need for the development of both new and cost-effective therapeutics. In this study, a novel combination of a corticosteroid and flavonoid was investigated on human retinal pigment epithelial cell lines to explore its potential pharmacological effect on AMD. Combination therapies, such as anti-VEGF (vascular endothelial growth factor) agents combined with photodynamic therapy and anti-VEGF agents in conjunction with corticosteroids, have been utilized previously and are known to be effective. However anti-VEGF injections are associated with serious side effects and are costly. Various disease conditions associated with AMD were stimulated on human retinal cells, which were then exposed to different concentrations of triamcinolone acetonide (TA) and quercetin (QCN) individually and in combination. This investigation aimed to assess their potential for the treatment of AMD. The combination of TA and QCN demonstrated a superior anti-inflammatory effect, as TA and QCN primarily act on different inflammatory signaling pathways. Furthermore, in terms of anti-VEGF activity, both drugs exert their effects through different mechanisms: QCN inhibits kinase pathways leading to the deactivation of VEGF receptors, whereas TA destabilises VEGF mRNA, resulting in increased suppression of VEGF-C with combination treatments. The anti-oxidant assay yielded similar outcomes, demonstrating a synergetic effect when treated with combination drugs. These findings collectively suggest TA and QCN as a promising combination therapy for targeting AMD with multiple pathological conditions.}, }
@article {pmid40837066, year = {2025}, author = {Velaga, SB and Alagorie, AR and Nittala, MG and Moore, NC and Song, YE and Haines, J and Pericak-Vance, MA and Stambolian, D and Hu, Z and He, Y and Sadda, SR}, title = {Longitudinal Assessment of Area of Reticular Pseudodrusen in Eyes with Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100881}, pmid = {40837066}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the change in the area of reticular pseudodrusen (RPD) and choroidal thickness over 2 years in eyes with age-related macular degeneration (AMD).<br><br>DESIGN: Longitudinal cohort study.<br><br>SUBJECTS: The study reviewed 1332 eyes from 666 subjects with baseline and 2-year follow-up data, of which 108 eyes were graded to have RPD. Among these, 35 eyes from 22 participants (mean age: 72.8 &#xb1; 8.9 years; range: 50-84; 37% female) were eligible for this analysis because they had early or intermediate AMD with RPD at baseline, absence of geographic atrophy at 2 years, and images that were gradable for the presence of RPD.<br><br>METHODS: Infrared reflectance (IR), blue-light fundus autofluorescence, and spectral-domain OCT were obtained for all subjects at baseline and at 2 years. Using the instrument software, a certified grader delineated the RPD area (mm[2]) on the IR image using the free hand tool. Choroidal thickness was measured for both baseline and month 24 using a previously described deep learning algorithm to compute a choroidal volume.<br><br>MAIN OUTCOME MEASURES: Changes in RPD area (mm[2]) and mean volumetric choroidal thickness (&#x3bc;m) between baseline and 2 years.<br><br>RESULTS: The RPD area increased significantly (P < 0.001) by month 24 compared with baseline with a mean increase of 6.23 &#xb1; 4.64 mm[2]. The mean volumetric choroidal thickness was not significantly different from baseline 182.2 &#xb1; 94.36 (134.20-227.90) to month 24 178.2 &#xb1; 41.10 (109-258).<br><br>CONCLUSIONS: In this longitudinal natural history analysis, we observed an increase in RPD area of >6 mm[2] over 2 years in the absence of a significant change in choroidal thickness. Although AMD eyes with presence of RPD typically have a thinner choroid, the increase in extent of these lesions does not appear to be associated with further thinning of the choroid.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40837068, year = {2025}, author = {Mukherjee, S and Vance, E and von der Emde, L and Arunachalam, T and De Silva, T and Thavikulwat, AT and Orndahl, C and Nyaiburi, C and Abraham, M and Hammel, K and Sadda, SR and Chew, EY and Pfau, M and Wong, WT and Jeffrey, BG and Keenan, TDL}, title = {Variation in Mesopic Retinal Sensitivity Relative to Distance from Geographic Atrophy in Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100879}, pmid = {40837068}, issn = {2666-9145}, abstract = {PURPOSE: To analyze the relationship between distance from geographic atrophy (GA) lesion borders and mesopic retinal sensitivity in age-related macular degeneration (AMD).<br><br>DESIGN: Exploratory analyses of the longitudinal microperimetry dataset from a recent phase II, prospective, single-arm, nonrandomized trial of oral minocycline for GA progression.<br><br>PARTICIPANTS: Individuals with GA from AMD in &#x2265;1 eye.<br><br>METHODS: Mesopic retinal sensitivity was assessed longitudinally with a fundus-guided microperimetry device at baseline, month 3, and every 6 months thereafter, using a custom T-shaped test pattern centered on the fovea. Individual test loci were superimposed on an aligned fundus autofluorescence image and distance from the closest GA lesion border (GA distance) was computed. The relationship between GA distance and retinal sensitivity was analyzed in study eyes using repeated-measures regression.<br><br>MAIN OUTCOME MEASURES: Mesopic retinal sensitivity.<br><br>RESULTS: The study population comprised 26 study eyes from 26 participants (mean age 74.2 years). Retinal sensitivity of extralesional testing loci increased steeply, as a quadratic function, between 0&#xb0; and 2.05&#xb0; (i.e., knot at 2.05&#xb0;; 95% confidence interval [CI] 1.26&#xb0;-2.84&#xb0;) of GA distance. Beyond 2.05&#xb0;, it increased linearly and less steeply. In nonlinear analyses accounting for nesting, a significant effect of GA distance on retinal sensitivity was observed. For GA distances <2.05&#xb0;, sensitivity increased quadratically by approximately 1.99 decibels (dB)/&#xb0; (95% CI: 1.15, 2.83 dB/&#xb0;; P < 0.001) or higher. For GA distances &#x2265;2.05&#xb0;, sensitivity increased at 0.56 dB/&#xb0; (95% CI: 0.42, 0.70 dB/&#xb0;; P < 0.001). There was also a significant effect of time on sensitivity (estimate: -0.07 dB/month; 95% CI: -0.08, -0.06 dB/month; P < 0.001).<br><br>CONCLUSIONS: The results demonstrate a perilesional zone 2&#xb0; (&#x223c;580 &#x3bc;m) around the GA border in which retinal sensitivity changes steeply according to GA distance. This zone presents an important focus for closer evaluation in interventional studies examining potential efficacy for the preservation or recovery of retinal function. With GA progression, decreased retinal sensitivity expands ahead of GA expansion itself, as an advancing wave. Overall, the degree and extent of decreased visual function beyond GA borders have important implications for the design of clinical trials, decision-making in clinical practice, and insights into AMD pathophysiology.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40837344, year = {2025}, author = {Walia, S and Morya, AK and Khullar, S and Aggarwal, S and Kaur, R}, title = {Role of alternative oral therapy for the management of wet age-related macular degeneration and proliferative diabetic retinopathy.}, journal = {World journal of diabetes}, volume = {16}, number = {8}, pages = {109231}, pmid = {40837344}, issn = {1948-9358}, abstract = {Proliferative diabetic retinopathy (PDR) affects approximately 6% of diabetic patients globally. The overall prevalence of diabetic retinopathy is around 22%. Wet age-related macular degeneration (ARMD), the sight-threatening type of ARMD, affects approximately 1.2%-1.3% of the general population and represents 15% of total ARMD cases. While intravitreal anti-vascular endothelial growth factor injections are still the mainstay therapy, there are a few challenges, such as frequent administration, cost burden, and compliance barriers that prompt the need for exploration into systemic oral alternative drugs like fenofibrate, candesartan, and vorolanib. These oral therapies have the advantage of being non-invasive and systemically accessible with few logistical burdens. This review highlights current evidence supporting the use of oral therapies in PDR and wet ARMD management, along with practical limitations and future prospects.}, }
@article {pmid40837411, year = {2025}, author = {Hao, X and Du, L and Liu, G and Li, Z and Wang, S}, title = {Human retinal organoids for modelling dry age-related macular degeneration and screening drugs.}, journal = {Genes &amp; diseases}, volume = {12}, number = {6}, pages = {101593}, pmid = {40837411}, issn = {2352-3042}, abstract = {Age-related macular degeneration (AMD) poses a significant threat to the vision of the elderly population globally. Unfortunately, there is no effective treatment available for dry AMD. In this study, we utilized human retinal organoids (ROs) stimulated with sodium iodate to establish a model for dry AMD. We assessed the apoptosis of retinal organoid cells and conducted RNA sequencing to analyze molecular changes. Our findings indicate that metformin and the fetal hemoglobin (HbF) inducer TN1 could protect ROs from sodium iodate induced damage and restore retinal function in murine model. The administration of metformin and TN1 alleviated apoptosis in ROs and improved visual function. Studies of molecular mechanisms indicated that the protective effects of metformin and TN1 may be related to the HMOX1 gene, providing valuable insights for the development of new therapies for dry AMD via targeting HMOX1 and its downstream pathways.}, }
@article {pmid40837450, year = {2025}, author = {George, LM and Ranjana, M and Quinodoz, M and Tang, RWC and Lim, WK and Gilhar, NG and Farooqui, SZ and Rivolta, C and Fenner, BJ}, title = {Early-onset macular drusen, a monogenic form of age-related macular degeneration.}, journal = {American journal of ophthalmology case reports}, volume = {39}, number = {}, pages = {102408}, pmid = {40837450}, issn = {2451-9936}, }
@article {pmid40837592, year = {2025}, author = {Lanzetta, P and Korobelnik, JF and Heier, JS and Leal, S and Holz, FG and Clark, WL and Eichenbaum, D and Iida, T and Sun, X and Berliner, AJ and Schulze, A and Schmelter, T and Schmidt-Ott, U and Zhang, X and Vitti, R and Chu, KW and Reed, K and Rao, R and Bhore, R and Cheng, Y and Wong, TY}, title = {Plain language summary of publication of the 48-week results from the PULSAR study investigating how well a new dose of aflibercept works and how safe it is for people with wet age-related macular degeneration.}, journal = {Therapeutic advances in ophthalmology}, volume = {17}, number = {}, pages = {25158414251356388}, doi = {10.1177/25158414251356388}, pmid = {40837592}, issn = {2515-8414}, abstract = {What is this summary about? • This is a summary of a publication about the PULSAR study, which was published in The Lancet scientific journal. • Wet age-related macular degeneration (or AMD) is a long-term eye disease in which abnormal blood vessels grow in the back of the eye. As these vessels leak fluid or blood, the word "wet" is part of the disease name. This affects the central part of a person's vision, which can make it hard for people to read, drive, or perform other daily activities. It is one of the main causes of visual loss in older people, and if it is left untreated, it can lead to rapid loss of vision. • People with wet AMD can be treated with anti-vascular endothelial growth factor (or anti-VEGF) medicine, given as an injection into the back of the eye. This type of medicine can improve vision by directly reducing the leakage into the macula and by stopping the growth of new, abnormal blood vessels. This leads to reduced swelling of the macula, which is measured by central retinal thickness. These therapies need frequent eye injections. One of the biggest difficulties for many people and their caregivers is that they need to keep up with visits for their injections that are often required to maintain good vision. • Aflibercept is an anti-VEGF medicine that health authorities across different countries have approved for the treatment of wet AMD, as well as other eye diseases, which we will not discuss in this material. People with wet AMD can receive injections of aflibercept 2 mg, given initially once per month for three months. After that, people usually receive treatment every 8 weeks, or sometimes less frequently, depending on their doctors' assessments of the disease state. • The PULSAR study was carried out to see if a higher, 8 mg, dose of aflibercept would provide the same treatment results as aflibercept 2 mg, but with the need for fewer injections. If fewer injections are necessary, this can potentially help patients and their caregivers keep up with treatment. • The PULSAR study involved a direct comparison of the two doses of this anti-VEGF medicine in patients with wet AMD who were placed into one of three treatment groups with different dosing intervals at random. What were the results? • Through the first year (or 48 weeks), participants who received injections of aflibercept 8 mg every 12 or 16 weeks after an injection once per month for three months, had improvements in vision that were similar to those of participants treated with aflibercept 2 mg every 8 weeks. • After the injection once per month for three months, at Week 16, there were fewer participants treated with the 8 mg dose who had abnormal fluid leakage in the macula compared to the 2 mg dose. • At Week 48, participants who received aflibercept 8 mg had similar decreases in the thickness of the retina in the central region as those treated with aflibercept 2 mg. • Most participants who received aflibercept 8 mg and completed 48 weeks of the study maintained their 12- or 16-week injection schedules, without needing to shorten the interval between injections. • Adverse events in participants treated with aflibercept 8 mg were also similar to those in participants treated with aflibercept 2 mg. What do the results mean? • Findings show that aflibercept 8 mg can improve vision to the same extent as aflibercept 2 mg in people with wet AMD, but with fewer injections than aflibercept 2 mg so that people can potentially keep up with their treatments more easily.}, }
@article {pmid40838197, year = {2025}, author = {Lam, BL and Zak, V and Gonzalez, VH and Gregori, NZ and Chavala, SH and Batabyal, S and Carlson, M and Kim, S and Ayyagari, A and Chang, J and Lane, H and Choudry, N and Koester, J and Von Tress, M and Piltz-Seymour, J and Sharif, NA and Tsang, SH and Mahajan, VB and Boyer, DS and Ho, AC and Barone, SB and Mohanty, SK}, title = {Safety and efficacy of MCO-010 optogenetic therapy in patients with Stargardt disease in USA (STARLIGHT): an open-label multi-center Ph2 trial.}, journal = {EClinicalMedicine}, volume = {87}, number = {}, pages = {103430}, pmid = {40838197}, issn = {2589-5370}, abstract = {BACKGROUND: Stargardt disease (SD) is an inherited degenerative retinal disease affecting rod and cone photoreceptors and retinal pigment epithelial (RPE) cells, leading to severe and irreversible vision loss. Optogenetics is a promising approach to restoring vision by photosensitizing spared healthy retinal neurons.<br><br>METHODS: The STARLIGHT phase 2 open-label study (NCT05417126) was conducted over 48-weeks at two US sites to assess the safety and efficacy of MCO-010 administered via a single intravitreal injection in the worse-seeing eye of SD patients. The study began on July 5, 2022, and was completed on September 28, 2023. MCO-010 targets bipolar cells rather than retinal ganglion cells (RGCs) to utilize more abundant cells that respond to ambient light while preserving natural visual processing pathways after treatment. Six adults (mean age 50 years, range 32-71 years, four males and two females) received 1.2E11 genome copies (gc)/eye of MCO-010. The primary outcome was the incidence, nature, severity of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), intraocular inflammation, retinal thickness, best-corrected visual acuity (BCVA), and lesion size. Secondary endpoints included change in BCVA, vision-guided mobility, and shape determination accuracy. Visual field perimetry and Michigan Retinal Degeneration Questionnaire (MRDQ) were exploratory endpoints.<br><br>FINDINGS: All six participants had at least one ocular TEAE; non-ocular TEAEs occurred in three participants. The most common TEAEs were conjunctival hemorrhage, ocular hypertension, and vitreous cells (two subjects). There were no deaths, hospitalization, loss of eye, retinal detachment, endophthalmitis, or TEAEs leading to study discontinuation. The BCVA (mean &#xb1; SD) of the six treated eyes at baseline and 48-week follow-up was 22.8 &#xb1; 9.87 (range 9-35), and 28.3 &#xb1; 13.28 (range 4-42) ETDRS letters, respectively. The BCVA change from baseline was 7.2 &#xb1; 11.74, 4.2 &#xb1; 14.81, and 5.5 &#xb1; 12.29 at 12, 24, and 48 weeks, respectively. With a wearable magnifier (low-vision glasses), the BCVA change was 17.8 &#xb1; 13.35, 15.7 &#xb1; 17.37, 13.3 &#xb1; 21.37 at 12, 24, and 48 weeks, respectively. The improvement in mean defect in visual field perimetry was 1.02 &#xb1; 3.54, 2.47 &#xb1; 5.00, and 2.63 &#xb1; 5.26 dB at 12, 24, and 48 weeks, respectively. Specific improvements were noted in reading, and color, and contrast domains of the MRDQ.<br><br>INTERPRETATION: MCO-010 optogenetic phase 2 results support further investigation for treatment SD. To our knowledge, this is the first report of improving on(eye)-chart vision of SD participants utilizing optogenetics.<br><br>FUNDING: Nanoscope Therapeutics Inc.}, }
@article {pmid40838944, year = {2025}, author = {Berlin, A and Goerdt, L and Clark, ME and Gao, L and Swain, TA and McGwin, G and Owsley, C and Sloan, KR and Curcio, CA}, title = {Advanced Analysis Tools for Two Wavelength Autofluorescence Imaging of Macular Xanthophyll Carotenoids: ALSTAR2 Baseline.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {8}, pages = {32}, pmid = {40838944}, issn = {2164-2591}, support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Male ; Young Adult ; Algorithms ; *Carotenoids ; *Macula Lutea/diagnostic imaging/metabolism ; *Macular Degeneration/metabolism/diagnostic imaging ; *Macular Pigment/metabolism ; *Optical Imaging/methods ; Tomography, Optical Coherence/methods ; *Xanthophylls/metabolism ; }, abstract = {PURPOSE: To allow exploration of xanthophyll carotenoids in vision and age-related macular degeneration progression using two-wavelength autofluorescence imaging for macular pigment optical density (MPOD), we developed tools for automatically centering and classifying the MPOD distribution pattern.<br><br>METHODS: A subset of the ALSTAR2 baseline cohort (NCT04112667) and 44 eyes of adults aged 20 to 30 years with healthy maculas were imaged with optical coherence tomography and two-wavelength autofluorescence (MPOD module, Heidelberg Engineering). Images underwent a quality review. Two custom FIJI plugins centered the MPOD distribution by five algorithms (FOVEA, HILLCLIMB, CENTROID, MAX, CONTOUR). Others automatically classified spatial distributions into four patterns from Obana et al: Peak, Ring, Mixed, and Dip.<br><br>RESULTS: Of 651 qualifying aged eyes and 44 young eyes, the HILLCLIMB and CONTOUR methods best agreed with a manually determined foveal center. Regarding spatial distribution pattern, 445 aged eyes (68.4%) showed peaks, 118 (18.1%) rings, 41 (6.3%) mixed, and 47 (7.2%) dips. In young eyes, 40 (90%) showed peaks, 1 (2.3%) rings, 3 (6.8%) mixed, and none showed dips. Notably, peaks were significantly (P&#xa0;<&#xa0;0.001) more prominent in men (74.1%) than women (65.0%) and pseudophakic (72.7%) than phakic (62.9%) eyes.<br><br>CONCLUSIONS: Automatic tools for MPOD centration are reliable and robust. Future studies will use the HILLCLIMB and CONTOUR algorithms.<br><br>TRANSLATIONAL RELEVANCE: Automated MPOD pattern assignment suggests that the spatial distribution of MPOD varies with gender, lens status, and possibly age. Our analytic software can be applied to large samples for studies of xanthophyll carotenoid impact on vision and age-related macular degeneration progression.}, }
@article {pmid40839112, year = {2025}, author = {Fried, S and Vorobichik Berar, O and David, D and Arazi, M and Klain, B and Cohen, GY and Fogel Levin, M and Platner, E and Katz, G and Hostovsky, A}, title = {Poor long-term fellow-eye outcomes after vitrectomy with subretinal tissue plasminogen activator for AMD-related submacular hemorrhage.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {263}, number = {11}, pages = {3113-3119}, pmid = {40839112}, issn = {1435-702X}, mesh = {Humans ; Male ; *Vitrectomy/methods ; Retrospective Studies ; Female ; *Tissue Plasminogen Activator/administration &amp; dosage ; *Visual Acuity ; Aged, 80 and over ; *Retinal Hemorrhage/etiology/diagnosis/therapy/surgery ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; Fibrinolytic Agents/administration &amp; dosage ; Aged ; Time Factors ; Treatment Outcome ; Intravitreal Injections ; Fluorescein Angiography ; Prognosis ; *Wet Macular Degeneration/complications/diagnosis ; Fundus Oculi ; }, abstract = {PURPOSE: To evaluate the long-term prognosis of the fellow-eye in patients with age-related macular degeneration (AMD) who underwent pars plana vitrectomy (PPV) with submacular tissue plasminogen activator injection (SM-tPA) for significant submacular hemorrhage.<br><br>METHODS: Retrospective single-center cohort study including all consecutive patients who underwent PPV with SM-tPA for AMD-related submacular hemorrhage (SMH) between 2010 and 2022, with a minimum follow-up of 2 years. Data was collected from electronic medical records and included demographic characteristics, visual acuity, optical coherence tomography findings, adverse events, further ocular diagnoses in the fellow-eye.<br><br>RESULTS: Forty-seven patients (57% male; mean age 80 years) were included, with a mean follow-up of 82 months. At baseline, most patients had AMD in the fellow-eye (62% dry-AMD; 30% wet-AMD). During follow-up, AMD progressed in 64% of the patients who did not have wet-AMD in their fellow eye at the time of presentation. Seven patients (15%) experienced SMH in the fellow-eye within 1 month to 5 years after initial surgery. The mean VA of the fellow-eye at presentation was 0.64 LogMAR, with a nonsignificant improvement in the first two years. Subsequently, a statistically significant VA deterioration was observed (final mean VA 0.8 LogMAR, p=0.009). By the final follow-up, 30% of patients had better VA in the operated eye, and 26% were legally blind in the fellow-eye.<br><br>CONCLUSION: Patients treated with SM-tPA are at high risk for AMD progression and vision loss in the fellow-eye. Close monitoring of the fellow eye is warranted, and treatment decisions for the involved eye should not be based solely on good fellow-eye vision, given the long-term risk of deterioration.}, }
@article {pmid40839325, year = {2025}, author = {Dohl, J and Burns, G and Singh, M}, title = {The intersection of mitochondria, lipids, and ferroptosis: a new avenue for dry age-related macular degeneration.}, journal = {Apoptosis : an international journal on programmed cell death}, volume = {30}, number = {11-12}, pages = {2526-2546}, pmid = {40839325}, issn = {1573-675X}, support = {R01 EY027363/EY/NEI NIH HHS/United States ; DGE-1839285//National Science Foundation/ ; RO1 EY027363/EY/NEI NIH HHS/United States ; }, mesh = {*Ferroptosis/genetics ; Humans ; *Mitochondria/metabolism/pathology ; *Lipid Metabolism ; *Macular Degeneration/metabolism/pathology ; Animals ; *Geographic Atrophy/metabolism/pathology/genetics ; }, abstract = {Age-related macular degeneration (AMD) is currently the leading cause of vision loss in developed countries. Despite decades of research and development, there are currently no treatments for the dry version of the illness. Dry AMD (DAMD) is a multifactorial disease stemming from dysfunction in the complement system, mitochondrial function, and lipid metabolism. While the complement system has been studied in-depth for its involvement in DAMD, mitochondria and lipids are understudied for their potential contributions to this process. Ferroptosis, an iron-dependent cell death mechanism, is associated with mitochondrial dysfunction and lipid dysregulation, and has been implicated as a driver of DAMD. This review describes the pathology of DAMD and the potential role of mitochondria, metabolism, and lipid dysregulation in the disease. We will highlight the intersection of pathways involving mitochondria, lipid dysregulation, and ferroptosis in DAMD progression, as well as the need for future studies to elucidate this connection.}, }
@article {pmid40840458, year = {2025}, author = {Mackenbrock, LHB and Xu, ATL and Łabuz, G and Augustin, VA and Yildirim, TM and Auffarth, GU and Khoramnia, R}, title = {Quantitative Analysis of Choroidal Vascular Remodeling after Cataract Surgery: Correlation with Preoperative Lens Opacity Grading.}, journal = {Klinische Monatsblatter fur Augenheilkunde}, volume = {242}, number = {8}, pages = {828-835}, doi = {10.1055/a-2644-4687}, pmid = {40840458}, issn = {1439-3999}, mesh = {Humans ; Male ; *Choroid/blood supply/diagnostic imaging ; Female ; Aged ; Tomography, Optical Coherence/methods ; *Vascular Remodeling/physiology ; *Cataract/diagnostic imaging ; Prospective Studies ; Middle Aged ; *Cataract Extraction ; Reproducibility of Results ; Aged, 80 and over ; Treatment Outcome ; *Phacoemulsification ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Cataract surgery has been shown to induce choroidal remodeling, but the underlying mechanisms remain poorly understood. This study investigates the relationship between preoperative lens opacity and postoperative changes in choroidal vascularity following phacoemulsification.<br><br>METHODS: This prospective study included 46 eyes from 46 patients undergoing routine cataract surgery. Choroidal vascularity was assessed using optical coherence tomography angiography (OCTA) before surgery and at 1, 4, and 12 weeks postoperatively. The choroidal vascularity index (CVI) was calculated using a custom computer script. Preoperative lens opacity was quantified using anterior segment optical coherence tomography (AS-OCT). Correlations between CVI changes and various surgical and anatomical parameters were analyzed.<br><br>RESULTS: The CVI decreased significantly, from 0.584&#x2009;&#xb1;&#x2009;0.036 preoperatively to 0.569&#x2009;&#xb1;&#x2009;0.037 at 12 weeks postoperatively (p&#x2009;=&#x2009;0.003). There was a significant negative correlation between the change in CVI and preoperative lens density (r&#x2009;=&#x2009;-&#x2009;0.333, p&#x2009;=&#x2009;0.036), as well as nuclear density (r&#x2009;=&#x2009;-&#x2009;0.328, p&#x2009;=&#x2009;0.039). No significant correlations were found between CVI change and cumulative dissipated energy, phacoemulsification time, fluid usage, or intraocular pressure change.<br><br>CONCLUSION: Cataract surgery induces a significant decrease in choroidal vascularity that persists for at least three months postoperatively. This decrease correlates with preoperative cataract density, suggesting that increased light transmission following lens replacement may lead to choroidal remodeling. Consequently, objective measurement of lens opacity may contribute to the decision-making process for timing cataract surgery; however, further studies are needed to evaluate its potential role in minimising short- and long-term complications, such as macular oedema or age-related macular degeneration.}, }
@article {pmid40841412, year = {2025}, author = {Saito, M and Imaizumi, K}, title = {Two-year results of switching to intravitreal administration of faricimab in patients with aflibercept-refractory neovascular age-related macular degeneration.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {30699}, pmid = {40841412}, issn = {2045-2322}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Female ; Male ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; Aged ; Intravitreal Injections ; Visual Acuity/drug effects ; Retrospective Studies ; Aged, 80 and over ; *Macular Degeneration/drug therapy/pathology ; Treatment Outcome ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Middle Aged ; Follow-Up Studies ; Drug Substitution ; Tomography, Optical Coherence ; Antibodies, Bispecific ; }, abstract = {We evaluated the efficacy of switching to intravitreal injection of faricimab (IVF) in patients with aflibercept-refractory neovascular age-related macular degeneration (nAMD) over 2 years of follow-up. We retrospectively reviewed 47 consecutive eyes of 45 Japanese patients with nAMD who switched from aflibercept to faricimab. Thirty-one eyes of 30 Japanese patients were included in this study. The mean visual acuity (BCVA) at month 24 was stable relative to the baseline. The mean central retinal thickness and subfoveal choroidal thinning significantly decreased at 24 months (P < 0.0001, P < 0.0001, respectively). At 24 months, 22 eyes (70.0%) achieved a dry macula and had improved VA levels with an improvement of 0.80 lines, which was significantly different from the remaining 9 eyes (P < 0.01). The mean interval of IVF was 11.8 weeks, which was significantly longer than that of aflibercept (10.0 weeks) at baseline (p = 0.014). Progression of macular atrophy or newly developing macular atrophy was seen in 3 eyes (9.7%), showing decline of 1.0 line, no other complications were seen. These results indicate that switching to IVF stabilized VA, significantly improved the anatomical changes and the achievement of a dry macula was significantly associated with the visual outcome, in patients with aflibercept-refractory nAMD over a 24-month period.}, }
@article {pmid40843649, year = {2025}, author = {Stráňava, J and Ugarova, D and Stepanov, A}, title = {Subhyaloid Hemorrhage after Bungee Jumping Experience. A Case Report.}, journal = {Ceska a slovenska oftalmologie : casopis Ceske oftalmologicke spolecnosti a Slovenske oftalmologicke spolecnosti}, volume = {81}, number = {Ahead of Print}, pages = {1-4}, doi = {10.31348/2025/31}, pmid = {40843649}, issn = {1211-9059}, mesh = {Humans ; Adult ; Male ; *Retinal Hemorrhage/etiology/surgery ; }, abstract = {Subhyaloid hemorrhage is defined as bleeding between the internal limiting membrane (ILM) and the posterior hyaloid membrane. The condition typically manifests itself in acute visual impairment. Causes include the Valsalva maneuver, Terson's syndrome, age-related macular degeneration (ARMD), trauma, hypercoagulable and hyperviscosity states, uncontrolled blood pressure, diabetes mellitus and leukemia. Prolonged presence of blood in the macular region can lead to the development of an epiretinal membrane and toxic damage to the retinal pigment epithelium and photoreceptors due to iron ions. In this case report we present a 32-year-old patient who was treated at the ophthalmology outpatient clinic of the Regional Hospital in Mladá Boleslav for subhyaloid hemorrhage in the right eye following a bungee jumping experience. The patient was successfully treated with Nd -YAG hyaloidotomy, which resulted in a good therapeutic outcome and full restoration of visual acuity.}, }
@article {pmid40843791, year = {2025}, author = {Amaral, DC and Magalhães, PLM and Alfatih, M and Miranda, BG and Abu Serhan, H and Jacometti, R and Ferreira, BFA and Sant'Ana, L and Santos, DH and Monteiro, MLR and Louzada, RN}, title = {CPAP Use and Retinal Disease Risk in Obstructive Apnea: A Cohort Study.}, journal = {Vision (Basel, Switzerland)}, volume = {9}, number = {3}, pages = {}, pmid = {40843791}, issn = {2411-5150}, abstract = {Obstructive sleep apnea (OSA) is a common condition associated with intermittent hypoxia, systemic inflammation, and vascular dysfunction; mechanisms implicated in retinal disease pathogenesis. This real-world retrospective cohort study used data from the TriNetX Research Network to assess whether continuous positive airway pressure (CPAP) therapy reduces retinal disease incidence among adults with OSA and BMI between 25.0 and 30.0 kg/m[2]. After 1:1 propensity score matching, 101,754 patients were included in the analysis. Retinal outcomes included diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion (RVO), and central serous chorioretinopathy (CSC). CPAP use was associated with a modest but statistically significant reduction in DR (3.2% vs. 3.4%, RR: 0.922, p = 0.016) and AMD (2.1% vs. 2.3%, RR: 0.906, p = 0.018), while no significant differences were found for RVO or CSC. These findings support prior evidence linking CPAP to improved retinal microvascular health and suggest a protective effect against specific retinal complications. Limitations include a lack of data on CPAP adherence, OSA severity, and imaging confirmation. Still, this study highlights the importance of interdisciplinary care between sleep and eye health, and the need for further prospective studies to validate CPAP's role in preventing retinal disease progression in OSA patients.}, }
@article {pmid40844677, year = {2026}, author = {Maehara, Y and Notomi, S and Shiose, S and Fukuda, Y and Kiyohara, K and Kano, K and Ishikawa, K and Hisatomi, T and Sonoda, KH}, title = {Switching to faricimab alleviates persistent subretinal fluid and pigment epithelial detachment in neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {70}, number = {1}, pages = {150-156}, pmid = {40844677}, issn = {1613-2246}, support = {JP21K09702//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; Retrospective Studies ; Female ; Tomography, Optical Coherence/methods ; Male ; *Retinal Detachment/diagnosis/drug therapy/etiology ; *Subretinal Fluid/drug effects ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage ; Intravitreal Injections ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis/complications ; Aged ; Drug Substitution ; Fluorescein Angiography ; Aged, 80 and over ; *Retinal Pigment Epithelium/pathology ; Follow-Up Studies ; Fundus Oculi ; Angiogenesis Inhibitors/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Middle Aged ; Dose-Response Relationship, Drug ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To evaluate structural outcomes, including subretinal fluid (SRF) and fibrovascular pigment epithelial detachment (fvPED) volume changes, after switching from aflibercept 2 mg to faricimab in Japanese patients with neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Retrospective, observational study.<br><br>METHODS: Patients with nAMD who were switched from aflibercept 2 mg to faricimab were enrolled. Changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and the volumes of SRF and fvPED were analyzed using three-dimensional spectral-domain optical coherence tomography data.<br><br>RESULTS: A total of 46 eyes from 46 patients were included. All had been maintained on fixed dosing due to difficulty in extending the injection interval. Patients had received a mean of 25.6 aflibercept 2&#xa0;mg injections, with a mean interval of 7.5&#xa0;weeks for the last three injections. Subsequently, three faricimab injections were given at similar intervals (7.6&#xa0;weeks). BCVA remained unchanged (p = 0.066), while CMT, SRF, and fvPED volumes significantly decreased (p < 0.01). A significant correlation was found between the reductions in SRF and fvPED volumes (p < 0.05).<br><br>CONCLUSIONS: Switching to faricimab led to favorable structural outcomes in nAMD patients previously treated with aflibercept 2&#xa0;mg, particularly by reducing SRF and fvPED.}, }
@article {pmid40845040, year = {2025}, author = {Sumi, S and Asaoka, R and Aoki, S and Kitamoto, K and Terao, R and Kawata, M and Inoue, T and Obata, R and Azuma, K}, title = {Corneal biomechanical predictors of intraocular pressure elevation after intravitreal anti-VEGF injection.}, journal = {PloS one}, volume = {20}, number = {8}, pages = {e0330574}, pmid = {40845040}, issn = {1932-6203}, mesh = {Humans ; *Intraocular Pressure/drug effects ; Male ; Female ; Aged ; Intravitreal Injections/adverse effects ; *Cornea/physiopathology/drug effects ; Retrospective Studies ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Biomechanical Phenomena ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Middle Aged ; Macular Degeneration/drug therapy/physiopathology ; Retinal Vein Occlusion/drug therapy/physiopathology ; }, abstract = {PURPOSE: To investigate whether corneal biomechanical parameters measured via Corvis ST can predict acute intraocular pressure (IOP) elevation following intravitreal anti-VEGF injection.<br><br>DESIGN: Retrospective observational study.<br><br>SUBJECTS: Forty eyes from patients with neovascular age-related macular degeneration or retinal vein occlusion who underwent anti-VEGF therapy.<br><br>METHODS: IOP was measured using the Corvis ST immediately before and 10 minutes after injection. The following biomechanical parameters were evaluated: DA Ratio MAX (2mm), biomechanically corrected IOP (bIOP), Peak Distance, Deflection Amplitude Max, Integrated Radius, and Stress-Strain Index (SSI).<br><br>MAIN OUTCOME MEASURES: Acute post-injection IOP elevation (continuous) and IOP spikes &#x2265;10 mmHg (binary).<br><br>RESULTS: The mean IOP increased significantly from 14.5&#x2009;&#xb1;&#x2009;3.17 to 24.7&#x2009;&#xb1;&#x2009;7.44 mmHg post-injection (p < 0.0001). IOP spikes &#x2265;10 mmHg occurred in 55% of eyes. On multivariate analysis, higher bIOP (&#x3b2; = +1.17, p = 0.048) and lower DA Ratio MAX (&#x3b2; = -5.40, p = 0.038) were independent predictors of IOP elevation. DA Ratio MAX was the only significant predictor of IOP spikes (OR = 0.70, 95% CI: 0.51-0.96, p = 0.035). ROC analysis showed that DA Ratio MAX alone (AUC = 0.739) outperformed bIOP (AUC = 0.607), with the combined model yielding the highest AUC (0.773). A cutoff of DA Ratio MAX &#x2264;4.936 provided 81.8% sensitivity and 42.9% specificity for predicting spikes.<br><br>CONCLUSIONS: DA Ratio MAX (2mm), reflecting global ocular compliance, was a significant predictor of acute IOP spikes after anti-VEGF injection. Alongside bIOP, it may be useful for pre-injection risk stratification of pressure-related complications.}, }
@article {pmid40846247, year = {2025}, author = {Yang, X and Ma, A and Liu, Y and He, Z and Yu, J and Su, S and Chen, J and Sang, A}, title = {Lysyl oxidase-like 2 inhibition alleviates subretinal fibrosis in neovascular age-related macular degeneration model.}, journal = {Experimental eye research}, volume = {260}, number = {}, pages = {110588}, doi = {10.1016/j.exer.2025.110588}, pmid = {40846247}, issn = {1096-0007}, mesh = {Animals ; *Amino Acid Oxidoreductases/antagonists &amp; inhibitors/genetics ; Fibrosis/prevention &amp; control ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; *Retinal Pigment Epithelium/pathology/metabolism/drug effects ; Oxidative Stress ; Epithelial-Mesenchymal Transition ; Cellular Senescence ; Cells, Cultured ; *Wet Macular Degeneration/pathology/metabolism/drug therapy ; Male ; Humans ; }, abstract = {Subretinal fibrosis is a significant contributing factor to the irreversible vision loss linked with neovascular age-related macular degeneration (nAMD). Cellular senescence, a process implicated in the development of nAMD, has been suggested to promote fibrosis through epithelial-mesenchymal transition (EMT). LOXL2 (Lysyl oxidase-like 2) is associated with a variety of fibrotic conditions. However, the role of LOXL2 in subretinal fibrosis remains to be elucidated. In the study, we induced retinal pigment epithelium (RPE) senescence in vitro and in vivo. Further analysis showed that conditioned medium from senescent RPE upregulated the expression of mesenchymal and fibrogenic markers in pre-senescent RPE. LOXL2 silencing was found to attenuate RPE senescence and suppress conditioned medium induced EMT, which was associated with reduced oxidative stress and linked to the TGF-β1/p38 MAPK pathway. In vivo studies confirmed these findings, showing that systemic LOXL2 inhibition reduced D-galactose (D-gal) induced senescence and subretinal fibrosis following laser injury in mice. This treatment also partially corrected the redox imbalance and abnormal activation of TGF-β1/p38 MAPK pathway. The findings indicate that LOXL2 inhibition may be a promising therapeutic approach to prevent subretinal fibrosis in nAMD, providing a novel intervention strategy for a condition for which there are currently no effective treatments.}, }
@article {pmid40848399, year = {2025}, author = {Jiang, Y and Wang, H and Jiang, L and Chen, J and Li, T and Zhang, G and Chen, X and Jiang, M and Sun, X}, title = {Generation of the induced pluripotent stem cell line SJTUGHi004-A derived from a Best's disease patient with c.763C &gt; T mutation in BEST1 gene.}, journal = {Stem cell research}, volume = {88}, number = {}, pages = {103806}, doi = {10.1016/j.scr.2025.103806}, pmid = {40848399}, issn = {1876-7753}, mesh = {Humans ; *Induced Pluripotent Stem Cells/metabolism/cytology/pathology ; *Bestrophins/genetics ; *Vitelliform Macular Dystrophy/genetics/pathology/metabolism ; Cell Line ; *Mutation ; Cell Differentiation ; Male ; Leukocytes, Mononuclear/metabolism ; }, abstract = {Best's disease (BD), referred to as Best vitelliform macular dystrophy, is an autosomal dominant macular degeneration caused by mutations in the BESTROPHIN1 (BEST1) gene. Here, we generated an induced pluripotent stem cell (iPSC) line by the non-integrative Sendai-virus delivery system derived from peripheral blood mononuclear cells (PBMCs) of a patient with c.763C > T mutation in the BEST1 gene. The iPSC line was characterized and validated for the karyotype stability, pluripotency markers, and differentiation potential in vitro, which may serve as a powerful model for exploring the pathological mechanism and pharmaceutical development.}, }
@article {pmid40849031, year = {2025}, author = {Johnston, W and Kim, SS and Kar, D and Gao, L and Clark, ME and McGwin, G and Sloan, KR and Owsley, C and Curcio, CA and Goerdt, L}, title = {Hypertransmission and Vision in Aging and Age-Related Macular Degeneration: Longitudinal Data From ALSTAR2.}, journal = {American journal of ophthalmology}, volume = {280}, number = {}, pages = {399-413}, doi = {10.1016/j.ajo.2025.08.038}, pmid = {40849031}, issn = {1879-1891}, mesh = {Humans ; Female ; Male ; Aged ; Prospective Studies ; Tomography, Optical Coherence/methods ; *Visual Acuity/physiology ; *Aging/physiology ; Fluorescein Angiography/methods ; Follow-Up Studies ; *Macular Degeneration/physiopathology/diagnosis ; *Night Vision/physiology ; Middle Aged ; *Color Vision/physiology ; Aged, 80 and over ; Mesopic Vision/physiology ; Dark Adaptation/physiology ; }, abstract = {PURPOSE: To investigate the presence of hypertransmission (HT) in normal aging, early (e)AMD, and intermediate (i)AMD, changes over 3 years, and the impact of HTs ≥ 250 µm (LHyperTD) on 7 tests of scotopic, mesopic, and photopic vision.<br><br>DESIGN: Prospective cohort study.<br><br>SUBJECTS: Participants of the Alabama Study on Early Age-Related Macular Degeneration 2.<br><br>METHODS: ALSTAR2 participants underwent spectral domain optical coherence tomography angiography (OCTA), color fundus photography, and vision testing at baseline and 3-year follow-up. HT presence and stepped diameters in choroidal en face slabs were assessed with custom review software. Only LHyperTD were analyzed at follow-up. AMD was staged via AREDS 9-step. Vision at baseline and follow-up between eyes with and without LHyperTD was analyzed with linear regression.<br><br>MAIN OUTCOME MEASURES: Presence, size, and illustrative examples of HT, association with tests of photopic, mesopic and scotopic vision.<br><br>RESULTS: Baseline data was available on 460 eyes of 460 patients (mean age 71.5 &#xb1; 5.7 years, 277 female; 236 normal, 134 eAMD, 90 iAMD). HT of any size were found in iAMD (86.7%), eAMD (35.1%), and normal (3.8%) eyes, with proportional LHyperTD (13.3% vs 4.2% vs 0.4%, P < .01). For 339 eyes (mean age 71.2 &#xb1; 5.8 years, 206 female, 181 normal, 92 eAMD, 66 iAMD), LHyperTD presence significantly increased in normal (P = .01) and iAMD (P < .01) but not in eAMD eyes. At baseline, photopic contrast sensitivity (CS), mesopic CS, and rod intercept time (for rod mediated dark adaptation, RMDA) were worse in eyes with LHyperTD compared to eyes without (all P < .01). At follow-up, the same were worse in LHyperTD (all P < .01), as well as low luminance visual acuity (P < .01) and scotopic light sensitivity (P = .05).<br><br>CONCLUSION: LHyperTD are rare in normal and eAMD eyes and associate with mesopic and scotopic visual functions in addition to risk-indicating RMDA. Delayed RMDA reflects other factors other than LHyperTD including differences in disease stage. Our analysis of HT < 250 &#xb5;m may inform other studies of early disease. LHyperTD are best utilized as imaging biomarkers for later stages of iAMD than ALSTAR2.}, }
@article {pmid40849032, year = {2025}, author = {Zhang, C and Aboukasm, G and Lai, DA and Leung, N and Zhu, D and Albini, TA and Yannuzzi, NA}, title = {Clinical Efficacy of Switching to Faricimab in Treatment Resistant Neovascular Age-Related Macular Degeneration: Systematic Review and Meta-analysis.}, journal = {American journal of ophthalmology}, volume = {280}, number = {}, pages = {248-266}, doi = {10.1016/j.ajo.2025.08.034}, pmid = {40849032}, issn = {1879-1891}, mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Drug Substitution ; Treatment Outcome ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; Tomography, Optical Coherence ; Antibodies, Bispecific ; }, abstract = {TOPIC: Faricimab in the treatment of treatment-resistant neovascular age-related macular degeneration (nAMD).<br><br>CLINICAL RELEVANCE: While many studies on faricimab in treatment-resistant eyes have reported improvements in retinal thickness (RT), the impact on visual acuity (VA) remains inconsistent. Additionally, variability in dosing protocols-with some studies utilizing loading interval for the first 3 injections while others continuing at the prior injection interval-introduces further uncertainty regarding the optimal treatment strategy. Understanding these differences is essential for guiding clinical decision-making and maximizing patient outcomes.<br><br>METHODS: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251000088). A systematic search of PubMed, Embase, and Scopus (February 3, 2025) identified studies evaluating the effects of switching to faricimab in treatment-resistant nAMD. Inclusion criteria required patients to have received &#x2265;3 prior anti-VEGF injections and &#x2265;3 faricimab injections, with reported outcomes on RT, VA, fluid status, or injection intervals. Outcomes were measured following completion of loading dose and at last follow up, ranging from 3 months to 1.5 years. Studies were assessed for bias using ROBINS-I and NIH Quality Assessment tool and assessed for certainty of evidence using GRADE. Meta-analyses were conducted using mean differences, odds ratio, and random-effects models.<br><br>RESULTS: Fourteen studies (926 eyes) met inclusion criteria. Switching to faricimab significantly reduced RT by 46.67 &#xb5;m (95% CI: 35.91-57.42, I[2] = 0%, 721 eyes). Eyes that followed a loading interval were found to have greater reduction in RT than those that did not (I[2] = 74.1%, 640 eyes). The odds of achieving a dry macula increased 4.35-fold (95% CI: 2.95-6.42, I[2] = 64%, 379 eyes). Eyes with baseline VA <65 ETDRS letters showed a gain of 3.16 letters (95% CI: 0.80-5.52, I[2] = 0%, 439 eyes). Injection intervals were extended by 1.56 weeks (95% CI: 0.71-2.40, I[2] = 86%, 591 eyes). Using GRADE, 4 outcomes were graded as either very low (VA, dryness, and treatment interval) or low (RT).<br><br>CONCLUSION: Switching to faricimab in treatment-resistant nAMD eyes significantly improved RT with no change in VA. This effect was greater with a loading interval protocol. Overall, there was an extension of injection intervals. Further prospective studies are needed to optimize dosing strategies and assess long-term efficacy.}, }
@article {pmid40849525, year = {2025}, author = {Du, Y and Jiang, S and Feng, L and Lu, J and Peng, H and Zhou, X}, title = {Proteomics on choroidal neovascularization based on itraq and the protective effect of TAB1 in CNV.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {31037}, pmid = {40849525}, issn = {2045-2322}, support = {81170858//National Natural Science Foundation of China/ ; 81170858//National Natural Science Foundation of China/ ; 81170858//National Natural Science Foundation of China/ ; 81170858//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology/genetics ; *Proteomics/methods ; Rats ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; Male ; Interleukin-6/metabolism ; Disease Models, Animal ; Signal Transduction ; Interleukin-18/metabolism ; Rats, Sprague-Dawley ; Cell Proliferation ; NF-kappa B/metabolism ; }, abstract = {Choroidal neovascularization (CNV) is a severe pathological outcome of age-related macular degeneration (AMD) which could lead to blindness. The present study was aimed at exploring the mechanisms of CNV, hoping to provide new clues in finding the treatment target of CNV. ITRAQ approach was applied to analyze the proteins in choroidal neovascularization of CNV and normal rats. KEGG and GO annotation were used to analyze the differently-expressed proteins. Western Blotting was used as the method to identify the differently-expressed proteins. TAB1, one of the differently-expressed proteins, was chosen as the study objective in the following research. AAV-TAB1 over-expression vehicle was constructed to investigate the function of TAB1 in CNV. IL-6 and IL-18 were tested with the use of ELISA. Western Blotting was used to test the expression of NF-kB pathway molecules. In terms of the results, expressions of 49 kinds of proteins were up-regulated in CNV rats while expressions of 241 kinds of proteins were down-regulated among the 4380 identified proteins. Overexpression of TAB1 significantly reduced areas of CNV lesions in vivo. Cell proliferation significantly increased in the TAB1 over-expressed group in RPE. IL-6 expression significantly increased in the TAB1-overexpression group while IL-18 expression significantly reduced. Western blotting results showed NF-kB pathway molecules were involved in it. The present study suggests TAB1 may play a protective role in CNV progression and the relative pathway owns the potential to be the treating target of CNV.}, }
@article {pmid40849608, year = {2025}, author = {Vedula, SS and Li, T}, title = {Cochrane corner: artificial intelligence for diagnosing exudative age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {39}, number = {15}, pages = {2736-2737}, pmid = {40849608}, issn = {1476-5454}, support = {1R01EY033065//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; UG1EY020522//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; }, }
@article {pmid40850524, year = {2025}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {Is acupuncture a viable therapeutic strategy for degenerative eye diseases? a systematic review and meta-analysis.}, journal = {Complementary therapies in medicine}, volume = {93}, number = {}, pages = {103235}, doi = {10.1016/j.ctim.2025.103235}, pmid = {40850524}, issn = {1873-6963}, mesh = {Humans ; *Acupuncture Therapy/methods ; *Eye Diseases/therapy ; Visual Acuity ; Intraocular Pressure ; }, abstract = {INTRODUCTION: Degenerative ocular diseases-glaucoma, age-related macular degeneration (AMD), optic atrophy, and retinitis pigmentosa (RP)-are major causes of irreversible vision loss. Acupuncture, a traditional Chinese therapy, has shown promise in improving visual function through neuroprotective and vascular mechanisms.<br><br>METHODOLOGY: A systematic review and meta-analysis were conducted using data from PubMed, Embase, Scopus, Web of Science, Google Scholar, and Cochrane Library. Randomized controlled trials (RCTs), cohort studies, and other observational studies examined acupuncture or electroacupuncture for degenerative ocular diseases. Quality was assessed using RoB 2.0 for RCTs and ROBINS-I for non-randomized studies. Meta-analyses and narrative syntheses were performed using RevMan and rbiostistics.<br><br>RESULTS: A total of 3362 records were identified, with 21 studies meeting inclusion criteria. Acupuncture shows improvements in visual acuity, ocular blood flow, and intraocular pressure (IOP) across conditions. Meta-analyses showed a significant improvement in total effective rate favoring acupuncture (OR = 3.52; 95&#x202f;% CI: 2.18-5.68; p&#x202f;<&#x202f;0.00001), with consistent benefits across RP, AMD, and optic atrophy. However, pooled data revealed no statistically significant improvement in visual acuity (MD = -0.03; p&#x202f;=&#x202f;0.50) or IOP (MD = -0.86&#x202f;mmHg; p&#x202f;=&#x202f;0.11). Randomized controlled trials comparing acupuncture to sham controls also showed non-significant trends. Despite some promising physiological and functional outcomes, results remain mixed, emphasizing the need for larger, well-designed studies.<br><br>CONCLUSION: Acupuncture shows potential benefits in treating degenerative eye diseases, especially in improving clinical response rates. However, its effects on visual acuity and IOP remain inconclusive, warranting further rigorous research.}, }
@article {pmid40850787, year = {2025}, author = {Cañizo-Outeiriño, A and Castro-Fernández, DC and Arias-Barquet, L and Fernández-Rodríguez, MI and Olivier-Pascual, N and Ortea, I and Pastor-Iodate, S and Rodríguez-De la Rúa-Franch, E and Ruiz-Moreno, JM and Ruiz-Moreno, &#xd3; and Sáenz de Viteri-Vázquez, M and Sala-Puigdollers, A and ,  and Fernández-Ferreiro, A}, title = {Pharmacoproteomics in the development of personalised medicine in Age-related Macular Degeneration (PHARPRO-AMD) study protocol.}, journal = {BMJ open ophthalmology}, volume = {10}, number = {1}, pages = {}, pmid = {40850787}, issn = {2397-3269}, mesh = {Humans ; *Precision Medicine/methods ; *Proteomics/methods ; Prospective Studies ; *Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Biomarkers/metabolism ; *Wet Macular Degeneration/drug therapy/metabolism ; Intravitreal Injections ; Male ; Aged ; Female ; Macular Degeneration/drug therapy ; Observational Studies as Topic ; Multicenter Studies as Topic ; }, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among people over 55 years of age globally, being neovascular AMD (nAMD) its most aggressive form. Its treatment consists of the use of drugs that block vascular endothelial growth factor (anti-VEGF). Proteomics may allow the identification of differentially expressed proteins between responders and non-responders to each anti-VEGF drug. Thus, the objective of Pharmacoproteomics in the development of personalised medicine in Age-related Macular Degeneration (PHARPRO-AMD) is to find new proteomic biomarkers, predictive of response to antiangiogenic treatment in patients with nAMD.<br><br>METHODS AND ANALYSIS: PHARPRO-AMD is a nationwide, multicentre, prospective, observational study. Treatment-na&#xef;ve patients with nAMD starting anti-VEGF therapy will be enrolled and followed up for 2 years. During this period, clinical variables will be gathered to classify treatment response. In addition, blood, tear and vitreous and aqueous humour samples will be collected and will undergo a ZenoSWATH proteomic analysis. Relevant biomarkers identified and response classification will be used to perform a multivariate logistic regression and construct receiver operating characteristic curves.<br><br>RESULTS: The study is expected to identify a panel of proteomic biomarkers predictive of anti-VEGF treatment response. Integrating data from invasive and non-invasive biological samples may enhance clinical applicability. Once validated, these biomarkers could support the design of future clinical trials on biomarker-guided therapies, helping to optimise treatment regimens and improve visual outcomes.<br><br>CONCLUSIONS: The PHARPRO-AMD study aims to provide proof-of-concept for biomarker-guided anti-VEGF therapy in nAMD, potentially improving vision outcomes. A notable limitation is the exclusion of patients with visual acuity above 73 Early Treatment of Diabetic Retinopathy Study letters, a criterion chosen to reduce potential ceiling effects and improve response assessment accuracy.<br><br>ETHICS AND DISSEMINATION: Approved by the Galician Network of Ethics Committees, with nationwide validity. Anonymised data will be deposited in open-access repositories and published in peer-reviewed journals.<br><br>TRIAL REGISTRATION NUMBER: Spanish Clinical Studies Registry (REec) (0033-2024-OBS).}, }
@article {pmid40852330, year = {2025}, author = {Dhoot, DS and Shah, CP and Silva, FQ and McCullough, AJ and Du, W and Moini, H and Kaiser, PK}, title = {Impact of Central Subfield Thickness Fluctuations on Visual Outcomes in Neovascular Age-Related Macular Degeneration in the VIEW Trials.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251359902}, pmid = {40852330}, issn = {2474-1272}, abstract = {Purpose: To evaluate the impact of central subfield thickness (CST) fluctuations on visual outcomes in treatment-naïve eyes with neovascular age-related macular degeneration from VIEW 1 and VIEW 2. Methods: Eyes were treated with intravitreal ranibizumab 0.5 mg every 4 weeks (Rq4) or aflibercept 2 mg every 4 or 8 weeks (2q4 or 2q8). The relationship between CST fluctuations and visual outcomes was evaluated via mixed model for repeated measures in quartiles of SDs of CST from baseline to week 52 (n = 1792; quartile 1: ≤27.6 µm; quartile 2: >27.6 to ≤42.5 µm; quartile 3: >42.5 to ≤65.3 µm; quartile 4: >65.3 µm) and weeks 12 to 52 (n = 1766; quartile 1: ≤27.0 µm; quartile 2: >27.0 to ≤43.2 µm; quartile 3: >43.2 to ≤67.8 µm; quartile 4: >67.8 µm). Results: Least squares mean best-corrected visual acuity (BCVA) gains from baseline to week 52 for quartile 1 to quartile 4 were 9.6, 10.1, 9.6, and 6.7 letters, respectively (quartile 4 vs quartile 1: nominal P = .0017). Least squares mean BCVA letter gains within each quartile treated with Rq4, 2q4, and 2q8, respectively, were 7.0, 10.3, and 10.2 (quartile 1); 11.3, 9.3, and 8.8 (quartile 2); 10.0, 9.3, and 10.1 (quartile 3); and 7.4, 8.4, and 6.2 (quartile 4). From weeks 12 to 52, least squares mean BCVA gains for quartile 1 to quartile 4 were 10.0, 9.7, 9.7, and 6.9 letters, respectively (quartile 4 vs quartile 1: nominal P = .0008). Least squares mean BCVA letter gains within each quartile treated with Rq4, 2q4, and 2q8, respectively, were 7.9, 10.7, and 10.6 (quartile 1); 10.7, 9.3, and 8.1 (quartile 2); 9.3, 9.5, and 10.9 (quartile 3); and 8.2, 8.0, and 6.4 (quartile 4). Conclusions: The highest CST fluctuation was associated with lower BCVA gains, irrespective of antivascular endothelial growth factor agent or regimen.}, }
@article {pmid40852622, year = {2025}, author = {Bikbov, MM and Kazakbaeva, GM and Panda-Jonas, S and Valishin, ID and Nizamutdinova, AM and Jonas, JB}, title = {Intravitreal panitumumab and retinal pigment epithelium proliferation in laser-induced retinal degeneration in rabbits.}, journal = {Frontiers in ophthalmology}, volume = {5}, number = {}, pages = {1641194}, pmid = {40852622}, issn = {2674-0826}, abstract = {PURPOSE: This study aims to examine the effect of intravitreally applied epidermal growth factor (EGF) receptor blocker panitumumab on the proliferation of retinal pigment epithelium cells (RPE) in an experimental model of localized retinal degeneration.<br><br>METHODS: The experimental study included rabbits with age of 2 to 3 months and body weight of 2.5-3 kg and which were randomly distributed into a study group and control group. The right eyes received two retinal argon laser coagulation spots (500 mW; diameter, 100 &#x3bc;m; duration, 0.5 s), applied with an interval of 2 min at the same location close to the vascular streak in the posterior fundus region. For five times at 2-day intervals, the rabbits of the study group received intravitreal injections of 1 mg panitumumab (0.10 mL), and the rabbits of the control group had intravitreal injections of 0.10 mL Ringer's solution. At baseline, at each time point of re-examination, and at study end, the animals were examined by fundus photography and optical coherence tomography of the laser spot.<br><br>RESULTS: The study included 19 rabbits (study group: 10 animals; control group: nine animals). After the third injection and at study end, the laser-induced area of depigmentation + hyperpigmentation combined did not vary significantly between the study group and the control group (1.43 &#xb1; 0.63 mm[2] versus 1.63 &#xb1; 0.77 mm[2]; P = 0.56; and 1.37 &#xb1; 0.63 mm[2] versus 1.61 &#xb1; 0.74 mm[2]; P = 0.46, respectively). At the same time points, the area with hyperpigmentation was significantly smaller in the study group than in the control group (0.16 &#xb1; 0.15 mm[2] versus 0.80 &#xb1; 0.59 mm[2]; P = 0.01; and 0.14 &#xb1; 0.14 mm[2] versus 0.70 &#xb1; 0.56 mm[2]; P = 0.02, respectively). At the same time points, the ratio of the hyperpigmented area to the combined depigmented + hyperpigmented area was significantly smaller in the study group than in the control group (0.11 &#xb1; 0.09 versus 0.43 &#xb1; 0.19 mm[2]; P < 0.001; and 0.10 &#xb1; 0.08 versus 0.35 &#xb1; 0.23mm[2]; P = 0.006, respectively).<br><br>CONCLUSIONS: These findings indicate that intravitreally administered panitumumab was associated with reduced subretinal hyperpigmentation in a laser-induced model of retinal injury. While this may reflect a modulation of the RPE response, including the potential suppression of RPE proliferation, further studies incorporating histological and molecular analyses are warranted to confirm its effect on subretinal fibrosis.}, }
@article {pmid40853572, year = {2025}, author = {Lacanilao, JPB and Artiaga, JCM}, title = {Polypoidal choroidal vasculopathy features among Filipino eyes with neovascular AMD: application of the Asia Pacific Ocular Smaging Society non-ICGA criteria.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {351}, pmid = {40853572}, issn = {1573-2630}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Retrospective Studies ; Cross-Sectional Studies ; Aged ; Male ; Middle Aged ; Aged, 80 and over ; *Fluorescein Angiography/methods ; Philippines/epidemiology ; *Choroid/blood supply ; *Wet Macular Degeneration/diagnosis/epidemiology/complications ; Fundus Oculi ; *Polyps/diagnosis/epidemiology ; Visual Acuity ; *Choroidal Neovascularization/diagnosis ; Societies, Medical ; Polypoidal Choroidal Vasculopathy ; }, abstract = {BACKGROUND/OBJECTIVES: To determine the proportion of eyes with optical coherence tomography (OCT) features of polypoidal choroidal vasculopathy (PCV) among patients diagnosed as neovascular age-related macular degeneration (nAMD) based on Asia-Pacific Ocular Imaging Society (APOIS) Diagnostic Criteria.<br><br>METHODS: This study was a retrospective cross-sectional review of OCT images. Medical records of treatment-na&#xef;ve nAMD patients between January 2018 and June 2023 were reviewed. Clinical and demographic profile at presentation was collected. OCT scans were reviewed for presence of APOIS Diagnostic Criteria. Eyes were classified as having PCV features (PCV) based on the presence of &#x2265;&#x2009;2 major OCT APOIS diagnostic criteria and then compared with eyes not having these features (non-PCV).<br><br>RESULTS: OCT scans of 45 eyes of 38 patients diagnosed with nAMD were analyzed. Mean age was 69.4 years old (range 53-83), 71.1% of patients were female, and 81.6% had unilateral disease. There was no statistically significant difference among clinical and demographic characteristics between PCV and non-PCV groups. Twenty-four eyes (53.3%) had &#x2265;&#x2009;2 major APOIS criteria for PCV. Among PCV eyes, sub-RPE ring-like lesion and double-layer sign were the most common major (87.5%) and minor OCT criteria (100%), respectively. Sharp-peaked PED (p&#x2009;<&#x2009;0.001), sub-RPE ring-like lesion (p&#x2009;<&#x2009;0.001), en face OCT complex RPE elevation (p&#x2009;=&#x2009;0.005) and double-layer sign criteria (p&#x2009;=&#x2009;0.007) were more frequent in the PCV than in the non-PCV group.<br><br>CONCLUSION: More than half of Filipino eyes diagnosed with nAMD fulfill the OCT criteria for PCV. The APOIS PCV Workgroup Criteria helps identify patients who will benefit from additional confirmatory and treatment options.}, }
@article {pmid40854166, year = {2025}, author = {Quarta, A and He, Y and Corradetti, G and Alhelaly, M and Soylu, C and Abbasgholizadeh, R and Popovic, M and Chujo, S and Chung, YC and Kwak, HD and Velaga, SB and Nittala, MG and Sadda, SR}, title = {Intraretinal Sclero-Choroidal Vessels in Eyes with Severe Chorioretinal Thinning: Hypothesis on Bruch's Membrane Failure.}, journal = {Retinal cases &amp; brief reports}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICB.0000000000001797}, pmid = {40854166}, issn = {1937-1578}, abstract = {PURPOSE: To describe the multimodal imaging features of intraretinal sclero-choroidal vessels (ISCVs) in eyes with severe chorioretinal thinning.<br><br>METHODS: A retrospective observational case series. We examined 6 eyes of 6 patients with advanced chorioretinal thinning presenting to the Doheny UCLA Eye Centers (pathologic myopia with posterior staphyloma, iatrogenic staphyloma, chronic anti-VEGF exposure, or non-myopic macular atrophy). All patients underwent structural optical coherence tomography (OCT), and when available, eyes were additionally imaged with OCT angiography (OCTA). Clinical records, fundus photography, and OCT scans were reviewed to assess vessel morphology, anatomical location and course, relationship to BM, and associated chorioretinal changes.<br><br>RESULTS: In all six cases, a large-caliber, non-exudative sclero-choroidal vessel was observed entering into the neurosensory retina. OCT consistently showed a hyperreflective tubular wall with a hyporeflective lumen, often occupying more than 50% of the retinal thickness at the point of entry. All vessels emerged at sites of focal BM disruption, typically within zones of marked choroidal thinning, posterior staphyloma, or atrophic remodeling. OCTA when available confirmed intraluminal flow, with no evidence of surrogate biomarkers of leakage or neovascular proliferation. Accurate identification required careful multimodal assessment to distinguish these ISCVs from mimicking conditions.<br><br>CONCLUSIONS: ISCVs represent a novel structural finding characterized by passive migration of a sclero-choroidal vessel into the retina through areas of BM disruption. ISCVs are non-proliferative and clinically stable, and should be distinguished from more typical exudative lesions on structural OCT. Recognition of ISCVs avoids misdiagnosis and unnecessary treatment.}, }
@article {pmid40854408, year = {2025}, author = {Yu, J and Yuan, J}, title = {Association between gut microbiota dysbiosis and age-related macular degeneration progression: A bioinformatics approach.}, journal = {Experimental eye research}, volume = {260}, number = {}, pages = {110596}, doi = {10.1016/j.exer.2025.110596}, pmid = {40854408}, issn = {1096-0007}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/genetics/microbiology ; *Macular Degeneration/genetics/metabolism ; Disease Progression ; *Computational Biology/methods ; Biomarkers/metabolism ; }, abstract = {Gut microbiota dysbiosis has been linked to the progression of age-related macular degeneration, though the underlying molecular mechanisms remain unclear. This study is the first to systematically link gutMGene-derived genes to AMD pathogenesis using a multi-algorithm machine learning approach. Using the gutMGene database, we identified gut microbiota-related genes and analyzed the GSE29801 dataset for differential expression. Our enrichment analysis revealed unique insights into the involvement of gut microbiota-related genes in inflammatory, immune response, and metabolic pathways in age-related macular degeneration. Machine learning algorithms (LASSO, Random Forest, XGBoost) identified five consistent biomarker genes: CXCL10, FADS3, GHRL, APOE, and VEGFA. A nomogram was developed to predict AMD risk, showing moderate-to-high predictive accuracy with area under the curve of 0.719 (GSE29801) and 0.933 (GSE99248). Gene set variation analysis indicated upregulation of inflammatory and immune pathways and downregulation of lipid metabolism pathways in age-related macular degeneration. Single-gene set enrichment analysis further underscored the roles of diagnostic genes in immune response and metabolic regulation. This study contributes novel evidence that gut microbiota dysbiosis influences AMD progression through systemic inflammatory and metabolic pathways, and highlights potential therapeutic targets.}, }
@article {pmid40855675, year = {2025}, author = {Rodriguez-Cruz, JJ and Cutrufello, J and Lam, M and Nallaparaju, S and Peppas, NA}, title = {Drug Delivery Technologies for the Treatment of Age-Related Macular Degeneration.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {39}, pages = {e03212}, pmid = {40855675}, issn = {2198-3844}, support = {2137420//National Science Foundation/ ; }, mesh = {Humans ; *Macular Degeneration/drug therapy ; *Drug Delivery Systems/methods ; *Angiogenesis Inhibitors/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; }, abstract = {Age-related macular degeneration (AMD) is a progressive and degenerative disease affecting the posterior segment of the eye. It currently affects millions of people worldwide, and the gold standard of treatment has remained unchanged for over 20 years. It consists of intravitreal injections of anti-vascular endothelial growth factor (Anti-VEGF), which pose significant challenges to patient compliance primarily due to accessibility issues, fear of injections in the eye, and high cost. In this review, a thorough description of the pathogenesis of AMD and the anatomical barriers is presented that must be considered for the design of newer drug delivery systems for the treatment of AMD. Likewise, a critical evaluation of the most recent research efforts in the literature regarding the treatment of AMD using novel drug delivery technologies is provided. Lastly, currently approved therapeutic agents are reviewed for AMD and provide an insight into the recent surge of biosimilars with an outlook on how future therapeutic approaches to AMD should be developed.}, }
@article {pmid40855963, year = {2026}, author = {Bommakanti, N and Momenaei, B and Wang, KY and Regillo, CD and Cohen, MN and Kuriyan, AE and Yonekawa, Y}, title = {Efficacy of Switching to Biosimilar Ranibizumab in Eyes Initially Treated with Reference Ranibizumab for Neovascular Age-Related Macular Degeneration, Diabetic Macular Edema, or Retinal Vein Occlusion.}, journal = {Current eye research}, volume = {51}, number = {2}, pages = {133-138}, doi = {10.1080/02713683.2025.2551165}, pmid = {40855963}, issn = {1460-2202}, mesh = {Humans ; *Ranibizumab/therapeutic use/administration &amp; dosage ; Retrospective Studies ; Intravitreal Injections ; Male ; Visual Acuity ; Female ; *Macular Edema/drug therapy/diagnosis/etiology/physiopathology ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged ; *Retinal Vein Occlusion/drug therapy/diagnosis/physiopathology/complications ; *Diabetic Retinopathy/drug therapy/diagnosis/physiopathology ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Biosimilar Pharmaceuticals/therapeutic use/administration &amp; dosage ; *Drug Substitution ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Follow-Up Studies ; Aged, 80 and over ; Middle Aged ; Fluorescein Angiography ; }, abstract = {PURPOSE: To assess the efficacy of ranibizumab-eqrn for neovascular age-related macular degeneration (nAMD), macular edema from retinal vein occlusion (RVO), and diabetic macular edema (DME) in eyes switched from reference ranibizumab.<br><br>METHODS: Single-center, retrospective chart review of eyes which received at least three ranibizumab followed by at least three ranibizumab-eqrn injections over a two-year period. Eyes which were initially treated with alternative anti-VEGF agents were eligible for inclusion. Eyes that received surgery, laser, or intravitreal corticosteroids were excluded. Central foveal thickness (CFT) was measured at the initial and final visit in the ranibizumab and ranibizumab-eqrn groups for a subset of eyes. Primary outcome measures included best available visual acuity (VA) and CFT. Secondary outcome measures included number of intravitreal injections, follow-up time, and treatment interval. Analysis was performed using Python.<br><br>RESULTS: 6233 Eyes from 4935 patients treated between June 6 2022 and June 6 2024 were included. 4692 (75.3%) eyes had nAMD, 1078 (17.3%) eyes had RVO, and 463 (7.4%) eyes had DME. Eyes received 7.1&#x2009;&#xb1;&#x2009;2.7 (total: 44500) ranibizumab injections over 10.5&#x2009;&#xb1;&#x2009;2.5&#x2009;months. After switching, eyes received 5.8&#x2009;&#xb1;&#x2009;2.2 (total: 35840) ranibizumab-eqrn over 8.5&#x2009;&#xb1;&#x2009;1.7&#x2009;months. Mean change in visual acuity was -1.0&#x2009;&#xb1;&#x2009;16.0 letters for ranibizumab vs. -0.6&#x2009;&#xb1;&#x2009;13.8 letters for ranibizumab-eqrn (p&#x2009;=&#x2009;0.15). Mean change in CFT in a subset of 100 eyes was 0.81&#x2009;&#xb1;&#x2009;56.3 microns for ranibizumab vs. -7.2&#x2009;&#xb1;&#x2009;50.6 microns for ranibizumab-eqrn (p&#x2009;=&#x2009;0.39). Mean injection interval increased from 8.3&#x2009;weeks to 8.9&#x2009;weeks in the ranibizumab vs. the ranibizumab-eqrn groups for all indications (p&#x2009;<&#x2009;0.01).<br><br>CONCLUSIONS: In this large real-world study, eyes with nAMD, RVO, and DME switched to ranibizumab-eqrn from reference ranibizumab demonstrated similar efficacy.}, }
@article {pmid40857064, year = {2026}, author = {Hui, VWK and Tsang, CW and Mohamed, S and Fong, AHC and Lai, TYY and Brelen, M and Szeto, SKH}, title = {SUBRETINAL TISSUE PLASMINOGEN ACTIVATOR WITHOUT VITRECTOMY FOR SUBMACULAR HEMORRHAGE DISPLACEMENT USING NANOVITREORETINAL GATEWAY DEVICE: A PILOT REPORT.}, journal = {Retinal cases &amp; brief reports}, volume = {20}, number = {1}, pages = {156-163}, doi = {10.1097/ICB.0000000000001699}, pmid = {40857064}, issn = {1937-1578}, support = {2024.136//Chinese University of Hong Kong/ ; }, mesh = {Humans ; *Tissue Plasminogen Activator/administration &amp; dosage ; Male ; *Retinal Hemorrhage/drug therapy/diagnosis/therapy ; Female ; Retrospective Studies ; Pilot Projects ; Aged ; *Fibrinolytic Agents/administration &amp; dosage ; Visual Acuity ; Middle Aged ; Vitrectomy ; Endotamponade/methods ; Intravitreal Injections ; Aged, 80 and over ; }, abstract = {PURPOSE: To evaluate the surgical outcome of subretinal tissue plasminogen activator delivered without vitrectomy for the displacement of submacular hemorrhage.<br><br>METHODS: A retrospective interventional case series of consecutive patients who underwent subretinal tissue plasminogen activator and intravitreal expansile gas without vitrectomy for submacular hemorrhage displacement. Concomitant injection of subretinal air and intravitreal ranibizumab and expansile gas was performed per surgeon's discretion.<br><br>RESULTS: Seven eyes from seven patients were included. Six eyes (85.7%) had polypoidal choroidal vasculopathy and one eye (14.3%) had wet age-related macular degeneration. The median baseline visual acuity was 0.014 (range 0.005-50.1) Early Treatment Diabetic Retinopathy Study letters, which improved to 35 (range 26.3-65.1), 35 (range 31.0-73.9), 35 (range 35-77.3), and 35 (range 5-80.2), Early Treatment Diabetic Retinopathy Study letters at 1 week, 1 month, 3 months, and 6 months, respectively. Visual gain of &#x2265;5 letters was achieved in most patients through 6 months. Successful displacement of blood away from fovea was achieved in 100% of eyes. The rate of postoperative vitreous hemorrhage, retinal pigment epithelium tear, and macular hole was 14.3% (one patient) each.<br><br>CONCLUSION: This novel, minimally invasive surgical technique is effective in displacing submacular hemorrhage and preserving vision.}, }
@article {pmid40858363, year = {2025}, author = {Ma, K and Ratnapriya, R}, title = {Molecular and genetic landscapes of retina and brain microglia in neurodegenerative diseases.}, journal = {Genome research}, volume = {35}, number = {10}, pages = {2143-2157}, pmid = {40858363}, issn = {1549-5469}, mesh = {*Microglia/metabolism/pathology ; Humans ; *Retina/metabolism/pathology ; *Brain/metabolism/pathology ; Genome-Wide Association Study ; *Macular Degeneration/genetics/pathology ; *Alzheimer Disease/genetics/pathology/metabolism ; *Neurodegenerative Diseases/genetics/pathology ; Transcriptome ; Epigenesis, Genetic ; }, abstract = {Microglia-driven dysregulation has emerged as a significant underlying mechanism in many neurodegenerative diseases, such as age-related macular degeneration (AMD) and Alzheimer's disease (AD). Although both brain and retinal microglia originate from the yolk sac, it is uncertain whether they share molecular similarities or genetic and molecular foundations related to neurodegenerative diseases. In this study, we examine the transcriptomic and epigenetic profiles of retina and brain microglia through integrative analyses of single-nucleus RNA sequencing (snRNA-seq) and single-nucleus ATAC sequencing (snATAC-seq) from 97 independent human samples across 11 different studies. Our findings reveal that retina and brain microglia share similar expression and regulatory profiles compared with other cell types in the retina and brain. By integrating genome-wide association study (GWAS) data with gene expression profiles, we demonstrate that genetic variants associated with AMD and AD are linked to microglia-specific gene signatures. Furthermore, integrating regulatory annotations with GWAS data shows that susceptibility loci for both AMD and AD are notably enriched in the open chromatin regions of microglia from the brain and retina, emphasizing their relevance to these neurodegenerative conditions. Finally, a comparison with microglia annotations from other tissues highlights the specific enrichment of microglia in relation to neurodegenerative diseases. These findings contribute to the understanding of the role of microglia in AMD and AD pathogenesis and offer an opportunity to utilize resources from both retinal and brain microglia to deepen our understanding of their contributions to genetic variations in neurodegenerative diseases.}, }
@article {pmid40858941, year = {2025}, author = {Hernandez, M and Romero-Vázquez, S and Recalde, S and Bezunartea, J and Orduña, MM and Belza-Zuazu, I and García-Layana, A and Adán, A and Fernández-Robredo, P and Molins, B}, title = {C-reactive protein dissociation drives choroidal neovascularization in age-related macular degeneration.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {31408}, pmid = {40858941}, issn = {2045-2322}, support = {PI19/00265//Instituto de Salud Carlos III/ ; PI19/00265//Instituto de Salud Carlos III/ ; PI19/00265//Instituto de Salud Carlos III/ ; PI19/00265//Instituto de Salud Carlos III/ ; PI19/00265//Instituto de Salud Carlos III/ ; PI19/00265//Instituto de Salud Carlos III/ ; PI19/00265//Instituto de Salud Carlos III/ ; RD16/0008//Red Tem&#xe1;tica de Investigaci&#xf3;n Cooperativa en Salud, OFTARED/ ; RD16/0008//Red Tem&#xe1;tica de Investigaci&#xf3;n Cooperativa en Salud, OFTARED/ ; RD16/0008//Red Tem&#xe1;tica de Investigaci&#xf3;n Cooperativa en Salud, OFTARED/ ; RD16/0008//Red Tem&#xe1;tica de Investigaci&#xf3;n Cooperativa en Salud, OFTARED/ ; RD21/0017/0009//Advanced Therapies Network, RICORS-TERAV/ ; RD21/0017/0009//Advanced Therapies Network, RICORS-TERAV/ ; RD21/0017/0009//Advanced Therapies Network, RICORS-TERAV/ ; RD21/0017/0009//Advanced Therapies Network, RICORS-TERAV/ ; SAF2016-81876-REDT//Red del complemento y Salud/ ; SAF2016-81876-REDT//Red del complemento y Salud/ ; SAF2016-81876-REDT//Red del complemento y Salud/ ; SAF2016-81876-REDT//Red del complemento y Salud/ ; SAF2016-81876-REDT//Red del complemento y Salud/ ; Complemento 2-CM//Red del complemento de la Comunidad de Madrid/ ; Complemento 2-CM//Red del complemento de la Comunidad de Madrid/ ; Complemento 2-CM//Red del complemento de la Comunidad de Madrid/ ; Complemento 2-CM//Red del complemento de la Comunidad de Madrid/ ; Complemento 2-CM//Red del complemento de la Comunidad de Madrid/ ; RD24/0007/0015//Carlos III Health Institute and co-financed by the European Union/ ; RD24/0007/0015//Carlos III Health Institute and co-financed by the European Union/ ; RD24/0007/0015//Carlos III Health Institute and co-financed by the European Union/ ; RD24/0007/0015//Carlos III Health Institute and co-financed by the European Union/ ; RD21/0002/0010//Inflammatory Diseases Network, RICORS-REI/ ; RD21/0002/0010//Inflammatory Diseases Network, RICORS-REI/ ; RD21/0002/0010//Inflammatory Diseases Network, RICORS-REI/ ; RD21/0002/0010//Inflammatory Diseases Network, RICORS-REI/ ; RD21/0002/0010//Inflammatory Diseases Network, RICORS-REI/ ; }, mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology/etiology ; *C-Reactive Protein/metabolism/administration &amp; dosage ; *Macular Degeneration/metabolism/pathology ; Mice ; Female ; Male ; Disease Models, Animal ; Fluorescein Angiography ; Mice, Inbred C57BL ; Retinal Pigment Epithelium/metabolism/pathology ; Humans ; Protein Isoforms/metabolism ; }, abstract = {Choroidal neovascularization (CNV) and inflammation play an important role in retinal disease development and the acute phase reactant C-reactive protein (CRP) has been shown to contribute to Age-related macular degeneration (AMD) in vitro. Our aim was to evaluate whether monomeric and pentameric CRP (pCRP, mCRP) isoforms contribute to CNV in vivo and to characterize the mechanism of CRP dissociation in-vivo and in vitro. Both CRP isoforms were intravitreally (IVT) or intravenously (IV) injected in mice, CNV was laser-induced, retinography and fluorescein angiography were performed to evaluate edema. Lectin, mCRP, F4/80 and C5b9 localization were assessed by immunofluorescence and visualized under a confocal microscope. CNV, intensity of fluorescence of mCRP (IF mCRP) was also quantified. To confirm pCRP dissociation in RPE cells and mice, pCRP was coupled to a fluorochrome and IVT injected. A statistical increase in CNV areas was observed in pCRP IVT injected males (p < 0.05) while a statistical decrease was shown in females (p < 0.05). After IV injection, pCRP males showed an increase in CNV areas only vs. mCRP injected mice (p < 0.05) and in females the injection of pCRP injected mice showed higher CNV areas vs. vehicle (p < 0.05) and vs. mCRP injected mice (p < 0.05). Retinal edema after IVT CRP injection was observed mainly in mCRP injected mice. In females there was an IF mCRP statistical decrease in pCRP IVT injected mice vs. vehicle and a statistical increase in pCRP IV injected mice vs. vehicle (p < 0.05). Mice injected with IVT isoforms showed F4/80 positive cells and C5b-9 deposition around the CNV areas. mCRP labeling was observed in the intercellular space of the endothelial cells in the angiogenic area and detected in pCRP IVT injected animals, demonstrating the dissociation of pCRP into mCRP both in vitro and in vivo in proinflammatory microenvironments. In conclusion, CRP administration increased the area of CNV and the edema observed in the subretinal space, suggesting that CRP is activated in the CNV inflammatory environment. In addition, we demonstrated that pCRP dissociates in vivo into mCRP in damaged areas close to CNV, hypothesizing that the CNV process is exacerbated by mCRP.}, }
@article {pmid40861328, year = {2025}, author = {Kritfuangfoo, T and Li, Y and Mieler, WF}, title = {Clinical Characteristics and Treatment Outcomes of Breakthrough Vitreous Hemorrhage in Peripheral Exudative Hemorrhagic Chorioretinopathy (PEHCR).}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {2821-2833}, pmid = {40861328}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate the clinical characteristics and treatment outcomes of breakthrough vitreous hemorrhage secondary to peripheral exudative hemorrhagic chorioretinopathy (PEHCR).<br><br>METHODS: This retrospective study included 14 eyes from 14 patients with vitreous hemorrhage secondary to peripheral retinochoroidal mass lesions. Data collected included demographic profiles, clinical presentation, multimodal imaging findings, and treatment outcomes following pars plana vitrectomy (PPV), intravitreal anti-VEGF injections, or laser photocoagulation.<br><br>RESULTS: The median age at presentation was 83 years (range, 58-91), with nine females (64.3%). Median presenting visual acuity (VA) was 1.3 logMAR (range, 0.3-2.7). All patients had normal intraocular pressure. Bilateral PEHCR was observed in 50%, though hemorrhage occurred unilaterally. Unifocal lesions were present in 71.4%, with a mean lesion thickness of 3.4 mm (range, 1.5-6.8 mm). Dense vitreous hemorrhage obscuring posterior pole details was seen in eight eyes (57.1%) and required PPV. The remaining six eyes, with moderate hemorrhage, improved spontaneously without surgery. Intravitreal anti-VEGF therapy was administered in five eyes for macular involvement or to prevent recurrent hemorrhage. At a median follow-up of 11.7 months (range, 3-63), median VA improved to 0.36 logMAR (range, 0.1-2.0). The mean VA gain was 0.76 logMAR in the vitrectomy group (p = 0.004) and 0.55 logMAR in eyes without macular involvement (p = 0.024). However, five eyes (35.7%) had final VA &#x2264; 20/200 due to macular pathology consistent with age-related macular degeneration or polypoidal choroidal vasculopathy-like changes.<br><br>CONCLUSION: PEHCR with breakthrough vitreous hemorrhage is a rare but important diagnostic consideration in patients presenting with peripheral retinochoroidal mass-like lesions. PPV and intravitreal anti-VEGF therapy may improve visual outcomes in these cases. However, visual recovery may be limited in cases with macular involvement due to irreversible retinal damage. Early diagnosis and tailored management are essential to optimize outcomes and avoid misdiagnosis.}, }
@article {pmid40861593, year = {2025}, author = {Gartaganis, P and Khamis, N and Hamoud Bedan, A and Driouich, Z and Ashraf, MO and Abucar Osman, S and Younis, S}, title = {A Comparative Assessment of Intraocular Pressure Changes After Aflibercept 8 mg and Faricimab-svoa Intravitreal Injections in Wet Age-Related Macular Degeneration.}, journal = {Cureus}, volume = {17}, number = {7}, pages = {e88617}, pmid = {40861593}, issn = {2168-8184}, abstract = {Introduction A standard practice for addressing wet age-related macular degeneration (WetAMD) is to deliver anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections. Formulations with higher concentrations, such as aflibercept 8 mg (Eylea HD; Bayer AG, Leverkusen, Germany), which are administered in larger volumes, may raise concerns about potential increases in intraocular pressure (IOP) and other ocular complications. The objective of this study was to evaluate and compare short-term IOP changes following intravitreal injection of aflibercept 8 mg (Eylea HD, 0.07 mL) versus faricimab-svoa (Vabysmo, 0.05 mL; Roche Pharma, Basel, Switzerland/Genentech, South San Francisco, CA, USA) in patients with WetAMD. Methods A retrospective observational analysis was conducted involving patients with WetAMD who received intravitreal injections of aflibercept 8 mg (n = 64 eyes) or faricimab-svoa (n = 73 eyes). IOP was measured before the injection and 30 minutes after. The research recorded lens condition, the need for paracentesis, and the application of Iopidine drops. Patients were categorized into phakic and pseudophakic subgroups, and further stratified based on post-injection IOP levels: <20 mmHg, 20-25 mmHg, 25-30 mmHg, and >30 mmHg. Results Both treatment groups showed notable increases in IOP at 30 minutes after injection (Eylea HD: +4.50 ± 4.32 mmHg, Vabysmo: +3.66 ± 5.20 mmHg; p = 0.083). However, there were no instances requiring paracentesis, and only one patient from each group needed Iopidine drops. Pseudophakic patients experienced slightly higher IOP increases (Eylea HD: +4.71 ± 4.18 mmHg, Vabysmo: +4.55 ± 5.65 mmHg; p = 0.784) compared to phakic patients. The majority of patients maintained IOP levels under 30 mmHg. Gender distribution was 49% male and 51% female. Conclusions Intravitreal injections of aflibercept 8 mg and faricimab-svoa caused a small and temporary increase in IOP and there were no cases requiring urgent management. Our results confirm the short-term ocular safety of aflibercept 8 mg and faricimab-svoa for the treatment of WetAMD and highlight the need for individualized monitoring for patients at risk of increased IOP.}, }
@article {pmid40862026, year = {2025}, author = {Rodrigues De Moura, M and Sasher, T and Smith, T}, title = {An Abnormal Presentation of Age-Related Macular Degeneration in a Young, Healthy Adult.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e90672}, pmid = {40862026}, issn = {2168-8184}, abstract = {Age-related macular degeneration (AMD) is a relatively uncommon diagnosis in patients under the age of 45. It typically manifests as a gradual or sudden loss of central vision, producing blurred images or wavy visual distortions. These symptoms can interfere not only with daily activities but also with more detailed visual tasks, significantly impacting quality of life. This case report illustrates the rare presentation of intermediate AMD in a 43-year-old male with no significant past medical history. The case also highlights the importance of maintaining routine health examinations, including annual primary care visits and baseline ophthalmologic examinations. Regular health screenings are vital for the early detection of potential diseases and are a crucial part of preventive medicine.}, }
@article {pmid40862273, year = {2025}, author = {Sezer, T and Altıkardeşler, E and Erdoğan, K and Arslan, B and Çolak, K}, title = {Evaluation of pain scores during intravitreal injection in systemic conditions and in conjunction with medications.}, journal = {Therapeutic advances in ophthalmology}, volume = {17}, number = {}, pages = {25158414241275360}, pmid = {40862273}, issn = {2515-8414}, abstract = {BACKGROUND: Intravitreal injection (IVI) is a common practice in today's ophthalmology clinics. The pain that patients will experience after the application may be important in compliance with the treatment.<br><br>OBJECTIVES: This study aimed to investigate the correlation between various clinical characteristics of patients receiving IVI and corresponding visual analogue scale (VAS) scores (0: no pain to 10: severe pain).<br><br>DESIGN: Single-centre, Prospective study.<br><br>METHODS: A total of 313 participants (168 females, 145 males) with a mean age of 66.91&#x2009;&#xb1;&#x2009;9.67&#x2009;years underwent IVI for diabetic retinopathy (DRP), retinal vein occlusion (RVO), or age-related macular degeneration (AMD). Eye examinations, including visual acuity and intraocular pressure measurements, were also conducted, and injection indications were determined based on dilated fundus examinations and spectral domain optical coherence tomography images. Following the injections, the researchers solicited VAS scores ranging from 0 to 10 (no pain to severe pain). The study explored the relationships between clinical characteristics, headache frequency, joint and muscle pain, analgesic use, surgical history, antidepressant use, vasovagal syncope, previous injections, and VAS score.<br><br>RESULTS: The mean VAS score was 4.77&#x2009;&#xb1;&#x2009;2.90. While DRP and RVO had similar VAS scores (4.95&#x2009;&#xb1;&#x2009;2.98 and 5.22&#x2009;&#xb1;&#x2009;2.70, respectively), the AMD group had significantly lower scores (4.09&#x2009;&#xb1;&#x2009;2.64). Compared with nonusers, antidepressant users had significantly greater VAS scores (5.79&#x2009;&#xb1;&#x2009;3.43) (4.52&#x2009;&#xb1;&#x2009;2.70) (p&#x2009;<&#x2009;0.05). Patients with a history of syncope had significantly greater VAS scores (p&#x2009;<&#x2009;0.05). In patients reporting monthly headaches, a positive correlation was found between headache frequency and VAS score (r&#x2009;=&#x2009;0.23, p&#x2009;<&#x2009;0.01).<br><br>CONCLUSION: For individuals experiencing daily headaches, inquiries about vasovagal syncope and antidepressant use may be beneficial, considering the potential association of these symptoms with higher VAS scores after IVIs.}, }
@article {pmid40862502, year = {2025}, author = {Kuo, D and Pajic, M and Hadziahmetovic, M}, title = {Ten years later: how is AI impacting retina care today?.}, journal = {Current opinion in ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICU.0000000000001167}, pmid = {40862502}, issn = {1531-7021}, support = {R21 EY033480/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: Artificial intelligence (AI) is transforming retina care, with deep learning (DL) models shaping a new era of improved screening accessibility, diagnostic precision, and personalized disease monitoring. This review highlights recent AI-powered clinical applications in diabetic retinopathy (DR), and age-related macular degeneration (AMD) care.<br><br>RECENT FINDINGS: Since the FDA's authorization of the first autonomous AI system for DR screening in 2018, multiple platforms have emerged, expanding access to diabetic eye care. Real-world studies have confirmed a significant improvement in screening adherence and diagnostic accuracy, illustrating AI's tangible impact on public health. Meanwhile, newly certified AI technologies that meet European regulatory standards are increasingly guiding clinical decision-making in the management of AMD and diabetic macular edema through automated analysis of optical coherence tomography (OCT) images. Most recently, FDA-authorized home OCT platforms are transforming AMD monitoring, enabling proactive and remote management of retinal fluid.<br><br>SUMMARY: As AI increasingly empowers patients and providers, its widespread success still depends on ongoing work, including thorough validation, outcome-based metrics, and improved workflow integration. The next decade will reveal whether AI in retina care transitions from a promising innovation to an essential and indispensable tool in modern retina.}, }
@article {pmid40863488, year = {2025}, author = {Qureshi, ADA and Malik, H and Naeem, A and Hassan, SN and Jeong, D and Naqvi, RA}, title = {ODDM: Integration of SMOTE Tomek with Deep Learning on Imbalanced Color Fundus Images for Classification of Several Ocular Diseases.}, journal = {Journal of imaging}, volume = {11}, number = {8}, pages = {}, pmid = {40863488}, issn = {2313-433X}, support = {NRF[2022-R1-G1A1(010226)]//National Research Foundation of Korea/ ; }, abstract = {Ocular disease (OD) represents a complex medical condition affecting humans. OD diagnosis is a challenging process in the current medical system, and blindness may occur if the disease is not detected at its initial phase. Recent studies showed significant outcomes in the identification of OD using deep learning (DL) models. Thus, this work aims to develop a multi-classification DL-based model for the classification of seven ODs, including normal (NOR), age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma (GLU), maculopathy (MAC), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR), using color fundus images (CFIs). This work proposes a custom model named the ocular disease detection model (ODDM) based on a CNN. The proposed ODDM is trained and tested on a publicly available ocular disease dataset (ODD). Additionally, the SMOTE Tomek (SM-TOM) approach is also used to handle the imbalanced distribution of the OD images in the ODD. The performance of the ODDM is compared with seven baseline models, including DenseNet-201 (R1), EfficientNet-B0 (R2), Inception-V3 (R3), MobileNet (R4), Vgg-16 (R5), Vgg-19 (R6), and ResNet-50 (R7). The proposed ODDM obtained a 98.94% AUC, along with 97.19% accuracy, a recall of 88.74%, a precision of 95.23%, and an F1-score of 88.31% in classifying the seven different types of OD. Furthermore, ANOVA and Tukey HSD (Honestly Significant Difference) post hoc tests are also applied to represent the statistical significance of the proposed ODDM. Thus, this study concludes that the results of the proposed ODDM are superior to those of baseline models and state-of-the-art models.}, }
@article {pmid40866110, year = {2026}, author = {Airaldi, M and Parrulli, S and Trinco, A and Cinus, F and Staurenghi, G and Pellegrini, M and Cereda, M}, title = {Impact of a laminar air flow portable device on post-intravitreal injection endophthalmitis rate.}, journal = {The British journal of ophthalmology}, volume = {110}, number = {2}, pages = {155-157}, doi = {10.1136/bjo-2025-327316}, pmid = {40866110}, issn = {1468-2079}, mesh = {Humans ; *Endophthalmitis/epidemiology/prevention &amp; control/etiology ; *Intravitreal Injections/adverse effects ; *Eye Infections, Bacterial/epidemiology/prevention &amp; control/etiology/microbiology ; Incidence ; Female ; Male ; *Environment, Controlled ; Retrospective Studies ; Middle Aged ; Aged ; }, abstract = {Intravitreal injections (IVIs) are the most common outpatient procedure worldwide, yet no consensus exists regarding their optimal setting. This study analysed 101 976 IVIs performed between 2017 and 2023, comparing endophthalmitis rates before and after introducing a mobile laminar air flow (LAF) device in a clean room. The incidence of endophthalmitis decreased from 0.033% to 0.013%, a 63.2% risk reduction (Odds Ratio=0.368, p=0.04). These findings suggest that mobile LAF enhances air quality and reduces infection risk, offering a cost-effective, efficient alternative to operating theatres for IVIs.}, }
@article {pmid40867504, year = {2025}, author = {Hussain, AA and Lee, Y}, title = {Extracellular Matrix (ECM) Aging in the Retina: The Role of Matrix Metalloproteinases (MMPs) in Bruch's Membrane Pathology and Age-Related Macular Degeneration (AMD).}, journal = {Biomolecules}, volume = {15}, number = {8}, pages = {}, pmid = {40867504}, issn = {2218-273X}, mesh = {*Bruch Membrane/pathology/metabolism ; Humans ; *Macular Degeneration/metabolism/pathology ; *Matrix Metalloproteinases/metabolism ; *Extracellular Matrix/metabolism/pathology ; Animals ; *Aging/metabolism/pathology ; *Retina/metabolism/pathology ; Retinal Pigment Epithelium/metabolism/pathology ; }, abstract = {The extracellular matrix (ECM) is a collagen-based scaffold that provides structural support and regulates nutrient transport and cell signaling. ECM homeostasis depends on a dynamic balance between synthesis and degradation, the latter being primarily mediated by matrix metalloproteinases (MMPs). These enzymes are secreted as pro-forms and require activation to degrade ECM components. Their activity is modulated by tissue inhibitors of metalloproteinases (TIMPs). Aging disrupts this balance, leading to the accumulation of oxidized, cross-linked, and denatured matrix proteins, thereby impairing ECM function. Bruch's membrane, a penta-laminated ECM structure in the eye, plays a critical role in supporting photoreceptor and retinal pigment epithelium (RPE) health. Its age-related thickening and decreased permeability are associated with impaired nutrient delivery and waste removal, contributing to the pathogenesis of age-related macular degeneration (AMD). In AMD, MMP dysfunction is characterized by the reduced activation and sequestration of MMPs, which further limits matrix turnover. This narrative review explores the structural and functional changes in Bruch's membrane with aging, the role of MMPs in ECM degradation, and the relevance of these processes to AMD pathophysiology, highlighting emerging regulatory mechanisms and potential therapeutic targets.}, }
@article {pmid40867529, year = {2025}, author = {Donaldson, KJ and Chrenek, MA and Boatright, JH and Nickerson, JM}, title = {High-Resolution Imaging and Interpretation of Three-Dimensional RPE Sheet Structure.}, journal = {Biomolecules}, volume = {15}, number = {8}, pages = {}, pmid = {40867529}, issn = {2218-273X}, support = {R01 EY028859/EY/NEI NIH HHS/United States ; P30 EY006360/EY/NEI NIH HHS/United States ; I21 RX001924/RX/RRD VA/United States ; R01 DC009246/DC/NIDCD NIH HHS/United States ; T32 EY007092/EY/NEI NIH HHS/United States ; I01 RX002806/RX/RRD VA/United States ; 5 R01 EY028450 01-05/EY/NEI NIH HHS/United States ; R01 EY021592/EY/NEI NIH HHS/United States ; R01 EY028450/EY/NEI NIH HHS/United States ; }, mesh = {*Retinal Pigment Epithelium/metabolism/cytology/diagnostic imaging/pathology ; *Imaging, Three-Dimensional/methods ; Humans ; Animals ; Microscopy, Confocal ; Macular Degeneration/pathology/metabolism ; Zonula Occludens-1 Protein/metabolism ; }, abstract = {The retinal pigment epithelium (RPE), a monolayer of pigmented cells, is critical for visual function through its interaction with the neural retina. In healthy eyes, RPE cells exhibit a uniform hexagonal arrangement, but under stress or disease, such as age-related macular degeneration (AMD), dysmorphic traits like cell enlargement and apparent multinucleation emerge. Multinucleation has been hypothesized to result from cellular fusion, a compensatory mechanism to maintain cell-to-cell contact and barrier function, as well as conserve resources in unhealthy tissue. However, traditional two-dimensional (2D) imaging using apical border markers alone may misrepresent multinucleation due to the lack of lateral markers. We present high-resolution confocal images enabling three-dimensional (3D) visualization of apical (ZO-1) and lateral (α-catenin) markers alongside nuclei. In two RPE damage models, we find that seemingly multinucleated cells are often single cells with displaced neighboring nuclei and lateral membranes. This emphasizes the need for 3D analyses to avoid misidentifying multinucleation and underlying fusion mechanisms. Lastly, images from the NaIO3 oxidative damage model reveal variability in RPE damage, with elongated, dysmorphic cells showing increased ZsGreen reporter protein expression driven by EMT-linked CAG promoter activity, while more regular RPE cells displayed somewhat reduced green signal more typical of epithelial phenotypes.}, }
@article {pmid40867611, year = {2025}, author = {Chen, Q and Zhang, T and Chen, Z and Zeng, J and O'Connor, A and Zhu, M and Gillies, MC and Lu, F and Zhu, L}, title = {Retinal Pigment Epithelium Transplantation in Retinal Disease: Clinical Trial Development, Challenges, and Future Directions.}, journal = {Biomolecules}, volume = {15}, number = {8}, pages = {}, pmid = {40867611}, issn = {2218-273X}, support = {82201212//National Natural Science Foundation of China/ ; Not//the Claffy Foundation Bright Idea Grant/ ; }, mesh = {Humans ; *Retinal Pigment Epithelium/transplantation ; Clinical Trials as Topic ; *Macular Degeneration/therapy ; *Retinal Diseases/therapy ; Animals ; }, abstract = {Replacement of the retinal pigment epithelium (RPE) is emerging as a promising approach to treat degenerative retinal diseases, including age-related macular degeneration and Stargardt disease, in which RPE function cannot otherwise be restored. Despite the limitations of existing treatments, advances in cell sourcing and surgical methods have enabled initial human trials of RPE transplantation, with early results indicating potential efficacy. This review comprehensively examines the evolution of RPE transplantation in recent decades, highlighting the advantages and limitations of different cell sources and delivery methods. Current clinical trial data are analyzed with a particular focus on immune rejection risks, surgical complications, and long-term safety. Despite encouraging safety profiles, achieving consistent and sustained visual improvement remains a challenge, as vision outcomes might be influenced by factors such as disease stage at intervention, transplantation site, number of cells transplanted, and duration of follow-up. Key challenges, such as cell or graft survival and integration with the host retina, are discussed in depth, as overcoming these obstacles is essential for achieving stable and effective RPE replacement. Future research directions, including innovations in biomaterials, molecular modification strategies, and personalized approaches, hold promise for enhancing the efficacy and durability of RPE transplantation for retinal disease.}, }
@article {pmid40867647, year = {2025}, author = {Maceroni, E and Cimini, A and Quintiliani, M and d'Angelo, M and Castelli, V}, title = {Retinal Gatekeepers: Molecular Mechanism and Therapeutic Role of Cysteine and Selenocysteine.}, journal = {Biomolecules}, volume = {15}, number = {8}, pages = {}, pmid = {40867647}, issn = {2218-273X}, mesh = {Humans ; *Selenocysteine/metabolism ; *Cysteine/metabolism ; Animals ; *Retina/metabolism/pathology/drug effects ; Oxidative Stress/drug effects ; Oxidation-Reduction ; Antioxidants/metabolism ; *Retinal Degeneration/metabolism/drug therapy ; Reactive Oxygen Species/metabolism ; }, abstract = {Oxidative stress is a key contributor to retinal degeneration, as the retina is highly metabolically active and exposed to constant light stimulation. This review explores the crucial roles of cysteine and selenocysteine in redox homeostasis and retinal protection. Cysteine, primarily synthesized via the transsulfuration pathway, is the rate-limiting precursor for glutathione (GSH), the most abundant intracellular antioxidant. Selenocysteine enables the enzymatic activity of selenoproteins, particularly glutathione peroxidases (GPXs), which counteract reactive oxygen species (ROS). Experimental evidence from retinal models confirms that depletion of cysteine or selenocysteine results in impaired antioxidant defense and photoreceptor death. Furthermore, dysregulation of these amino acids contributes to the pathogenesis of age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR). Therapeutic approaches including N-acetylcysteine, selenium compounds, and gene therapy targeting thioredoxin systems have demonstrated protective effects in preclinical studies. Targeting cysteine and selenocysteine-dependent systems, as well as modulating the KEAP1-NRF2 pathway, may offer promising strategies for managing retinal neurodegeneration. Advancing our understanding of redox mechanisms and their role in retinal cell viability could unlock new precision treatment strategies for retinal diseases.}, }
@article {pmid40867892, year = {2025}, author = {Chaudhary, S and Moon, J and Hu, Z and Kriukov, E and Pestun, S and Baranov, PY and Ng, YE and D'Amore, PA}, title = {The Mechanism of PMC (2,2,5,7,8-Pentamethyl-6-chromanol), a Sterically Hindered Phenol Antioxidant, in Rescuing Oxidized Low-Density-Lipoprotein-Induced Cytotoxicity in Human Retinal Pigment Epithelial Cells.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {8}, pages = {}, pmid = {40867892}, issn = {2076-3921}, support = {P30EYE003790/EY/NEI NIH HHS/United States ; }, abstract = {Geographic atrophy or late-stage dry age-related macular degeneration (AMD) is characterized by drusen deposition and progressive retinal pigment epithelium (RPE) degeneration, leading to irreversible vision loss. The formation of drusen leads to dyshomeostasis, oxidative stress, and irreversible damage to the RPE. In this study, we used an in vitro model of oxidized low-density lipoprotein (ox-LDL)-induced human RPE damage/death to investigate the mechanism through which a sterically hindered phenol antioxidant compound, PMC (2,2,5,7,8-pentamethyl-6-chromanol), protects the RPE against ox-LDL-induced damage. We show that PMC exerts its protective effect by preventing the upregulation of stress-responsive heme oxygenase-1 (HMOX1/HO-1) and NAD(P)H: quinone oxidoreductase (NQO1) at the mRNA and protein levels. This effect was due to PMC's blockade of ROS generation, which in turn blocked nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, ultimately preventing the upregulation of antioxidant response elements (AREs), including HMOX1 and NQO1. The key role of HO-1 was demonstrated when the protective effect of PMC was inhibited by the knockdown of HMOX1. Additionally, PMC treatment under different experimental conditions and at different time points revealed that the continuous presence of PMC is required for the optimal protection against ox-LDL-induced cytotoxicity, defining the cellular pharmacokinetics of this molecule. Our data demonstrate the involvement of a key antioxidant pathway through which PMC mitigates the oxidative stress induced by ox-LDL and provides a potential therapeutic strategy for suppressing RPE degeneration/damage during AMD progression.}, }
@article {pmid40868995, year = {2025}, author = {Grupenmacher, AT and Augusto, BO and Fetter, BZ and Rocha, JP and Araujo, DL and Kniggendorf, V and Nader, HB and Regatieri, CVS and Dreyfuss, JL}, title = {Antiangiogenic Activity of 6-O-Desulfated Modified Heparin: Suppression of Choroidal Neovascularization.}, journal = {International journal of molecular sciences}, volume = {26}, number = {16}, pages = {}, pmid = {40868995}, issn = {1422-0067}, support = {2015/03964-6//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 421697/2021-0//National Council for Scientific and Technological Development/ ; }, mesh = {Animals ; *Choroidal Neovascularization/drug therapy/pathology/metabolism ; *Heparin/pharmacology/chemistry/analogs &amp; derivatives/therapeutic use ; *Angiogenesis Inhibitors/pharmacology/chemistry/therapeutic use ; Rats ; Humans ; Cell Proliferation/drug effects ; Cell Movement/drug effects ; Rats, Zucker ; Disease Models, Animal ; Fibroblast Growth Factor 2/metabolism ; Macular Degeneration/drug therapy ; Human Umbilical Vein Endothelial Cells ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness worldwide, primarily due to pathological choroidal neovascularization (CNV). Our study investigates a chemically modified heparin derivative as a novel strategy to selectively modulate angiogenic signaling, offering a reduced anticoagulant risk and preclinical support for AMD treatment. We explored the therapeutic potential of 6-O-desulfated heparin (Hep-6Od) as an antiangiogenic agent with diminished anticoagulant activity. Synthesized via selective 6-O-desulfation and characterized using nuclear magnetic resonance (NMR), Hep-6Od demonstrated safety in retinal pigment epithelial cells with no cytotoxic effects at various concentrations. In vitro, the compound significantly inhibited endothelial cell proliferation, migration, and capillary tube formation. Differential scanning fluorimetry (DSF) assays confirmed molecular interaction between Hep-6Od and fibroblast growth factor 2 (FGF-2), suggesting interference with pro-angiogenic signaling pathways. In vivo, a laser-induced CNV model in lean Zucker rats showed a dose-dependent reduction in neovascular lesion areas after an intravitreal Hep-6Od injection. Compared to unfractionated heparin, Hep-6Od exhibited reduced anticoagulant effects in PT and aPTT assays while maintaining robust antiangiogenic properties. These findings support Hep-6Od as a promising alternative to anti-vascular endothelial growth factor (VEGF) therapies for AMD treatment, potentially expanding current retinal vascular disease interventions. The results underscore its potential to transform AMD management, pending further clinical validation and awaiting confirmation in further studies.}, }
@article {pmid40869227, year = {2025}, author = {Klusek, K and Kijowska, M and Kiełbus, M and Sławińska, J and Kuźmiuk, D and Chorągiewicz, T and Rejdak, R and Dolar-Szczasny, J}, title = {The Supportive Role of Plant-Based Substances in AMD Treatment and Their Potential.}, journal = {International journal of molecular sciences}, volume = {26}, number = {16}, pages = {}, pmid = {40869227}, issn = {1422-0067}, mesh = {Humans ; *Macular Degeneration/drug therapy/metabolism ; *Antioxidants/therapeutic use/pharmacology ; Animals ; Oxidative Stress/drug effects ; Anti-Inflammatory Agents/therapeutic use/pharmacology ; Curcumin/therapeutic use ; Polyphenols/therapeutic use/pharmacology ; Anthocyanins/therapeutic use/pharmacology ; }, abstract = {There is growing interest in the use of natural plant-derived compounds, such as polyphenols (including curcumin), flavonoids, silymarin, anthocyanins, lutein, and zeaxanthin, for the treatment of age-related macular degeneration (AMD). These substances exhibit antioxidant, anti-inflammatory, and protective effects on retinal cells, contributing to the preservation of retinal integrity by modulating the key pathogenic mechanisms of AMD, including oxidative stress, chronic inflammation, and pathological neovascularization. Consequently, they hold potential to support conventional therapeutic approaches and slow disease progression. Current studies highlight their promising role as adjunctive agents in AMD management. This literature review provides a comprehensive analysis of the potential role of the aforementioned natural plant-derived compounds in the prevention and supportive treatment of age-related macular degeneration. It also discusses their natural sources, modes of administration and supplementation, and highlights the importance of a nutrient-rich diet as a key factor in maintaining ocular health. Furthermore, the review synthesizes current scientific knowledge on the ability of natural antioxidants to slow the progression of AMD and outlines future research directions aimed at improving diagnostic methods and developing more effective preventive and therapeutic strategies.}, }
@article {pmid40869660, year = {2025}, author = {Gwon, HN and Son, HJ and Shin, YJ}, title = {Association of Body Metrics and Ocular Diseases.}, journal = {Journal of clinical medicine}, volume = {14}, number = {16}, pages = {}, pmid = {40869660}, issn = {2077-0383}, support = {Hallym University Research Fund//Hallym University/ ; NRF-2023R1A2C2002674//National Research Foundation (NRF) grant by the Korea government/ ; }, abstract = {Background/Objectives: The relationship between systemic health and ocular diseases is well-documented, with various body metrics potentially playing significant roles in the pathogenesis of cataracts, glaucoma, and age-related macular degeneration (AMD). However, comprehensive studies linking these metrics with ocular health are sparse. This study aims to explore the associations between height, weight, waist circumference, and BMI with the prevalence and current status of cataracts, glaucoma, and AMD in a large cohort. Methods: We used data from Korean National Health and Nutrition Survey (KNHANES 2015-2021), a national, cross-sectional health examination and survey, for which representative data on the health, nutritional status, and physical activities of the Korean general population are collected by the Korea Centers for Disease Control and Prevention (KCDC). We compared height, weight, waist circumference, and BMI among patients with diagnosed and current cataracts, glaucoma, and AMD versus those without these conditions. Statistical analyses included t-tests and Pearson correlation analyses to examine the relationships between body metrics and ocular diseases. Results: Our findings indicate that shorter height and lower weight are associated with diagnosed cataracts and glaucoma but not with their current status. A greater waist circumference was observed in patients with diagnosed cataracts, glaucoma, and AMD compared to controls, suggesting central obesity as a potential associated factor. No significant differences in BMI were found in patients with current ocular diseases. Additionally, certain body metrics were correlated with refractive errors and visual acuity, suggesting broader implications for ocular health. Conclusions: The study highlights significant associations between body metrics and the risk of developing cataracts, glaucoma, and AMD. AMD was found to be more closely related to systemic diseases, such as diabetes and hypertension, than to body metrics. These findings suggest that interventions targeting obesity and metabolic health could potentially reduce the risk or severity of these common ocular conditions. Further research is needed to confirm these relationships and explore underlying mechanisms.}, }
@article {pmid40872771, year = {2025}, author = {Ayala-Peña, VB}, title = {HSV-1 Infection in Retinal Pigment Epithelial Cells: A Possible Contribution to Age-Related Macular Degeneration.}, journal = {Viruses}, volume = {17}, number = {8}, pages = {}, pmid = {40872771}, issn = {1999-4915}, mesh = {*Herpesvirus 1, Human/physiology/pathogenicity ; Humans ; *Macular Degeneration/virology/pathology/metabolism ; *Retinal Pigment Epithelium/virology/pathology/metabolism ; *Herpes Simplex/virology/complications ; Animals ; Amyloid beta-Peptides/metabolism ; }, abstract = {Herpes simplex virus type 1 (HSV-1) is associated with eye infections. Specifically, the acute consequences of eye infections have been extensively studied. This review gathers information on possible collateral damage caused by HSV-1 in the retina, such as age-related macular degeneration (AMD), a neurodegenerative disease. The synthesis and accumulation of Amyloid-β peptide (Aβ) is a key hallmark in these types of pathologies. AMD is a disease of multifactorial origin, and viral infections play an important role in its development. It is known that once this virus has entered the eye, it can infect adjacent cells, thus having the ability to infect almost any cell type with great tropism. In the retina, retinal pigment epithelial (RPE) cells are primarily involved in AMD. This work reviews publications that show that RPE can produce Aβ, and once they are infected by HSV-1, the release is promoted. Also, all the information available in the literature that explains how these events may be interconnected has been compiled. This information is valuable when planning new treatments for multifactorial neurodegenerative diseases.}, }
@article {pmid40873164, year = {2025}, author = {Sharma, KK and Durgapal, S and Tyagi, SJ and Varshney, P and Kumar, G}, title = {Innovations in mRNA-Based Nanoparticle for the Treatment of Ocular Disorders: A Comprehensive Review.}, journal = {Current pharmaceutical design}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113816128391408250804231522}, pmid = {40873164}, issn = {1873-4286}, abstract = {The eye, due to its complex anatomy and physiology, presents numerous barriers that restrict the access of drug molecules to the site of action for the maintenance of optimal concentration. Thus, limited drug bioavailability is one of the significant issues with commercially existing drug delivery systems in achieving overall therapeutic effectiveness. Recently, the field of ocular health and management has garnered much attention for the innovation of efficient nanotechnology approaches to overcome the constraints imposed by the intricate anatomy and physiology of the eye. Hypothesizing that the conjugation of mRNA-based therapies with the latest nano delivery systems can overcome these barriers, this review was designed to explore the outstanding potential of these approaches for the management of ocular disorders. With extensive investigations of current findings, the authors believe that such integrations present exciting opportunities to pave the way for the development of effective approaches for various ocular disorders such as uveitis, Leber congenital amaurosis, age-related macular degeneration, retinitis pigmentosa, and many more. Moreover, the approaches exploiting the combination of mRNA and nanotechnology offer effective solutions to address the limitations of currently available management strategies. This review presents various innovative mRNA-based nanotechnology approaches, their mechanisms, challenges, and prospects for further development, focusing on the immense potential of mRNA-based strategies to revolutionize the landscape of ocular therapeutics.}, }
@article {pmid40874294, year = {2025}, author = {Kaźmierski, R}, title = {Age-related macular degeneration and risk of stroke: an unresolved issue.}, journal = {Neurologia i neurochirurgia polska}, volume = {59}, number = {4}, pages = {307-309}, doi = {10.5603/pjnns.104996}, pmid = {40874294}, issn = {0028-3843}, }
@article {pmid40874698, year = {2025}, author = {Olivieri, C and Fai, A and Bhutto, IA and McLeod, DS and Neri, G and Reibaldi, M and Edwards, MM and Borrelli, E}, title = {Retinal Vessel Changes in Geographic Atrophy in AMD: Insights From Imaging and Histology.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {11}, pages = {69}, pmid = {40874698}, issn = {1552-5783}, support = {P30 EY001765/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Geographic Atrophy/diagnosis/pathology/etiology/physiopathology ; Tomography, Optical Coherence/methods ; Female ; Male ; *Retinal Vessels/pathology/diagnostic imaging ; Aged ; Fluorescein Angiography/methods ; *Retinal Pigment Epithelium/pathology ; Aged, 80 and over ; Middle Aged ; *Macular Degeneration/complications ; Fundus Oculi ; }, abstract = {PURPOSE: The purpose of this study was to investigate retinal vascular changes in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) using swept-source optical coherence tomography angiography (SS-OCTA), and to correlate imaging findings with histology.<br><br>METHODS: Sixty subjects were enrolled: 20 with GA, 20 with intermediate AMD, and 20 healthy controls. SS-OCTA imaging was used to quantify retinal perfusion density (PD) and vessel length density (VLD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and full retina. A topographical analysis distinguished regions with and without retinal pigment epithelium (RPE) atrophy in GA eyes. Additionally, flat-mount immunohistochemistry was performed on a donor eye with GA to assess retinal vasculature. Main outcome measures included PD and VLD across SCP, DCP, and full retina, in regions with and without RPE atrophy.<br><br>RESULTS: Retinal PD and VLD were significantly reduced in GA eyes compared with intermediate AMD eyes, particularly in the DCP. Topographical analysis revealed more pronounced vascular impairment in areas with RPE atrophy, whereas regions without RPE atrophy in GA eyes exhibited perfusion comparable to intermediate AMD and healthy controls. Histological analysis confirmed a substantial reduction in vascular density within atrophic regions.<br><br>CONCLUSIONS: Retinal vascular changes in GA predominantly occur within regions of RPE atrophy. The preservation of perfusion in regions without RPE atrophy suggests that vascular impairment is localized. These findings underscore the importance of regional analysis and histopathologic correlation in understanding vascular remodeling in GA. Future longitudinal OCTA studies are warranted to clarify the temporal progression of these vascular alterations in relation to RPE atrophy.}, }
@article {pmid40874706, year = {2025}, author = {Chen, W and Li, Z and Zhou, X and Li, C and Lin, Y}, title = {Identification of Biomarkers for Oxidative Stress in Age-Related Macular Degeneration: Combining Transcriptomics and Mendelian Randomization Analysis.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {8}, pages = {42}, pmid = {40874706}, issn = {2164-2591}, mesh = {*Oxidative Stress/genetics/physiology ; Biomarkers/analysis/metabolism ; *Macular Degeneration/diagnosis/genetics/physiopathology/prevention &amp; control ; Mendelian Randomization Analysis ; Machine Learning ; Gene Expression Profiling/methods ; Gene Expression Regulation ; Datasets as Topic ; Humans ; }, abstract = {PURPOSE: Oxidative stress has long been recognized as a significant influence in the pathophysiology of age-related macular degeneration (AMD). Therefore there is a need to explore the relationship between oxidative stress-related biomarkers and AMD.<br><br>METHODS: Based on Gene Expression Omnibus database-Gene Expression Omnibus Series (GSE)29801 and GSE135092 datasets, three machine learning methods were used to screen biomarkers. The Wilcoxon test was used to compare the percentage of immune cells in control and AMD samples. The causal relationship between biomarkers and AMD was explored in a series of Mendelian randomization (MR) analyses. Ultimately, the expression levels of biomarkers were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in the simulated AMD cell model.<br><br>RESULTS: A total of 16 differentially expressed oxidative stress-related genes (DE-OSRGs) were screened. Functional enrichment analysis indicated that DE-OSRGs participated in cellular senescence, cell cycle regulation, and PPAR signaling pathways. Machine learning methods were used to screen for five biomarkers (GFAP, Stearoyl-CoA desaturase [SCD], BCKDHB, GPX8, and MSRB2). The qRT-PCR results showed that the expression levels of five biomarkers were significantly different between the simulated AMD cell model and control groups. Spearman correlation analysis showed that GPX8 had the highest positive correlation with M2 macrophages (correlation coefficient [cor] = 0.36, P < 0.01), and SCD had a strong negative correlation with eosinophils (cor = -0.28, P < 0.05). MR results revealed that BCKDHB played a crucial role as a risk factor for AMD (odds ratio > 1, P < 0.05).<br><br>CONCLUSIONS: This study screened the biomarkers related to oxidative stress in AMD, providing a certain theoretical basis for the prevention and clinical diagnosis of AMD.<br><br>TRANSLATIONAL RELEVANCE: Identifying biomarkers with diagnostic value for AMD could provide new understanding of its pathogenesis, and open up potential targets for clinical intervention.}, }
@article {pmid40874774, year = {2025}, author = {Magdum, R and Aher, PS and Pancholi, T and Chodvadiya, S and Kamdar, GA and Gupta, A and Gupta, A and Gupta, P}, title = {Optical Coherence Tomography Analysis of Macular Edema Across Disease Spectra.}, journal = {Annals of African medicine}, volume = {}, number = {}, pages = {}, doi = {10.4103/aam.aam_263_25}, pmid = {40874774}, issn = {0975-5764}, abstract = {INTRODUCTION: Macular edema (ME) is a leading cause of visual impairment associated with various retinal pathologies. Spectral-domain optical coherence tomography (SD-OCT) provides high-resolution imaging, allowing detailed assessment of ME patterns and structural changes.<br><br>AIM: The aim of this study was to evaluate the distribution and characteristics of ME across different etiologies using SD-OCT.<br><br>MATERIALS AND METHODS: This cross-sectional observational study included patients with ME from diverse etiologies. SD-OCT was used to assess central macular thickness, retinal volume, cystoid spaces (CS), epiretinal membrane (ERM), hyperreflective foci, and disorganization of retinal inner layers (DRIL).<br><br>RESULTS: A total of 54% of the study participants were female, with a mean age of 57 years. Diabetes mellitus (50.4%) was the most common etiology, followed by retinal vein occlusions, age-related macular degeneration, ERM, and inflammatory causes. CS were observed in 49.6% of cases, and DRIL in 48%. Severe visual impairment was more frequent in diabetic and vaso-occlusive cases.<br><br>CONCLUSION: SD-OCT effectively identifies structural patterns in ME across etiologies, assisting in diagnosis and management planning.}, }
@article {pmid40874965, year = {2025}, author = {Ono, T and Iwasaki, T and Sakisaka, T and Mori, Y and Nejima, R and Miyai, T and Miyata, K}, title = {Visual acuity and ocular comorbidities in patients aged 100 years and older: A retrospective, crosssectional study.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {263}, number = {12}, pages = {3563-3570}, pmid = {40874965}, issn = {1435-702X}, mesh = {Humans ; *Visual Acuity/physiology ; Cross-Sectional Studies ; Retrospective Studies ; Female ; Aged, 80 and over ; Male ; *Intraocular Pressure/physiology ; Comorbidity ; *Cataract/epidemiology/physiopathology ; *Glaucoma/epidemiology/physiopathology ; *Eye Diseases/epidemiology/physiopathology ; }, abstract = {PURPOSE: The centenarian population is increasing with an increase in global life expectancy. However, data on visual status and ocular diseases in this age group remain limited. We aimed to assess visual acuity and ocular comorbidities in patients aged ≥ 100 years.<br><br>METHODS: This retrospective cross-sectional study included patients aged&#x2009;&#x2265;&#x2009;100 years who visited Miyata Eye Hospital between January 2016 and December 2024. Data on best-corrected visual acuity (BCVA), intraocular pressure, and ocular comorbidities were extracted from medical records. Multivariate linear regression was performed to analyse the associations between BCVA and ocular diseases.<br><br>RESULTS: This study included 50 eyes of 25 patients. The mean age was 100.8&#x2009;&#xb1;&#x2009;1.0 years, and 80.0% of the eyes belonged to women. The mean BCVA was 1.01&#x2009;&#xb1;&#x2009;0.93 logarithm of the minimum angle of resolution. The most common ocular conditions were dry eye (54%), glaucoma (46%), cataract (40%), and macular degeneration (40%). Multivariate analysis revealed that cataract (p&#x2009;=&#x2009;0.019) and uveitis (p&#x2009;=&#x2009;0.003) were significantly linked to poor visual acuity.<br><br>CONCLUSION: Cataracts and uveitis were the most significant factors contributing to visual impairment in centenarian patients. Thus, an improved understanding of the ocular health status is crucial for maintaining visual function and quality of life in this unique population.}, }
@article {pmid40875052, year = {2025}, author = {Hikichi, T and Kurabe, H and Notoya, A and Oguro, Y and Hirano, M and Doi, Y}, title = {Morphologic changes of the double-layer sign during anti-vascular endothelial growth factor therapy in eyes with neovascular age-related macular degeneration.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {363}, pmid = {40875052}, issn = {1573-2630}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage ; Male ; Female ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Ranibizumab/administration &amp; dosage ; Fluorescein Angiography/methods ; *Visual Acuity ; Follow-Up Studies ; Aged, 80 and over ; Fundus Oculi ; *Bevacizumab/administration &amp; dosage ; *Macula Lutea/pathology ; }, abstract = {PURPOSE: To evaluate longitudinal morphologic changes of the double-layer sign (DLS) on optical coherence tomography (OCT) in eyes with neovascular age-related macular degeneration (nAMD) presenting with exudative macular neovascularization (eMNV) undergoing anti-vascular endothelial growth factor (VEGF) therapy.<br><br>METHODS: This retrospective study included 207 consecutive treatment-na&#xef;ve eyes (207 patients) with nAMD presenting with eMNV and a DLS treated with intravitreal anti-VEGF injections and were followed for&#x2009;&#x2265;&#x2009;12&#xa0;months. All eyes received 3 monthly loading injections followed by either treat-and-extend (TAE) or pro re nata (PRN) retreatment, per predefined criteria. DLS area, length, and height were measured at baseline, after loading, and 12&#xa0;months.<br><br>RESULTS: All 207 eyes demonstrated significant reductions in mean&#x202f;(&#xb1;&#x2009;standard deviation) DLS area, length, and height 1&#xa0;month after the third monthly injection (165&#x2009;&#xb1;&#x2009;188&#xa0;&#xb5;m[2], 1446&#x2009;&#xb1;&#x2009;639&#xa0;&#xb5;m, and 202&#x2009;&#xb1;&#x2009;109&#xa0;&#xb5;m, respectively) compared with baseline (302&#x2009;&#xb1;&#x2009;264&#xa0;&#xb5;m[2], 1801&#x2009;&#xb1;&#x2009;573&#xa0;&#xb5;m, and 282&#x2009;&#xb1;&#x2009;150&#xa0;&#xb5;m, respectively) (P&#x2009;=&#x2009;0.001, P&#x2009;=&#x2009;0.001, and P&#x2009;=&#x2009;0.024, respectively). At 12&#xa0;months the mean change in DLS area was -&#xa0;141&#xa0;&#xb5;m[2] [95%&#x202f;confidence interval (CI) -&#xa0;185&#xa0;to -&#xa0;98], and median (95% CI) injection number was 8.1 (7.9 to 8.4). Eyes with subretinal and/or intraretinal fluid (SRF/IRF) at 12&#xa0;months showed re-enlargement of DLS parameters, whereas eyes without SRF/IRF maintained the post-treatment decrease.<br><br>CONCLUSION: DLS morphology regresses after anti-VEGF therapy, and persistent or recurrent fluid is associated with less durable regression. The DLS regresses in response to anti-VEGF therapy, and its behaviour correlates with the clinical course of exudative MNV associated with a DLS. DLS monitoring may complement-but not replace-multimodal imaging when assessing MNV activity.}, }
@article {pmid40876568, year = {2025}, author = {Gao, J and Luo, T and Qu, W and Wang, W and Mo, Y}, title = {Potential role of endoplasmic reticulum quality control in retinal degenerative diseases.}, journal = {Neuroscience}, volume = {587}, number = {}, pages = {27-37}, doi = {10.1016/j.neuroscience.2025.08.052}, pmid = {40876568}, issn = {1873-7544}, mesh = {Humans ; *Endoplasmic Reticulum/metabolism ; Animals ; *Endoplasmic Reticulum Stress/physiology ; *Retinal Degeneration/metabolism/pathology ; Endoplasmic Reticulum-Associated Degradation/physiology ; Autophagy/physiology ; }, abstract = {The endoplasmic reticulum (ER) is the largest organelle in eukaryotic cells, and it plays a crucial role in regulating various biological processes, including protein folding, translation, and structural maturation. Accurate protein modification is essential for maintaining oxidative stress, apoptosis, and cellular senescence in the organism. The regulation of protein homeostasis involves three biological processes: endoplasmic reticulum stress (ERS), endoplasmic reticulum autophagy (ERPA), and endoplasmic reticulum-associated degradation (ERAD). Retinal degenerative disease (RDD) is a blinding eye conditions that cause severe vision loss. Although the pathogenesis of RDD is complex, previous data suggest that ER plays a key role in the development of a variety of eye diseases, such as diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD), and axial myopia. Based on this, this paper will review the process of endoplasmic reticulum quality control (ERQC) and summarize the pathological mechanisms of the aforementioned eye diseases from the perspective of ERQC, providing new insights for the treatment of RDD.}, }
@article {pmid40876598, year = {2026}, author = {Korobelnik, JF and Lanzetta, P and Leal, S and Holz, FG and Clark, WL and Eichenbaum, D and Iida, T and Sun, X and Berliner, AJ and Schulze, A and Zhao, M and Schmelter, T and Schmidt-Ott, U and Zhang, X and Morgan-Warren, P and Hasanbasic, Z and Vitti, R and Chu, KW and Reed, K and Bhore, R and Cheng, Y and Bai, Z and Hirshberg, B and Yancopoulos, GD and Wong, TY and , }, title = {Intravitreal Aflibercept 8 mg in Neovascular Age-Related Macular Degeneration: Ninety-Six-Week Results from the Randomized Phase 3 PULSAR Trial.}, journal = {Ophthalmology}, volume = {133}, number = {1}, pages = {39-50}, doi = {10.1016/j.ophtha.2025.08.022}, pmid = {40876598}, issn = {1549-4713}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects/therapeutic use ; Dose-Response Relationship, Drug ; Double-Blind Method ; Fluorescein Angiography ; Follow-Up Studies ; Intravitreal Injections ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use/adverse effects ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity/physiology ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; }, abstract = {PURPOSE: To report the efficacy, durability, and safety of intravitreal aflibercept 8 mg versus intravitreal aflibercept 2 mg every 8 weeks (2q8) in patients with neovascular age-related macular degeneration (nAMD) through 96 weeks, PULSAR (ClinicalTrials.gov identifier, NCT04423718).<br><br>DESIGN: Phase 3, randomized, noninferiority, 96-week trial.<br><br>PARTICIPANTS: Treatment-naive adults &#x2265; 50 years with nAMD.<br><br>METHODS: Patients were randomized 1:1:1 to intravitreal aflibercept 8 mg every 12 or 16 weeks (8q12 or 8q16), or 2q8, after 3 initial monthly doses; dosing intervals in 8-mg groups were modified based on prespecified criteria.<br><br>MAIN OUTCOME MEASURES: Change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT), proportion of patients maintaining or extending the randomized dosing intervals, and safety outcomes.<br><br>RESULTS: Of 1009 patients treated, 869 patients (8q12, n = 291; 8q16, n = 292; 2q8, n = 286) completed treatment through week 96. Least squares (LS) mean change from baseline in BCVA at week 96 was +5.6 (95% confidence interval [Cl], 4.1-7.1), +5.5 (95% Cl, 4.0-7.0), and +6.6 (95% Cl, 5.2-8.0) letters in the 8q12, 8q16, and 2q8 groups, respectively; 8q12 and 8q16 differences versus 2q8 in LS mean BCVA changes at week 96 met the noninferiority criteria specified for the primary end point at week 48. Mean (standard deviation) change in CRT from baseline was -143.9 (123.6) &#x3bc;m, -153.4 (140.8) &#x3bc;m, and -135.8 (133.1) &#x3bc;m in the 8q12, 8q16, and 2q8 groups, respectively. Patients completing 96 weeks of treatment in the 8q12, 8q16, and 2q8 groups received a mean of 9.7, 8.2, and 12.8 active injections, respectively. Of these, 87% of patients in the 8q12 group had last assigned dosing intervals of 12 weeks or more, whereas 78%, 53%, and 31% of patients in the 8q16 group qualified for last assigned dosing intervals of &#x2265; 16 weeks, &#x2265; 20 weeks, and 24 weeks, respectively. Incidence of ocular treatment-emergent adverse events was similar across groups.<br><br>CONCLUSIONS: Aflibercept 8 mg delivered sustained disease control in patients with nAMD, maintaining improvements in visual and anatomic outcomes through week 96 with extended dosing intervals and similar safety profile to aflibercept 2 mg.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40880799, year = {2025}, author = {Zingale, GA and Pandino, I and Trivellato, D and Cavaterra, D and Munari, F and Grasso, G and Bell, PA and Oddone, F and Bocedi, A and Coletta, M and Assfalg, M and D'Onofrio, M and Tundo, GR and Sbardella, D}, title = {SpectraSage unveils specific proteolytic patterns of 20S on mono-ubiquitylated Tau proteoforms involved in neurodegeneration.}, journal = {Chemical science}, volume = {16}, number = {36}, pages = {16979-16992}, pmid = {40880799}, issn = {2041-6520}, abstract = {The ubiquitin proteasome system is a critical regulator of proteostasis and shows altered activity and composition in neurodegenerative diseases affecting both the brain (e.g., Alzheimer's disease) and the retina/optic nerve (e.g., age-related macular degeneration, glaucoma). A common feature of neurodegeneration is the progressive accumulation of amyloidogenic proteins such as beta-amyloid and tau protein (MAPT gene). There is compelling evidence that the aggregation propensity of tau protein is regulated by post-synthetic modifications including phosphorylation and ubiquitylation. These alterations are gaining increasing pathological relevance not only for brain tauopathies but also for the retinal/optic nerve degenerative diseases. In this regard, site-specific mono-ubiquitylated (Ub) tau proteoforms, have been recently identified in neurodegenerative brains. In this work, the cleavage patterns of the uncapped 20S proteasome acting on mono-Ub regio-isomers of tauK18, which covers the 4RD domain, have been unveiled by using SpectraSage, a novel proteomics software conceived for the MS1 identification of complex branched peptide and here introduced for the first time. Ub position was found to affect regio-isomers susceptibility to proteolysis and unexpectedly long Ub-tauK18 branched peptides have been identified, proving distinct catalytic preferences. These findings show that the 20S digests mono-Ub proteins through specific enzymatic mechanisms and the implications of the latter on neurodegeneration are discussed.}, }
@article {pmid40881432, year = {2025}, author = {Li, C and Lu, YC and Chen, MX}, title = {Cuproptosis-related signature and immune infiltration in age-related macular degeneration.}, journal = {International journal of ophthalmology}, volume = {18}, number = {9}, pages = {1640-1649}, pmid = {40881432}, issn = {2222-3959}, abstract = {AIM: To investigate cuproptosis-related molecular and immune infiltration in age-related macular degeneration (AMD) development and establish a predictive model.<br><br>METHODS: The expression profiles of cuproptosis-related genes and immune signature in AMD based on the microarray dataset GSE29801 were analyzed. A total of 142 AMD samples were used to identify the cuproptosis-related differentially expressed genes (Cu-DEGs), together with the immune cell infiltration. To further refine the list of potential genes for AMD diagnosis, three machine learning techniques were used, and an external dataset were applied for confirming the accuracy of the predictive performance. Reverse transcription polymerase chain reaction (RT-PCR) were also performed to examine the level of mRNA of hub genes. The activated immune responses and Cu-DEGs were assessed between AMD and controls.<br><br>RESULTS: Six genes, including ATP7A, DBT, VEGFA, UBE2D3, CP, SLC31A1, were screened as cuproptosis-signature in AMD via three machine learning methods. Next, SLC31A1 and VEGFA was selected as hub genes by performance evaluation in an external dataset GSE160011, further analysis showed that SLC31A1 and VEGFA were associated with pathways related to immune signaling and immune function, which were then observed in relation to infiltrating immune cells. Finally, the mRNA expression levels of SLC31A1 and VEGFA were significantly higher in laser induced choroidal neovascularization (CNV) group than in control group detected by RT-PCR.<br><br>CONCLUSION: In this study, the possible relationship between cuproptosis and AMD is expounded systematically. A predictive model is developed to assess the risk of cuproptosis-related genes and their clinical prognostic value in AMD patients.}, }
@article {pmid40881438, year = {2025}, author = {Yang, ZR and Li, C and Xing, DJ and Wei, GX and Zhao, CC and Zhou, M and Ma, XH and Zhao, Y and Yang, S and Yu, RG and Li, ZQ}, title = {Exploring the role of hyperreflective walls as a biomarker for the management of cystoid macular edema.}, journal = {International journal of ophthalmology}, volume = {18}, number = {9}, pages = {1697-1704}, pmid = {40881438}, issn = {2222-3959}, abstract = {AIM: To investigate the prevalence and clinical implications of hyperreflective walls (HRW) in foveal cystoid spaces in patients with cystoid macular edema (CME) caused by retinal diseases and noninfectious uveitis (NIU).<br><br>METHODS: This retrospective cross-sectional study included 443 eyes with CME secondary to diabetic macular edema (DME), retinal vein occlusion (RVO), retinitis pigmentosa (RP), neovascular age-related macular degeneration (nAMD), and NIU. Demographic data, HRW features, and other spectral domain optical coherence tomography (SD-OCT) biomarkers were analyzed.<br><br>RESULTS: HRW was observed in 40.9% of DME eyes (present, n=77, 38 males, 58.30&#xb1;12.04y; absent, n=111, 50 males, 55.95&#xb1;10.56y), 32.5% of RVO eyes (present, n=49, 22 males, 64.53&#xb1;11.90y; absent, n=102, 42 males, 60.67&#xb1;11.73y), 31.4% of nAMD eyes (present, n=16, 8 males, 70.13&#xb1;7.75y; absent, n=35, 13 males, 73.91&#xb1;9.11y), 57.1% of RP eyes (present, n=12, 4 males, 40.50&#xb1;12.06y; absent, n=9, 4 males, 44.11&#xb1;14.32y), and 18.8% of uveitic macular edema (UME) eyes (present, n=6, 3 males, 30.83&#xb1;16.23y; absent, n=26, 12 males, 43.46&#xb1;17.58y). HRW was significantly associated with vitreoretinal abnormalities [odds ratio (OR), 2.202; 95% confidence interval (95%CI), 1.342-3.613; P=0.002], hyperreflective foci (OR, 3.33; 95%CI, 1.884-5.883; P<0.001), inner retinal layer disorganization (OR, 1.816; 95%CI, 1.087-3.035; P=0.023), external limiting membrane disruptions (OR, 3.476; 95%CI, 1.839-6.574; P<0.001), and disrupted ellipsoid zone length (OR, 1.001; 95%CI, 1.000-1.002; P=0.04), and a high HRW height in the foveal cystoid spaces (OR, 1.003; 95%CI, 1.001-1.006; P=0.003).<br><br>CONCLUSION: HRW in foveal cystoid spaces is a common OCT finding in CME and is associated with more severe retinal structural damage and worse visual acuity. HRW may be utilized as a prognostic OCT biomarker for disease severity and treatment response in patients with CME. This study suggests that early detection of HRW and optimization of treatment strategies may improve patient prognosis.}, }
@article {pmid40881439, year = {2025}, author = {Gong, YJ and Zou, ZL and Qiu, KR and Wang, Q and Zhou, XL}, title = {Integration of multi-omics data reveals dysregulated RNA methylation in retinal pigment epithelium drives age-related macular degeneration.}, journal = {International journal of ophthalmology}, volume = {18}, number = {9}, pages = {1626-1639}, pmid = {40881439}, issn = {2222-3959}, abstract = {AIM: To investigate the role of RNA methylation in retinal pigment epithelial (RPE) cells in age-related macular degeneration (AMD).<br><br>METHODS: RNA methylation-related gene expression profiles of AMD patient and normal control retinal pigment epithelium were evaluated by single-cell transcriptome from 34 samples (11 from normal donors and 23 from AMD patients). The causal relationship between RNA methylation dysfunction and AMD was analyzed by summary-data-based Mendelian randomization (SMR) using AMD GWAS data and multi-omics quantitative trait loci (QTL), including expression QTLs (eQTLs), protein QTLs (pQTLs), splicing QTLs (sQTLs), and m[6]A-QTLs (mQTLs). Additionally, machine learning models were applied to validate the causal association between RNA methylation dysfunction and AMD using Bulk RNA sequencing data from 31 normal donors and 37 AMD patients.<br><br>RESULTS: The single-cell transcriptome data analysis revealed massive dysregulation of RNA methylation-related gene expression in the RPE of AMD patients. SMR revealed causal associations between key RNA methylation regulators (METTL3, NSUN6, and MRM1, etc.) and AMD onset. Machine learning models further validated these findings and demonstrated a high accuracy of AMD risk prediction by using the above-identified RNA methylation-related genes: METTL3, NSUN6, and MRM1. Furthermore, METTL3 and NSUN6 were found to have a protective effect, while MRM1 was associated with an increased risk of AMD.<br><br>CONCLUSION: The results reveal the implication of dysregulation of RNA methylation-related gene expression in the RPE of AMD patients and further demonstrated a causal association between RNA methylation-related genes (METTL3, NSUN6, and MRM1) and AMD. These findings highlight the importance of RNA methylation in the pathogenesis of AMD and offer potential biomarkers and therapeutic targets for AMD management.}, }
@article {pmid40881460, year = {2025}, author = {Dwomoh, EA and Prasad, A and Nanda, T}, title = {Sterile Intraocular Inflammation in Patients Receiving Both Faricimab and High-Dose Aflibercept in Consecutive Order.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251365391}, pmid = {40881460}, issn = {2474-1272}, abstract = {Purpose: To describe 3 cases of intraocular inflammation (IOI) in patients who received faricimab and high-dose aflibercept in consecutive order. Methods: Retrospective case review. Results: Three patients, 2 with neovascular age-related macular degeneration (nAMD) and 1 with central retinal vein occlusion (CRVO), transitioned from 2 mg aflibercept to either faricimab (in cases 1 and 2) or high-dose aflibercept (in case 3) due to persistent disease activity. In all cases, contemporary medication provided minimal effect. Subsequently, patients in cases 1 and 2 were switched to high-dose aflibercept at their next visit, and the patient in case 3 was switched to faricimab. On follow-up, the disease worsened in all 3 cases. Each patient returned to their previous drug. Shortly after, each patient developed an episode of IOI. Conclusions: Patients receiving different high-dose or longer-acting agents in short order may be at risk for developing antidrug antibodies and IOI.}, }
@article {pmid40882516, year = {2025}, author = {Anitua, E and Reparaz, I and Alkhraisat, MH}, title = {Plasma rich in growth factors as a treatment for ocular fundus diseases: Mapping current applications and future directions.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {191}, number = {}, pages = {118440}, doi = {10.1016/j.biopha.2025.118440}, pmid = {40882516}, issn = {1950-6007}, mesh = {Humans ; *Intercellular Signaling Peptides and Proteins/administration &amp; dosage/therapeutic use ; *Retinal Diseases/therapy ; *Platelet-Rich Plasma ; Animals ; Fundus Oculi ; Treatment Outcome ; }, abstract = {Posterior segment diseases are a leading cause of irreversible blindness and remain challenging to treat with current therapies. Blood-derived products have emerged as promising regenerative tools due to their anti-inflammatory, neuroprotective, and regenerative properties. This review synthesizes evidence from 46 clinical studies published between 2019 and 2025, covering 1253 patients and 1570 eyes treated with platelet-rich derivatives for ocular fundus diseases. The most frequent indications were structural defects (59 %), inherited retinal dystrophies (11 %), optic neuropathies (11 %), age-related macular degeneration (7 %), and vascular dysfunctions (5 %). These therapies were administered via various routes, including intravitreal, subtenon, suprachoroidal, and subretinal injections, as well as eye drops and fibrin membranes. Across pathologies, platelet-derived therapies demonstrated high anatomical success rates, functional improvements, and low incidence of adverse events, most of which were transient and mild. Among the different formulations, plasma rich in growth factors (PRGF-Endoret®) stood out for its standardized preparation, immunosafe profile, and versatility in application. Despite promising clinical outcomes, heterogeneity in study designs, small sample sizes, and lack of standardized protocols limit generalizability. Further randomized controlled trials and mechanistic studies are needed to validate efficacy, define optimal formulations, and identify the patient populations most likely to benefit. Blood-derived products represent a promising therapeutic avenue in regenerative ophthalmology and may serve as effective adjuncts or alternatives in managing complex retinal and optic nerve disorders.}, }
@article {pmid40882639, year = {2025}, author = {Farjood, F and Nandakumar, S and Bertucci, T and Kiehl, T and Lotz, S and Wang, Y and Black, J and Sai, S and Kozak, J and Arduini, BL and Temple, S and Boles, NC and Stern, JH}, title = {Single-cell transcriptome and surfaceome profiling of the adult human retinal pigment epithelium.}, journal = {Stem cell reports}, volume = {20}, number = {9}, pages = {102611}, pmid = {40882639}, issn = {2213-6711}, support = {R01 EY029281/EY/NEI NIH HHS/United States ; U01 EY030581/EY/NEI NIH HHS/United States ; UG3 EY031810/EY/NEI NIH HHS/United States ; UH3 EY031810/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/cytology ; *Single-Cell Analysis/methods ; *Transcriptome ; *Gene Expression Profiling ; Adult ; Cells, Cultured ; Biomarkers/metabolism ; }, abstract = {The retinal pigment epithelium (RPE) is a pigmented monolayer of cells beneath the neural retina that supports photoreceptor cell function essential for vision. Our study explores the diversity of adult human RPE subpopulations and associated implications for retinal biology. Employing cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), we identified distinct RPE cell subpopulations characterized by unique single-cell transcriptomic and surface protein signatures. Immunohistochemical analysis using CITE-seq markers demonstrated that different RPE subpopulations had previously unappreciated spatial patterns. Enrichment by CITE-seq surface marker selection revealed that different RPE subpopulations have distinct functions. By comparing native RPE cells isolated from the adult RPE layer to cultured RPE cells, we demonstrated that most RPE subpopulations were preserved during culture, a finding with relevance to an RPE cell product currently in clinical trial for treatment of non-exudative age-related macular degeneration. These findings deepen understanding of human RPE biology and provide valuable insights to optimize RPE-cell-based therapy.}, }
@article {pmid40885407, year = {2026}, author = {Giannopoulos, NG and Macri, CZ and Seneviratne, IAK and Bacchi, S and Sun, MT and Chan, WO}, title = {A narrative review of the psychological impact of intravitreal injections.}, journal = {Survey of ophthalmology}, volume = {71}, number = {1}, pages = {179-188}, doi = {10.1016/j.survophthal.2025.08.017}, pmid = {40885407}, issn = {1879-3304}, mesh = {Humans ; *Intravitreal Injections/psychology/adverse effects ; *Anxiety/psychology/etiology ; *Retinal Diseases/drug therapy/psychology ; *Angiogenesis Inhibitors/administration &amp; dosage ; }, abstract = {Intravitreal injections (IVI) are a common, effective therapy for multiple retinal diseases although can be associated with significant psychological effects that reduce adherence to treatment. We reviewed the psychological impacts of IVI to characterise their causes, consequences, and solutions. We searched the electronic databases PubMed, OVID Medline, OVID Embase, Google Scholar and Cochrane Reviews and retrieved 1252 peer-reviewed articles. Thirty-four articles were ultimately included and analysed. The majority of retrieved articles pertained to anxiety; however, other impacts were also identified with limited available evidence regarding depression. Pre-procedural anxiety was generally mild to moderate and reported in 17.3-85 % of patients undergoing IVI. Key contributing factors to anxiety included a lack of patient education, pain and discomfort during the procedure, and travel and waiting times. Potential strategies to reduce anxiety included person-centred education, alternatives to speculum use, reducing clinic wait times, and music or handholding during the procedure. Patients experience significant anxiety from IVI, owing to multiple factors, including lack of education about the procedure, lack of procedural familiarity, and pain, which require a patient-centred approach to addressing that considers individual needs and preferences. Little data pertain to non-anxiety effects of IVI, and thus further research may identify additional barriers to adherence and their solutions.}, }
@article {pmid40885419, year = {2025}, author = {Mahmoudzadeh, R and Zaichik, M and Farhani, K and Salabati, M and Randolph, J}, title = {Antidepressant Use and Incidence and Progression of Age-Related Macular Degeneration in a National United States Database.}, journal = {American journal of ophthalmology}, volume = {280}, number = {}, pages = {458-471}, doi = {10.1016/j.ajo.2025.08.052}, pmid = {40885419}, issn = {1879-1891}, mesh = {Humans ; Male ; Female ; United States/epidemiology ; Retrospective Studies ; Incidence ; Disease Progression ; Aged ; Databases, Factual ; Middle Aged ; *Antidepressive Agents/therapeutic use/adverse effects ; *Wet Macular Degeneration/epidemiology/diagnosis/chemically induced ; Selective Serotonin Reuptake Inhibitors/therapeutic use ; Propensity Score ; Risk Factors ; *Macular Degeneration/epidemiology ; Aged, 80 and over ; Antidepressive Agents, Tricyclic/therapeutic use ; }, abstract = {OBJECTIVE: To evaluate the association between antidepressant use and the risk of developing nonexudative and exudative age-related macular degeneration (AMD), as well as the progression from nonexudative to exudative AMD, in patients using selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs).<br><br>DESIGN: Retrospective clinical cohort study.<br><br>SUBJECTS: Patients aged &#x2265;40 years identified from the TriNetX database (October 2004-October 2023). Individuals were grouped based on exclusive use of SSRIs, SNRIs, or TCAs and compared to a control group without antidepressant use. Patients using multiple antidepressant classes were excluded.<br><br>METHODS: Propensity score matching (PSM) was applied to adjust for 17 confounders, including age, sex, smoking status, hypertension, and cardiovascular disease. The primary outcomes were the incidence of nonexudative AMD, exudative AMD, and progression from nonexudative to exudative AMD.<br><br>MAIN OUTCOME MEASURES: Risk ratios (RRs) comparing the incidence of nonexudative AMD, exudative AMD, and AMD progression in each antidepressant group versus matched controls.<br><br>RESULTS: After PSM, the analysis included 633 535 SSRI users, 826 404 SNRI users, and 501 873 TCA users. Compared to controls, antidepressant use was associated with a significantly reduced risk of nonexudative AMD (RR 0.606 for SSRIs; 0.141 for SNRIs; 0.234 for TCAs), exudative AMD (RR 0.733 for SSRIs; 0.161 for SNRIs; 0.267 for TCAs), and progression to exudative AMD (RR 0.701 for SSRIs; 0.665 for SNRIs; 0.676 for TCAs).<br><br>CONCLUSIONS: Use of SSRIs, SNRIs, or TCAs was associated with a lower risk of AMD onset and progression. Potential mechanisms include reduced inflammation, decreased oxidative stress, and neuroprotection via upregulation of brain-derived neurotrophic factors and suppression of proinflammatory cytokines. These findings are exploratory and hypothesis-generating, and further prospective and mechanistic studies are needed to better understand the relationship between antidepressant use and AMD pathophysiology.}, }
@article {pmid40885885, year = {2025}, author = {Bao, S and Yang, Z and Zhang, Z and Qu, J and Sun, J}, title = {AttResAMD: An Attention-Driven Deep Learning Framework for Expert-Level Automated Classification of Age-Related Macular Degeneration from Fundus Photography.}, journal = {Interdisciplinary sciences, computational life sciences}, volume = {}, number = {}, pages = {}, pmid = {40885885}, issn = {1867-1462}, }
@article {pmid40886207, year = {2025}, author = {Ekinci, O}, title = {Successful treatment of Charles Bonnet syndrome after cerebellar stroke in a patient with binocular macular degeneration with low dose brexpiprazole: a case report.}, journal = {Acta neurologica Belgica}, volume = {125}, number = {6}, pages = {1681-1684}, pmid = {40886207}, issn = {2240-2993}, }
@article {pmid40886774, year = {2025}, author = {Lai, TYY and Kataoka, K and Hsieh, YT and Apte, RS and Bhende, M and Chang, A and Chiakitmongkol, V and Chen, Y and Chen, LJ and Cheung, GCM and Chhablani, J and Fong, KCS and Guymer, RH and Gomi, F and Huang, SS and Kim, JE and Kokame, GT and Koh, A and Li, X and Lim, JI and Ng, DSC and Okada, AA and Radke, NV and Sadda, SR and Sasaki, M and Sivaprasad, S and Shanmugam, MP and Verma, L and Wong, TY and Zhang, X and Lam, DSC}, title = {International consensuses and guidelines on etiology, diagnosis, treatment, and future developments of neovascular age-related macular degeneration (nAMD) by the Asia-Pacific Vitreo-retina Society (APVRS), the Asia-Pacific Ocular Imaging Society (APOIS) and the Academy of the Asia-Pacific Professors of Ophthalmology (AAPPO).}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {100242}, doi = {10.1016/j.apjo.2025.100242}, pmid = {40886774}, issn = {2162-0989}, abstract = {Neovascular age-related degeneration (nAMD) is one of the leading causes of visual impairment in older populations in the developed world. With the aging population, the incidence of nAMD is growing globally. Despite advancements in diagnostic investigations and treatment modalities over the past three decades, there remains considerable controversies in the pathogenesis, classification and optimal management strategies. An international panel of 31 experts from 11 countries/regions prepared and voted on consensus statements in five key areas: (1) etiology controversies; (2) diagnosis controversies; (3) treatment controversies; (4) future development controversies; and (5) healthcare deliveries controversies. Among the 31 consensus statements, 28 (90.3 %) have achieved over 75 % agreement. These statements can provide a practical guide for ophthalmologists to provide the optimal care of patients with nAMD and for planning future research priorities in order to address the unmet needs in nAMD.}, }
@article {pmid40888531, year = {2026}, author = {Charmasson, M and Mairot, K and Gascon, P and Dalmas, F and David, T and Comet, A}, title = {Short-term efficacy of faricimab switch on retinal exudative signs in patients requiring frequent anti-VEGF injections : A real-life study.}, journal = {European journal of ophthalmology}, volume = {36}, number = {2}, pages = {321-329}, doi = {10.1177/11206721251374263}, pmid = {40888531}, issn = {1724-6016}, mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; Female ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Aged ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Tomography, Optical Coherence ; Visual Acuity ; Ranibizumab/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Fluorescein Angiography ; Treatment Outcome ; Follow-Up Studies ; Aged, 80 and over ; Drug Substitution ; Subretinal Fluid ; Time Factors ; Exudates and Transudates ; Middle Aged ; Fundus Oculi ; Antibodies, Bispecific ; }, abstract = {ObjectiveTo evaluate the efficacy of switching from anti-vascular endothelial growth factor (VEGF) to faricimab in reducing exudative signs in age-related macular degeneration (AMD) patients receiving regular injections (every 8 weeks or less) without restarting a standard induction regimen.MethodsThis retrospective, observational, multicenter study included patients with exudative AMD previously treated with aflibercept 2 mg or ranibizumab every ≤8 weeks and switched to faricimab while maintaining their previous injection interval. The first follow-up visit occured after switching to faricimab, with a single injection, and corresponded to the pre-existing injection interval. Primary outcomes included changes in subretinal (SRF) and intraretinal fluid (IRF).ResultsAmong 39 patients (47 eyes), the proportion of eyes with SRF decreased from 43.1% to 23.5% (p < 0.01) and IRF from 43.8% to 19.6% (p < 0.01). SRF height significantly reduced from 75.3 μm to 60 μm (p = 0.04). Pigment epithelial detachment (PED) height decreased from 223 μm to 164μm (p < 0.01), and central retinal thickness (CRT) declined from 273.7 μm to 268 μm (p < 0.01). Injection intervals extended by an average of 7 days (40 to 47 days, p < 0.01). No significant changes in BCVA (p = 0.14) were observed. No adverse events were reported.ConclusionsSwitching to faricimab without restarting an induction phase effectively reduces SRF and IRF while modestly extending injection intervals in patients requiring frequent anti-VEGF injections. These findings suggest a potential benefit in treatment burden reduction. Further studies are needed to assess long-term visual outcomes and safety.}, }
@article {pmid40889610, year = {2025}, author = {Navratil, EM and Wenzel, PA and Flamme-Wiese, MJ and Miller, JEB and Wiley, LA and Stone, EM and Tucker, BA and Mullins, RF}, title = {Sialoglycoconjugate profiling of human choroid, retinal pigment epithelium, and basal laminar deposits.}, journal = {Experimental eye research}, volume = {260}, number = {}, pages = {110618}, pmid = {40889610}, issn = {1096-0007}, support = {P30 EY025580/EY/NEI NIH HHS/United States ; R01 EY024605/EY/NEI NIH HHS/United States ; R01 EY033308/EY/NEI NIH HHS/United States ; T32 GM145441/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Retinal Pigment Epithelium/metabolism ; *Choroid/metabolism ; Aged ; Aged, 80 and over ; *Macular Degeneration/metabolism ; Female ; Male ; Plant Lectins/metabolism ; *Glycoconjugates/metabolism ; Middle Aged ; Ribosome Inactivating Proteins ; }, abstract = {Age-related macular degeneration is a leading cause of central vision loss in the elderly. Early hallmarks of the disease include basal laminar deposit beneath the retinal pigment epithelium (RPE) and choriocapillaris degeneration. We utilized sialic acid binding lectins Sambucus nigra/Elderberry Bark Lectin (EBL) and Maackia amurensis lectin II (MAL-II), to assess the localization of ɑ-2,6 and ɑ-2,3 sialic acids, respectively, in human macular retina, RPE, basal laminar deposits, and choroid. Photoreceptor carbohydrate epitopes differ based on retinal topography, with MAL-II recognizing foveal (but not extrafoveal) cones. Both MAL-II and EBL react with apical RPE, and both bind basal laminar deposits. In the choroid, MAL-II predominantly labels the choriocapillaris endothelium, while EBL also shows robust labeling of Bruch's membrane and extracellular domains surrounding the microvasculature (intercapillary pillars). EBL labeling overlaps with the distribution of complement factor H to a greater extent than MAL-II. After treatment with neuraminidase to remove terminal sialic acids, a battery of lectins was applied to sections of choroids. Lectins that recognize β-galactose, N-acetyllactosamine, galactose (β-1,3) N-acetylgalactosamine, and ɑ- or β-N-acetylgalactosamine showed increased reactivity, indicating the presence of abundant sialoglycans in basal laminar deposits. This study provides insight into the location and partial identities of sialoglycoconjugates in the human choroid, with possible implications for understanding the pathogenesis of macular degeneration.}, }
@article {pmid40889611, year = {2025}, author = {Alzu'bi, A and Momany, S and Aleshawi, A and Tashtoush, M and Al-Dwairi, R}, title = {The utility of artificial intelligence in characterization and detecting causes of macular edema: A spectral-domain OCT-based algorithm study.}, journal = {Experimental eye research}, volume = {260}, number = {}, pages = {110619}, doi = {10.1016/j.exer.2025.110619}, pmid = {40889611}, issn = {1096-0007}, mesh = {*Macular Edema/diagnosis/etiology/diagnostic imaging ; Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; *Algorithms ; *Diabetic Retinopathy/complications/diagnosis ; *Artificial Intelligence ; Deep Learning ; Macular Degeneration/complications/diagnosis ; Neural Networks, Computer ; }, abstract = {BACKGROUND: Macular Edema (ME), a prevalent cause of vision loss, can arise from various retinal conditions, most notably diabetic macular edema (DME) and age-related macular degeneration (AMD). Accurate and timely differentiation among these causes is necessary for appropriate treatment; however, it remains a diagnostic challenge. This research addresses the gap in automated ME classification by developing and evaluating a deep learning framework capable of distinguishing between DME, AMD, and normal retinal conditions using optical coherence tomography (OCT) images.<br><br>METHODS: A retrospective dataset comprising 1040 OCT images from King Abdullah University Hospital (KAUH) was used in conjunction with a public dataset for benchmarking. The dataset was divided into annotated and non-annotated images, with preprocessing, augmentation, and simulated segmentation applied to improve the model performance. We benchmarked and evaluated three pretrained convolutional neural networks-ResNet152, InceptionV3, and MobileNetV2.<br><br>RESULTS: Among the models, InceptionV3 and ResNet152 achieved the highest accuracies (95&#xa0;%-98&#xa0;%) across both datasets. MobileNetV2, on the other hand, showed moderate accuracy on the KAUH dataset (89&#xa0;%) but exhibited strong performance on the public dataset (97&#xa0;%). Explainable AI (XAI) techniques, specifically Grad-CAM, were applied to visualize the model predictions, and the outcomes were manually validated against annotated data to assess interpretability.<br><br>CONCLUSIONS: The findings support the integration of a robust CNN architecture and XAI techniques to enhance diagnostic precision and aid clinical decision-making in ophthalmology.}, }
@article {pmid40889625, year = {2025}, author = {Agathos, CP and Shanidze, NM and Fletcher, DC}, title = {Importance of Screening for Contrast Sensitivity, Falls, and Mobility Limitations in Older Adults With Maculopathy.}, journal = {American journal of ophthalmology}, volume = {280}, number = {}, pages = {481-492}, pmid = {40889625}, issn = {1879-1891}, support = {90REGE0018/ACL/ACL HHS/United States ; R01 EY036172/EY/NEI NIH HHS/United States ; T32 EY025201/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Contrast Sensitivity/physiology ; Cross-Sectional Studies ; Female ; Male ; Aged ; *Accidental Falls/statistics &amp; numerical data ; Visual Acuity/physiology ; Middle Aged ; *Mobility Limitation ; *Macular Degeneration/physiopathology/diagnosis/complications ; Surveys and Questionnaires ; *Vision, Low/physiopathology/rehabilitation/diagnosis ; Aged, 80 and over ; Vision, Binocular/physiology ; *Vision Screening/methods ; Postural Balance/physiology ; }, abstract = {OBJECTIVE: Assess the potential value of adding questions on falls/balance difficulties due to vision loss and testing contrast sensitivity (CS) in patients with maculopathy (mainly age-related macular degeneration, AMD) to help guide referral for mobility rehabilitation.<br><br>DESIGN: Cross-sectional study.<br><br>PARTICIPANTS: A total of 125 patients over 55 years old with binocular maculopathy and intact peripheral vision presenting for a low vision rehabilitation consultation.<br><br>METHODS: Patients were asked questions regarding difficulties with their balance and mobility, including the 9-item Glaucoma Activity Limitation questionnaire (GAL-9). For analysis, patients were grouped by visual impairment severity using better-eye visual acuity (VA) and binocular CS.<br><br>MAIN OUTCOME MEASURES: Visual function, self-reported balance and mobility difficulties, falls history, and rehabilitation referrals were examined across visual impairment severity groups.<br><br>RESULTS: Total 52% of patients reported balance or gait difficulties and 36% attributed mobility limitations to vision loss. Increasing vision deficit severity related to greater mobility concerns (>50% of patients in the severe categories rated difficulty as 3/5 or higher) and higher referral rates. Scores on the GAL-9 increased with greater vision loss and were predicted by CS, female sex, larger relative scotomata and falls history (R[2] = 0.45, P < .0001). CS was a better predictor of mobility difficulties than VA. Based on reported concerns, 31.2% of patients were referred to orientation and mobility training and/or physical therapy (>50% in the severe groups).<br><br>CONCLUSIONS: Mobility limitations and falls affect a substantial proportion of AMD patients yet may go undiscussed in eye clinics. Incorporating screening questions and explicit discussion of mobility difficulties in clinical practice in maculopathy can help elucidate patient mobility limitations. Realization of these limitations is the prerequisite to initiate appropriate referrals to low vision and mobility specialists to improve mobility and manage falls risk. Clinical practice may also benefit from assessment of CS as this is a better indicator of difficulties in daily living. Our results, along with prior literature, underscore the need to recognize the role of central vision loss, and vision loss more broadly, in mobility decline. Thus, a central vision loss-specific mobility questionnaire may be needed to facilitate patient screening in the future.}, }
@article {pmid40890572, year = {2025}, author = {Lynch, AM and Drolet, DW and Trinder, KM and Gupta, S and Westacott, MJ and Janjic, N and Palestine, AG and Patnaik, JL and Mathias, MT and Mandava, N and Wagner, BD}, title = {Proteomic profiles in the aqueous following anti-vegf therapy in treatment naïve neovascular age-related macular degeneration.}, journal = {Clinical proteomics}, volume = {22}, number = {1}, pages = {32}, pmid = {40890572}, issn = {1542-6416}, abstract = {BACKGROUND/STUDY OBJECTIVES: Age-related macular degeneration (AMD), a degenerative disease of the photoreceptor support system of the macula, is a leading cause of vision loss in individuals over 60 years of age. In this exploratory longitudinal study, we studied VEGF-related proteins and other protein concentrations in the aqueous humor of patients with treatment naïve neovascular AMD (defined as patients with a previously untreated and recently diagnosed advanced neovascular form of AMD (NVAMD) who were eligible for an intra-vitreal administration of an anti-VEGF agent to treat choroidal neovascularization). The objectives of this small pilot study were: (1) To determine levels of VEGF-related proteins in the aqueous humor of treatment naïve NVAMD patients compared with control patients, (2) To determine whether levels of VEGF-related proteins change over time with anti-VEGF injections in NVAMD patients, (3) To put these differences into perspective relative to all protein targets and identify other off-target (non-VEGF) proteins that may be related to NVAMD or NVAMD treatment.<br><br>METHODS: We used an aptamer-based proteomic technology to study protein concentrations. Cases had a sample of aqueous collected immediately prior to starting the anti-VEGF intra-vitreal injection and at two follow-up visits. Controls were cataract patients with no AMD. Aqueous was collected at the time of cataract surgery.<br><br>RESULTS: Comparison between 9 cases and 11 controls revealed 56 proteins, out of 3,803 targets, with significant differences in baseline levels. After treatment, a decline in aqueous VEGF concentrations was indicated from two aptamer reagents, while a third recorded a significant increase. Interference studies demonstrated that the increase in levels observed for the latter reagent was due to measuring both drug-bound and free VEGF concentrations (total VEGF) while the others measured only free VEGF.<br><br>CONCLUSIONS: In this exploratory study, 56 proteins were identified that could potentially be linked with NVAMD. In interference studies free aqueous VEGF levels declined while total VEGF levels increased following anti-VEGF treatment. No large off-target effects on the proteome were observed with treatment. We illustrate how the protein interactome can mask or potentially unmask binding epitopes leading to signal changes not necessarily related to the absolute protein level.}, }
@article {pmid40890721, year = {2025}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {Can artificial intelligence with multimodal imaging outperform traditional methods in predicting age-related macular degeneration progression? A systematic review and exploratory meta-analysis.}, journal = {BMC medical informatics and decision making}, volume = {25}, number = {1}, pages = {321}, pmid = {40890721}, issn = {1472-6947}, mesh = {Humans ; *Macular Degeneration/diagnostic imaging/diagnosis ; *Artificial Intelligence/standards ; Disease Progression ; *Multimodal Imaging/methods/standards ; Sensitivity and Specificity ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, and its prevalence is expected to rise with aging populations. Early prediction of AMD progression is critical for effective management. This systematic review and meta-analysis evaluate the accuracy, sensitivity, and specificity of artificial intelligence (AI) algorithms in in detecting and predicting progression of AMD.<br><br>METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review and meta-analysis were conducted from inception to February 7th, 2025. We included five studies that assessed the performance of AI algorithms in predicting AMD progression using multimodal imaging. Data on accuracy, sensitivity, and specificity were extracted, and meta-analysis was performed using Comprehensive Meta-Analysis software version 3.7. Heterogeneity was assessed using the I&#xb2; statistic.<br><br>RESULTS: Of the five studies, AI models demonstrated superior accuracy (mean difference: 0.07, 95% CI: 0.07, 0.07; p&#x2009;<&#x2009;0.00001) and sensitivity (mean difference: 0.08, 95% CI: 0.08, 0.08; p&#x2009;<&#x2009;0.00001) compared to retinal specialists. Specificity also showed a minimal but significant advantage for AI (mean difference: 0.01, 95% CI: 0.01, 0.01; p&#x2009;<&#x2009;0.00001). Importantly, heterogeneity was minimal to absent across all analyses (I&#xb2; = 0-0.42%), supporting the reliability and consistency of pooled findings.<br><br>CONCLUSION: AI algorithms outperform retinal specialists in predicting AMD progression, particularly in accuracy and sensitivity. These findings support the potential of AI in AMD prediction; however, given the limited number of included studies, the results should be interpreted as exploratory and in need of validation through future large-scale, prospective studies.}, }
@article {pmid40893118, year = {2026}, author = {Wakugawa, S and Imanaga, N and Terao, N and Kuroshima, C and Miyara, Y and Maehira, M and Koizumi, H}, title = {CHANGES IN WIDEFIELD CHOROIDAL THICKNESS AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.}, journal = {Retina (Philadelphia, Pa.)}, volume = {46}, number = {1}, pages = {98-107}, doi = {10.1097/IAE.0000000000004651}, pmid = {40893118}, issn = {1539-2864}, support = {23K15911//Japan Society for the Promotion of Science/ ; 24K12767//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; Tomography, Optical Coherence/methods ; *Choroid/pathology ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Male ; Female ; Intravitreal Injections ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; Ranibizumab/therapeutic use ; Visual Acuity/physiology ; Aged, 80 and over ; Bevacizumab ; Fluorescein Angiography ; Retrospective Studies ; Middle Aged ; Follow-Up Studies ; Choroidal Neovascularization/drug therapy ; }, abstract = {PURPOSE: This study aimed to investigate changes in choroidal thickness using widefield optical coherence tomography after anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (AMD).<br><br>METHODS: We examined 69 patients with unilateral neovascular AMD. All patients underwent three monthly intravitreal injections of anti-VEGF agents. Widefield choroidal thickness within an 18-mm circular grid centered on the fovea, subdivided into nine areas, was evaluated at baseline and at 3 months.<br><br>RESULTS: Forty-two and 27 patients were classified into the AMD and pachychoroid neovasculopathy (PNV) groups, respectively. At 3 months, the treated eyes in both groups showed significantly and extensively reduced choroidal thickness (P < 0.01 for all areas). The untreated fellow eyes in the PNV group also showed decreased choroidal thickness at 3 months (P < 0.05 for all areas). Complete retinal fluid resolution was significantly associated with a greater decrease ratio of choroidal thickness in the PNV group (P < 0.05 for all areas).<br><br>CONCLUSION: Anti-VEGF therapy for neovascular AMD led to extensively decreased choroidal thickness. In patients with PNV, a greater decrease in overall choroidal thickness appeared to be associated with more effective resolution of retinal fluid. Observation of widefield choroidal thickness may be important for the management of neovascular AMD.}, }
@article {pmid40893119, year = {2026}, author = {Barthelemy, N and Tailor, P and Sridhar, J and Samarakoon, T and Sengillo, JD}, title = {EFFECTS OF SOCIOECONOMIC FACTORS ON VISUAL OUTCOME AND MANAGEMENT OF PATIENTS WITH WET AGE-RELATED MACULAR DEGENERATION.}, journal = {Retina (Philadelphia, Pa.)}, volume = {46}, number = {1}, pages = {115-124}, doi = {10.1097/IAE.0000000000004649}, pmid = {40893119}, issn = {1539-2864}, mesh = {Humans ; Retrospective Studies ; *Wet Macular Degeneration/drug therapy/physiopathology/economics/diagnosis ; Male ; *Visual Acuity/physiology ; Female ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Aged ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Bevacizumab/administration &amp; dosage ; Socioeconomic Factors ; Aged, 80 and over ; Ranibizumab/administration &amp; dosage ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Middle Aged ; Follow-Up Studies ; Recombinant Fusion Proteins/administration &amp; dosage ; Treatment Outcome ; United States/epidemiology ; }, abstract = {PURPOSE: To analyze the relationship between socioeconomic status and neovascular age-related macular degeneration outcomes and management.<br><br>METHODS: Retrospective analysis of 1,449 patients diagnosed with neovascular age-related macular degeneration, treated with anti-vascular endothelial growth factor between January 2016 and January 2024.<br><br>RESULTS: Lower income was associated with poorer baseline (P < 0.001) and final (P < 0.001) best-corrected visual acuity. Worse final visual acuity correlated with lower baseline best-corrected visual acuity (P < 0.001), lower income (P = 0.05), and older age (P < 0.001); insurance type did not (P = 0.558). Non-Hispanic/non-Latino patients exhibited a higher rate of delayed injections per scheduled visit than Hispanics (P =0.002). Ethnicity correlated with insurance status (P = 0.008); Hispanic or Latino patients more often had Medicaid or commercial insurance; non-Hispanics/non-Latino patients more often had Medicare. Higher-income patients were more likely to receive aflibercept (P < 0.001) and faricimab (P =0.021). Hispanic or Latino were more likely to receive bevacizumab (OR 2.49; P < 0.001), but insurance type modified this association (OR 3.42; P = 0.010).<br><br>CONCLUSION: Lower income correlated with worse neovascular age-related macular degeneration visual outcomes, and the type of anti-vascular endothelial growth factor treatment used varied across income and ethnicity groups, but not insurance type.}, }
@article {pmid40893340, year = {2025}, author = {Sattah, N and Zhao, W and Choi, A and Chi, M and Sarici, K and Weng, P and Morgan, R and Zheng, Y and Karthik, N and Vajzovic, L and Hadziahmetovic, M}, title = {Effect of Faricimab on Visual Acuity and Retinal Structure in Neovascular Age-Related Macular Degeneration Previously Treated With Anti-VEGF Therapy.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251366393}, pmid = {40893340}, issn = {2474-1272}, abstract = {Purpose: To evaluate the effects of switching from traditional antivascular endothelial growth factor (anti-VEGF) therapies to faricimab, a biclonal antibody that targets both VEGF and angiopoietin-2, on eyes with neovascular age-related macular degeneration (nAMD). Methods: This study retrospectively reviewed patients with nAMD who were previously treated with bevacizumab, ranibizumab, or aflibercept and then switched to faricimab. We compared injection frequency and visual acuity (VA) during the time period before faricimab initiation (1 year prior) and after initiation (6-12 months after). Optical coherence tomography images were analyzed from initiation to final follow-up (6-12 months after initiation). Results: We evaluated 84 eyes of 68 patients. Following faricimab initiation, eyes had a reduced mean ± SE central macular thickness (CMT) (282.3 ± 16.2 μm vs 244.8 ± 14.3 μm; P < .01). Annual injection frequency increased from 7.73 ± 0.33 to 8.66 ± 0.28 injections (P < .001). VA did not change significantly during the year before faricimab initiation (P = .539) but decreased after initiation (from 0.56 ± 0.05 logMAR to 0.66 ± 0.06 logMAR; P < .01). Four eyes developed macular atrophy following faricimab initiation (P < .01). Conclusions: Eyes with nAMD that were previously treated with anti-VEGF therapy and later switched to faricimab showed reduced CMT; however, some patients had increased injection frequency, decreased VA, and macular atrophy. These findings should be explored further using larger datasets.}, }
@article {pmid40893620, year = {2025}, author = {Wu, Z and Blodi, BA and Holz, FG and Jaffe, GJ and Liakopoulos, S and Sadda, SR and Schmitz-Valckenberg, S and Bonse, M and Brown, T and Choong, J and Clifton, B and Corradetti, G and Hodgson, LAB and Lentzsch, AM and Mahmoudi, A and Pak, JW and Saßmannshausen, M and Skalak, C and von der Emde, L and Winkler, J and Guymer, RH}, title = {OCT-Defined Atrophic Age-Related Macular Degeneration Changes Associated with Deep Visual Sensitivity Losses: A Multicenter Study.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100884}, pmid = {40893620}, issn = {2666-9145}, abstract = {PURPOSE: To identify combination(s) of OCT changes that define atrophic age-related macular degeneration (AMD) lesions associated with repeatable deep visual sensitivity defects.<br><br>DESIGN: Reader study.<br><br>PARTICIPANTS: One hundred seventy-one OCT scans from 60 eyes of 53 participants.<br><br>METHODS: Participants underwent 2 high-density targeted microperimetry tests (Macular Integrity Assessment device with Goldmann Size III stimuli) per visit of a 3.5&#xb0; (approximately 1000 &#x3bc;m) diameter region-of-interest that had evidence of at least incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA). OCT B-scans within the region sampled on microperimetry were annotated by 12 readers from 6 established reading centers for 7 different features related to RPE and outer retinal atrophy. The prevalence of the presence of a repeatable &#x2264;10 decibel (dB) defect on microperimetry for lesions categorized by 18 different combinations of such features, or criteria, was determined.<br><br>MAIN OUTCOME MEASURES: The criteria for OCT-defined atrophic changes showing a &#x2265;90% prevalence of a repeatable &#x2264;10 dB defect, which has previously shown to be characteristic of regions with a truly nonresponding test location on microperimetry.<br><br>RESULTS: Sixty percent of complete RPE and outer retinal atrophy (cRORA) lesions-based on the presence of hypertransmission and RPE abnormalities &#x2265;250 &#x3bc;m in width, with evidence of overlying photoreceptor (PR) degeneration, on an OCT B-scan-had a repeatable &#x2264;10 dB defect. However, between 92% and 98% of lesions with both hypertransmission and complete RPE loss &#x2265;500 &#x3bc;m, and with evidence of any size of any feature of overlying PR degeneration, had a repeatable &#x2264;10 dB defect, depending on the criteria considered. Between 92% and 95% of lesions with hypertransmission &#x2265;500 &#x3bc;m and either overlying external limiting membrane disruption, or outer plexiform layer and inner nuclear layer subsidence, and/or hyporeflective wedge-shaped band(s) &#x2265;500 &#x3bc;m, with or without RPE abnormalities, had a repeatable &#x2264;10 dB defect.<br><br>CONCLUSIONS: This study identified various criteria for OCT-defined atrophic AMD lesions with functional characteristics that can be expected of regions with a truly nonresponding test location on high-density targeted microperimetry testing (i.e., having a &#x2265;90% prevalence of a repeatable &#x2264;10 dB defect). Such OCT-defined lesions could thus serve as functionally relevant clinical endpoints of end-stage atrophic AMD to facilitate preventative treatment trials.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40893621, year = {2025}, author = {Jonas, JB and Jonas, RA and Bikbov, MM and Kazakbaeva, GM and Wang, YX and Nangia, V and Panda-Jonas, S}, title = {Macular Atrophic versus Subretinal Proliferative Changes in Myopic and Age-Related Macular Degeneration: The 2-Continent Eye Study.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100885}, pmid = {40893621}, issn = {2666-9145}, abstract = {OBJECTIVE: To assess the prevalences of subfoveal retinal pigment epithelium (RPE) loss versus subfoveal tissue proliferation as causes of vision loss in patients with late-stage age-related macular degeneration (AMD) or myopic macular atrophy.<br><br>DESIGN: Population-based studies conducted in Russia, China, and India and histological examination of enucleated human globes.<br><br>PARTICIPANTS: The Russian Ural Eye and Medical Study (n = 5899 participants; age: &#x2265;40 years), Ural Very Old Study (n = 1526; age: 85+ years), Beijing Eye Study (n = 3468; age: &#x2265;40 years), and Central India Eye and Medical Study (n = 4711) were conducted in rural and urban regions in Bashkortostan/Russia, Beijing/China, and Nagpur/India, respectively. The histological study part included human eyes enucleated because of reasons like malignant melanomas, or were post mortem enucleated.<br><br>METHODS: The participants underwent a series of general medical and ophthalmological examinations including OCT of the macula. In the histological study part, the enucleated globes were histomorphometrically examined.<br><br>MAIN OUTCOME MEASURES: Presence of RPE loss and of subretinal proliferations.<br><br>RESULTS: In all 4 population-based studies combined, late-stage AMD and myopic macular atrophy were detected in 291 eyes and 46 eyes, respectively. Retinal pigment epithelium cell loss was dominant in 136 (94%) out of 145 eyes with geographic atrophy and in 35 (76%) out of 46 eyes with myopic macular atrophy, whereas subretinal proliferations were predominantly present in 127 (87%) out of 146 eyes with neovascular AMD. Among all 337 eyes with late AMD or myopic macular atrophy, RPE loss was the main cause for vision loss in 190 (56%) eyes and subretinal proliferations in 147 (44%) eyes, with no significant difference (P > 0.05) between the study cohorts. In the histological specimen, subretinal proliferations included melanin-bearing cells in contact with a periodic acid-Schiff-positive membrane, resembling RPE cells.<br><br>CONCLUSIONS: Subretinal proliferations in the foveal region were the main reason for central visual acuity loss in 44% of all eyes with late AMD or myopic macular atrophy in 4 population-based studies. Subretinal foveal RPE cell proliferation and RPE loss are roughly equally important as a cause of vision loss in AMD and myopic macular atrophy.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40893624, year = {2025}, author = {Erb, BM and Botros, E and Saunders, TF and Haas, AM and Voland, R and Linderman, R and Domalpally, A and Csaky, KG}, title = {Investigating Macular Tissue Integrity Index as a Novel Biomarker in Geographic Atrophy.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100871}, pmid = {40893624}, issn = {2666-9145}, abstract = {PURPOSE: The rate of geographic atrophy (GA) enlargement is commonly used as an outcome in clinical trials. However, this metric typically lacks specificity for central macular involvement and structure-function relationships. We propose a targeted approach in monitoring GA progression within the central macula, highlighting the limited benefit of including GA expansion beyond the 3-mm perifoveal zone when analyzing visual function. This study evaluates how retinal tissue and photoreceptor integrity within the central 1-mm and 3-mm circles centered on the fovea correlate with visual function.<br><br>DESIGN: Retrospective, longitudinal analysis of a GA clinical trial cohort.<br><br>SUBJECTS: Forty-three eyes from 43 participants enrolled in GA clinical trials.<br><br>METHODS: Baseline and 1-year fundus autofluorescence (FAF) and OCT scans were analyzed. The percentages of non-GA areas within the 1-mm and 3-mm circles centered on the fovea were quantified to calculate the Macular Tissue Integrity Index (MTII) using FAF images. The percentages of intact ellipsoid zones within the same circles were used to define the EZ Integrity Index (EZII). Longitudinal changes in MTII and EZII were compared to overall GA area growth and change in visual acuity (VA).<br><br>MAIN OUTCOME MEASURES: Correlations between MTII, EZII, GA area, and VA (best-corrected VA [BCVA] and low-luminance VA [LLVA]) were assessed.<br><br>RESULTS: Macular Tissue Integrity Index and EZII within the central 1 mm correlated significantly with BCVA (R[2] = 0.20, P = 0.003 and R[2] = 0.29, P < 0.001, respectively), while EZII in the 3-mm zone correlated with both BCVA and LLVA (R[2] = 0.17, P < 0.01 for both). Changes in MTII or EZII over time were not associated with GA area growth or with baseline integrity indices.<br><br>CONCLUSIONS: Macular Tissue Integrity Index and EZII are novel biomarkers for macular photoreceptor integrity, with distinct correlations to BCVA and LLVA depending on the measurement zone. These findings support the utility of MTII and EZII in assessing macular integrity and highlight the heterogeneity of GA progression, warranting further validation in larger studies.}, }
@article {pmid40894055, year = {2025}, author = {Arnal, L and Mesfin, Y and Xu, C and Salvi, A and Mishra, K and Ludwig, CA}, title = {Beyond Refractive Error: Myopia's Exponential Burden on Retinal Health with Each Diopter.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {40894055}, issn = {2693-5015}, support = {K23 EY035741/EY/NEI NIH HHS/United States ; P30 EY026877/EY/NEI NIH HHS/United States ; }, abstract = {BACKGROUND: As myopia reaches epidemic levels worldwide, its role in driving vision-threatening retinal complications is increasingly urgent. This study quantifies the burden of myopia by examining its association with key retinal diseases and how risk escalates with increasing severity.<br><br>METHODS: We conducted a retrospective cohort study using the STARR clinical data warehouse, including all patients with &#x2265;1 documented eye visit. Myopia severity was defined by spherical equivalent and axial length, classifying patients as non-myopic, myopic, highly myopic, or severely myopic. Primary outcomes included six retinal diseases associated with myopia: choroidal neovascularization (CNV), myopic macular degeneration (MMD), foveoschisis, macular hole (MH), rhegmatogenous retinal detachment (RRD), and foveal retinal detachment (FRD). Adjusted logistic regression estimated odds by myopia severity and spherical equivalent. Mean age at diagnosis was compared across groups.<br><br>RESULTS: Retinal complications occurred at younger ages with increasing myopia severity. Compared to non-myopes, myopic, highly myopic, and severely myopic patients had 2.45 (95% CI: 2.36-2.55), 2.46 (95% CI: 2.31-2.62), and 8.15 (95% CI: 7.17-9.27) times higher odds, respectively, of developing any retinal complication. Per diopter increase in myopia, the odds of each complication increased: CNV (OR 1.11; 95% CI: 1.09-1.12), MMD (OR 1.22; 95% CI: 1.18-1.25), foveoschisis (OR 1.22; 95% CI: 1.16-1.28), MH (OR 1.06; 95% CI: 1.05-1.08), FRD (OR 1.23; 95% CI: 1.16-1.32), and RRD (OR 1.10; 95% CI: 1.10-1.11). In severe myopes, odds were markedly elevated: CNV (OR 22.90), MMD (OR 60.19), foveoschisis (OR 102.98), MH (OR 6.69), FRD (OR 22.72), and RRD (OR 6.84).<br><br>CONCLUSIONS: Myopia is independently associated with higher odds of retinal diseases, and this risk increases incrementally with severity. These findings support a dose-response relationship and highlight the importance of early risk stratification, tailored monitoring, and timely referral in patients with high and severe myopia.}, }
@article {pmid40895634, year = {2025}, author = {Liang, X and Wang, J and Zhang, Y and Zheng, H}, title = {Association of serum 25-hydroxyvitamin D levels with age-related macular degeneration and its clinical correlates: a cross-sectional study.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1635739}, pmid = {40895634}, issn = {1664-2392}, mesh = {Humans ; Cross-Sectional Studies ; Female ; *Macular Degeneration/blood/epidemiology/diagnosis ; Male ; *Vitamin D/blood/analogs &amp; derivatives ; Aged ; Middle Aged ; *Biomarkers/blood ; China/epidemiology ; Aged, 80 and over ; }, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults, with significant inter-individual variability in clinical progression. Vitamin D, known for its role in calcium homeostasis and anti-inflammatory pathways, may be implicated in AMD pathogenesis. This study aimed to investigate serum 25-hydroxyvitamin D [25(OH)D] levels in AMD patients and their association with clinical phenotypes.<br><br>METHODS: This single-center, cross-sectional observational study was conducted at Tianjin Eye Hospital, China, involving 210 participants (100 AMD patients and 110 healthy controls). Exclusion criteria included conditions affecting vitamin D metabolism and recent vitamin D supplementation. Comprehensive ophthalmic assessments and laboratory tests were performed. Data were analyzed using R software, employing Student's t-tests, ANONA, chi-squared tests, Pearson correlation and linear regression models.<br><br>RESULTS: AMD patients exhibited significantly lower serum 25(OH)D levels than controls (22.98 &#xb1; 7.30 ng/mL vs. 26.12 &#xb1; 9.81 ng/mL, p=0.013). Within the AMD group, late-stage patients had lower 25(OH)D levels than early-stage patients (22.53 &#xb1; 8.14 ng/mL vs. 23.46 &#xb1; 6.36 ng/mL, p=0.019) and higher CRP levels (0.31 &#xb1; 0.19 mg/L vs. 0.17 &#xb1; 0.05 mg/L, p=0.015). ROC curve analysis indicated moderate diagnostic utility of 25(OH)D for distinguishing AMD patients from controls (AUC=0.714, 95% CI: 0.58-0.73, p<0.01), but limited ability to differentiate early vs. late-stage AMD Linear regression analysis revealed positive associations between 25(OH)D levels and apolipoprotein E (ApoE, &#x3b2;=0.157, p=0.04) and serum creatinine (&#x3b2;=0.18, p=0.02).<br><br>CONCLUSION: This study provides evidence linking lower serum 25(OH)D levels to the presence and severity of AMD, particularly in late-stage disease.}, }
@article {pmid40896239, year = {2025}, author = {Lorenz, K and Haritoglou, C and Barthelmes, D and Sefat, AMM and Berk, H and Beeke, E and Scheffler, M and Iwersen, M and Müller, B and Ziemssen, F and , }, title = {Treatment Regimens with Ranibizumab in Neovascular Age-Related Macular Degeneration: Real-World Results from the PACIFIC Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {2927-2937}, pmid = {40896239}, issn = {1177-5467}, abstract = {INTRODUCTION: Intravitreal anti-VEGF is the gold standard for treating neovascular age-related macular degeneration (nAMD). The treatment success depends not only on drug efficacy but also on regimen feasibility for physicians and patients. The implementation of different regimen might lead to varying outcomes. "Treat-and-extend" aims to minimize undertreatment with injections at each visit and tailored intervals. This study investigates the utilization and effectiveness of ranibizumab in nAMD, focusing on different treatment regimens in real-world settings.<br><br>MATERIALS AND METHODS: The PACIFIC study, a non-interventional, prospective, multicenter study, included nAMD patients treated with ranibizumab at 185 sites across Germany, the Netherlands and Switzerland. Over 24 months, functional and morphological outcomes were documented for 3051 patients over 24 months, highlighting the practiced treatment regimens.<br><br>RESULTS: A pattern of an observational approach with nevertheless increasing interval extension prevailed (70.4%, 1028 pre-treated; 68.6%, 1090 treatment-na&#xef;ve patients), emerging as the preferred strategy within the first 3 months. Across all regimens, the average number of injections was comparable (mean &#xb1; SD: 7.34&#xa0;&#xb1;&#xa0;5.30 in pre-treated; 7.26&#xa0;&#xb1;&#xa0;4.70 in treatment-na&#xef;ve patients). The treat and extend regimen, however, demonstrated superior effectiveness in improving visual acuity, particularly among treatment-na&#xef;ve patients (number of injections: 7.89&#xa0;&#xb1;&#xa0;5.54 pre-treated; 9.54&#xa0;&#xb1;&#xa0;5.42 treatment-na&#xef;ve patients).<br><br>CONCLUSION: Over 2-year observational period, the treat and extend regimen emerged as a highly effective approach, particularly for those newly diagnosed, with a low risk of undertreatment. Despite its benefits, an unconscious shift to a observe-and-extend or "monitor-and-extend" approach occurred early in treatment, highlighting the need for tailored approaches to optimize patient outcomes in clinical practice.}, }
@article {pmid40896240, year = {2025}, author = {Qian, T and Zhou, Y and Zhou, H and Wu, W and Yuan, Y and Yu, S and Xu, X}, title = {Intravitreal Double-Dose Conbercept Injection for the Treatment of Neovascular Age-Related Macular Degeneration: A Pilot Real-Life Clinical Practice Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {2965-2976}, pmid = {40896240}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate the efficacy and safety of conbercept for neovascular age-related macular degeneration (nAMD) when administered at the labeled dose (0.5 mg) and double dose (1.0 mg).<br><br>METHODS: Patients with nAMD were randomized to either 1.0 mg or 0.5 mg groups. The 1.0 mg group received intravitreal injection of 1.0 mg conbercept once monthly for the first three months, followed by a pro re nata regimen (3+PRN). The 0.5 mg group received 3+PRN regimens of intravitreal 0.5 mg conbercept throughout the treatment period. Changes in best corrected visual acuity (BCVA), central macular thickness (CMT), and maximum pigment epithelial detachment (PED) height from baseline were compared between the two treatment groups at 1-, 3-, 6-, and 12-month follow-ups.<br><br>RESULTS: Thirty-three patients completed the study, including 16 in the 0.5 mg group with an average age of 74.00 &#xb1; 8.23 years, and 17 in the 1.0 mg group with an average age of 72.29 &#xb1; 6.47 years. At 3-month, BCVA improvement in the 1.0 mg group was significantly higher than in the 0.5 mg group (P = 0.0450), though no differences were observed at other time points. There was no statistical difference in CMT reduction at any follow-up points. Regarding PED height reduction, a significant difference was observed at the 1-month follow-up (P = 0.0345), but not at the 3-, 6-, or 12-month follow-ups. After drying the macula, the recurrence interval of fluid in the 1.0 mg group was significantly longer than in the 0.5 mg group (P = 0.0360). No related adverse event was reported in either group.<br><br>CONCLUSION: While the 1.0 mg group showed a transient but significant BCVA improvement at 3 months and a longer recurrence interval, further large-scale trials are needed to validate these preliminary findings.<br><br>TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn/, ChiCTR2000029503). Registration date: 03/02/2020.}, }
@article {pmid40900080, year = {2025}, author = {Yang, J and Bernardo-Colón, A and Becerra, SP}, title = {Lack of Pnpla2 Accelerates Progression of AMD-Like Features in Mice.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {12}, pages = {11}, pmid = {40900080}, issn = {1552-5783}, mesh = {Animals ; Mice ; *Macular Degeneration/metabolism/genetics/pathology/physiopathology ; *Retinal Pigment Epithelium/metabolism/pathology ; Electroretinography ; Disease Progression ; Disease Models, Animal ; *Lipase/genetics/physiology ; Cellular Senescence/physiology ; Mice, Inbred C57BL ; Mice, Knockout ; Tight Junctions/metabolism ; Zonula Occludens-1 Protein/metabolism ; Acyltransferases ; }, abstract = {PURPOSE: Lipid accumulation in the retinal pigment epithelium (RPE) contributes to cellular stress and progression of age-related macular degeneration (AMD). However, the regulation of lipid homeostasis in AMD development is not fully elucidated. The study investigates the effects of Pnpla2 deletion, a gene involved in lipid regulation, on key markers of RPE senescence and aging with potential relevance to AMD.<br><br>METHODS: RPE flat mounts and retinal cryosections were analyzed from Pnpla2-/- and Pnpla2+/+ mice aged 3 months. Senescence-associated &#x3b2;-galactosidase (SA-&#x3b2;-gal) activity was assessed in flat mounts. DAPI was used to quantify RPE cells with single or multiple nuclei. Immunohistofluorescence was carried out to assess RPE tight junctions and expression of senescence and AMD markers using antibodies to zonula occludens 1 (ZO-1), phospho-histone (P-&#x3b3;-H2AX), apolipoprotein E (ApoE), and high mobility group box 1 (HMGB1). Fundus imaging was acquired, and electroretinography (ERG) assessed visual function.<br><br>RESULTS: Pnpla2-/- RPE exhibited increased SA-&#x3b2;-gal activity, multinucleation of the population, and the translocation of HMGB1 from nucleus to cytoplasm, indicative of cellular senescence. Tight junctions were disrupted. The number of P-&#x3b3;-H2AX-positive RPE cells increased by 50%, suggesting increased DNA damage. ApoE levels were elevated in Bruch's membrane and subretinal regions. At 3 months of age, attenuation of ERG c-wave amplitude was observed in both Pnpla2-/- and Pnpla2+/- mice. By 7 months of age, Pnpla2+/- mice exhibited continued attenuation of ERG c-wave amplitude and developed white spots.<br><br>CONCLUSIONS: Pnpla2 deficiency accelerates cellular features of RPE aging and generates AMD-like features. These findings underscore the importance of PNPLA2 in mitigating AMD progression and highlight its significance in retinal health and degeneration.}, }
@article {pmid40900875, year = {2025}, author = {Kaur, R and Morya, AK and Gupta, PC and Aggarwal, S and Menia, NK and Kaur, A and Kaur, S and Sinha, S}, title = {Artificial intelligence-based apps for screening and diagnosing diabetic retinopathy and common ocular disorders.}, journal = {World journal of methodology}, volume = {15}, number = {4}, pages = {107166}, pmid = {40900875}, issn = {2222-0682}, abstract = {Artificial intelligence (AI), encompassing machine learning and deep learning, is being extensively used in medical sciences. It is slated to positively impact the diagnosis and prognostication of various diseases. Deep learning, a subset of AI, has been instrumental in diagnosing diabetic retinopathy (DR), diabetic macular edema, glaucoma, age-related macular degeneration, and numerous other ocular diseases. AI performs equally well in the early prediction of glaucoma and age-related macular degeneration. Integrating AI with telemedicine promises to improve healthcare delivery, although challenges persist in implementing AI algorithms, especially in developing countries. This review provides a comprehensive summary of AI, its applications in ophthalmology, particularly DR, the diverse algorithms utilized for different ocular conditions, and prospects for the future integration of AI in eye care.}, }
@article {pmid40901439, year = {2025}, author = {Wildan, A and Rachmawati, B and Kartasasmita, AS and Rahmi, FL and Maharani,  and Istiadi, H and Syifarahmah, A and Nurdiansyah, I and Wulandari, NF and Salsabilah, S}, title = {Development of a BALB/c mice model for blue light retinal damage.}, journal = {Journal of advanced pharmaceutical technology &amp; research}, volume = {16}, number = {3}, pages = {139-143}, pmid = {40901439}, issn = {2231-4040}, abstract = {Blue light exposure can damage the retina, resulting in retinal atrophy and significant vision loss. Currently, no efficient animal models can observe retinal damage caused by blue light within a defined timeframe. Creating a BALB/c mouse model for blue light-induced retinal damage is expected to enhance research focused on the prevention and treatment of age-related macular degeneration. This study explores the potential effect of blue light exposure on the BALB/c mice model by analysing apoptosis and retinal degeneration. Anatomical Pathology Laboratory of Diponegoro University and The Integrated Research and Testing Laboratory of Gadjah Mada University. This study design was a posttest-only control group design. Ten five-week-old BALB/c mice were divided into two groups. The exposure group received 10,000 lux of blue light in the special cage for 2 weeks, 3 h daily. Caspase-3 expression was assessed through polymerase chain reaction testing, and retinal thickness was analyzed using hematoxylin and eosin staining. We used the Shapiro-Wilk test to evaluate data normality. Parametric t-tests and nonparametric Mann-Whitney tests were applied to compare groups, with P < 0.05 considered significant. The average whole retinal thickness of the exposed group was 152.812 ± 20.919 µm, while the control group was 214.948 ± 53.284 µm (P = 0.04). The average caspase-3 expression in the exposed group was 19.03 ± 8.57 µm, while the control group was 5.78 ± 2.63 µm (P = 0.011). This approach, utilizing animal models for blue light exposure, can be employed to learn about retinal damage caused by blue light.}, }
@article {pmid40902799, year = {2026}, author = {Lakhani, M and Kwan, ATH and Kundapur, D and Popovic, MM and Damji, KF and Hurley, BR}, title = {Association of Anti-VEGF Therapy with Reported Ocular Adverse Events: A Global Pharmacovigilance Analysis.}, journal = {Ophthalmology. Retina}, volume = {10}, number = {3}, pages = {265-282}, doi = {10.1016/j.oret.2025.08.018}, pmid = {40902799}, issn = {2468-6530}, mesh = {Humans ; *Pharmacovigilance ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Female ; Male ; Aged ; Ranibizumab/adverse effects ; Intravitreal Injections ; Recombinant Fusion Proteins/adverse effects ; Adverse Drug Reaction Reporting Systems ; United States/epidemiology ; Receptors, Vascular Endothelial Growth Factor ; *Wet Macular Degeneration/drug therapy ; Retinal Vein Occlusion/drug therapy ; Aged, 80 and over ; *Macular Edema/drug therapy ; Retrospective Studies ; Middle Aged ; Antibodies, Monoclonal, Humanized/adverse effects ; }, abstract = {OBJECTIVE: Anti-VEGF therapies have transformed the management of neovascular age-related macular degeneration, diabetic macular edema, and macular edema secondary to retinal vein occlusion. This class-wide pharmacovigilance study evaluated the disproportionality of reported ocular adverse events (AEs) among anti-VEGF agents using postmarketing data.<br><br>DESIGN: A population-based, observational pharmacovigilance study.<br><br>PARTICIPANTS: Reports from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database (January 2004-September 2024) for individuals treated with anti-VEGF agents.<br><br>METHODS: Ocular AEs were identified from FAERS, and disproportionality was assessed by comparing each anti-VEGF agent to background reporting using reporting odds ratios (RORs, 95% confidence interval [CI]); signals were considered significant if information component (IC025) > 0. Ranibizumab, aflibercept, brolucizumab, and faricimab were evaluated to compare ocular AE profiles among agents.<br><br>MAIN OUTCOME MEASURES: Disproportionality of reported ocular AEs among anti-VEGF agents.<br><br>RESULTS: Across included patients receiving anti-VEGF agents with ocular AEs, most were female and aged 65 to 85 years. When comparing intraocular inflammation (IOI) signals across anti-VEGF agents, the strongest association was observed with brolucizumab (ROR = 633.32), followed by faricimab (ROR = 156.44), aflibercept (ROR = 51.29), and ranibizumab (ROR = 16.90). Faricimab was notably associated with elevated disproportionality signals for reports of anterior segment inflammation, including anterior chamber flare (ROR = 270.95), unspecified anterior chamber inflammation (ROR = 226.28), iridocyclitis (ROR = 214.60), and iritis (ROR = 88.90). For posterior segment involvement, increased reporting of vitritis was observed with brolucizumab (ROR = 1769.33), faricimab (ROR = 466.99), aflibercept (ROR = 165.31), and ranibizumab (ROR = 56.67). Rare but clinically significant complications were reported across all agents, including for reports of endophthalmitis (aflibercept ROR = 208.88, ranibizumab ROR = 114.69, faricimab ROR = 99.75, and brolucizumab ROR = 56.15), noninfectious endophthalmitis (aflibercept, ROR = 846.11, 244.42 for brolucizumab, 65.45 for ranibizumab, and 59.08 for faricimab), and pseudoendophthalmitis, which showed the strongest signal with faricimab (ROR = 262.31; all 95% CI = 29.37-649.50, P < 0.0001, IC025 > 0). Faricimab also demonstrated increased reporting of retinal vascular inflammation but showed comparatively lower signals for noninflammatory occlusive events and other serious ocular complications relative to other anti-VEGF agents.<br><br>CONCLUSIONS: This global pharmacovigilance study revealed variability in ocular AE reporting across anti-VEGF agents. Brolucizumab showed the strongest signal for IOI, whereas aflibercept showed the highest signal for endophthalmitis. Continued postmarketing monitoring is warranted to define evolving safety profiles across anti-VEGF agents.<br><br>FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid40902824, year = {2026}, author = {Parmar, UPS and Arora, A and Agarwal, A and Gangaputra, S and Agrawal, R and Gupta, V}, title = {Detection and quantification of fluorescein angiography leakage: From manual grading to advances in machine learning.}, journal = {Survey of ophthalmology}, volume = {71}, number = {2}, pages = {613-626}, doi = {10.1016/j.survophthal.2025.08.015}, pmid = {40902824}, issn = {1879-3304}, mesh = {Humans ; *Fluorescein Angiography/methods ; *Machine Learning ; *Retinal Vessels/pathology/diagnostic imaging ; *Retinal Diseases/diagnosis ; Fundus Oculi ; Capillary Permeability/physiology ; }, abstract = {Fluorescein angiography (FA) has long been a cornerstone for evaluating retinal vascular leakage in diseases like uveitis, diabetic retinopathy, and macular degeneration, but its interpretation relies on subjective grading that can vary between clinicians. With the emergence of artificial intelligence (AI), there is a push to transform this qualitative assessment into objective, quantifiable metrics. We conducted a comprehensive literature search using PubMed, Embase, and Scopus, combining keywords and MeSH terms related to fluorescein angiography leakage, artificial intelligence, and retinal vascular diseases. Studies were included if they assessed FA leakage using manual, semi-automated, or AI-based methods and were peer-reviewed, published in English, and focused on human subjects. Our review charts the evolution from manual grading to modern machine learning techniques that segment and measure leakage using various angiograms. These AI-based approaches enable standardized, reproducible leakage indices that correlate with disease severity, inform treatment decisions, stratify high-risk patients, and facilitate sensitive monitoring of therapeutic response. We also introduce the concept of "minimal residual disease" in this context. By moving from coarse, subjective estimations to precise digital biomarkers, AI-driven FA leakage quantification promises to improve clinical care and research endpoints in retinal disease.}, }
@article {pmid40904726, year = {2025}, author = {Cheng, S and Chen, Z and Peng, F and Deng, P and Wang, M and Liu, S and Du, Y and Zuo, G}, title = {Exploration Progress on Inflammatory Responses and Immune Regulatory Mechanisms in Diabetic Retinopathy.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {11895-11909}, pmid = {40904726}, issn = {1178-7031}, abstract = {Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes. In recent years, with the number of diabetic patients increasing annually, the number of DR patients has also been rising, and it has become one of the major blinding eye diseases worldwide. The pathogenesis of DR has not been fully clarified but includes microvascular lesions and metabolic factors. However, with the continuous exploration of the pathogenesis of DR, immune system disorders and inflammation have also been found to be important pathogenic mechanisms of DR and research on inflammation and immune mechanisms in DR have received increasing attention. This article reviews aspects such as the activation of inflammatory cells, the expression of inflammatory factors, and the complement system and explores the important roles of inflammation and immune mechanisms in the pathogenesis of DR, providing a theoretical basis for a deeper understanding of DR and potential explorations of new therapeutic strategies for DR.}, }
@article {pmid40905027, year = {2025}, author = {}, title = {Erratum: Determinants of Healthcare Professionals' Knowledge on Age-Related Macular Degeneration Risk Factors in Ethiopia [Corrigendum].}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {3009-3010}, doi = {10.2147/OPTH.S562800}, pmid = {40905027}, issn = {1177-5467}, abstract = {[This corrects the article DOI: 10.2147/OPTH.S514480.].}, }
@article {pmid40905748, year = {2025}, author = {Miller, A and Crossland, MD and Macnaughton, J and Latham, K}, title = {The Usefulness of a Wearable Electronic Vision Enhancement System for People With Age-Related Macular Degeneration: A Randomized Crossover Trial.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {9}, pages = {8}, pmid = {40905748}, issn = {2164-2591}, mesh = {Humans ; Female ; *Macular Degeneration/rehabilitation/physiopathology ; Male ; Cross-Over Studies ; *Wearable Electronic Devices ; Quality of Life ; Aged, 80 and over ; Aged ; Visual Acuity/physiology ; *Vision, Low/rehabilitation ; *Sensory Aids ; Middle Aged ; }, abstract = {PURPOSE: To determine the usefulness of a wearable electronic vision enhancement system (wEVES) for people with age-related macular degeneration (AMD).<br><br>METHODS: Thirty-four adults with AMD, 64.7% female, mean age 80.2(&#xb1;6.0), were recruited from a UK low vision service. A 12-week non-masked randomized crossover trial compared wEVES usefulness with participants' existing low vision solutions. Primary outcome measures were visual ability, vision-related quality of life (VRQoL), device usage, and user-reported preferred device. Secondary outcomes were adverse effects, willingness to purchase, and qualitative reactions.<br><br>RESULTS: Overall visual ability improved with wEVES compared to existing solutions alone (mean difference -0.26; 95% confidence interval [CI], -0.48 to -0.04; P = 0.02). The wEVES were used for varied activities, including distance tasks, with few reported alternative strategies. However, these findings did not translate into changes in VRQoL (mean difference 0.10; 95% CI, -0.27 to 0.46; P = 0.59) or sustained device use. The wEVES were not the most preferred device for any task or individual, even when self-reported performance surpassed existing solutions. Adverse effects were minor, but participants' satisfaction and willingness to use wEVES declined significantly from trial baseline to end.<br><br>CONCLUSIONS: The wEVES improved self-reported visual ability, indicating their potential to support vision rehabilitation for people with AMD, albeit in a device that was largely not preferred over existing solutions. A user-led home trial evaluated using mixed methods is more indicative of the usefulness of wEVES for people with AMD than a short clinical demonstration.<br><br>TRANSLATIONAL RELEVANCE: To understand the usefulness of wEVES for people with AMD, broader measures than visual function and visual ability should be applied within longer user-led assessments.}, }
@article {pmid40906190, year = {2025}, author = {Mansour, AM and Gad, MS and Habib, S and Elmasry, K}, title = {Bidirectional Hypoxic Extracellular Vesicle Signaling Between Müller Glia and Retinal Pigment Epithelium Regulates Retinal Metabolism and Barrier Function.}, journal = {Biology}, volume = {14}, number = {8}, pages = {}, pmid = {40906190}, issn = {2079-7737}, support = {P30EY031631//This work is supported by the Start-up fund from Augusta University, the Dental College of Georgia for KE and NIH core grant P30EY031631 to Vision Discovery Institute at Medical Col-lege of Georgia, Augusta University, Augusta, GA, USA./ ; }, abstract = {The retina is highly sensitive to oxygen and blood supply, and hypoxia plays a key role in retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Müller glial cells, which are essential for retinal homeostasis, respond to injury and hypoxia with reactive gliosis, characterized by the upregulation of the glial fibrillary acidic protein (GFAP) and vimentin, cellular hypertrophy, and extracellular matrix changes, which can impair retinal function and repair. The retinal pigment epithelium (RPE) supports photoreceptors, forms part of the blood-retinal barrier, and protects against oxidative stress; its dysfunction contributes to retinal degenerative diseases such as AMD, retinitis pigmentosa (RP), and Stargardt disease (SD). Extracellular vesicles (EVs) play a crucial role in intercellular communication, protein homeostasis, and immune modulation, and have emerged as promising diagnostic and therapeutic tools. Understanding the role of extracellular vesicles' (EVs') signaling machinery of glial cells and the retinal pigment epithelium (RPE) is critical for developing effective treatments for retinal degeneration. In this study, we investigated the bidirectional EV-mediated crosstalk between RPE and Müller cells under hypoxic conditions and its impact on cellular metabolism and retinal cell integrity. Our findings demonstrate that RPE-derived extracellular vesicles (RPE EVs) induce time-dependent metabolic reprogramming in Müller cells. Short-term exposure (24 h) promotes pathways supporting neurotransmitter cycling, calcium and mineral absorption, and glutamate metabolism, while prolonged exposure (72 h) shifts Müller cell metabolism toward enhanced mitochondrial function and ATP production. Conversely, Müller cell-derived EVs under hypoxia influenced RPE metabolic pathways, enhancing fatty acid metabolism, intracellular vesicular trafficking, and the biosynthesis of mitochondrial co-factors such as ubiquinone. Proteomic analysis revealed significant modulation of key regulatory proteins. In Müller cells, hypoxic RPE-EV exposure led to reduced expression of Dyskerin Pseudouridine Synthase 1 (DKc1), Eukaryotic Translation Termination Factor 1 (ETF1), and Protein Ser/Thr phosphatases (PPP2R1B), suggesting alterations in RNA processing, translational fidelity, and signaling. RPE cells exposed to hypoxic Müller cell EVs exhibited elevated Ribosome-binding protein 1 (RRBP1), RAC1/2, and Guanine Nucleotide-Binding Protein G(i) Subunit Alpha-1 (GNAI1), supporting enhanced endoplasmic reticulum (ER) function and cytoskeletal remodeling. Functional assays also revealed the compromised barrier integrity of the outer blood-retinal barrier (oBRB) under hypoxic co-culture conditions. These results underscore the adaptive but time-sensitive nature of retinal cell communication via EVs in response to hypoxia. Targeting this crosstalk may offer novel therapeutic strategies to preserve retinal structure and function in ischemic retinopathies.}, }
@article {pmid40907629, year = {2025}, author = {Ng, PQ and Huang, K and McLellan, FC and Yang, M and Lennikov, A and Hu, Z and Chaudhary, S and Appiah, AC and Vuong, ML and Shu, DY}, title = {Dimethyl fumarate is an inhibitor of pathological angiogenesis.}, journal = {Cellular signalling}, volume = {136}, number = {}, pages = {112106}, doi = {10.1016/j.cellsig.2025.112106}, pmid = {40907629}, issn = {1873-3913}, mesh = {*Dimethyl Fumarate/pharmacology/therapeutic use ; Animals ; Humans ; Mice ; Endothelial Cells/drug effects/metabolism ; *Neovascularization, Pathologic/drug therapy/pathology ; Vascular Endothelial Growth Factor A/metabolism ; Cell Proliferation/drug effects ; Cell Movement/drug effects ; *Angiogenesis Inhibitors/pharmacology ; Mice, Inbred C57BL ; Choroid/drug effects ; }, abstract = {Vascular endothelial growth factor (VEGF), a pro-angiogenic molecule, supports blood vessel growth during wound healing but also drives pathological neovascularization in blinding eye diseases such as neovascular age-related macular degeneration (nAMD). Dimethyl fumarate (DMFu), an FDA-approved drug for multiple sclerosis, has shown promising anti-inflammatory properties in the retinal pigment epithelium, a crucial structure disrupted in nAMD. Here, we extend the therapeutic potential of DMFu by discerning the anti-angiogenic capabilities of DMFu in choroidal and retinal endothelial cells. Choroidal endothelial cell proliferation was significantly attenuated by DMFu in the mouse choroidal sprouting assay. Even in the presence of VEGF, DMFu disrupted cell migration and tube formation in human microvascular retinal endothelial cells (HRECs). Bulk RNA sequencing highlighted that DMFu successfully ameliorated the expression of VEGF-controlled gene expression. Weighted gene co-expression network and gene set enrichment analyses confirmed downregulation of pathways involved in branching blood vessel morphogenesis but also revealed novel transcriptional mechanisms of action, including control of microtubule transport and ATP synthesis coupled electron transport. DMFu induced a decrease in maximal mitochondrial respiration, an increase in glycolysis and glycolytic capacity and reduced Complex II protein expression of the SDHB subunit on western blot. Such metabolic rewiring may limit the bioenergetic demands required to support angiogenic growth. With therapies available for nAMD being both limited and invasive, DMFu is a contender to be rapidly repurposed as an oral, patient-friendly therapeutic alternative.}, }
@article {pmid40908046, year = {2026}, author = {Yu, J and Zhang, Y and Ho, M and Kam, KW and Young, AL and Pang, CP and Tham, CC and Yam, JC and Chen, LJ}, title = {Association of leucocyte telomere length with incident age-related macular degeneration: a prospective UK Biobank Study.}, journal = {The British journal of ophthalmology}, volume = {110}, number = {2}, pages = {166-172}, doi = {10.1136/bjo-2025-327492}, pmid = {40908046}, issn = {1468-2079}, mesh = {Humans ; Female ; Male ; United Kingdom/epidemiology ; *Leukocytes/metabolism/pathology ; *Macular Degeneration/epidemiology/genetics ; Aged ; Prospective Studies ; Incidence ; Middle Aged ; Biological Specimen Banks ; Risk Factors ; *Telomere/genetics ; Follow-Up Studies ; Genetic Predisposition to Disease ; Longitudinal Studies ; UK Biobank ; }, abstract = {PURPOSE: There have been conflicting findings on the role of leucocyte telomere length (LTL) in the risk of age-related macular degeneration (AMD). In this study, we evaluated the associations between LTL and the risk of incident AMD and explored whether age, sex and/or genetic predisposition to AMD can modify these associations.<br><br>METHODS: We conducted a longitudinal cohort study involving 332&#x2009;123 AMD-free participants with complete baseline covariates and LTL data from the UK Biobank. We employed multivariable Cox proportional hazards models to test the association between LTL and AMD incidence, estimating the HRs and 95% CIs. Genetic risk was assessed using polygenic risk score (PRS).<br><br>RESULTS: During a median follow-up of 13.63 years, 6754 participants (2.03%) developed AMD. Shorter LTL was not associated with incident AMD risk (HR=1.042, 95%&#x2009;CI: 0.992 to 1.094; p=0.10) after adjusting for multiple confounders. Sex showed an interactive effect with LTL (p=0.01 for interaction) on incident AMD risk, while age and PRS did not modify these associations. We identified a significant association between shorter LTL and incident AMD risk in females (HR=1.093, 95%&#x2009;CI: 1.025 to 1.166; p=0.007), but not in males. Moreover, shorter LTL was associated with thinner photoreceptor segments only in females at both baseline and repeated assessments (&#x3b2;=-0.141&#x2009;&#xb5;m, 95%&#x2009;CI: -0.267 to -0.016; &#x3b2;=-0.345&#x2009;&#xb5;m, 95%&#x2009;CI: -0.649 to -0.041, p<0.05).<br><br>CONCLUSIONS: Shorter LTL increased the risk of incident AMD in females, suggesting LTL as a potential biomarker for AMD development with sex-specific function.}, }
@article {pmid40908402, year = {2025}, author = {Holmes, C and Kazantzis, D and Raza, SA and Wijesingha, N and Taylor, TR and Hagag, A and Riedl, S and Mai, J and Rueckert, D and Bogunović, H and Scholl, H and Schmidt-Erfurth, U and Fritsche, L and Lotery, A and Sivaprasad, S}, title = {Using adaptive optics to assess hyporeflective clump speed and size in age-related macular degeneration in the PINNACLE Study. (PINNACLE Study Report 6).}, journal = {Eye (London, England)}, volume = {39}, number = {15}, pages = {2793-2799}, pmid = {40908402}, issn = {1476-5454}, support = {/WT_/Wellcome Trust/United Kingdom ; 210572/Z/18/Z//Wellcome Trust (Wellcome)/ ; }, mesh = {Humans ; Tomography, Optical Coherence/methods ; *Ophthalmoscopy/methods ; Aged ; *Retinal Pigment Epithelium/pathology ; Female ; Male ; *Macular Degeneration/diagnosis ; Aged, 80 and over ; Middle Aged ; Geographic Atrophy ; }, abstract = {BACKGROUND/OBJECTIVES: Hyporeflective clumps (HRC) are a common finding in adaptive optics ophthalmoscopy (AOO) of age-related macular degeneration (AMD). They appear on optical coherence tomography (OCT) as hyperreflective foci (HRF) or abutting the retinal pigment epithelium (RPE) layer as RPE thickening. The cellular origin of HRF is debated between migrated RPE cells and mononuclear phagocytes (MP). Microglial cells are MP known to migrate at 0.02 µm/s, but RPE migration speed is unknown. Phenotyping HRCs by migration speed and size may improve our understanding of HRFs.<br><br>METHODS: Patients with non-neovascular AMD were imaged with the RTX1 retinal camera (Imagine Eyes, Orsey, France). Pairs of AOO images taken 1-3&#x2009;h apart were centred on areas with multiple HRCs and compared to identify mobile HRCs. Macular OCT scans were performed immediately after initial AOO.<br><br>RESULTS: A total of 21 pairs of images from 14 eyes of 12 patients were of adequate quality to assess HRCs. There were 411 measurable HRCs, with a mean diameter of 15.9&#x2009;&#xb1;&#x2009;6.0&#x2009;&#xb5;m. The HRCs were larger in images of atrophy (p&#x2009;<&#x2009;0.001). Within the timeframe assessed, most HRCs remained static, but mobile HRCs were not uncommon and migrated up to 0.015&#x2009;&#xb5;m/s. HRFs on OCT corresponding to mobile HRCs on AOO appeared adjacent to the RPE or in the interdigitation zone.<br><br>CONCLUSION: AOO can detect HRC movement in AMD in images captured a mean of 105.5&#x2009;min apart. HRC size and movement speed are consistent with microglial cells, but may also represent RPE cells. HRCs appear larger in images of atrophy.}, }
@article {pmid40909754, year = {2025}, author = {Ozaki, A and Kawai, A and Akiba, R and Okayama, S and Ohno, N and Kajita, K and Masuda, T and Yokota, S and Ito, SI and Peiyan, D and Onoue, K and Yonemura, S and Kondo, M and Kurimoto, Y and Fu, Y and Mandai, M}, title = {Genome-edited retinal organoids restore host bipolar connectivity in the primate macula.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40909754}, issn = {2692-8205}, support = {U24 EY033272/EY/NEI NIH HHS/United States ; }, abstract = {Retinal organoids (ROs) represent a promising regenerative strategy for restoring vision in retinal degenerative diseases, but whether host cone bipolar cells (BCs) in the primate macula can rewire with transplanted photoreceptors remains unresolved. Here, we transplanted genome-edited human retinal organoids lacking ON-BCs (Islet-1 [-]/[-] ROs) into a non-human primate macular degeneration model. Remarkably, host rod and cone BCs extended dendrites toward grafted photoreceptors, forming functional synapses confirmed by immunohistochemistry, ultrastructural imaging, and focal macular electroretinography. Both ON- and OFF-pathway connectivity was rebuilt, providing the first demonstration of host-graft synaptic integration in the primate macula. These results establish that primate cone circuits retain a surprising capacity for rewiring and highlight genome-edited ROs as a powerful platform for vision restoration. Our findings represent a critical translational step toward stem cell-based therapies capable of repairing central vision in patients with advanced macular degeneration.}, }
@article {pmid40909979, year = {2025}, author = {Morse, AR and Hark, LA and Seiple, WH and Gorroochurn, P and Tang, H and Rojas, R and Chen, R and Horowitz, JD and Bearelly, S and Diaconita, V and Shukla, AG and Wang, Y and Maruri, SC and Torres, DR and Cioffi, GA and Chang, S and Tezel, T}, title = {Association of Behavioral Factors with Activation in Patients with Age-Related Macular Degeneration or Diabetic Retinopathy.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {3059-3069}, pmid = {40909979}, issn = {1177-5467}, abstract = {INTRODUCTION: Activation is the degree that individuals have the knowledge, skills, beliefs, and behaviors necessary for effective health-care self-management. Those with higher activation are more likely to engage in behaviors associated with improved care outcomes, including increased medication and appointment adherence. Identifying and addressing patients' activation levels and associated behaviors at the outset of care can help to develop interventions to improve patients' participation in their healthcare. Our objective was to study the association of psychosocial factors with activation to identify behavioral factors that could increase activation.<br><br>METHODS: Individuals with bilateral AMD or DR (n = 1146) were identified from electronic medical records at a single academic medical center. Randomly selected potential participants (n = 682) were sent a letter inviting their participation. Consenting participants (AMD n = 161; DR n = 94) were administered the Patient Activation Measure (PAM), the National Eye Institute Visual Function Questionnaire-8 (NEI-VFQ), Multidimensional Health Locus of Control - form C (MHLC), Perceived Medical Condition Self-Management Scale (PMCSMS), Patient Health Questionnaire-9 (PHQ-9), a measure of health literacy and a sociodemographic health questionnaire by phone.<br><br>RESULTS: In multivariable analysis of participants with AMD, for each unit increase in MHLC Internal score, mean PAM score increased by 0.50 (P = 0.001).&#xa0;In multivariable analysis of participants with DR, for each unit increase in MHLC Chance, mean PAM score decreased by 0.48 (P = 0.0391). Differences on MHLC Internal and Chance scores among and between those with dry or wet AMD and non-proliferative or proliferative DR were all significant (P < 0.001).<br><br>DISCUSSION: In this cross-sectional cohort study of 255 participants with bilateral diabetic retinopathy or age-related macular degeneration, higher internal LOC and lower external LOC were associated with higher activation scores. Interventions that increase patient activation may increase internal LOC and reduce external LOC, improving patients' participation in their care, and improve health-care outcomes.}, }
@article {pmid40909980, year = {2025}, author = {Lin, T and Luo, S and Zhuang, C and Xiao, H and Ding, X and Li, S}, title = {Caregiver Burden Among Patients Receiving Anti-VEGF Intravitreal Injections for AMD and DR: A Cross-Sectional Study in Guangzhou.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {3071-3078}, pmid = {40909980}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate the caregiver burden and its associated factors among patients receiving anti-VEGF intravitreal injections for age-related macular degeneration (AMD) and diabetic retinopathy (DR) in a tertiary hospital in Guangzhou, China.<br><br>METHODS: This cross-sectional study recruited 88 patients who received intravitreal anti-VEGF injections and their primary caregivers. Patients completed the Activities of Daily Living (ADL) scale, while caregivers completed the Zarit Burden Interview (ZBI) and the Connor-Davidson Resilience Scale (CD-RISC). One-way ANOVA and Pearson correlation analysis were conducted to assess the associations between patient function, caregiver burden, and related sociodemographic factors.<br><br>RESULTS: The mean ADL score of patients was 18.99 &#xb1; 8.34, while the mean caregiver burden score was 18.22 &#xb1; 18.04. A significant positive correlation was found between the patient's ADL score and caregiver burden (r = 0.405, p < 0.01). Caregivers who were employed part-time or not cohabiting with patients reported significantly higher burden scores (p = 0.034 and p = 0.03, respectively). Additionally, the caregiver burden among DR patients was higher than among AMD patients (p = 0.026).<br><br>CONCLUSION: Significant caregiver burden exists among those assisting patients receiving intravitreal injections, especially for DR patients and those with reduced ADL function. Caregiver availability and living arrangements should be considered in the design of follow-up schedules to improve treatment adherence and outcomes.}, }
@article {pmid40911453, year = {2026}, author = {Chen, X and Chan, W and Meng, Y and Liu, R and Yu, Y and Hu, S and Han, J and Wang, X and Zhou, J and Qiu, B and Wang, Y}, title = {Multi-Channel Temporal Interference Retinal Stimulation Based on Reinforcement Learning.}, journal = {IEEE journal of biomedical and health informatics}, volume = {30}, number = {3}, pages = {2101-2112}, doi = {10.1109/JBHI.2025.3605434}, pmid = {40911453}, issn = {2168-2208}, mesh = {Humans ; *Retina/physiology ; Algorithms ; *Electric Stimulation Therapy/methods ; Finite Element Analysis ; *Signal Processing, Computer-Assisted ; *Machine Learning ; }, abstract = {Retinal degenerative diseases such as age-related macular degeneration and retinitis pigmentosa cause severe vision impairment, while current electrical stimulation therapies are limited by poor spatial targeting precision. As a promising non-invasive alternative, the efficacy of temporal interference stimulation (TIS) for retinal targeting depends on optimized multi-electrode parameters. This study reconstructed a whole-head finite element model with detailed ocular structures and applied reinforcement learning (RL)-based multi-channel electrode parameter optimization to retinal stimulation. Systematic evaluation demonstrated that the focal precision of TIS improves with increasing channel numbers (consistent across all subject head models), with RL significantly outperforming conventional genetic algorithms (GA) and unsupervised neural networks (USNN) in focusing capability. Furthermore, by implementing the computationally intensive envelope calculation using the JAX framework, we achieved a nearly order-of-magnitude reduction in optimization time (to approx. 2 minutes per run on an RTX 4090D), significantly enhancing the practical feasibility of the proposed RL framework. This work provides a novel and computationally efficient methodology for precise non-invasive neuromodulation parameter optimization, applicable not only to retinal diseases but potentially to broader neurological conditions.}, }
@article {pmid40913076, year = {2025}, author = {Tsai, HR and Chang, WC and Lee, YC}, title = {Association between atrial fibrillation and age-related macular degeneration: A nationwide cohort study.}, journal = {Eye (London, England)}, volume = {39}, number = {15}, pages = {2800-2807}, pmid = {40913076}, issn = {1476-5454}, support = {TCMF-P 112-07//Buddhist Tzu Chi Medical Foundation/ ; }, mesh = {Humans ; *Atrial Fibrillation/epidemiology/complications ; Male ; Female ; Taiwan/epidemiology ; Aged ; Retrospective Studies ; Incidence ; *Macular Degeneration/epidemiology ; Middle Aged ; Risk Factors ; Aged, 80 and over ; Databases, Factual ; Proportional Hazards Models ; }, abstract = {BACKGROUND/OBJECTIVES: Atrial fibrillation (AF) and age-related macular degeneration (AMD) are common debilitating conditions that share pathomechanisms involving chronic inflammation and oxidative stress. However, the association between AMD and AF, which is important for comprehending the pathogenesis, referral, and treatment strategies of these diseases, remains unknown.<br><br>SUBJECTS/METHODS: This nationwide population-based retrospective cohort study used claims data from the National Health Insurance Research Database of Taiwan. From 1 January 2003 to 31 December 2018, an AF and AMD cohort of 34,236 and 31,766 patients, respectively, along with their matched control cohorts, were constructed using stabilised inverse probability of treatment weighting. The primary outcomes were the incidence of AMD following newly diagnosed AF and the incidence of AF following newly diagnosed AMD. A Cox regression model was used to estimate hazard ratios (HR) for these outcomes. Subgroup analysis based on AMD subtype and stratified analyses by age and sex were also conducted.<br><br>RESULTS: Compared with controls, patients with AF had a significantly increased risk of developing AMD (HR 1.10; 95% confidence interval [CI] 1.04-1.17). Similarly, patients with AMD had a significantly increased risk of developing AF (HR 1.08; 95%CI 1.02-1.15). Further subgroup analysis revealed a reciprocal association between AF and dry AMD. Age- and sex-stratified analyses demonstrated increasing risk trends for AF and AMD.<br><br>CONCLUSIONS: AF and AMD may share common underlying risk factors and pathophysiological mechanisms. Our findings identified a reciprocal association between AF and AMD. Further research is warranted to elucidate the pathophysiology of AF and AMD.}, }
@article {pmid40914442, year = {2026}, author = {Song, W and Chen, W and Chi, J and Liu, X and Zhu, W}, title = {The role of lipid metabolism disorder in the progression and treatment of ocular vascular diseases.}, journal = {Survey of ophthalmology}, volume = {71}, number = {1}, pages = {1-13}, doi = {10.1016/j.survophthal.2025.09.002}, pmid = {40914442}, issn = {1879-3304}, mesh = {Humans ; *Lipid Metabolism/physiology ; Disease Progression ; *Lipid Metabolism Disorders/complications/physiopathology/metabolism ; Diabetic Retinopathy/metabolism ; *Retinal Diseases/metabolism ; Macular Degeneration/metabolism ; }, abstract = {Lipid metabolism plays a critical role in maintaining normal physiological functions and is strongly linked to the pathogenesis of ocular vascular diseases. We examine how disorders of lipid metabolism drive progression in ocular vascular diseases, including diabetic retinopathy, age-related macular degeneration, retinal vascular occlusive diseases, and retinopathy of prematurity. These disorders are classified as a related group due to their common feature of impaired ocular vascularization. Glaucoma has also been increasingly recognized as a condition resulting from both retinal and choroidal blood flow abnormalities, with shared lipid metabolism disturbances contributing to its pathogenesis. Lipid components such as fatty acids may exacerbate retinal and choroidal damage by promoting neovascularization and inflammatory responses. Additionally, lipid metabolic dysregulation negatively influences the retinal and choroidal microenvironment by increasing oxidative stress and inhibiting autophagy. We also discuss emerging therapeutic strategies targeting lipid metabolism, highlighting their potential in preventing or mitigating ocular vascular diseases. These include lipid-modulating agents and their use in combination with established therapies. Understanding the influence of lipid metabolism on the pathophysiology of these diseases could pave the way for the development of novel treatment approaches. These advancements hold potential to improve visual prognosis in patients with ocular vascular diseases. Identifying the specific roles and molecular targets associated with lipid metabolism in ocular vascular diseases will offer valuable insights into disease mechanisms. This knowledge will lay the groundwork for personalized and more effective clinical interventions.}, }
@article {pmid40914928, year = {2025}, author = {Liu, H and Ouyang, Y and Ge, H}, title = {SIRT1 as a potential target for age-related eye diseases: mechanisms and therapeutic strategies.}, journal = {Human cell}, volume = {38}, number = {6}, pages = {155}, pmid = {40914928}, issn = {1749-0774}, support = {2023HX015//Heilongjiang Charity Federation of China/ ; 2022HX005//Harbin Charity Federation/ ; }, mesh = {*Sirtuin 1/genetics/physiology/metabolism ; Humans ; *Eye Diseases/therapy/genetics ; Oxidative Stress/genetics ; *Aging/genetics ; Apoptosis/genetics ; *Molecular Targeted Therapy ; Diabetic Retinopathy/genetics/therapy ; Macular Degeneration/genetics/therapy ; Autophagy/genetics ; Cataract/genetics/therapy ; Cellular Senescence/genetics ; Glaucoma/genetics/therapy ; Inflammation ; Dry Eye Syndromes/genetics/therapy ; }, abstract = {Age-related eye diseases (AREDs) are the leading cause of visual impairment in the elderly, affecting the structure of the anterior and posterior segments of the eye, significantly reducing the quality of life of patients, and even leading to irreversible blindness. Typical AREDs include age-related cataract (ARC), dry eye disease (DED), age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), the global prevalence of which continues to rise, becoming a serious public health concern. SIRT1 is an NAD + dependent deacetylase, which plays an important physiological regulatory role in ocular tissues, mainly affecting gene expression and various cellular processes by regulating the acetylation status of substrate proteins. Studies have shown that SIRT1 plays a key role in oxidative stress, inflammation, autophagy, apoptosis and metabolism, and its expression or activity decreases can accelerate cell senescence and promote the occurrence and development of AREDs. In addition, SIRT1 expression levels and changes in its activity have been shown to be strongly associated with AREDs, making it a potential target for disease intervention and therapy. Therefore, this review systematically summarizes the biological role and regulatory mechanism of SIRT1 in AREDs, and explored its potential value as a therapeutic target, providing theoretical basis for future drug development and clinical transformation.}, }
@article {pmid40915427, year = {2026}, author = {Loh, NC and Rojas-Carabali, W and Lim, YH and Bong, JE and Villabona-Martinez, V and Cifuentes-González, C and Kumar, M and Sadda, S and Schmetterer, L and Cheung, CMG and Gupta, V and Grewal, DS and Fekrat, S and de-la-Torre, A and Lee, B and Wei, X and Nivison-Smith, L and Agrawal, R}, title = {Choroidal vascularity index as a marker of health and disease: systematic review and meta-analyses.}, journal = {Survey of ophthalmology}, volume = {71}, number = {1}, pages = {35-52}, doi = {10.1016/j.survophthal.2025.09.003}, pmid = {40915427}, issn = {1879-3304}, mesh = {Female ; Humans ; Pregnancy ; Biomarkers ; *Choroid/blood supply ; *Tomography, Optical Coherence/methods ; }, abstract = {The Choroidal Vascularity Index (CVI), derived from optical coherence tomography (OCT), has emerged as a potential biomarker for detecting vascular changes. Understanding its variability across physiological states, ocular conditions, and systemic diseases is crucial for its integration into clinical practice. We evaluated variations in CVI across different physiological states (e.g., first-trimester pregnancy), ocular conditions (e.g., age-related macular degeneration[AMD]), and systemic diseases (e.g., diabetes mellitus) compared to healthy controls. From 1210 identified articles, 63 studies (7316 participants: 4000 controls and 3316 cases) met inclusion criteria. Data covered 12 distinct conditions and physiological states. Most studies were conducted in Europe and Asia, predominantly using spectral-domain OCT machines with a low risk of bias. Increased CVI was seen in some physiological states (e.g., Valsalva maneuver, first-trimester pregnancy) and some disorders (e.g. active panuveitis, inactive thyroid eye disease). Reduced CVI was found in diabetes mellitus (both with or without diabetic retinopathy), hyperopic amblyopia, and AMD. CVI demonstrates potential as a biomarker to differentiate between physiological states and pathological conditions compared to healthy controls. These findings underscore the choroid's adaptive response to systemic and ocular challenges, highlighting CVI's relevance in understanding disease mechanisms and monitoring health.}, }
@article {pmid40915520, year = {2026}, author = {Shen, M and Berni, A and Liu, J and Hiya, F and Herrera, G and El-Mulki, OS and Beqiri, S and Cheng, Y and Kastner, J and Trivizki, O and Kumar, S and Zhang, Y and Le, VH and O'Brien, RC and Nicola, MD and Yehoshua, Z and Dubovy, SR and Wang, RK and Gregori, G and Rosenfeld, PJ}, title = {Real-World Experience With Intravitreal Pegcetacoplan for the Treatment of Geographic Atrophy in Age-Related Macular Degeneration.}, journal = {American journal of ophthalmology}, volume = {281}, number = {}, pages = {31-41}, doi = {10.1016/j.ajo.2025.09.006}, pmid = {40915520}, issn = {1879-1891}, mesh = {Humans ; *Geographic Atrophy/drug therapy/diagnosis/etiology/physiopathology ; Intravitreal Injections ; Retrospective Studies ; Male ; Female ; Tomography, Optical Coherence/methods ; Visual Acuity/physiology ; Aged ; Fluorescein Angiography/methods ; Aged, 80 and over ; Angiogenesis Inhibitors/therapeutic use ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Treatment Outcome ; Middle Aged ; }, abstract = {PURPOSE: To report on the real-world experience of using intravitreal pegcetacoplan for the treatment of geographic atrophy (GA) in age-related macular degeneration (AMD).<br><br>DESIGN: Retrospective interventional case series.<br><br>METHODS: Eyes with symptomatic GA secondary to AMD were treated with 15 mg of intravitreal pegcetacoplan and participated in an ongoing prospective swept-source optical coherence tomography angiography (SS-OCTA) imaging study. All eyes underwent SS-OCTA imaging before and during pegcetacoplan therapy to assess for GA lesion size, the presence of nonexudative macular neovascularization (MNV), and the onset of exudation. The growth rate of GA and best-corrected visual acuity (BCVA) were assessed for eyes followed for 1 year.<br><br>RESULTS: From April 12, 2023, to November 11, 2024, 154 eyes were injected with pegcetacoplan, and 103 eyes had 1-year follow-up. At baseline, 11 eyes had been previously treated with anti-VEGF therapy, and 9 eyes were diagnosed with treatment-na&#xef;ve nonexudative MNV by SS-OCTA. Each eye received an average of 10 &#xb1; 2 injections, with an average interval of 1.2 months between injections. For the 97 eyes with 1 year of follow-up and measurable GA, the square-root (sqrt) GA growth rate after pegcetacoplan treatment was 0.24 &#xb1; 0.15 mm/year. Of these 97 eyes, 63 eyes had prior annual visits before pegcetacoplan treatment was started. In these eyes, the annual sqrt GA growth rate was 0.33 &#xb1; 0.22 mm/year before pegcetacoplan and 0.21 &#xb1; 0.12 mm/year after pegcetacoplan, resulting in a 37% decrease in the growth rate (P < .001). There were no significant differences in GA growth rate between foveal and nonfoveal GA, either before or after the use of pegcetacoplan (all P &#x2265; .80). The mean BCVA declined from 63 &#xb1; 14 to 59 &#xb1; 15 letters over 1 year (P = .001), with no significant difference between foveal and nonfoveal GA (P = .36). Among the 29 eyes developing exudation during pegcetacoplan treatment, 19 (66%) had no evidence of any detectable MNV at baseline and during treatment on SS-OCTA.<br><br>CONCLUSIONS: Eyes treated with pegcetacoplan after 1 year had a 37% reduction in GA growth rate compared with their prior annual growth rate. Pegcetacoplan slowed the growth for foveal and nonfoveal GA at a similar rate. Most of the pegcetacoplan-associated exudation was not due to detectable MNV.}, }
@article {pmid40917264, year = {2025}, author = {Lishinsky-Fischer, N and Cnaany, Y and Nitzan, I and Chowers, I and Levy, J}, title = {Longitudinal Assessment of Age-Related Macular Degeneration and Risk of Dementia Using Clinical Setting Data.}, journal = {Ophthalmology science}, volume = {5}, number = {6}, pages = {100891}, pmid = {40917264}, issn = {2666-9145}, abstract = {OBJECTIVE: To examine whether there is an association between age-related macular degeneration (AMD) and dementia using a large, multi-institutional clinical data.<br><br>DESIGN: A retrospective cohort study.<br><br>PARTICIPANTS: Patients with AMD, including both neovascular AMD (nvAMD) and non-neovascular AMD (non-nvAMD) types, along with matched controls who had a record of eye examination but no diagnosis of AMD.<br><br>METHODS: Data were extracted from the 3 largest TriNetX networks (Global, United States, and Europe, Middle East, and Africa [EMEA]). Dementia diagnoses (Alzheimer disease [AD], vascular dementia, and unspecified dementia) and dementia-related medication use were compared between AMD and non-AMD groups. Diagnoses were identified using International Classification of Diseases, 10th Revision codes. Survival analyses were performed using Kaplan-Meier curves, and hazard ratios (HRs) were estimated using Cox proportional hazards models across 5-, 7-, and 10-year follow-up periods.<br><br>MAIN OUTCOME MEASURES: Hazard ratios for dementia subtypes in AMD patients versus non-AMD patients and in nvAMD patients versus non-nvAMD patients.<br><br>RESULTS: No significant association between AMD and AD was observed in the global network. In the United States, AMD was associated with a reduced risk of AD at 5 and 7 years (HR = 0.79 and 0.75; P < 0.0001), but not at 10 years. In the EMEA cohort, a protective association emerged at 7 and 10 years (HR = 0.16 and 0.33; P = 0.0063 and 0.0265). Vascular dementia showed no global association but was reduced in the United States at 5 and 7 years (HR = 0.73 and 0.79; P < 0.0001 and 0.0003). Unspecified dementia was associated with increased risk globally (HR = 1.17-1.27; P &#x2264; 0.0016), while the US data indicated a protective trend at 5 and 7 years. Dementia medication use was elevated in the global network at 7 years (HR = 1.27, P < 0.0001), but lower in the United States across all time points (P < 0.01). The negative control outcome (appendicitis) showed no difference between groups. No significant differences in AD or vascular dementia were found between nvAMD and non-AMD patients, although unspecified dementia and dementia medication use were lower in the nvAMD group.<br><br>CONCLUSIONS: Age-related macular degeneration was not consistently positively associated with AD or vascular dementia across networks. Regional variation, particularly negative associations in the United States, suggests underlying health care or diagnostic differences.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid40918516, year = {2025}, author = {Zhou, H and Pang, J and Wu, B and Zhuang, Y and Li, S and Jiang, J}, title = {Dihydromyricetin attenuates age-related macular degeneration: pharmacological effects and exploration of putative targets.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1588970}, pmid = {40918516}, issn = {1663-9812}, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults, with limited effective treatments available. This study aimed to investigate the pharmacological effects of dihydromyricetin (DHM) on AMD and to identify its putative pharmacological targets through network analysis and molecular docking approaches.<br><br>METHODS: In vitro experiments established an AMD model using sodium iodate (SI)-induced ARPE-19 cells, with CCK-8 assays determining 15 mM SI as the optimal modeling concentration and 100 &#x3bc;M DHM as the optimal treatment concentration. For in vivo validation, an AMD model was generated in C57 mice via tail vein injection of SI (30 mg/kg). Subsequent oral gavage with DHM (50 or 100 mg/kg) was administered. Integrated network analysis, molecular docking, and RT- qPCR validation were employed.<br><br>RESULTS: RT-qPCR analysis revealed that DHM reversed SI-induced aberrant expression of AMD-associated biomarkers (ICAM-1, APOE, HTRA1, ABCA4). Light microscopy and flow cytometry demonstrated DHM's significant mitigation of SI-triggered cellular morphological alterations and apoptosis (35% reduction). Western blot analysis further confirmed DHM-mediated suppression of apoptosis through regulation of p53, Bax, cleaved caspase-3, and Bcl-2 expression. High-dose DHM significantly attenuated retinal thinning (10.7% reduction), decreased pigment loss, and ameliorated structural disorganization in the outer nuclear layer (ONL). These analyses predicted seven putative targets implicated in functional categories including neurodegeneration, apoptosis, and DNA modification. Subsequent PPI network construction and GO/KEGG enrichment analyses revealed these targets' involvement in biological processes such as angiogenesis and extracellular matrix organization.<br><br>CONCLUSION: In conclusion, the present study demonstrates that DHM can mitigate AMD-related damage in both in vitro and in vivo models, while predicting putative targets and signaling pathways through which DHM may exert its effects against AMD. These findings offer promising directions for the development of AMD therapies and lay the groundwork for further investigation into DHM as a candidate drug for treating and preventing AMD.}, }
@article {pmid40919301, year = {2025}, author = {Abou-Samra, A and Barazi, MD and Abbas, A and Sabbagh, O and Bade, Y and Do, BK and Du, J and Ebert, J and Fein, J and Levinson, JD and Melamud, A and Sabbagh, O and Ali, MH}, title = {Real-World Experience of Geographic Atrophy Treatment With Avacincaptad Pegol.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251367100}, pmid = {40919301}, issn = {2474-1272}, abstract = {Purpose:To present the first real-world safety data describing the clinical experience of geographic atrophy (GA) treatment with avacincaptad pegol in a large cohort. Methods: A retrospective, observational cohort study was conducted within the PRISM Vision Group by filtering for J codes for avacincaptad pegol from August 3, 2023, to October 10, 2024. Results: The study included 461 eyes of 335 patients with GA who were treated with intravitreal avacincaptad pegol 2 mg (0.1 mL of 20 mg/mL) injections. The mean follow-up time was 120 days. The mean injection interval was 52 days. Fourteen eyes (3%) developed an acute rise in intraocular pressure, and there were no reports of endophthalmitis, intraocular inflammation, or nonarteritic anterior ischemic optic neuropathy. Eight eyes (2.03%) converted to neovascular age-related macular degeneration, with an average of 2 injections before conversion and a predicted annualized rate of conversion of approximately 6.17%. One eye (0.2%) developed a vitreous hemorrhage. Conclusions: This study describes the real-world safety profile of avacincaptad pegol that may aid clinicians in understanding the risk of adverse events associated with this relatively new treatment for GA.}, }
@article {pmid40920153, year = {2025}, author = {Kozina, EV and Samoylov, AN and Aksenov, KD and Aksenova, LE}, title = {[Algorithm for predicting treatment outcomes in vascular pigment epithelial detachment in neovascular age-related macular degeneration].}, journal = {Vestnik oftalmologii}, volume = {141}, number = {4}, pages = {12-18}, doi = {10.17116/oftalma202514104112}, pmid = {40920153}, issn = {0042-465X}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Detachment/diagnosis/etiology/drug therapy ; Algorithms ; Male ; Female ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; Treatment Outcome ; *Wet Macular Degeneration/complications/diagnosis/drug therapy ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; Fluorescein Angiography/methods ; Intravitreal Injections ; }, abstract = {UNLABELLED: Automated analysis of optical coherence tomography (OCT) biomarkers improves the prediction of results of loading anti-VEGF therapy of vascular pigment epithelial detachment (PED) associated with neovascular age-related macular degeneration (nAMD).<br><br>OBJECTIVE: This study evaluated the effectiveness of OCT biomarker analysis algorithm in predicting the anatomical outcomes of loading anti-VEGF therapy for vascular PED in nAMD.<br><br>MATERIAL AND METHODS: OCT scans performed prior to loading anti-VEGF therapy were analyzed using the algorithm in 69 treatment-na&#xef;ve nAMD patients (70 eyes) with vascular PED exceeding 200 &#xb5;m in height. Qualitative biomarkers included subretinal fluid (SRF), intraretinal fluid (IRF), hyperreflective material beneath the PED, PED defects, and hyperreflective foci in the outer retinal layers. Quantitative parameters - height, width, and area of PED - were manually measured and segmented using a U-NET-based neural network.<br><br>RESULTS: The algorithm predicted flattening of higher (499.2&#xb1;198.1 &#x3bc;m) and wider (3205.6&#xb1;734.2 &#x3bc;m) PEDs containing large hyperreflective foci in the mid-retinal layers and defects in PED (n=35 eyes). Resistance to loading therapy was predicted in lower (430.1&#xb1;126.4 &#x3bc;m) and narrower (2824.1&#xb1;732.8 &#x3bc;m) PEDs with sub-PED hyperreflective material without IRF (n=31 eyes). Risk of retinal pigment epithelium (RPE) tear was predicted for PEDs higher than 600 &#x3bc;m (mean 587.4&#xb1;193.6 &#x3bc;m) in the presence of SRF but without PED defects (n=4 eyes). The automated OCT biomarker analysis algorithm effectively predicted resistance of PEDs with the lowest height, width, and area. Greater PED area and width were predictive of flattening, while PED height over 600 &#x3bc;m, calculated using the algorithm, was a predictor of RPE tear.<br><br>CONCLUSION: The developed OCT biomarker analysis algorithm enables effective prediction of anatomical outcomes following loading anti-VEGF therapy in vascular PED in nAMD.}, }
@article {pmid40920159, year = {2025}, author = {Dotsenko, KR and Zolotarev, AV and Karlova, EV and Zamytskiy, EA and Zubkova, EY and Balandina, EV and Ilyasova, NY and Demin, NS and Ionov, AY}, title = {[Nanosecond retinal laser therapy: three years of practical experience].}, journal = {Vestnik oftalmologii}, volume = {141}, number = {4}, pages = {60-65}, doi = {10.17116/oftalma202514104160}, pmid = {40920159}, issn = {0042-465X}, mesh = {Humans ; Male ; Visual Acuity ; Female ; Tomography, Optical Coherence/methods ; Aged ; Follow-Up Studies ; *Macular Degeneration/surgery/diagnosis/physiopathology ; Treatment Outcome ; *Retina/surgery/pathology ; Middle Aged ; *Laser Coagulation/methods ; }, abstract = {OBJECTIVE: This study evaluated the outcomes of a 36-month follow-up after treatment with the ELLEX 2RT nanosecond laser.<br><br>MATERIAL A